Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries.

PubMed

Naing, Cho; Aung, Kyan; Win, Daw-Khin; Wah, Mak Joon

2010-11-01

Chloroquine (CQ) is a relatively inexpensive drug for treatment of malaria. If efficacy of CQ is still assumed, then it should be indicated in malaria treatment policies as the drug of choice for uncomplicated Plasmodium vivax malaria in endemic countries with resource constraints. The objective of this review is to summarize the existing evidence on the relative efficacy and safety of CQ in treating patients with uncomplicated P. vivax malaria in endemic countries. We searched online data bases (PUBMED, MEDLINE, EMBASE, The Cochrane Library) and the reference lists of the retrieved articles. Fifteen randomized controlled trials (n=6215) assessing the relative efficacy and safety of CQ for treatment of uncomplicated P. vivax malaria were included. CQ monotherapy was compared to CQ plus primaquine (PQ), artemisinin/artemether, artemisinin based combination therapy, quinine, CQ plus tafenoquine, chlorguanil plus dapsone, azithromycin, or placebo. Treatment efficacy was not significantly different between the CQ monotherapy group and that of the CQ with PQ 14 day group at 28 day follow-up (55/711, 7.7% vs 35/712, 4.9%; P=0.16). Evidence from the trials identified for this review draw a fairly clear conclusion about the relative efficacy and safety of CQ for treating uncomplicated P. vivax malaria infection. However, further research in this field with well powered, randomized, non-inferiority design, using the standardized protocol is needed. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Evaluating the Treatment Costs for Uncomplicated Malaria at a Public Healthcare Facility in Nigeria and the Implications.

PubMed

Ezenduka, Charles C; Falleiros, Daniel Resende; Godman, Brian B

2017-09-01

Accurate information on the facility costs of treatment is essential to enhance decision making and funding for malaria control. The objective of this study was to estimate the costs of providing treatment for uncomplicated malaria through a public health facility in Nigeria. Hospital costs were estimated from a provider perspective, applying a standard costing procedure. Capital and recurrent expenditures were estimated using an ingredient approach combined with step-down methodology. Costs attributable to malaria treatment were calculated based on the proportion of malaria cases to total outpatient visits. The costs were calculated in local currency [Naira (N)] and converted to US dollars at the 2013 exchange rate. Total annual costs of N28.723 million (US$182,953.65) were spent by the facility on the treatment of uncomplicated malaria, at a rate of US$31.49 per case, representing approximately 25% of the hospital's total expenditure in the study year. Personnel accounted for over 82.5% of total expenditure, followed by antimalarial medicines at 6.6%. More than 45% of outpatients visits were for uncomplicated malaria. Changes in personnel costs, drug prices and malaria prevalence significantly impacted on the study results, indicating the need for improved efficiency in the use of hospital resources. Malaria treatment currently consumes a considerable amount of resources in the facility, driven mainly by personnel cost and a high proportion of malaria cases. There is scope for enhanced efficiency to prevent waste and reduce costs to the provider and ultimately the consumer.

Impact of the method of G6PD deficiency assessment on genetic association studies of malaria susceptibility.

PubMed

Johnson, Marla K; Clark, Tamara D; Njama-Meya, Denise; Rosenthal, Philip J; Parikh, Sunil

2009-09-30

Clinical association studies have yielded varied results regarding the impact of glucose-6-phosphate dehydrogenase (G6PD) deficiency upon susceptibility to malaria. Analyses have been complicated by varied methods used to diagnose G6PD deficiency. We compared the association between uncomplicated malaria incidence and G6PD deficiency in a cohort of 601 Ugandan children using two different diagnostic methods, enzyme activity and G6PD genotype (G202A, the predominant East African allele). Although roughly the same percentage of males were identified as deficient using enzyme activity (12%) and genotype (14%), nearly 30% of males who were enzymatically deficient were wild-type at G202A. The number of deficient females was three-fold higher with assessment by genotype (21%) compared to enzyme activity (7%). Heterozygous females accounted for the majority (46/54) of children with a mutant genotype but normal enzyme activity. G6PD deficiency, as determined by G6PD enzyme activity, conferred a 52% (relative risk [RR] 0.48, 95% CI 0.31-0.75) reduced risk of uncomplicated malaria in females. In contrast, when G6PD deficiency was defined based on genotype, the protective association for females was no longer seen (RR = 0.99, 95% CI 0.70-1.39). Notably, restricting the analysis to those females who were both genotypically and enzymatically deficient, the association of deficiency and protection from uncomplicated malaria was again demonstrated in females, but not in males (RR = 0.57, 95% CI 0.37-0.88 for females). This study underscores the impact that the method of identifying G6PD deficient individuals has upon association studies of G6PD deficiency and uncomplicated malaria. We found that G6PD-deficient females were significantly protected against uncomplicated malaria, but this protection was only seen when G6PD deficiency is described using enzyme activity. These observations may help to explain the discrepancy in some published association studies involving G6PD deficiency and uncomplicated malaria.

Case management of malaria in Swaziland, 2011-2015: on track for elimination?

PubMed

Dlamini, S V; Kosgei, R J; Mkhonta, N; Zulu, Z; Makadzange, K; Zhou, S; Owiti, P; Sikhondze, W; Namboze, J; Reid, A; Kunene, S

2018-04-25

Objective: To assess adherence to malaria diagnosis and treatment guidelines (2010 and 2014) in all health care facilities in Swaziland between 2011 and 2015. Methods: This was a cross-sectional descriptive study involving all health care facilities that diagnosed and managed malaria cases in Swaziland. Patients' age, sex, diagnosis method and type of treatment were analysed. Results: Of 1981 records for severe and uncomplicated malaria analysed, 56% of cases were uncomplicated and 14% had severe malaria. The type of malaria was not recorded for 30% of cases. Approximately 71% of cases were confirmed by rapid diagnostic tests (RDT) alone, 3% by microscopy alone and 26% by both RDT and microscopy. Of the uncomplicated cases, 93% were treated with artemether-lumefantrine (AL) alone, 5% with quinine alone and 2% with AL and quinine. Amongst the severe cases, 11% were treated with AL alone, 44% with quinine alone and 45% with AL and quinine. For severe malaria, clinics and health centres prescribed AL alone more often than hospitals (respectively 13%, 12% and 4%, P = 0.03). Conclusion: RDTs and/or microscopy results are used at all facilities to inform treatment. Poor recording of malaria type causes difficulties in assessing the prescription of antimalarial drugs.

Malaria and nutritional status among children with severe acute malnutrition in Niger: a prospective cohort study.

PubMed

Oldenburg, Catherine E; Guerin, Philippe J; Berthé, Fatou; Grais, Rebecca F; Isanaka, Sheila

2018-03-07

The relationship between malaria infection and nutritional status is complex and previous studies suggest malaria may increase the incidence and severity of malnutrition while malnutrition may increase the risk of malaria infection. Here, we report bi-directional associations between malaria and nutritional status among children with uncomplicated severe acute malnutrition (SAM). The present study is a secondary analysis of a randomized controlled trial for the treatment of uncomplicated SAM in Niger. Children between 6-59 months were enrolled and followed for 12 weeks. Malaria infection was assessed using an HRP2 rapid diagnostic test at admission and at any follow-up visit with fever. We assessed the association of 1) nutritional status at admission on malaria incidence using Cox proportional hazards regression, and 2) malaria infection at admission on nutritional recovery, weight and height gain using linear regression. Of 2,399 children included in the analysis, 1,327 (55.3%) were infected with malaria at admission. Malaria incidence was 12.1 cases per 100 person-months among those without malaria infection at admission. Nutritional status at admission was not associated with malaria incidence. Children with malaria infection at admission, subsequently treated with an artemisinin based combination therapy, had increased weight gain (0.38 g/kg/day, 95% confidence interval [CI] 0.07 to 0.69) and reduced height gain (-0.002 mm/day, 95% CI -0.004 to -0.0008). Malaria infection was common among children treated for uncomplicated SAM. Malaria infection may impair height gain. Proper medical and nutritional management should be assured to prevent adverse effects of malaria infection.

Treatment of acute uncomplicated falciparum malaria with artemether-lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study.

PubMed

Hatz, Christoph; Soto, Jaime; Nothdurft, Hans Dieter; Zoller, Thomas; Weitzel, Thomas; Loutan, Louis; Bricaire, Francois; Gay, Frederick; Burchard, Gerd-Dieter; Andriano, Kim; Lefèvre, Gilbert; De Palacios, Patricia Ibarra; Genton, Blaise

2008-02-01

The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

Drug use in the management of uncomplicated malaria in public health facilities in the Democratic Republic of the Congo.

PubMed

Ntamabyaliro, Nsengi Y; Burri, Christian; Nzolo, Didier B; Engo, Aline B; Lula, Yves N; Mampunza, Samuel M; Nsibu, Célestin N; Mesia, Gauthier K; Kayembe, Jean-Marie N; Likwela, Joris L; Kintaudi, Leon M; Tona, Gaston L

2018-05-03

Malaria the first causes of death from parasitic infection worldwide. Interventions to reduce the burden of malaria have produced a tremendous drop in malaria morbidity and mortality. However, progress is slower in DRC, which shares with Nigeria 39% of deaths related to malaria globally. Inappropriate use of drugs may be one of the factors of this below-average performance. The aim of this study was to describe the use of drugs in the management of uncomplicated malaria in public health facilities in DRC. A drug use study was carried out in DRC from January to March 2014. In each of the former 11 provinces of DRC, one Rural Health Centre, one Urban Health Centre and one General Hospital were selected. In each of them, 100 patient's files containing prescription of anti-malarials from January to December 2013 were randomly selected. Among them, all of the files with diagnosis of uncomplicated malaria were included in this study. Prescribed anti-malarials, co-prescribed drugs and their indications were collected. Descriptive analyses were performed. A total of 2300 files out of 3300 (69.7%) concerned uncomplicated malaria and were included in analysis. Malaria treatment was initiated after a positive RDT or microscopy in 51.5% of cases, upon suspicion without requesting biological confirmation in 37% and despite negative results in 11%. Twenty-nine (29) different treatment regimens were used. The drugs recommended by the National Malaria Control Programme were used in 54.3% of cases (artesunate-amodiaquine 37.4% or artemether-lumefantrine 16.9%). The second most used anti-malarial was quinine (32.4%). Apart from anti-malarials, an average of 3.1 drugs per patient were prescribed, among which antibiotics (67.9%), analgesics and non-steroidal anti-inflammatory (NSAIDs) (all abbreviations to be explicated on first use) (70.6%), vitamins (29.1%), anaemia drugs, including blood transfusion (9.1%) and corticosteroids (5.7%), In 51.4% of cases there was no indication for the concomitant medication. Management of uncomplicated malaria in DRC is characterized by a low adherence to treatment policy, numerous treatment regimens, and abundant concomitant medication potentially harmful to the patient. This may contribute to the low performance of DRC in malaria control. Determinant of this irrational use of drugs need to be assessed in order to formulate and implement efficient corrective measures.

Impact of combining intermittent preventive treatment with home management of malaria in children less than 10 years in a rural area of Senegal: a cluster randomized trial.

PubMed

Tine, Roger C K; Faye, Babacar; Ndour, Cheikh T; Ndiaye, Jean L; Ndiaye, Magatte; Bassene, Charlemagne; Magnussen, Pascal; Bygbjerg, Ib C; Sylla, Khadim; Ndour, Jacques D; Gaye, Oumar

2011-12-13

Current malaria control strategies recommend (i) early case detection using rapid diagnostic tests (RDT) and treatment with artemisinin combination therapy (ACT), (ii) pre-referral rectal artesunate, (iii) intermittent preventive treatment and (iv) impregnated bed nets. However, these individual malaria control interventions provide only partial protection in most epidemiological situations. Therefore, there is a need to investigate the potential benefits of integrating several malaria interventions to reduce malaria prevalence and morbidity. A randomized controlled trial was carried out to assess the impact of combining seasonal intermittent preventive treatment in children (IPTc) with home-based management of malaria (HMM) by community health workers (CHWs) in Senegal. Eight CHWs in eight villages covered by the Bonconto health post, (South Eastern part of Senegal) were trained to diagnose malaria using RDT, provide prompt treatment with artemether-lumefantrine for uncomplicated malaria cases and pre-referral rectal artesunate for complicated malaria occurring in children under 10 years. Four CHWs were randomized to also administer monthly IPTc as single dose of sulphadoxine-pyrimethamine (SP) plus three doses of amodiaquine (AQ) in the malaria transmission season, October and November 2010. Primary end point was incidence of single episode of malaria attacks over 8 weeks of follow up. Secondary end points included prevalence of malaria parasitaemia, and prevalence of anaemia at the end of the transmission season. Primary analysis was by intention to treat. The study protocol was approved by the Senegalese National Ethical Committee (approval 0027/MSP/DS/CNRS, 18/03/2010). A total of 1,000 children were enrolled. The incidence of malaria episodes was 7.1/100 child months at risk [95% CI (3.7-13.7)] in communities with IPTc + HMM compared to 35.6/100 child months at risk [95% CI (26.7-47.4)] in communities with only HMM (aOR = 0.20; 95% CI 0.09-0.41; p = 0.04). At the end of the transmission season, malaria parasitaemia prevalence was lower in communities with IPTc + HMM (2.05% versus 4.6% p = 0.03). Adjusted for age groups, sex, Plasmodium falciparum carriage and prevalence of malnutrition, IPTc + HMM showed a significant protective effect against anaemia (aOR = 0.59; 95% CI 0.42-0.82; p = 0.02). Combining IPTc and HMM can provide significant additional benefit in preventing clinical episodes of malaria as well as anaemia among children in Senegal.

Treatment of Febrile illness with artemisinin combination therapy: prevalence and predictors in five African household surveys.

PubMed

Vialle-Valentin, Catherine E; LeCates, Robert F; Zhang, Fang; Ross-Degnan, Dennis

2015-01-01

To evaluate the determinants of compliance with national policies recommending Artemisinin Combination Therapy (ACT) for the treatment of uncomplicated malaria in the community. We used data from Gambia, Ghana, Kenya, Nigeria, and Uganda national household surveys that were conducted with a standardized World Health Organization (WHO) methodology to measure access to and use of medicines. We analyzed all episodes of acute fever reported in the five surveys. We used logistic regression models accounting for the clustered design of the surveys to identify determinants of seeking care in public healthcare facilities, of being treated with antimalarials, and of receiving ACT. Overall, 92% of individuals with a febrile episode sought care outside the home, 96% received medicines, 67% were treated with antimalarials, and 16% received ACT. The choice of provider was influenced by perceptions about medicines availability and affordability. In addition, seeking care in a public healthcare facility was the single most important predictor of treatment with ACT [odds ratio (OR): 4.64, 95% confidence intervals (CI): 2.98-7.22, P < 0.001]. Children under 5 years old were more likely than adults to be treated with antimalarials [OR: 1.28, CI: 0.91-1.79, not significant (NS)] but less likely to receive ACT (OR: 0.80, CI: 0.57-1.13, NS). Our results confirm the high prevalence of presumptive antimalarial treatment for acute fever, especially in public healthcare facilities where poor people seek care. They show that perceptions about access to medicines shape behaviors by directing patients and caregivers to sources of care where they believe medicines are accessible. The success of national policies recommending ACT for the treatment of uncomplicated malaria depends not only on restricting ACT to confirmed malaria cases, but also on ensuring that ACT is available and affordable for those who need it.

The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria.

PubMed

Ambler, Michael T; Dubowitz, Lilly M; Arunjerdja, Ratree; Hla, Eh Paw; Thwai, Kyaw Lay; Viladpainguen, Jacher; Singhasivanon, Pratap; Luxemburger, Christine; Nosten, François; McGready, Rose

2009-09-02

Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children. Children, aged between three months and five years, with acute uncomplicated Plasmodium falciparum malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28. From December 1994 to July 1997, 91 children with uncomplicated P. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033). In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.

Efficacy of Chloroquine as a first line agent in the treatment of uncomplicated malaria due to Plasmodium vivax in children and treatment practices in Pakistan: A Pilot study.

PubMed

Waqar, Talal; Khushdil, Arshad; Haque, Khalid

2016-01-01

To ascertain the efficacy of chloroquine as first line agent in treatment of uncomplicated malaria -caused by Plasmodium vivax in children---and to determine its current treatment practice in Pakistan. This pilot study was conducted at the Paediatrics Department of Combined Military Hospital (CMH), Lahore, Pakistan. Forty-eight children between six months and twelve years of age having positive blood film for Plasmodium vivax were included. They were treated with chloroquine as a drug of - choice. Efficacy of chloroquine was assessed by clinical response, absence of parasitaemia on day seven and twenty-eight after initiation of therapy. A survey was also conducted to determine the first line therapeutic choice of Paediatricians in the treatment of uncomplicated Plasmodium vivax malaria in children in Pakistan. The results showed 100% efficacy of chloroquine in treating uncomplicated malaria caused by Plasmodium vivax in children. Artemisin was preferred by 74.28% Paediatricians' in combination therapy as 1st line treatment. Guidelines proposed by Malaria Control Programme Pakistan (MCPP) in collaboration with World Health Organization (WHO) are comprehensive but not being adhered to. The recently reported resistance of Plasmodium vivax to artemisin should urge measures to implement WHO guidelines.

Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda.

PubMed

Lwanira, Catherine Nassozi; Kironde, Fred; Kaddumukasa, Mark; Swedberg, Göte

2017-08-09

Host genetics play an important role in Plasmodium falciparum malaria susceptibility. However, information on host genetic factors and their relationships with malaria in the vaccine trial site of Iganga, Uganda is limited. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. In a 1-year longitudinal cohort study, 423 children aged below 9 years were recruited and their malaria episodes were investigated. Host genetic polymorphisms were assessed by PCR-RFLP, haemoglobin electrophoresis and DNA sequencing. Using a multivariate negative binomial regression model, estimates of the impact of human genetic polymorphisms on malaria incidence were performed. In all statistical tests, a P value of <0.05 was considered as significant. The prevalences of sickle cell haemoglobin trait, G6PD c.202 G>A (rs 1050828) and NOS2 -954 G>C (rs 1800482) variants were 26.6, 22.7 and 17.3%, respectively. Inducible nitric oxide synthase 2 (NOS2 -954 G>C; rs 1800482) heterozygosity was associated with lower incidence of malaria in all age groups {Adjusted incident rates ratio (aIRR) 0.59; 95% CI [0.386-0.887]; P = 0.012)}. About 4% of study subjects had co-existence of sickle cell Hb trait and G6PD deficiency. Sickle cell Hb heterozygotes (Hb AS) aged less than 1 year experienced significantly more malaria episodes annually than children with normal haemoglobin (Hb AA) {aIRR = 1.98; 95% CI [1.240-3.175]; P = 0.004}. There was no significant influence of the sickle cell trait on malaria incidence among older children of 1-9 years. Mutation (NOS2 -954 G>C; rs 1800482) of nitric oxide synthase 2 gene promoter was associated with a lower incidence of acute malaria. The normal haemoglobin (wild genotype; HbAA) was associated with reduced malaria incidence rates during the first year of life. More understanding of the interplay between host genetics and malaria susceptibility is required.

Treating uncomplicated malaria in children: comparing artemisinin-based combination therapies.

PubMed

Yeka, Adoke; Harris, Jamal C

2010-12-01

In response to increased resistance to conventional drugs, the WHO is promoting artemisinin-based combination therapy (ACT) for treating uncomplicated malaria. The objective of this report is to review the available evidence on the efficacy and effectiveness, acceptability, and deployment of ACT in resource-limited settings with a focus on sub-Saharan Africa. ACTs are very effective in the treatment of uncomplicated Plasmodium falciparum malaria in children. ACTs are relatively safe and tolerable with no reported resistance in sub-Saharan Africa despite indications of delayed clearance of infections in south-east Asia. The major challenges to the widespread use of ACT include its high cost, availability, and inefficient delivery due to, among other things, weak healthcare systems. ACTs are an essential tool in the fight to control and eliminate malaria. They are currently the most effective drugs against P. falciparum malaria. They should be deployed through programs that address availability, cost, adherence, and quality assurance. Initiatives including home-based management of malaria, improving public sector procurement and supply chains, and reducing private sector pricing should make ACTs more accessible for sub-Saharan African children who bear the brunt of the burden of malarial disease.

Plasmodium vivax Hospitalizations in a Monoendemic Malaria Region: Severe Vivax Malaria?

PubMed Central

Quispe, Antonio M.; Pozo, Edwar; Guerrero, Edith; Durand, Salomón; Baldeviano, G. Christian; Edgel, Kimberly A.; Graf, Paul C. F.; Lescano, Andres G.

2014-01-01

Severe malaria caused by Plasmodium vivax is no longer considered rare. To describe its clinical features, we performed a retrospective case control study in the subregion of Luciano Castillo Colonna, Piura, Peru, an area with nearly exclusive vivax malaria transmission. Severe cases and the subset of critically ill cases were compared with a random set of uncomplicated malaria cases (1:4). Between 2008 and 2009, 6,502 malaria cases were reported, including 106 hospitalized cases, 81 of which fit the World Health Organization definition for severe malaria. Of these 81 individuals, 28 individuals were critically ill (0.4%, 95% confidence interval = 0.2–0.6%) with severe anemia (57%), shock (25%), lung injury (21%), acute renal failure (14%), or cerebral malaria (11%). Two potentially malaria-related deaths occurred. Compared with uncomplicated cases, individuals critically ill were older (38 versus 26 years old, P < 0.001), but similar in other regards. Severe vivax malaria monoinfection with critical illness is more common than previously thought. PMID:24752683

Plasmodium vivax hospitalizations in a monoendemic malaria region: severe vivax malaria?

PubMed

Quispe, Antonio M; Pozo, Edwar; Guerrero, Edith; Durand, Salomón; Baldeviano, G Christian; Edgel, Kimberly A; Graf, Paul C F; Lescano, Andres G

2014-07-01

Severe malaria caused by Plasmodium vivax is no longer considered rare. To describe its clinical features, we performed a retrospective case control study in the subregion of Luciano Castillo Colonna, Piura, Peru, an area with nearly exclusive vivax malaria transmission. Severe cases and the subset of critically ill cases were compared with a random set of uncomplicated malaria cases (1:4). Between 2008 and 2009, 6,502 malaria cases were reported, including 106 hospitalized cases, 81 of which fit the World Health Organization definition for severe malaria. Of these 81 individuals, 28 individuals were critically ill (0.4%, 95% confidence interval = 0.2-0.6%) with severe anemia (57%), shock (25%), lung injury (21%), acute renal failure (14%), or cerebral malaria (11%). Two potentially malaria-related deaths occurred. Compared with uncomplicated cases, individuals critically ill were older (38 versus 26 years old, P < 0.001), but similar in other regards. Severe vivax malaria monoinfection with critical illness is more common than previously thought. © The American Society of Tropical Medicine and Hygiene.

Genetic diversity of Plasmodium falciparum isolates from naturally infected children in north-central Nigeria using the merozoite surface protein-2 as molecular marker.

PubMed

Oyedeji, Segun Isaac; Awobode, Henrietta Oluwatoyin; Anumudu, Chiaka; Kun, Jürgen

2013-08-01

To characterize the genetic diversity of Plasmodium falciparum (P. falciparum) field isolates in children from Lafia, North-central Nigeria, using the highly polymorphic P. falciparum merozoite surface protein 2 (MSP-2) gene as molecular marker. Three hundred and twenty children were enrolled into the study between 2005 and 2006. These included 140 children who presented with uncomplicated malaria at the Dalhatu Araf Specialist Hospital, Lafia and another 180 children from the study area with asymptomatic infection. DNA was extracted from blood spot on filter paper and MSP-2 genes were genotyped using allele-specific nested PCR in order to analyze the genetic diversity of parasite isolates. A total of 31 and 34 distinct MSP-2 alleles were identified in the asymptomatic and uncomplicated malaria groups respectively. No difference was found between the multiplicity of infection in the asymptomatic group and that of the uncomplicated malaria group (P>0.05). However, isolates of the FC27 allele type were dominant in the asymptomatic group whereas isolates of the 3D7 allele type were dominant in the uncomplicated malaria group. This study showed a high genetic diversity of P. falciparum isolates in North-central Nigeria and is comparable to reports from similar areas with high malaria transmission intensity. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

The Treatment of Plasmodium knowlesi Malaria.

PubMed

Barber, Bridget E; Grigg, Matthew J; William, Timothy; Yeo, Tsin W; Anstey, Nicholas M

2017-03-01

Plasmodium knowlesi occurs across Southeast Asia and is the most common cause of malaria in Malaysia. High parasitaemias can develop rapidly, and the risk of severe disease in adults is at least as high as in falciparum malaria. Prompt initiation of effective treatment is therefore essential. Intravenous artesunate is highly effective in severe knowlesi malaria and in those with moderately high parasitaemia but otherwise uncomplicated disease. Both chloroquine and artemisinin-combination therapy (ACT) are highly effective for uncomplicated knowlesi malaria, with faster parasite clearance times and lower anaemia rates with ACT. Given the difficulties with microscope diagnosis of P. knowlesi, a unified treatment strategy of ACT for all Plasmodium species is recommended in coendemic regions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria

PubMed Central

Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau; Lavstsen, Thomas; Aide, Pedro; Jiménez, Alfons; Turner, Louise; Gupta, Himanshu; De Las Salas, Briegel; Mandomando, Inacio; Wang, Christian W.; Petersen, Jens E. V.; Muñoz, Jose; Gascón, Joaquim; Macete, Eusebio; Alonso, Pedro L.; Chitnis, Chetan E.

2016-01-01

Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLβ12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLβ12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction. PMID:27835682

Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

PubMed

Mwaiswelo, Richard; Ngasala, Billy E; Jovel, Irina; Gosling, Roland; Premji, Zul; Poirot, Eugenie; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas

2016-06-10

This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart™) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm. Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient patients, two in AL and one in AL + PQ arm, but none in genotypically hemizygous/homozygous patients. All patients with acute haemolytic anaemia recovered without medical intervention. The findings support that the WHO recommendation of adding a single low-dose of PQ to standard AL regimen is safe for the treatment of acute uncomplicated P. falciparum malaria regardless of G6PD status in Tanzania. Trial registration number NCT02090036.

Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

PubMed

Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

2009-02-01

In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

Cost-effectiveness of artemisinin-naphthoquine versus artemether-lumefantrine for the treatment of uncomplicated malaria in Papua New Guinean children.

PubMed

Moore, Brioni R; Davis, Wendy A; Clarke, Philip M; Robinson, Leanne J; Laman, Moses; Davis, Timothy M E

2017-10-30

A recent randomized trial showed that artemisinin-naphthoquine (AN) was non-inferior to artemether-lumefantrine (AL) for falciparum malaria and superior for vivax malaria in young Papua New Guinean children. The aim of this study was to compare the cost-effectiveness of these two regimens. An incremental cost-effectiveness analysis was performed using data from 231 children with Plasmodium falciparum and/or Plasmodium vivax infections in an open-label, randomized, parallel-group trial. Recruited children were randomized 1:1 to receive once daily AN for 3 days with water or twice daily AL for 3 days given with fat. World Health Organisation (WHO) definitions were used to determine clinical/parasitological outcomes. The cost of transport between the home and clinic, plus direct health-care costs, served as a basis for determining each regimen's incremental cost per incremental treatment success relative to AL by Day 42 and its cost per life year saved. In the usual care setting, AN was more effective for the treatment of uncomplicated malaria in children aged 0.5-5.9 years. AL and AN were equally efficacious for the treatment of falciparum malaria, however AN had increased anti-malarial treatment costs per patient of $10.46, compared with AL. AN was the most effective regimen for treatment of vivax malaria, but had increased treatment costs of $14.83 per treatment success compared with AL. Whilst AN has superior overall efficacy for the treatment of uncomplicated malaria in PNG children, AL was the less costly regimen. An indicative extrapolation estimated the cost per life year saved by using AN instead of AL to treat uncomplicated malaria to be $12,165 for girls and $12,469 for boys (discounted), which means AN may not be cost-effective and affordable for PNG at current cost. However, AN may become acceptable should it become WHO prequalified and/or should donated/subsidized drug supply become available.

Comparison of allele frequencies of Plasmodium falciparum merozoite antigens in malaria infections sampled in different years in a Kenyan population.

PubMed

Ochola-Oyier, Lynette Isabella; Okombo, John; Wagatua, Njoroge; Ochieng, Jacob; Tetteh, Kevin K; Fegan, Greg; Bejon, Philip; Marsh, Kevin

2016-05-06

Plasmodium falciparum merozoite antigens elicit antibody responses in malaria-endemic populations, some of which are clinically protective, which is one of the reasons why merozoite antigens are the focus of malaria vaccine development efforts. Polymorphisms in several merozoite antigen-encoding genes are thought to arise as a result of selection by the human immune system. The allele frequency distribution of 15 merozoite antigens over a two-year period, 2007 and 2008, was examined in parasites obtained from children with uncomplicated malaria. In the same population, allele frequency changes pre- and post-anti-malarial treatment were also examined. Any gene which showed a significant shift in allele frequencies was also assessed longitudinally in asymptomatic and complicated malaria infections. Fluctuating allele frequencies were identified in codons 147 and 148 of reticulocyte-binding homologue (Rh) 5, with a shift from HD to YH haplotypes over the two-year period in uncomplicated malaria infections. However, in both the asymptomatic and complicated malaria infections YH was the dominant and stable haplotype over the two-year and ten-year periods, respectively. A logistic regression analysis of all three malaria infection populations between 2007 and 2009 revealed, that the chance of being infected with the HD haplotype decreased with time from 2007 to 2009 and increased in the uncomplicated and asymptomatic infections. Rh5 codons 147 and 148 showed heterogeneity at both an individual and population level and may be under some degree of immune selection.

Treatment outcomes in a safety observational study of dihydroartemisinin/piperaquine (Eurartesim(®)) in the treatment of uncomplicated malaria at public health facilities in four African countries.

PubMed

Adjei, Alexander; Narh-Bana, Solomon; Amu, Alberta; Kukula, Vida; Nagai, Richard Afedi; Owusu-Agyei, Seth; Oduro, Abraham; Macete, Eusebio; Abdulla, Salim; Halidou, Tinto; Sie, Ali; Osei, Isaac; Sevene, Esperance; Asante, Kwaku-Poku; Mulokozi, Abdunoor; Compaore, Guillaume; Valea, Innocent; Adjuik, Martin; Baiden, Rita; Ogutu, Bernhards; Binka, Fred; Gyapong, Margaret

2016-01-27

Dihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children. This paper reports the clinical outcomes following administration of DHQ-PQ in real-life conditions in public health facilities in Burkina Faso, Ghana, Mozambique, and Tanzania for the treatment of confirmed uncomplicated malaria. An observational, non-comparative, longitudinal study was conducted on 10,591 patients with confirmed uncomplicated malaria visiting public health facilities within seven health and demographic surveillance system sites in four African countries (Ghana, Tanzania, Burkina Faso, Mozambique) between September 2013 and April 2014. Patients were treated with DHA-PQ based on body weight and followed up for 28 days to assess the clinical outcome. A nested cohort of 1002 was intensely followed up. Clinical outcome was assessed using the proportion of patients who reported signs and symptoms of malaria after completing 3 days of treatment. A total of 11,097 patients were screened with 11,017 enrolled, 94 were lost to follow-up, 332 withdrew and 10,591 (96.1%) patients aged 6 months-85 years met protocol requirements for analysis. Females were 52.8 and 48.5% were <5 years of age. Malaria was diagnosed by microscopy and rapid diagnostic test in 69.8% and 29.9%, respectively. At day 28, the unadjusted risk of recurrent symptomatic parasitaemia was 0.5% (51/10,591). Most of the recurrent symptomatic malaria patients (76%) were children <5 years. The mean haemoglobin level decreased from 10.6 g/dl on day 1 to 10.2 g/dl on day 7. There was no significant renal impairment in the nested cohort during the first 7 days of follow-up with minimal non-clinically significant changes noted in the liver enzymes. DHA-PQ was effective and well tolerated in the treatment of uncomplicated malaria and provides an excellent alternative first-line ACT in sub-Saharan Africa.

Therapeutic Response to Dihydroartemisinin-Piperaquine for P. falciparum and P. vivax Nine Years after Its Introduction in Southern Papua, Indonesia.

PubMed

Poespoprodjo, Jeanne Rini; Kenangalem, Enny; Wafom, Johny; Chandrawati, Freis; Puspitasari, Agatha M; Ley, Benedikt; Trianty, Leily; Korten, Zoé; Surya, Asik; Syafruddin, Din; Anstey, Nicholas M; Marfurt, Jutta; Noviyanti, Rintis; Price, Ric N

2018-03-01

Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days. Clinical and laboratory data were collected daily until parasite clearance and then weekly for 6 weeks. Molecular analysis was undertaken for all patients with recurrent parasitemia. A total of 129 study patients were enrolled in the study. At day 42, the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence intervals [CI]: 87.4-99.9) in the 61 patients with P. falciparum malaria, and 98.2% [95% CI: 90.3-100] in the 56 patients with P. vivax malaria. By day 2, 98% (56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax had cleared their peripheral parasitemia; none of the patients were still parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that none (0/61) had K13 mutations associated previously with artemisinin resistance or increased copy number of plasmepsin 2-3 (0/61). In the absence of artemisinin resistance, DHP has retained high efficacy for the treatment of uncomplicated malaria despite extensive drug pressure over a 9-year period.

Efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria: revisiting molecular markers in an area of emerging AQ and SP resistance in Mali

PubMed Central

Tekete, Mamadou; Djimde, Abdoulaye A; Beavogui, Abdoul H; Maiga, Hamma; Sagara, Issaka; Fofana, Bakary; Ouologuem, Dinkorma; Dama, Souleymane; Kone, Aminatou; Dembele, Demba; Wele, Mamadou; Dicko, Alassane; Doumbo, Ogobara K

2009-01-01

Background To update the National Malaria Control Programme of Mali on the efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria. Methods During the malaria transmission seasons of 2002 and 2003, 455 children – between six and 59 months of age, with uncomplicated malaria in Kolle, Mali, were randomly assigned to one of three treatment arms. In vivo outcomes were assessed using WHO standard protocols. Genotyping of msp1, msp2 and CA1 polymorphisms were used to distinguish reinfection from recrudescent parasites (molecular correction). Results Day 28 adequate clinical and parasitological responses (ACPR) were 14.1%, 62.3% and 88.9% in 2002 and 18.2%, 60% and 85.2% in 2003 for chloroquine, amodiaquine and sulphadoxine-pyrimethamine, respectively. After molecular correction, ACPRs (cACPR) were 63.2%, 88.5% and 98.0% in 2002 and 75.5%, 85.2% and 96.6% in 2003 for CQ, AQ and SP, respectively. Amodiaquine was the most effective on fever. Amodiaquine therapy selected molecular markers for chloroquine resistance, while in the sulphadoxine-pyrimethamine arm the level of dhfr triple mutant and dhfr/dhps quadruple mutant increased from 31.5% and 3.8% in 2002 to 42.9% and 8.9% in 2003, respectively. No infection with dhps 540E was found. Conclusion In this study, treatment with sulphadoxine-pyrimethamine emerged as the most efficacious on uncomplicated falciparum malaria followed by amodiaquine. The study demonstrated that sulphadoxine-pyrimethamine and amodiaquine were appropriate partner drugs that could be associated with artemisinin derivatives in an artemisinin-based combination therapy. PMID:19245687

Increasing incidence of malaria in children despite insecticide-treated bed nets and prompt anti-malarial therapy in Tororo, Uganda

PubMed Central

2012-01-01

Background The burden of malaria has decreased in parts of Africa following the scaling up of control interventions. However, similar data are limited from high transmission settings. Methods A cohort of 100 children, aged six weeks to 10 months of age, were enrolled in an area of high malaria transmission intensity and followed through 48 months of age. Children were given a long-lasting insecticide-treated bed net (LLIN) at enrolment and received all care, including monthly blood smears and treatment with artemisinin-based combination therapy (ACT) for uncomplicated malaria, at a dedicated clinic. The incidence of malaria was estimated by passive surveillance and associations between malaria incidence and age, calendar time and season were measured using generalized estimating equations. Results Reported compliance with LLINs was 98% based on monthly routine evaluations. A total of 1,633 episodes of malaria were observed, with a median incidence of 5.3 per person-year (PPY). There were only six cases of complicated malaria, all single convulsions. Malaria incidence peaked at 6.5 PPY at 23 months of age before declining to 3.5 PPY at 48 months. After adjusting for age and season, the risk of malaria increased by 52% from 2008 to 2011 (RR 1.52, 95% CI 1.10-2.09). Asymptomatic parasitaemia was uncommon (monthly prevalence <10%) and rarely observed prior to 24 months of age. Conclusions In Tororo, despite provision of LLINs and prompt treatment with ACT, the incidence of malaria is very high and appears to be rising. Additional malaria control interventions in high transmission settings are likely needed. Trial registration Current Controlled Trials Identifier NCT00527800 PMID:23273022

Therapeutic efficacy and safety of dihydroartemisinin-piperaquine versus artesunate-mefloquine in uncomplicated Plasmodium falciparum malaria in India

PubMed Central

2012-01-01

Background Resistance in Plasmodium falciparum to commonly used anti-malarial drugs, especially chloroquine, is being increasingly documented in India. By 2007, the first-line treatment for uncomplicated malaria has been revised to recommend artemisinin-based combination therapy (ACT) for all confirmed P. falciparum cases. Objective The objective of this study was to compare the efficacy, safety and tolerability between dihydroartemisinin-piperaquine (DP) and artesunate plus mefloquine (A + M) drug combinations in the treatment of uncomplicated P. falciparum malaria in India. Methods Between 2006 and 2007, 150 patients with acute uncomplicated P. falciparum malaria were enrolled, randomized to DP (101) or A + M (49) and followed up for 63 days as part of an open-label, non-inferiority, randomized, phase III multicenter trial in Asia. Results The heterogeneity analysis showed no statistically significant difference between India and the other countries involved in the phase III study, for both the PCR-corrected and uncorrected cure rates. As shown at the whole study level, both forms of ACT were highly efficacious in India. In fact, in the per protocol population, the 63-day cure rates were 100% for A + M and 98.8% for DP. The DP combination exerted a significant post-treatment prophylactic effect, and compared with A + M a significant reduction in the incidence of new infections for DP was observed (respectively 17.1% versus 7.5% of patients experienced new infection within follow up). Parasite and fever clearance was rapid in both treatment arms (median time to parasite clearance of one day for both groups). Both DP and A + M were well tolerated, with the majority of adverse events of mild or moderate severity. The frequencies of individual adverse events were generally similar between treatments, although the incidence of post treatment adverse events was slightly higher in patients who received A + M with respect to those treated with DP. Conclusion DP is a new ACT displaying high efficacy and safety in the treatment of uncomplicated P. falciparum malaria and could potentially be considered for the first-line treatment of uncomplicated falciparum malaria in India. Trial registration Current Controlled Trials ISRCTN 81306618 PMID:22818552

Modeling the public health impact of malaria vaccines for developers and policymakers

PubMed Central

2013-01-01

Background Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model’s functionality is demonstrated through a hypothetical vaccine. Methods The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. Results The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. Conclusions The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions. PMID:23815273

Modeling the public health impact of malaria vaccines for developers and policymakers.

PubMed

Nunes, Julia K; Cárdenas, Vicky; Loucq, Christian; Maire, Nicolas; Smith, Thomas; Shaffer, Craig; Måseide, Kårstein; Brooks, Alan

2013-07-01

Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine. The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions.

Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of Dihydroartemisinin-Piperaquine in Patients with Uncomplicated Falciparum Malaria in Vietnam ▿

PubMed Central

Nguyen, Dao Van Hoang; Nguyen, Quoc Phuc; Nguyen, Ngoa Dang; Le, Thuy Thi Thanh; Nguyen, The Duy; Dinh, Duy Ngoc; Nguyen, Thanh Xuan; Bui, Dai; Chavchich, Marina; Edstein, Michael D.

2009-01-01

Compared to healthy subjects, malaria patients show a reduction in the mean oral clearance (1.19 versus 5.87 liters/h/kg of body weight) and apparent volume of distribution (1.47 versus 8.02 liters/kg) of dihydroartemisinin in Vietnamese patients following treatment with dihydroartemisinin-piperaquine (Artekin) for uncomplicated Plasmodium falciparum. Dihydroartemisinin is responsible for most of the ex vivo antimalarial activity of dihydroartemisinin-piperaquine. PMID:19528277

Use of HRP-2-based rapid diagnostic test for Plasmodium falciparum malaria: assessing accuracy and cost-effectiveness in the villages of Dielmo and Ndiop, Senegal.

PubMed

Ly, Alioune Badara; Tall, Adama; Perry, Robert; Baril, Laurence; Badiane, Abdoulaye; Faye, Joseph; Rogier, Christophe; Touré, Aissatou; Sokhna, Cheikh; Trape, Jean-François; Michel, Rémy

2010-06-04

In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP. A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT. A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700 euros per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs. A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable.

Health worker adherence to malaria treatment guidelines at outpatient health facilities in southern Malawi following implementation of universal access to diagnostic testing.

PubMed

Namuyinga, Ruth J; Mwandama, Dyson; Moyo, Dubulao; Gumbo, Austin; Troell, Peter; Kobayashi, Miwako; Shah, Monica; Bauleni, Andrew; Vanden Eng, Jodi; Rowe, Alexander K; Mathanga, Don P; Steinhardt, Laura C

2017-01-23

Appropriate diagnosis and treatment are essential for reducing malaria mortality. A cross-sectional outpatient health facility (HF) survey was conducted in southern Malawi from January to March 2015 to determine appropriate malaria testing and treatment practices four years after implementation of a policy requiring diagnostic confirmation before treatment. Enrolled patients were interviewed, examined and had their health booklet reviewed. Health workers (HWs) were asked about training, supervision and access to the 2013 national malaria treatment guidelines. HFs were assessed for malaria diagnostic and treatment capacity. Weighted descriptive analyses and logistic regression of patient, HW and HF characteristics related to testing and treatment were performed. An evaluation of 105 HFs, and interviews of 150 HWs and 2342 patients was completed. Of 1427 suspect uncomplicated malaria patients seen at HFs with testing available, 1072 (75.7%) were tested, and 547 (53.2%) tested positive. Testing was more likely if patients spontaneously reported fever (odds ratio (OR) 2.6; 95% confidence interval (CI) 1.7-4.0), headache (OR 1.5; 95% CI 1.1-2.1) or vomiting (OR 2.0; 95% CI 1.0-4.0) to HWs and less likely if they reported skin problems (OR 0.4; 95% CI 0.2-0.6). Altogether, 511 (92.7%) confirmed cases and 98 (60.3%) of 178 presumed uncomplicated malaria patients (at HFs without testing) were appropriately treated, while 500 (96.6%) of 525 patients with negative tests did not receive anti-malarials. Only eight (5.7%) suspect severe malaria patients received appropriate pre-referral treatment. Appropriate treatment was more likely for presumed uncomplicated malaria patients (at HFs without testing) with elevated temperature (OR 1.5/1 °C increase; 95% CI 1.1-1.9), who reported fever to HWs (OR 5.7; 95% CI 1.9-17.6), were seen by HWs with additional supervision visits in the previous 6 months (OR 1.2/additional visit; 95% CI 1.0-1.4), or were seen by older HWs (OR 1.1/year of age; 95% CI 1.0-1.1). Correct testing and treatment practices were reasonably good for uncomplicated malaria when testing was available. Pre-referral treatment for suspect severe malaria was unacceptably rare. Encouraging HWs to elicit and appropriately respond to patient symptoms may improve practices.

Uncomplicated malaria in children: The place of rapid diagnostic test.

PubMed

Elechi, Hassan Abdullahi; Rabasa, Adamu Ibrahim; Bashir, Muhammad Faruk; Gofama, Mustapha Modu; Ibrahim, Halima Abubakar; Askira, Umoru Muhammed

2015-01-01

Malaria has remained a major cause of morbidity and mortality among the under-five children in Nigeria. Prompt and accurate diagnosis of malaria is necessary in controlling this high burden and preventing unnecessary use of anti-malarial drugs. Malaria rapid diagnostic test (MRDT) offers the hope of achieving this goal. However, the performance of these kits among the most vulnerable age group to malaria is inadequate. In this cross-sectional study, 433 out-patients, aged <5 years with fever or history of fever were enrolled. Each candidate was tested for malaria parasitaemia using ACON; malaria pf. Thick and thin films were also prepared from the same finger prick blood for each candidate. Malaria rapid diagnostic test had sensitivity of 8.3%, specificity of 100%, positive predictive value (PPV) of 100% and negative predictive value (NPV) of 74%. The sensitivity of MRDT increased with increasing age. This effect of age on sensitivity was statistically significant (P = 0.007). Similarly parasite density had significant effect on the sensitivity of MRDT (P = <0.001). Histidine-rich protein-2 based MRDT is not a reliable mean of diagnosing malaria in the under-five age children with acute uncomplicated malaria.

Treatment regimens for pregnant women with falciparum malaria.

PubMed

Moore, Brioni R; Salman, Sam; Davis, Timothy M E

2016-08-01

With increasing parasite drug resistance, the WHO has updated treatment recommendations for falciparum malaria including in pregnancy. This review assesses the evidence for choice of treatment for pregnant women. Relevant studies, primarily those published since 2010, were identified from reference databases and were used to identify secondary data sources. Expert commentary: WHO recommends use of intravenous artesunate for severe malaria, quinine-clindamycin for uncomplicated malaria in first trimester, and artemisinin combination therapy for uncomplicated malaria in second/third trimesters. Because fear of adverse outcomes has often excluded pregnant women from conventional drug development, available data for novel therapies are usually based on preclinical studies and cases of inadvertent exposure. Changes in antimalarial drug disposition in pregnancy have been observed but are yet to be translated into specific treatment recommendations. Such targeted regimens may become important as parasite resistance demands that drug exposure is optimized.

Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

PubMed Central

Blair, Silvia; Akinyi Okoth, Sheila; Udhayakumar, Venkatachalam; Marcet, Paula L.; Escalante, Ananias A.; Alexander, Neal; Rojas, Carlos

2016-01-01

Plasmodium vivax recurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicated P. vivax infection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity of P. vivax strains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence of P. vivax malaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites. PMID:27185794

Severe Plasmodium knowlesi Malaria in a Tertiary Care Hospital, Sabah, Malaysia

PubMed Central

William, Timothy; Menon, Jayaram; Rajahram, Giri; Chan, Leslie; Ma, Gordon; Donaldson, Samantha; Khoo, Serena; Fredrick, Charlie; Jelip, Jenarun; Anstey, Nicholas M.

2011-01-01

The simian parasite Plasmodium knowlesi causes severe human malaria; the optimal treatment remains unknown. We describe the clinical features, disease spectrum, and response to antimalarial chemotherapy, including artemether-lumefantrine and artesunate, in patients with P. knowlesi malaria diagnosed by PCR during December 2007–November 2009 at a tertiary care hospital in Sabah, Malaysia. Fifty-six patients had PCR-confirmed P. knowlesi monoinfection and clinical records available for review. Twenty-two (39%) had severe malaria; of these, 6 (27%) died. Thirteen (59%) had respiratory distress; 12 (55%), acute renal failure; and 12, shock. None experienced coma. Patients with uncomplicated disease received chloroquine, quinine, or artemether-lumefantrine, and those with severe disease received intravenous quinine or artesunate. Parasite clearance times were 1–2 days shorter with either artemether-lumefantrine or artesunate treatment. P. knowlesi is a major cause of severe and fatal malaria in Sabah. Artemisinin derivatives rapidly clear parasitemia and are efficacious in treating uncomplicated and severe knowlesi malaria. PMID:21762579

Provider Profiling: A Population Health Improvement Tool for the Southeast Military Health System

DTIC Science & Technology

1999-06-01

weeks to five years of age who were diagnosed with a first episode of uncomplicated episode of acute otitis media and were prescribed an antibiotic...episode of uncomplicated episode of acute otitis media and were prescribed an antibiotic other than a preferred antimicrobial agent. DENOMINATOR Number of...enrolled children six weeks to five years of age who were diagnosed with a first episode of acute otitis media . Benchmark INDUSTRY STANDARD Measure

Feasibility of Malaria Diagnosis and Management in Burkina Faso, Nigeria, and Uganda: A Community-Based Observational Study.

PubMed

Ajayi, IkeOluwapo O; Nsungwa-Sabiiti, Jesca; Siribié, Mohamadou; Falade, Catherine O; Sermé, Luc; Balyeku, Andrew; Afonne, Chinenye; Sanou, Armande K; Kabarungi, Vanessa; Oshiname, Frederick O; Gansane, Zakaria; Kyaligonza, Josephine; Jegede, Ayodele S; Tiono, Alfred B; Sirima, Sodiomon B; Diarra, Amidou; Yusuf, Oyindamola B; Fouque, Florence; Castellani, Joëlle; Petzold, Max; Singlovic, Jan; Gomes, Melba

2016-12-15

 Malaria-endemic countries are encouraged to increase, expedite, and standardize care based on parasite diagnosis and treat confirmed malaria using oral artemisinin-based combination therapy (ACT) or rectal artesunate plus referral when patients are unable to take oral medication.  In 172 villages in 3 African countries, trained community health workers (CHWs) assessed and diagnosed children aged between 6 months and 6 years using rapid histidine-rich protein 2 (HRP2)-based diagnostic tests (RDTs). Patients coming for care who could take oral medication were treated with ACTs, and those who could not were treated with rectal artesunate and referred to hospital. The full combined intervention package lasted 12 months. Changes in access and speed of care and clinical course were determined through 1746 random household interviews before and 3199 during the intervention.  A total of 15 932 children were assessed: 6394 in Burkina Faso, 2148 in Nigeria, and 7390 in Uganda. Most children assessed (97.3% [15 495/15 932]) were febrile and most febrile cases (82.1% [12 725/15 495]) tested were RDT positive. Almost half of afebrile episodes (47.6% [204/429]) were RDT positive. Children eligible for rectal artesunate contributed 1.1% of episodes. The odds of using CHWs as the first point of care doubled (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.9-2.4; P < .0001). RDT use changed from 3.2% to 72.9% (OR, 80.8; 95% CI, 51.2-127.3; P < .0001). The mean duration of uncomplicated episodes reduced from 3.69 ± 2.06 days to 3.47 ± 1.61 days, Degrees of freedom (df) = 2960, Student's t (t) = 3.2 (P = .0014), and mean duration of severe episodes reduced from 4.24 ± 2.26 days to 3.7 ± 1.57 days, df = 749, t = 3.8, P = .0001. There was a reduction in children with danger signs from 24.7% before to 18.1% during the intervention (OR, 0.68; 95% CI, .59-.78; P < .0001).  Provision of diagnosis and treatment via trained CHWs increases access to diagnosis and treatment, shortens clinical episode duration, and reduces the number of severe cases. This approach, recommended by the World Health Organization, improves malaria case management.  ISRCTN13858170. © 2016 World Health Organization; licensee Oxford Journals.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial.

PubMed

De la Hoz Restrepo, Fernando; Porras Ramírez, Alexandra; Rico Mendoza, Alejandro; Córdoba, Freddy; Rojas, Diana Patricia

2012-12-01

In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28-day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. assessed through adverse events. A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

Open-label, randomized, non-inferiority clinical trial of artesunate-amodiaquine versus artemether-lumefantrine fixed-dose combinations in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire.

PubMed

Toure, Offianan A; Assi, Serge B; N'Guessan, Tiacoh L; Adji, Gbessi E; Ako, Aristide B; Brou, Marie J; Ehouman, Marie F; Gnamien, Laeticia A; Coulibaly, M'Lanhoro A A; Coulibaly, Baba; Beourou, Sylvain; Bassinka, Issiaka; Soumahoro, Adama; Kadjo, Florence; Tano, Mea A

2014-11-19

Emergence of artemisinin resistance has raised concerns that the most potent anti-malarial drug may be under threat. Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are, respectively, the first- and second-line treatments for uncomplicated falciparum malaria in Côte d'Ivoire. Constant monitoring by National Malaria Control Programme (NMCP) of drug efficacy is an important tool in establishing rational anti-malarial drug policies in Côte d'Ivoire. In an open label, randomized controlled clinical trial, children and adults were randomized to receive AS-AQ or AL. Both drug regimens were given for three days, and follow-up was for 42 days. The primary endpoint was the 42-day cure rate and was defined as proportion of patients with PCR-corrected cure rate after 42 days of follow-up. A total of 383 patients who were attending the Anonkoua-koute (Abidjan), Petit Paris (Korhogo) and Libreville (Man) hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive AS-AQ (188) and AL (195). The intention-to-treat analysis showed effectiveness rates of 94.7% and 96.4% for AS-AQ and AL, respectively on day 42. After adjustment for PCR, these rates were 96.8% and 99%, respectively. At day 42, in per-protocol analysis, Adequate clinical and parasitological response (ACPR) PCR uncorrected was 97.8% and 97.4% for AS-AQ and AL, respectively. The PCR adjusted ACPR was 100% for each combination and both regimens were well tolerated. This study has shown the high efficacy of AS-AQ in patients of all ages with acute uncomplicated falciparum malaria and AS-AQ was non-inferior to AL. Continuous efficacy monitoring is recommended.

Costs and cost-effectiveness of malaria control interventions - a systematic review

PubMed Central

2011-01-01

Background The control and elimination of malaria requires expanded coverage of and access to effective malaria control interventions such as insecticide-treated nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment (IPT), diagnostic testing and appropriate treatment. Decisions on how to scale up the coverage of these interventions need to be based on evidence of programme effectiveness, equity and cost-effectiveness. Methods A systematic review of the published literature on the costs and cost-effectiveness of malaria interventions was undertaken. All costs and cost-effectiveness ratios were inflated to 2009 USD to allow comparison of the costs and benefits of several different interventions through various delivery channels, across different geographical regions and from varying costing perspectives. Results Fifty-five studies of the costs and forty three studies of the cost-effectiveness of malaria interventions were identified, 78% of which were undertaken in sub-Saharan Africa, 18% in Asia and 4% in South America. The median financial cost of protecting one person for one year was $2.20 (range $0.88-$9.54) for ITNs, $6.70 (range $2.22-$12.85) for IRS, $0.60 (range $0.48-$1.08) for IPT in infants, $4.03 (range $1.25-$11.80) for IPT in children, and $2.06 (range $0.47-$3.36) for IPT in pregnant women. The median financial cost of diagnosing a case of malaria was $4.32 (range $0.34-$9.34). The median financial cost of treating an episode of uncomplicated malaria was $5.84 (range $2.36-$23.65) and the median financial cost of treating an episode of severe malaria was $30.26 (range $15.64-$137.87). Economies of scale were observed in the implementation of ITNs, IRS and IPT, with lower unit costs reported in studies with larger numbers of beneficiaries. From a provider perspective, the median incremental cost effectiveness ratio per disability adjusted life year averted was $27 (range $8.15-$110) for ITNs, $143 (range $135-$150) for IRS, and $24 (range $1.08-$44.24) for IPT. Conclusions A transparent evidence base on the costs and cost-effectiveness of malaria control interventions is provided to inform rational resource allocation by donors and domestic health budgets and the selection of optimal packages of interventions by malaria control programmes. PMID:22050911

Mind the gap: knowledge and practice of providers treating uncomplicated malaria at public and mission health facilities, pharmacies and drug stores in Cameroon and Nigeria

PubMed Central

Mangham-Jefferies, Lindsay; Hanson, Kara; Mbacham, Wilfred; Onwujekwe, Obinna; Wiseman, Virginia

2015-01-01

Background Artemisinin combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Cameroon since 2004 and Nigeria since 2005, though many febrile patients receive less effective antimalarials. Patients often rely on providers to select treatment, and interventions are needed to improve providers’ practice and encourage them to adhere to clinical guidelines. Methods Providers’ adherence to malaria treatment guidelines was examined using data collected in Cameroon and Nigeria at public and mission facilities, pharmacies and drug stores. Providers’ choice of antimalarial was investigated separately for each country. Multilevel logistic regression was used to determine whether providers were more likely to choose ACT if they knew it was the first-line antimalarial. Multiple imputation was used to impute missing data that arose when linking exit survey responses to details of the provider responsible for selecting treatment. Results There was a gap between providers’ knowledge and their practice in both countries, as providers’ decision to supply ACT was not significantly associated with knowledge of the first-line antimalarial. Providers were, however, more likely to supply ACT if it was the type of antimalarial they prefer. Other factors were country-specific, and indicated providers can be influenced by what they perceived their patients prefer or could afford, as well as information about their symptoms, previous treatment, the type of outlet and availability of ACT. Conclusions Public health interventions to improve the treatment of uncomplicated malaria should strive to change what providers prefer, rather than focus on what they know. Interventions to improve adherence to malaria treatment guidelines should emphasize that ACT is the recommended antimalarial, and it should be used for all patients with uncomplicated malaria. Interventions should also be tailored to the local setting, as there were differences between the two countries in providers’ choice of antimalarial, and who or what influenced their practice. PMID:25339637

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

PubMed

Vaughan-Williams, Charles H; Raman, Jaishree; Raswiswi, Eric; Immelman, Etienne; Reichel, Holger; Gate, Kelly; Knight, Steve

2012-12-28

Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

Three case definitions of malaria and their effect on diagnosis, treatment and surveillance in Cox's Bazar district, Bangladesh.

PubMed

Montanari, R M; Bangali, A M; Talukder, K R; Baqui, A; Maheswary, N P; Gosh, A; Rahman, M; Mahmood, A H

2001-01-01

In countries where malaria is endemic, routine blood slide examinations remain the major source of data for the public health surveillance system. This approach has become inadequate, however, as the public health emphasis has changed from surveillance of laboratory-confirmed malaria infections to the early detection and treatment of the disease. As a result, it has been advocated that the information collected about malaria be changed radically and should include the monitoring of morbidity and mortality, clinical practice and quality of care. To improve the early diagnosis and prompt treatment (EDPT) of malaria patients, three malaria case definitions (MCDs) were developed, with treatment and reporting guidelines, and used in all static health facilities of Cox's Bazar district, Bangladesh (population 1.5 million). The three MCDs were: uncomplicated malaria (UM); treatment failure malaria (TFM); and severe malaria (SM). The number of malaria deaths was also reported. This paper reviews the rationale and need for MCDs in malaria control programmes and presents an analysis of the integrated surveillance information collected during the three-year period, 1995-97. The combined analysis of slide-based and clinical data and their related indicators shows that blood slide analysis is no longer used to document fever episodes but to support EDPT, with priority given to SM and TFM patients. Data indicate a decrease in the overall positive predictive value of the three MCDs as malaria prevalence decreases. Hence the data quantify the extent to which the mainly clinical diagnosis of UM leads to over-diagnosis and over-treatment in changing epidemiological conditions. Also the new surveillance data show: a halving in the case fatality rate among SM cases (from 6% to 3.1%) attributable to improved quality of care, and a stable proportion of TFM cases (around 7%) against a defined population denominator. Changes implemented in the EDPT of malaria patients and in the surveillance system were based on existing staff capacity and routine reporting structures.

Feasibility of home management using ACT for childhood malaria episodes in an urban setting

PubMed Central

Nsagha, Dickson S; Elat, Jean-Bosco N; Ndong, Proper AB; Tata, Peter N; Tayong, Maureen-Nill N; Pokem, Francois F; Wankah, Christian C

2012-01-01

Background Over 90% of malaria cases occur in Sub-Saharan Africa, where a child under the age of 5 years dies from this illness every 30 seconds. The majority of families in Sub- Saharan Africa treat malaria at home, but therapy is often incomplete, hence the World Health Organization has adopted the strategy of home management of malaria to solve the problem. The purpose of this study was to determine community perception and the treatment response to episodes of childhood malaria in an urban setting prior to implementation of home management using artemisinin-based combination therapy (ACT). Methods This qualitative exploratory study on the home management of malaria in urban children under 5 years of age used 15 focus group discussions and 20 in-depth interviews in various categories of caregivers of children under 5 years. One hundred and eighteen people participated in the focus group discussions and 20 in the in-depth interviews. The study explored beliefs and knowledge about malaria, mothers’ perception of home management of the disease, health-seeking behavior, prepackaged treatment of malaria using ACT and a rapid diagnostic test, preferred channels for home management of uncomplicated malaria, communication, the role of the community in home management of malaria, and the motivation of drug distributors in the community. Results The mothers’ perception of malaria was the outcome of events other than mosquito bites. Home treatment is very common and is guided by the way mothers perceive signs and symptoms of malaria. Frequent change of malarial drugs by the national health policy and financial difficulties were the main problems mothers faced in treating febrile children. Rapid diagnostic testing and prepackaged ACT for simple malaria in children under 5 years would be accepted if it was offered at an affordable price. Tribalism and religious beliefs might hinder the delivery of home management of malaria. The availability of rapid diagnostic testing and ACT all year round is one of the challenges of home management of malaria. Although radio and television featured among the current sources of information within the community, meetings, churches, schools, and other public gatherings were the best venues for social mobilization, while community health workers and community leaders were the best sensitization agents for positive behavior change to adhere to home management of malaria. Monetary incentives should be offered to community drug distributors. This should be deducted from the combined price of ACT and rapid diagnostic testing. Conclusion For successful implementation of home management of malaria, there should be proper education, social mobilization of the population, and continuous monitoring and evaluation of field activities to ensure adequate stocks of ACT and rapid diagnostic testing within the framework of the intervention. PMID:22328833

Serum laminin in malaria.

PubMed Central

Wenisch, C; Graninger, W; Viravan, C; Looareesuwan, S; Parschalk, B; Wernsdorfer, W

1994-01-01

AIM--To determine serum laminin concentrations in patients with uncomplicated Plasmodium falciparum malaria. METHODS--An enzyme linked immunosorbent assay (ELISA) was used to determine serum laminin concentrations in 54 patients with acute uncomplicated P falciparum malaria during and after treatment, and in 17 control subjects in Bangkok, Thailand. RESULTS--Raised concentrations of soluble laminin were observed in patients (mean (SD) concentration 628 (225) ng/ml), compared with normal controls (490 (116) ng/ml), during the acute phase of the disease. During treatment, serum laminin concentrations decreased and returned to normal within three days. Serum laminin concentrations were correlated with parasite counts before treatment, and with the serum concentration of soluble intercellular adhesion molecule-1 (ICAM-1), soluble E-selectin, and soluble tumour necrosis factor receptor at 55 kilodaltons. CONCLUSIONS--These findings are compatible with an increased production or release of laminin in P falciparum malaria, which could indicate a role for the subendothelial basement membrane in the pathogenesis of the disease. PMID:7525659

Use of HRP-2-based rapid diagnostic test for Plasmodium falciparum malaria: assessing accuracy and cost-effectiveness in the villages of Dielmo and Ndiop, Senegal

PubMed Central

2010-01-01

Background In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck®). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck® compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP. Methods A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT. Results A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700€ per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs. Conclusions A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable. PMID:20525322

Outcome of artemether-lumefantrine treatment for uncomplicated malaria in HIV-infected adult patients on anti-retroviral therapy.

PubMed

Maganda, Betty A; Minzi, Omary M S; Kamuhabwa, Appolinary A R; Ngasala, Billy; Sasi, Philip G

2014-05-30

Malaria and HIV infections are both highly prevalent in sub-Saharan Africa, with HIV-infected patients being at higher risks of acquiring malaria. The majority of antiretroviral (ART) and anti-malarial drugs are metabolized by the CYP450 system, creating a chance of drug-drug interaction upon co-administration. Limited data are available on the effectiveness of the artemether-lumefantrine combination (AL) when co-administered with non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this study was to compare anti-malarial treatment responses between HIV-1 infected patients on either nevirapine- or efavirenz-based treatment and those not yet on ART (control-arm) with uncomplicated falciparum malaria, treated with AL. This was a prospective, non-randomized, open-label study conducted in Bagamoyo district, with three arms of HIV-infected adults: efavirenz-based treatment arm (EFV-arm) n = 66, nevirapine-based treatment arm (NVP-arm) n = 128, and control-arm n = 75, with uncomplicated malaria. All patients were treated with AL and followed up for 28 days. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with AL by day 28. Day 28 ACPR was 97.6%, 82.5% and 94.5% for the NVP-arm, EFV-arm and control-arm, respectively. No early treatment or late parasitological failure was reported. The cumulative risk of recurrent parasitaemia was >19-fold higher in the EFV-arm than in the control-arm (Hazard ratio [HR], 19.11 [95% confidence interval {CI}, 10.5-34.5]; P < 0.01). The cumulative risk of recurrent parasitaemia in the NVP-arm was not significantly higher than in the control-arm ([HR], 2.44 [95% {CI}, 0.79-7.6]; P = 0.53). The median (IQR) day 7 plasma concentrations of lumefantrine for the three arms were: 1,125 ng/m (638.8-1913), 300.4 ng/ml (220.8-343.1) and 970 ng/ml (562.1-1729) for the NVP-arm, the EFV-arm and the control-arm, respectively (P < 0.001). In all three arms, the reported adverse events were mostly mild. After 28 days of follow-up, AL was statistically safe and effective in the treatment of uncomplicated malaria in the NVP-arm. The results of this study also provide an indication of the possible impact of EFV on the performance of AL and the likelihood of it affecting uncomplicated falciparum malaria treatment outcome.

Relative Susceptibilities of ABO Blood Groups to Plasmodium falciparum Malaria in Ghana.

PubMed

Afoakwah, Richmond; Aubyn, Edmond; Prah, James; Nwaefuna, Ekene Kwabena; Boampong, Johnson N

2016-01-01

The clinical outcome of falciparum malaria in endemic areas is influenced by erythrocyte polymorphisms including the ABO blood groups. Studies have reported association of ABO blood group to resistance, susceptibility, and severity of P. falciparum malaria infection. Individuals with blood group "A" have been found to be highly susceptible to falciparum malaria whereas blood group "O" is said to confer protection against complicated cases. We analyzed samples from 293 young children less than six years old with malaria in the Korle-Bu Teaching Hospital in Accra, Ghana. It was observed that group O was present in about 16.1% of complicated cases weighed against 40.9% of uncomplicated controls. Individuals with complicated malaria were about twice likely to be of blood groups A and B compared to group O (A versus O, OR = 1.90, 95% CI = 1.59-2.26, P < 0.0001; B versus O, OR = 1.82. 95% CI = 1.57-2.23, P < 0.0001). Blood group O participants with complicated diseases had low parasitaemia compared to the other blood groups (P < 0.0001). This may give blood group O individuals a survival advantage over the other groups in complicated malaria as suggested. Participants with complicated falciparum malaria were generally anaemic and younger than those with uncomplicated disease.

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

PubMed Central

2012-01-01

Background Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. Methods An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Results Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. Conclusions The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation. PMID:23272998

Feasibility of Malaria Diagnosis and Management in Burkina Faso, Nigeria, and Uganda: A Community-Based Observational Study

PubMed Central

Ajayi, IkeOluwapo O.; Nsungwa-Sabiiti, Jesca; Siribié, Mohamadou; Falade, Catherine O.; Sermé, Luc; Balyeku, Andrew; Afonne, Chinenye; Sanou, Armande K.; Kabarungi, Vanessa; Oshiname, Frederick O.; Gansane, Zakaria; Kyaligonza, Josephine; Jegede, Ayodele S.; Tiono, Alfred B.; Sirima, Sodiomon B.; Diarra, Amidou; Yusuf, Oyindamola B.; Fouque, Florence; Castellani, Joëlle; Petzold, Max; Singlovic, Jan; Gomes, Melba

2016-01-01

Background. Malaria-endemic countries are encouraged to increase, expedite, and standardize care based on parasite diagnosis and treat confirmed malaria using oral artemisinin-based combination therapy (ACT) or rectal artesunate plus referral when patients are unable to take oral medication. Methods. In 172 villages in 3 African countries, trained community health workers (CHWs) assessed and diagnosed children aged between 6 months and 6 years using rapid histidine-rich protein 2 (HRP2)–based diagnostic tests (RDTs). Patients coming for care who could take oral medication were treated with ACTs, and those who could not were treated with rectal artesunate and referred to hospital. The full combined intervention package lasted 12 months. Changes in access and speed of care and clinical course were determined through 1746 random household interviews before and 3199 during the intervention. Results. A total of 15 932 children were assessed: 6394 in Burkina Faso, 2148 in Nigeria, and 7390 in Uganda. Most children assessed (97.3% [15 495/15 932]) were febrile and most febrile cases (82.1% [12 725/15 495]) tested were RDT positive. Almost half of afebrile episodes (47.6% [204/429]) were RDT positive. Children eligible for rectal artesunate contributed 1.1% of episodes. The odds of using CHWs as the first point of care doubled (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.9–2.4; P < .0001). RDT use changed from 3.2% to 72.9% (OR, 80.8; 95% CI, 51.2–127.3; P < .0001). The mean duration of uncomplicated episodes reduced from 3.69 ± 2.06 days to 3.47 ± 1.61 days, Degrees of freedom (df) = 2960, Student's t (t) = 3.2 (P = .0014), and mean duration of severe episodes reduced from 4.24 ± 2.26 days to 3.7 ± 1.57 days, df = 749, t = 3.8, P = .0001. There was a reduction in children with danger signs from 24.7% before to 18.1% during the intervention (OR, 0.68; 95% CI, .59–.78; P < .0001). Conclusions. Provision of diagnosis and treatment via trained CHWs increases access to diagnosis and treatment, shortens clinical episode duration, and reduces the number of severe cases. This approach, recommended by the World Health Organization, improves malaria case management. Clinical Trials Registration. ISRCTN13858170. PMID:27941101

Mind the gap: knowledge and practice of providers treating uncomplicated malaria at public and mission health facilities, pharmacies and drug stores in Cameroon and Nigeria.

PubMed

Mangham-Jefferies, Lindsay; Hanson, Kara; Mbacham, Wilfred; Onwujekwe, Obinna; Wiseman, Virginia

2015-11-01

Artemisinin combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Cameroon since 2004 and Nigeria since 2005, though many febrile patients receive less effective antimalarials. Patients often rely on providers to select treatment, and interventions are needed to improve providers' practice and encourage them to adhere to clinical guidelines. Providers' adherence to malaria treatment guidelines was examined using data collected in Cameroon and Nigeria at public and mission facilities, pharmacies and drug stores. Providers' choice of antimalarial was investigated separately for each country. Multilevel logistic regression was used to determine whether providers were more likely to choose ACT if they knew it was the first-line antimalarial. Multiple imputation was used to impute missing data that arose when linking exit survey responses to details of the provider responsible for selecting treatment. There was a gap between providers' knowledge and their practice in both countries, as providers' decision to supply ACT was not significantly associated with knowledge of the first-line antimalarial. Providers were, however, more likely to supply ACT if it was the type of antimalarial they prefer. Other factors were country-specific, and indicated providers can be influenced by what they perceived their patients prefer or could afford, as well as information about their symptoms, previous treatment, the type of outlet and availability of ACT. Public health interventions to improve the treatment of uncomplicated malaria should strive to change what providers prefer, rather than focus on what they know. Interventions to improve adherence to malaria treatment guidelines should emphasize that ACT is the recommended antimalarial, and it should be used for all patients with uncomplicated malaria. Interventions should also be tailored to the local setting, as there were differences between the two countries in providers' choice of antimalarial, and who or what influenced their practice. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014.

Challenges in implementing uncomplicated malaria treatment in children: a health facility survey in rural Malawi.

PubMed

Kabaghe, Alinune N; Phiri, Mphatso D; Phiri, Kamija S; van Vugt, Michèle

2017-10-18

Prompt and effective malaria treatment are key in reducing transmission, disease severity and mortality. With the current scale-up of artemisinin-based combination therapy (ACT) coverage, there is need to focus on challenges affecting implementation of the intervention. Routine indicators focus on utilization and coverage, neglecting implementation quality. A health system in rural Malawi was assessed for uncomplicated malaria treatment implementation in children. A cross-sectional health facility survey was conducted in six health centres around the Majete Wildlife Reserve in Chikwawa district using a health system effectiveness approach to assess uncomplicated malaria treatment implementation. Interviews with health facility personnel and exit interviews with guardians of 120 children under 5 years were conducted. Health workers appropriately prescribed an ACT and did not prescribe an ACT to 73% (95% CI 63-84%) of malaria rapid diagnostic test (RDT) positive and 98% (95% CI 96-100%) RDT negative children, respectively. However, 24% (95% CI 13-37%) of children receiving artemisinin-lumefantrine had an inappropriate dose by weight. Health facility findings included inadequate number of personnel (average: 2.1 health workers per 10,000 population), anti-malarial drug stock-outs or not supplied, and inconsistent health information records. Guardians of 59% (95% CI 51-69%) of children presented within 24 h of onset of child's symptoms. The survey presents an approach for assessing treatment effectiveness, highlighting bottlenecks which coverage indicators are incapable of detecting, and which may reduce quality and effectiveness of malaria treatment. Health service provider practices in prescribing and dosing anti-malarial drugs, due to drug stock-outs or high patient load, risk development of drug resistance, treatment failure and exposure to adverse effects.

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

PubMed Central

Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G

2008-01-01

Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713 PMID:18503714

Artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria

PubMed Central

Ehrhardt, Stephan; Meyer, Christian G

2009-01-01

The World Health Organization strongly recommends artemisinin-based combination therapy (ACT) regimens for the treatment of uncomplicated Plasmodium falciparum malaria cases in endemic areas. Among the combinations of compounds that are available at present, excellent results have been obtained for the artemisinin derivative artemether, in a combination galenic preparation with lumefantrine (artemether–lumefantrine, AL). Here, the pharmacological properties and the therapeutic options of both substances are briefly reviewed and a cursory overview is given on recent trials that have compared the therapeutic effects of AL in the standard 6-dose regimen with other antimalarials and combinations. In order to ensure the most achievable and reliable adherence and compliance of children in the treatment of malaria, a dispersible formulation of AL is now attainable. Recent reports on the emergence of resistance to ACT regimens in Asia, however, are alarming. PMID:19851528

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

PubMed

Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

2017-04-06

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59-1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40-0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96-1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57-0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46-1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61-1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

Randomized, Prospective, Three-Arm Study to Confirm the Auditory Safety and Efficacy of Artemether-Lumefantrine in Colombian Patients with Uncomplicated Plasmodium falciparum Malaria

PubMed Central

Carrasquilla, Gabriel; Barón, Clemencia; Monsell, Edwin M.; Cousin, Marc; Walter, Verena; Lefèvre, Gilbert; Sander, Oliver; Fisher, Laurel M.

2012-01-01

The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7–6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2–4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria. PMID:22232454

Randomized, prospective, three-arm study to confirm the auditory safety and efficacy of artemether-lumefantrine in Colombian patients with uncomplicated Plasmodium falciparum malaria.

PubMed

Carrasquilla, Gabriel; Barón, Clemencia; Monsell, Edwin M; Cousin, Marc; Walter, Verena; Lefèvre, Gilbert; Sander, Oliver; Fisher, Laurel M

2012-01-01

The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7-6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2-4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.

Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children

PubMed Central

Oguche, Stephen; Okafor, Henrietta U.; Watila, Ismaila; Meremikwu, Martin; Agomo, Philip; Ogala, William; Agomo, Chimere; Ntadom, Godwin; Banjo, Olajide; Okuboyejo, Titilope; Ogunrinde, Gboye; Odey, Friday; Aina, Olugbemiga; Sofola, Tolulope; Sowunmi, Akintunde

2014-01-01

The efficacy of 3-day regimens of artemether-lumefantrine and artesunate-amodiaquine were evaluated in 747 children < 5 years of age with uncomplicated malaria from six geographical areas of Nigeria. Fever clearance was significantly faster (P = 0.006) and the proportion of children with parasitemia 1 day after treatment began was significantly lower (P = 0.016) in artesunate-amodiaquine—compared with artemether-lumefantrine-treated children. Parasite clearance times were similar with both treatments. Overall efficacy was 96.3% (95% confidence interval [CI] 94.5–97.6%), and was similar for both regimens. Polymerase chain reaction-corrected parasitologic cure rates on Day 28 were 96.9% (95% CI 93.9–98.2%) and 98.3% (95% CI 96.1–99.3%) for artemether-lumefantrine and artesunate-amodiaquine, respectively. Gametocyte carriage post treatment was significantly lower than pretreatment (P < 0.0001). In anemic children, mean time to recovery from anemia was 10 days (95% CI 9.04–10.9) and was similar for both regimens. Both treatments were well tolerated and are safe and efficacious treatments of uncomplicated falciparum malaria in young Nigerian children. PMID:25246693

Evaluation of the sensitivity of a pLDH-based and an aldolase-based rapid diagnostic test for diagnosis of uncomplicated and severe malaria caused by PCR-confirmed Plasmodium knowlesi, Plasmodium falciparum, and Plasmodium vivax.

PubMed

Barber, Bridget E; William, Timothy; Grigg, Matthew J; Piera, Kim; Yeo, Tsin W; Anstey, Nicholas M

2013-04-01

Plasmodium knowlesi can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all Plasmodium species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal Plasmodium species, using a pan-Plasmodium lactate dehydrogenase (pLDH)-P. falciparum histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-Plasmodium aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed Plasmodium monoinfection, the sensitivity of the pLDH component of the pLDH-PfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed P. knowlesi, P. falciparum, and P. vivax infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all Plasmodium species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for P. knowlesi. More sensitive RDTs are needed in regions of P. knowlesi endemicity.

Prenatal exposure to Plasmodium falciparum increases frequency and shortens time from birth to first clinical malaria episodes during the first two years of life: prospective birth cohort study.

PubMed

Sylvester, Boniphace; Gasarasi, Dinah B; Aboud, Said; Tarimo, Donath; Massawe, Siriel; Mpembeni, Rose; Swedberg, Gote

2016-07-22

Prenatal exposure to Plasmodium falciparum affects development of protective immunity and susceptibility to subsequent natural challenges with similar parasite antigens. However, the nature of these effects has not been fully elucidated. The aim of this study was to determine the effect of prenatal exposure to P. falciparum on susceptibility to natural malaria infection, with a focus on median time from birth to first clinical malaria episode and frequency of clinical malaria episodes in the first 2 years of life. A prospective birth cohort study was conducted in Rufiji district in Tanzania, between January 2013 and December 2015. Infants born to mothers with P. falciparum in the placenta at time of delivery were defined as exposed, and infants born to mothers without P. falciparum parasites in placenta were defined as unexposed. Placental infection was established by histological techniques. Out of 206 infants recruited, 41 were in utero exposed to P. falciparum and 165 infants were unexposed. All infants were monitored for onset of clinical malaria episodes in the first 2 years of life. The outcome measure was time from birth to first clinical malaria episode, defined by fever (≥37 °C) and microscopically determined parasitaemia. Median time to first clinical malaria episode between exposed and unexposed infants was assessed using Kaplan-Meier survival analysis and comparison was done by log rank. Association of clinical malaria episodes with prenatal exposure to P. falciparum was assessed by multivariate binary logistic regression. Comparative analysis of mean number of clinical malaria episodes between exposed and unexposed infants was done using independent sample t test. The effect of prenatal exposure to P. falciparum infection on clinical malaria episodes was statistically significant (Odds Ratio of 4.79, 95 % CI 2.21-10.38, p < 0.01) when compared to other confounding factors. Median time from birth to first clinical malaria episode for exposed and unexposed infants was 32 weeks (95 % CI 30.88-33.12) and 37 weeks (95 % CI 35.25-38.75), respectively, and the difference was statistically significant (p = 0.003). The mean number of clinical malaria episodes in exposed and unexposed infants was 0.51 and 0.30 episodes/infant, respectively, and the difference was statistically significant (p = 0.038). Prenatal exposure to P. falciparum shortens time from birth to first clinical malaria episode and increases frequency of clinical malaria episodes in the first 2 years of life.

MBL-2 polymorphisms (codon 54 and Y-221X) and low MBL levels are associated with susceptibility to multi organ dysfunction in P. falciparum malaria in Odisha, India.

PubMed

Das, Bidyut K; Panda, Aditya K

2015-01-01

Mannose binding lectin, a plasma protein protects host from virus, bacteria, and parasites. Deficiency in MBL levels has been associated with susceptibility to various infectious diseases including P. falciparum malaria. Common MBL polymorphisms in promoter and coding regions are associated with decrease in plasma MBL levels or production of deformed MBL, respectively. In the present study, we hypothesized that MBL2 variants and plasma MBL levels could be associated with different clinical phenotypes of severe P. falciparum malaria. A hospital based study was conducted in eastern Odisha, India which is endemic to P. falciparum malaria. Common MBL-2 polymorphisms (codon 54, H-550L, and Y-221X) were typed in 336 cases of severe malaria (SM) [94 cerebral malaria (CM), 120 multi-organ dysfunction (MOD), 122 non-cerebral severe malaria (NCSM)] and 131 un-complicated malaria patients (UM). Plasma MBL levels were quantified by ELISA. Severe malaria patients displayed lower plasma levels of MBL compared to uncomplicated falciparum malaria. Furthermore, on categorization of severe malaria patients into various subtypes, plasma MBL levels were very low in MOD patients compared to other categories. Higher frequency of AB genotype and allele B was observed in MOD compared to UM (AB genotype: P = 0.006; B allele: P = 0.008). In addition, prevalence of YX genotype of MBL Y-221X polymorphism was also statistically more frequent in MOD case than UM (P = 0.009). The observations of the present study reveal that MBL-2 polymorphisms (codon 54 and Y-221X) and lower plasma MBL levels are associated with increased susceptibility to multi organ dysfunctions in P. falciparum malaria.

Differences in Gene Transcriptomic Pattern of Plasmodium falciparum in Children with Cerebral Malaria and Asymptomatic Carriers

PubMed Central

Almelli, Talleh; Nuel, Grégory; Bischoff, Emmanuel; Aubouy, Agnès; Elati, Mohamed; Wang, Christian William; Dillies, Marie-Agnès; Coppée, Jean-Yves; Ayissi, Georges Nko; Basco, Leonardo Kishi; Rogier, Christophe; Ndam, Nicaise Tuikue; Deloron, Philippe; Tahar, Rachida

2014-01-01

The mechanisms underlying the heterogeneity of clinical malaria remain largely unknown. We hypothesized that differential gene expression contributes to phenotypic variation of parasites which results in a specific interaction with the host, leading to different clinical features of malaria. In this study, we analyzed the transcriptomes of isolates obtained from asymptomatic carriers and patients with uncomplicated or cerebral malaria. We also investigated the transcriptomes of 3D7 clone and 3D7-Lib that expresses severe malaria associated-variant surface antigen. Our findings revealed a specific up-regulation of genes involved in pathogenesis, adhesion to host cell, and erythrocyte aggregation in parasites from patients with cerebral malaria and 3D7-Lib, compared to parasites from asymptomatic carriers and 3D7, respectively. However, we did not find any significant difference between the transcriptomes of parasites from cerebral malaria and uncomplicated malaria, suggesting similar transcriptomic pattern in these two parasite populations. The difference between isolates from asymptomatic children and cerebral malaria concerned genes coding for exported proteins, Maurer's cleft proteins, transcriptional factor proteins, proteins implicated in protein transport, as well as Plasmodium conserved and hypothetical proteins. Interestingly, UPs A1, A2, A3 and UPs B1 of var genes were predominantly found in cerebral malaria-associated isolates and those containing architectural domains of DC4, DC5, DC13 and their neighboring rif genes in 3D7-lib. Therefore, more investigations are needed to analyze the effective role of these genes during malaria infection to provide with new knowledge on malaria pathology. In addition, concomitant regulation of genes within the chromosomal neighborhood suggests a common mechanism of gene regulation in P. falciparum. PMID:25479608

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis

PubMed Central

Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Titouna, Afaf; Elmaraezy, Ahmed; Trang, Nguyen Thi Huyen; Phuoc Long, Nguyen; Hoang Anh, Nguyen; Diem Nghi, Tran; The Hung, Bui; Van Hieu, Mai; Ky Anh, Nguyen; Huy, Nguyen Tien; Hirayama, Kenji

2017-01-01

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59–1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40–0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96–1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57–0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61–1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender. PMID:28382932

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.

PubMed

Kone, Abdoulaye K; Sagara, Issaka; Thera, Mahamadou A; Dicko, Alassane; Guindo, Aldiouma; Diakite, Seidina; Kurantsin-Mills, Joseph; Djimde, Abdoulaye; Walcourt, Asikiya; Doumbo, Ogabara

2010-11-21

Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.

Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

PubMed Central

Dobbs, Katherine R.; Embury, Paula; Odada, Peter S.; Rosa, Bruce A.; Mitreva, Makedonka; Kazura, James W.; Dent, Arlene E.

2017-01-01

BACKGROUND. Inflammation and monocytes are thought to be important to human malaria pathogenesis. However, the relationship of inflammation and various monocyte functions to acute malaria, recovery from acute malaria, and asymptomatic parasitemia in endemic populations is poorly understood. METHODS. We evaluated plasma cytokine levels, monocyte subsets, monocyte functional responses, and monocyte inflammatory transcriptional profiles of 1- to 10-year-old Kenyan children at the time of presentation with acute uncomplicated malaria and at recovery 6 weeks later; these results were compared with analogous data from asymptomatic children and adults in the same community. RESULTS. Acute malaria was marked by elevated levels of proinflammatory and regulatory cytokines and expansion of the inflammatory “intermediate” monocyte subset that returned to levels of healthy asymptomatic children 6 weeks later. Monocytes displayed activated phenotypes during acute malaria, with changes in surface expression of markers important to innate and adaptive immunity. Functionally, acute malaria monocytes and monocytes from asymptomatic infected children had impaired phagocytosis of P. falciparum–infected erythrocytes relative to asymptomatic children with no blood-stage infection. Monocytes from both acute malaria and recovery time points displayed strong and equivalent cytokine responsiveness to innate immune agonists that were independent of infection status. Monocyte transcriptional profiles revealed regulated and balanced proinflammatory and antiinflammatory and altered phagocytosis gene expression patterns distinct from malaria-naive monocytes. CONCLUSION. These observations provide insights into monocyte functions and the innate immune response during uncomplicated malaria and suggest that asymptomatic parasitemia in children is not clinically benign. FUNDING. Support for this work was provided by NIH/National Institute of Allergy and Infectious Diseases (R01AI095192-05), the Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene, and the Rainbow Babies & Children’s Foundation. PMID:28931756

Comparison of azithromycin plus chloroquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children in Africa: a randomized, open-label study.

PubMed

Chandra, Richa; Ansah, Patrick; Sagara, Issaka; Sie, Ali; Tiono, Alfred B; Djimde, Abdoulaye A; Zhao, Qinying; Robbins, Jeffery; Penali, Louis K; Ogutu, Bernhards

2015-03-10

This randomized, open-label study was conducted to establish the non-inferiority of a combination of azithromycin (AZ) and chloroquine (CQ) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in children from six sites in sub-Saharan Africa. Children with uncomplicated Plasmodium falciparum malaria between six and 59 months of age were randomized 1:1 to either AZCQ (30 mg/kg AZ + 10 mg/kg CQ base) or AL per prescribing information for three days (Days 0, 1, 2). Each site could enrol in the study population once the treatment of uncomplicated malaria in five children five to 12 years of age was deemed to be effective and well tolerated. The primary efficacy evaluation was the proportion of subjects in both the modified intent-to-treat (MITT) and per-protocol (PP) populations with an adequate clinical and parasitological response (PCR corrected) at Day 28. Non-inferiority was concluded if the lower bound of the 95% confidence interval comparing the two groups was 10 percentage points or greater. A total of 255 children were enrolled in the efficacy analysis (AZCQ, n = 124; AL, n = 131). The PCR corrected clearance rates were 89% (AZCQ) versus 98% (AL) for MITT, a difference of -9.10 (95% confidence interval; -16.02, -2.18) and 93% (AZCQ) versus 99% (AL) for PP, a difference of -6.08 (-12.10, -0.05). Early and late treatment failures were more common in subjects receiving AZCQ. Adverse events were more common in subjects treated with AZCQ. Drug concentrations obtained at specified time points following AZCQ administration had a large coefficient of variation partially due to sparse sampling with sample collection time window. In this study, non-inferiority of AZCQ to AL was not demonstrated. ClinicalTrials.gov NCT00677833 .

What determines providers' stated preference for the treatment of uncomplicated malaria?

PubMed

Mangham-Jefferies, Lindsay; Hanson, Kara; Mbacham, Wilfred; Onwujekwe, Obinna; Wiseman, Virginia

2014-03-01

As agents for their patients, providers often make treatment decisions on behalf of patients, and their choices can affect health outcomes. However, providers operate within a network of relationships and are agents not only for their patients, but also other health sector actors, such as their employer, the Ministry of Health, and pharmaceutical suppliers. Providers' stated preferences for the treatment of uncomplicated malaria were examined to determine what factors predict their choice of treatment in the absence of information and institutional constraints, such as the stock of medicines or the patient's ability to pay. 518 providers working at non-profit health facilities and for-profit pharmacies and drug stores in Yaoundé and Bamenda in Cameroon and in Enugu State in Nigeria were surveyed between July and December 2009 to elicit the antimalarial they prefer to supply for uncomplicated malaria. Multilevel modelling was used to determine the effect of financial and non-financial incentives on their preference, while controlling for information and institutional constraints, and accounting for the clustering of providers within facilities and geographic areas. 69% of providers stated a preference for artemisinin-combination therapy (ACT), which is the recommended treatment for uncomplicated malaria in Cameroon and Nigeria. A preference for ACT was significantly associated with working at a for-profit facility, reporting that patients prefer ACT, and working at facilities that obtain antimalarials from drug company representatives. Preferences were similar among colleagues within a facility, and among providers working in the same locality. Knowing the government recommends ACT was a significant predictor, though having access to clinical guidelines was not sufficient. Providers are agents serving multiple principals and their preferences over alternative antimalarials were influenced by patients, drug company representatives, and other providers working at the same facility and in the local area. Efforts to disseminate drug policy should target the full range of actors involved in supplying drugs, including providers, employers, suppliers and local communities. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adverse effects of mefloquine for the treatment of uncomplicated malaria in Thailand: A pooled analysis of 19, 850 individual patients.

PubMed

Lee, Sue J; Ter Kuile, Feiko O; Price, Ric N; Luxemburger, Christine; Nosten, François

2017-01-01

Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders. In total 19,850 patients received seven different regimens containing either 15 or 24-25 mg/kg of MQ, the latter given either as a single dose, or split over two or three days. The analysis focused on (predominantly) gastrointestinal and neuropsychiatric events as compared to the new fixed dose combination of MQ plus artesunate given as equal doses of 8 mg/kg MQ per day over three days. Gastrointestinal side effects were dose-dependent and associated with the severity of malaria symptoms. Serious neuropsychiatric side effects associated with MQ use were rare: for a single 25 mg/kg dose it was 11.9 per 10,000 treatments (95% confidence interval, CI, 4-285) vs. 7.8 (3-15) for the 15 mg/kg dose. The risk with 25 mg/kg was much higher when it was given as repeat dosing in patients who had failed treatment with 15 mg/kg MQ in the preceding month; (RR 6.57 (95% CI 1.33 to 32.4), p = 0.0077). MQ was best tolerated as 15 mg/kg or as 24 mg/kg when given over three days in combination with artesunate. We conclude that the tolerance of a single dose of MQ in the treatment of uncomplicated malaria is moderate, but can be improved by administering it as a split dose over three days.

Pyronaridine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a randomized controlled non-inferiority trial.

PubMed

Roth, Johanna M; Sawa, Patrick; Makio, Nicodemus; Omweri, George; Osoti, Victor; Okach, Selpha; Choy, Felix; Schallig, Henk D F H; Mens, Pètra

2018-05-15

Pyronaridine-artesunate is a novel artemisinin-based combination therapy. The efficacy and safety of pyronaridine-artesunate were compared with artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children. This phase III open-label randomized controlled non-inferiority trial was conducted in Western Kenya. Children aged 6 months to ≤ 12 years with a bodyweight > 5 kg and microscopically confirmed P. falciparum malaria were randomly assigned in a 1:1 ratio to orally receive pyronaridine-artesunate or artemether-lumefantrine, dosed according to bodyweight, for 3 days. Of 197 participants, 101 received pyronaridine-artesunate and 96 received artemether-lumefantrine. The day-28 adequate clinical and parasitological response in the per-protocol population, PCR-corrected for reinfections, was 98.9% (93/94, 95% CI 94.2-99.8) for pyronaridine-artesunate and 96.4% (81/84, 95% CI 90.0-98.8) for artemether-lumefantrine. Pyronaridine-artesunate was found to be non-inferior to artemether-lumefantrine: the treatment difference was 2.5% (95% CI - 2.8 to 9.0). Adverse events occurred in 41.6% (42/101) and 34.4% (33/96) of patients in the pyronaridine-artesunate group and the artemether-lumefantrine group, respectively. No participants were found to have alanine or aspartate aminotransferase levels > 3 times the upper limit of normal. Pyronaridine-artesunate was well tolerated, efficacious and non-inferior to artemether-lumefantrine for the treatment of uncomplicated P. falciparum malaria in Kenyan children. Results are in line with previous reports and inclusion of pyronaridine-artesunate in paediatric malaria treatment programmes should be considered. This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine-artesunate&cond=Malaria&cntry=KE&rank=1.

Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria

PubMed Central

Zani, Babalwa; Gathu, Michael; Donegan, Sarah; Olliaro, Piero L; Sinclair, David

2014-01-01

Background The World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs. Objectives To evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013. Selection criteria Randomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria. Data collection and analysis Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy’ and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. Main results We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women. DHA-P versus artemether-lumefantrine In Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower with DHA-P (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials, 5417 participants, high quality evidence). DHA-P has a longer prophylactic effect on new infections which may last for up to 63 days (PCR-unadjusted treatment failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high quality evidence). In Asia and Oceania, no differences have been shown at day 28 (four trials, 1143 participants, moderate quality evidence), or day 63 (one trial, 323 participants, low quality evidence). Compared to artemether-lumefantrine, no difference was seen in prolonged QTc (low quality evidence), and no cardiac arrhythmias were reported. The frequency of other adverse events is probably similar with both combinations (moderate quality evidence). DHA-P versus artesunate plus mefloquine In Asia, over 28 days follow-up, DHA-P is as effective as artesunate plus mefloquine at preventing further parasitaemia (PCR-unadjusted treatment failure: eight trials, 3487 participants, high quality evidence). Once adjusted by PCR to exclude new infections, treatment failure at day 28 was below 5% for both ACTs in all eight trials, but lower with DHA-P in two trials (PCR-adjusted treatment failure: RR 0.41 95% CI 0.21 to 0.80, eight trials, 3482 participants, high quality evidence). Both combinations contain partner drugs with very long half-lives and no consistent benefit in preventing new infections has been seen over 63 days follow-up (PCR-unadjusted treatment failure: five trials, 2715 participants, moderate quality evidence). In the only trial from South America, there were fewer recurrent parastaemias over 63 days with artesunate plus mefloquine (PCR-unadjusted treatment failure: RR 6.19, 95% CI 1.40 to 27.35, one trial, 445 participants, low quality evidence), but no differences were seen once adjusted for new infections (PCR-adjusted treatment failure: one trial, 435 participants, low quality evidence). DHA-P is associated with less nausea, vomiting, dizziness, sleeplessness, and palpitations compared to artesunate plus mefloquine (moderate quality evidence). DHA-P was associated with more frequent prolongation of the QTc interval (low quality evidence), but no cardiac arrhythmias were reported. Authors' conclusions In Africa, dihydroartemisinin-piperaquine reduces overall treatment failure compared to artemether-lumefantrine, although both drugs have PCR-adjusted failure rates of less than 5%. In Asia, dihydroartemisinin-piperaquine is as effective as artesunate plus mefloquine, and is better tolerated. PLAIN LANGUAGE SUMMARY Dihydroartemisinin-piperaquine for treating uncomplicated malaria This review summarises trials evaluating the effects of dihydroartemisinin-piperaquine (DHA-P) compared to other artemisinin-based combination therapies recommended by the World Health Organization. After searching for relevant trials up to July 2013, we included 27 randomized controlled trials, enrolling 16,382 adults and children and conducted between 2002 and 2010. What is uncomplicated malaria and how might dihydroartemisinin-piperaquine work Uncomplicated malaria is the mild form of malaria which usually causes a fever, with or without headache, tiredness, muscle pains, abdominal pains, nausea, and vomiting. If left untreated, uncomplicated malaria can develop into severe malaria with kidney failure, breathing difficulties, fitting, unconsciousness, and eventually death. DHA-P is one of five artemisinin-based combination therapies the World Health Organization currently recommends to treat malaria. These combinations contain an artemisinin component (such as dihydroartemisinin) which works very quickly to clear the malaria parasite from the person's blood, and a longer acting drug (such as piperaquine) which clears the remaining parasites from the blood and may prevent new infections with malaria for several weeks. What the research says DHA-P versus artemether lumefantrine In studies of people living in Africa, both DHA-P and artemether-lumefantrine are very effective at treating malaria (high quality evidence). However, DHA-P cures slightly more patients than artemether-lumefantrine, and it also prevents further malaria infections for longer after treatment (high quality evidence). DHA-P and artemether-lumefantrine probably have similar side effects (moderate quality evidence). DHA-P versus artesunate plus mefloquine In studies of people living in Asia, DHA-P is as effective as artesunate plus mefloquine at treating malaria (moderate quality evidence). Artesunate plus mefloquine probably causes more nausea, vomiting, dizziness, sleeplessness, and palpitations than DHA-P (moderate quality evidence). Overall, in some people, DHA-P has been seen to cause short term changes in electrocardiographs tracing the conduction of the heart rhythm (low quality evidence), but these small changes on the electrocardiograph resolved within one week without serious consequences. PMID:24443033

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

PubMed Central

2011-01-01

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance. PMID:21609473

Response of falciparum malaria to different antimalarials in Myanmar.

PubMed Central

Ejov, M. N.; Tun, T.; Aung, S.; Sein, K.

1999-01-01

The purpose of the study was to ascertain the therapeutic efficacy of different treatments for uncomplicated falciparum malaria in the hospitals in Sagaing, northern and eastern Shan, to facilitate updating the existing national antimalarial drug policy. The proposed 14-day trial for monitoring the efficacy of treatments of uncomplicated falciparum malaria is an efficient method for identifying treatment failure patterns at the intermediate level (township hospital) in the Union of Myanmar. Minimal clinical and parasitological data for days 0-14 were required to classify treatment failure and success. Clinical and parasitiological responses on day 3 and days 4-14 were used as clear examples of early and late treatment failure, respectively. Mefloquine is five times more likely to be effective than chloroquine and sulfadoxine pyrimethamine (S-P), whereas chloroquine and S-P treatments have nearly identical failure patterns. The alarming frequency of clinical and parasitological failure (failure rate > 50%) following chloroquine treatment was reported in Sagaing and following S-P treatment in Sagaing and eastern Shan. PMID:10212515

Decreasing Efficacy of Antimalarial Combination Therapy in Uganda Explained by Decreasing Host Immunity Rather than Increasing Drug Resistance

PubMed Central

Greenhouse, Bryan; Slater, Madeline; Njama-Meya, Denise; Nzarubara, Bridget; Maiteki-Sebuguzi, Catherine; Clark, Tamara D.; Staedke, Sarah G.; Kamya, Moses R.; Hubbard, Alan; Rosenthal, Philip J.; Dorsey, Grant

2009-01-01

Background Improved control efforts are reducing the burden of malaria in Africa, but may result in decreased antimalarial immunity. Methods A cohort of 129 children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for 396 episodes of uncomplicated malaria over a 29 month period as part of a longitudinal clinical trial. Results The risk of treatment failure increased over the course of the study from 5% to 21% (HR=2.4/yr, 95%CI=1.3–4.3). Parasite genetic polymorphisms were associated with an increased risk of failure, but their prevalence did not change over time. Three markers of antimalarial immunity were associated with a decreased risk of treatment failure: increased age (HR=0.5/5yrs, 95%CI=0.2–1.2), living in an area of higher malaria incidence (HR=0.26, 95%CI=0.11–0.64), and recent asymptomatic parasitemia (HR=0.06, 95%CI=0.01–0.36). In multivariate analysis, adjustment for recent asymptomatic parasitemia, but not parasite polymorphisms, removed the association between calendar time and the risk of treatment failure (HR=1.5/yr, 95%CI=0.7–3.4), suggesting that worsening treatment efficacy was best explained by decreasing host immunity. Conclusion Declining immunity in our study population appeared to be the primary factor underlying decreased efficacy of amodiaquine+sulfadoxine-pyrimethamine. With improved malaria control efforts, decreasing immunity may unmask resistance to partially efficacious drugs. PMID:19199542

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children

PubMed Central

Nyirenda, James T.; Tembo, Dumizulu L.; Storm, Janet; Dube, Queen; Msefula, Chisomo L.; Jambo, Kondwani C.; Mwandumba, Henry C.; Heyderman, Robert S.; Gordon, Melita A.

2017-01-01

ABSTRACT Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S. Typhimurium were reduced in febrile P. falciparum-infected children (median, −0.20 log10 [interquartile range {IQR}, −1.85, 0.32]) compared to nonfebrile malaria-negative children (median, −1.42 log10 [IQR, −2.0, −0.47], P = 0.052). In relation to SBA, C3 deposition on S. Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S. Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 0.25 log10 [IQR, −0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, −1.0 log10 [IQR, −1.68, −0.16]). In relation to WBBA, S. Typhimurium-specific NRBA was reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S. Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further. PMID:28515136

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children.

PubMed

Nyirenda, Tonney S; Nyirenda, James T; Tembo, Dumizulu L; Storm, Janet; Dube, Queen; Msefula, Chisomo L; Jambo, Kondwani C; Mwandumba, Henry C; Heyderman, Robert S; Gordon, Melita A; Mandala, Wilson L

2017-07-01

Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S Typhimurium were reduced in febrile P. falciparum -infected children (median, -0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], P = 0.052). In relation to SBA, C3 deposition on S Typhimurium was significantly reduced in febrile P. falciparum -infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S Typhimurium was significantly reduced in febrile P. falciparum -infected children (median, 0.25 log10 [IQR, -0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10 [IQR, -1.68, -0.16]). In relation to WBBA, S Typhimurium-specific NRBA was reduced in febrile P. falciparum -infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in children from settings of malaria endemicity. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further. Copyright © 2017 Nyirenda et al.

Use of a Dual-Antigen Rapid Diagnostic Test to Screen Children for Severe Plasmodium falciparum Malaria in a High-Transmission, Resource-Limited Setting.

PubMed

Boyce, Ross; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar; Siedner, Mark J

2017-10-16

In rural areas, many patients with malaria seek care at peripheral health facilities or community case management programs. While this strategy is effective for the management of uncomplicated malaria, severe malaria necessitates prompt detection and referral to facilities with adequate resources. In this prospective, observational cohort study, we assessed the accuracy of a dual-band (histidine-rich protein-2/pan-lactate dehydrogenase [HRP2/pLDH]) rapid diagnostic test (RDT) to differentiate uncomplicated from severe malaria. We included children aged <12 years who presented to a rural clinic in western Uganda with a positive HRP2 or HRP2/pLDH RDT. We estimated the test characteristics of a dual-antigen (HRP2+/pLDH+) band positive RDT compared to World Health Organization-defined clinical and laboratory criteria to detect severe malaria. A total of 2678 children underwent testing for malaria with an RDT, and 83 (9.0%) satisfied criteria for severe malaria. The sensitivity and specificity of a HRP2+/pLDH+ result for severe malaria was 97.6% (95% confidence interval [CI], 90.8%-99.6%) and 75.6% (95% CI, 73.8%-77.4%), respectively. An HRP2+/pLDH+ result was significantly more sensitive (97.6% vs 68.7%, P < .001) for the detection of severe malaria compared to algorithms that incorporate screening for danger signs. A positive dual-antigen (HRP2/pLDH) RDT has higher sensitivity than the use of clinical manifestations to detect severe malaria, making it a promising tool in the triage of children with malaria in low-resource settings. Additional work is needed to operationalize diagnostic and treatment algorithms that include dual-antigen RDTs to avoid over referral. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

PubMed Central

2010-01-01

Background Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). Conclusions The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT. PMID:21092137

“…still waiting for chloroquine”: the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district

PubMed Central

2014-01-01

Background Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. Objectives To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Methods Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Results Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing advertisements of other drugs and conflicts between patients and providers. Conclusion Effective health policy communication is important for the uptake of new drug interventions and adherence to treatment regimens. Besides, prompt access to effective treatment may not be achieved if beneficiaries are not adequately informed about treatment policy changes. Future changes in treatment policy should ensure that the communication strategy is designed to pass sustained, accurate and effective messages that account for local contexts. PMID:25005337

"…still waiting for chloroquine": the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district.

PubMed

Okungu, Vincent; Gilson, Lucy

2014-07-08

Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing advertisements of other drugs and conflicts between patients and providers. Effective health policy communication is important for the uptake of new drug interventions and adherence to treatment regimens. Besides, prompt access to effective treatment may not be achieved if beneficiaries are not adequately informed about treatment policy changes. Future changes in treatment policy should ensure that the communication strategy is designed to pass sustained, accurate and effective messages that account for local contexts.

Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria.

PubMed

Van Malderen, Carine; Van Geertruyden, Jean-Pierre; Machevo, Sonia; González, Raquel; Bassat, Quique; Talisuna, Ambrose; Yeka, Adoke; Nabasumba, Carolyn; Piola, Patrice; Daniel, Atwine; Turyakira, Eleanor; Forret, Pascale; Van Overmeir, Chantal; van Loen, Harry; Robert, Annie; D' Alessandro, Umberto

2012-07-10

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria. This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p=0.56). The risk of a Hb drop≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p=0.76) or CDA treatment (AOR: 1.28; p=0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p=0.25) of experiencing a Hb drop≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p=0.49). The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.

Clinical diagnosis of uncomplicated malaria in Sri Lanka.

PubMed

van der Hoek, W; Premasiri, D A; Wickremasinghe, A R

1998-06-01

To assess the possibility of developing a protocol for the clinical diagnosis of malaria, a study was done at the regional laboratory of the Anti-Malaria Campaign in Puttalam, Sri Lanka. Of a group of 502 patients, who suspected they were suffering from malaria, 97 had a positive blood film for malaria parasites (71 Plasmodium vivax and 26 P. falciparum). There were no important differences in signs and symptoms between those with positive and those with negative blood films. It is argued that it is unlikely that health workers can improve on the diagnosis of malaria made by the patients themselves, if laboratory facilities are not available. For Sri Lanka the best option is to expand the number of facilities where microscopic examination for malaria parasites can take place.

A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy.

PubMed

Manyando, Christine; Kayentao, Kassoum; D'Alessandro, Umberto; Okafor, Henrietta U; Juma, Elizabeth; Hamed, Kamal

2012-05-01

Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL) in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the WHO recommendation to treat uncomplicated falciparum malaria with quinine plus clindamycin in early pregnancy and ACT in later pregnancy.

Response of imported malaria patients to antimalarial medicines in Sri Lanka following malaria elimination.

PubMed

Dharmawardena, Priyani; Rodrigo, Chaturaka; Mendis, Kamini; de A W Gunasekera, W M Kumudu T; Premaratne, Risintha; Ringwald, Pascal; Fernando, Deepika

2017-01-01

After eliminating local malaria transmission and being certified as a malaria-free country, Sri Lanka is facing the challenge of imported malaria. At the same time, the country has the unique opportunity to be a case study for other countries in a similar situation by approaching this issue systematically, guided by evidence. This study demonstrates the importance of developing a mechanism to detect imported malaria and adopting an evidence-based approach to study the resistance of imported malaria to anti-malarial medicines. This is a prospective study of patients diagnosed with imported malaria in Sri Lanka and treated according to the national treatment guidelines, over 24 months (2015/2016). The clinical features, time to diagnosis, origin of the infection, infecting species, parasite density and the treatment given were recorded. All patients were followed up for 28 days, and in the case of Plasmodium vivax and P. ovale infections, the follow up period was extended to 12 months to establish treatment failures and relapses. Fifty nine uncomplicated and 15 severe imported malaria cases were reported in Sri Lanka during the study period. Most of these infections originated in either Sub-Saharan Africa or South and Southeast Asia. Having a P. vivax infection and low parasitic counts were significantly associated with relative diagnostic delay. One of the 14 uncomplicated P. falciparum patients and two of the 12 severe P. falciparum malaria patients who were followed up till day 28 had a late clinical failure. The others responded adequately to treatment both clinically and parasitologically. There was no treatment failure reported amongst any other species. This study, which is the first to assess the therapeutic response of imported malaria in Sri Lanka after elimination, demonstrates that the current antimalarial treatment policies and strategies in Sri Lanka have been effective against infections acquired overseas up until the end of year 2016.

Cost-effectiveness of dihydroartemisinin-piperaquine compared with artemether-lumefantrine for treating uncomplicated malaria in children at a district hospital in Tanzania.

PubMed

Mori, Amani T; Ngalesoni, Frida; Norheim, Ole F; Robberstad, Bjarne

2014-09-15

Dihydroartemisinin-piperaquine (DhP) is highly recommended for the treatment of uncomplicated malaria. This study aims to compare the costs, health benefits and cost-effectiveness of DhP and artemether-lumefantrine (AL) alongside "do-nothing" as a baseline comparator in order to consider the appropriateness of DhP as a first-line anti-malarial drug for children in Tanzania. A cost-effectiveness analysis was performed using a Markov decision model, from a provider's perspective. The study used cost data from Tanzania and secondary effectiveness data from a review of articles from sub-Saharan Africa. Probabilistic sensitivity analysis was used to incorporate uncertainties in the model parameters. In addition, sensitivity analyses were used to test plausible variations of key parameters and the key assumptions were tested in scenario analyses. The model predicts that DhP is more cost-effective than AL, with an incremental cost-effectiveness ratio (ICER) of US$ 12.40 per DALY averted. This result relies on the assumption that compliance to treatment with DhP is higher than that with AL due to its relatively simple once-a-day dosage regimen. When compliance was assumed to be identical for the two drugs, AL was more cost-effective than DhP with an ICER of US$ 12.54 per DALY averted. DhP is, however, slightly more likely to be cost-effective compared to a willingness-to-pay threshold of US$ 150 per DALY averted. Dihydroartemisinin-piperaquine is a very cost-effective anti-malarial drug. The findings support its use as an alternative first-line drug for treatment of uncomplicated malaria in children in Tanzania and other sub-Saharan African countries with similar healthcare infrastructures and epidemiology of malaria.

Therapeutic efficacy trial of artemisinin-based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo, 2012-2013.

PubMed

Dorkenoo, Améyo M; Yehadji, Degninou; Agbo, Yao M; Layibo, Yao; Agbeko, Foli; Adjeloh, Poukpessi; Yakpa, Kossi; Sossou, Efoe; Awokou, Fantchè; Ringwald, Pascal

2016-06-22

Since 2005, the Togo National Malaria Control Programme has recommended two different formulations of artemisinin-based combination therapy (ACT), artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL), for the treatment of uncomplicated malaria. Regular efficacy monitoring of these two combinations is conducted every 2 or 3 years. This paper reports the latest efficacy assessment results and the investigation of mutations in the k13 propeller domain. The study was conducted in 2012-2013 on three sentinel sites of Togo (Lomé, Sokodé and Niamtougou). Children aged 6-59 months, who were symptomatically infected with Plasmodium falciparum, were treated with either AL (Coartem(®), Novartis Pharma, Switzerland) or ASAQ (Co-Arsucam(®), Sanofi Aventis, France). The WHO standard protocol for anti-malarial treatment evaluation was used. The primary end-point was 28-day adequate clinical and parasitological response (ACPR), corrected to exclude reinfection using polymerase-chain reaction (PCR) genotyping. A total of 523 children were included in the study. PCR-corrected ACPR was 96.3-100 % for ASAQ and 97-100 % for AL across the three study sites. Adverse events were negligible: 0-4.8 % across all sites, for both artemisinin-based combinations. Upon investigation of mutations in the k13 propeller domain, only 9 (1.8 %) mutations were reported, three in each site. All mutant parasites were cleared before day 3. All day 3 positive patients were infected with k13 wild type parasites. The efficacy of AL and ASAQ remains high in Togo, and both drugs are well tolerated. ASAQ and AL would be recommended for the treatment of uncomplicated malaria in Togo.

Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety.

PubMed

Frey, Sarabel G; Chelo, David; Kinkela, Mina N; Djoukoue, Florence; Tietche, Felix; Hatz, Christoph; Weber, Peter

2010-10-21

Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d) and mefloquine (125 mg/d). Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed.

Recurrent uncomplicated cystitis in women: allowing patients to self-initiate antibiotic therapy.

PubMed

2014-02-01

Acute uncomplicated cystitis is a lower urinary tract infection occurring in the absence of anatomic or functional abnormalities of the urinary tract or any other complicating factors.The organism responsible is often an enterobacterium, especially Escherichia coli. What is the role of antibiotic therapy for non-pregnant women with recurrent acute uncomplicated cystitis? We reviewed the available evidence using the standard Prescrire methodology. A single oral dose of fosfomycin trometamol is the antibiotic of choice for treating an episode of acute uncomplicated cystitis. Alternative antibiotics are certain fluoroquinolones or co-trimoxazole (a fixed-dose combination of sulfamethoxazole and trimethoprim). For recurrent acute uncomplicated cystitis, cranberry juice has modest efficacy in reducing the frequency of episodes. A number of non-drug measures are typically proposed, although their effects are unproven: drinking sufficient fluids and urinating regularly; urinating after sexual intercourse; and avoiding spermicides. The strategy that results in the lowest antibiotic exposure is a short course of antibiotics for each episode of urinary tract infection, initiated as soon as clinical symptoms appear. Long-term antibiotic therapy is sometimes offered. According to one systematic review, women taking long-term prophylactic antibiotic therapy had about 6 times fewer clinical recurrences than with placebo. According to one randomised trial, 3 g of fosfomycin trometamol taken as a single dose every ten days reduced the frequency of recurrence, resulting in 0.14 episodes of infection per year on average versus about 3 episodes with placebo (p < 0.001). The amount of antibiotic used when fosfomycin trometamol is taken every 10 days for 6 months is equivalent to treatment of 18 acute episodes of cystitis. When cystitis appears to be associated with sexual intercourse, two small randomised trials suggest that routine postcoital antibiotic treatment is more effective than placebo and as effective as long-term antibiotic therapy. Adverse effects, some of which can be serious, depend on the antibiotic used. The development of resistance among enterobacteria is one argument for limiting the use of antibiotics, in order to preserve their efficacy in serious infections. In practice, the strategy that uses the fewest antibiotics is to treat each episode as soon as the first clinical symptoms appear. Cases in which the frequency of recurrence warrants regular antibiotic prophylaxis are rare. The optimal antibiotic regimen in these cases has not been determined, either in clinical trials or by consensus.

The Association between Nutritional Status and Malaria in Children from a Rural Community in the Amazonian Region: A Longitudinal Study

PubMed Central

Alexandre, Márcia Almeida Araújo; Benzecry, Silvana Gomes; Siqueira, Andre Machado; Vitor-Silva, Sheila; Melo, Gisely Cardoso; Monteiro, Wuelton Marcelo; Leite, Heitor Pons; Lacerda, Marcus Vinícius Guimarães; Alecrim, Maria das Graças Costa

2015-01-01

Background The relationship between malaria and undernutrition is controversial and complex. Synergistic associations between malnutrition and malaria morbidity and mortality have been suggested, as well as undernutrition being protective against infection, while other studies found no association. We sought to evaluate the relationship between the number of malaria episodes and nutritional statuses in a cohort of children below 15 years of age living in a rural community in the Brazilian Amazon. Methodology/Principal Findings Following a baseline survey of clinical, malaria and nutritional assessment including anthropometry measurements and hemoglobin concentration, 202 children ranging from 1 month to 14 years of age were followed for one year through passive case detection for malaria episodes. After follow-up, all children were assessed again in order to detect changes in nutritional indicators associated with malaria infection. We also examined the risk of presenting malaria episodes during follow-up according to presence of stunting at baseline. Children who suffered malaria episodes during follow-up presented worse anthropometric parameters values during this period. The main change was a reduction of the linear growth velocity, associated with both the number of episodes and how close the last or only malaria episode and the second anthropometric assessment were. Changes were also observed for indices associated with chronic changes, such as weight-for-age and BMI-for-age, which conversely, were more frequently observed in children with the last or only episode occurring between 6 and 12 months preceding the second nutritional assessment survey. Children with inadequate height-for-age at baseline (Z-score < -2) presented lower risk of suffering malaria episodes during follow-up as assessed by both the log-rank test (p =0.057) and the multivariable Cox-proportional hazards regression (Hazard Ratio = 0.31, 95%CI [0.10; 0.99] p=0.049). Conclusions Malaria was associated with impaired nutritional status amongst children in an endemic area of the Western Brazilian Amazon where P. vivax predominates. Our data all supports that the association presents differential effects for each age group, suggesting distinct pathophysiology pathways. We were also able to demonstrate that undernourishment at baseline was protective to malaria during follow-up. These findings support an intriguing interaction between these conditions in the rural Amazon and the need for a more integrative approach by health systems in endemic areas. PMID:25928774

Dihydroartemisinin-Piperaquine and Artemether-Lumefantrine for Treating Uncomplicated Malaria in African Children: A Randomised, Non-Inferiority Trial

PubMed Central

Bassat, Quique; Mulenga, Modest; Tinto, Halidou; Piola, Patrice; Borrmann, Steffen; Menéndez, Clara; Nambozi, Michael; Valéa, Innocent; Nabasumba, Carolyn; Sasi, Philip; Bacchieri, Antonella; Corsi, Marco; Ubben, David; Talisuna, Ambrose; D'Alessandro, Umberto

2009-01-01

Background Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. Methodology/Principal Findings The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6–59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2∶1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of −5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were −2.80% and −2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%–15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%–27.88%) for AL (p<0.0001). Conclusions/Significance DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. Trial Registration Controlled-trials.com ISRCTN16263443 PMID:19936217

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study.

PubMed

Ngasala, Billy E; Malmberg, Maja; Carlsson, Anja M; Ferreira, Pedro E; Petzold, Max G; Blessborn, Daniel; Bergqvist, Yngve; Gil, José P; Premji, Zul; Mårtensson, Andreas

2011-03-16

Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046). Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

In vivo testing of the therapeutic efficacy of chloroquine on falciparum malaria infections in Chirundu, Mashonaland West, Zimbabwe.

PubMed

Barduagni, P; Schwartz, U; Nyamayaro, W; Chauke, T L

1998-10-01

To detect the level of the in vivo chloroquine efficacy in falciparum malaria infections, in order to assess the need for change in the management and treatment of uncomplicated malaria. Prospective descriptive study. Chirundu Rural Clinic, Mashonaland West Province. 63 patients confirmed by a positive blood slide for P. falciparum who attended Chirundu clinic, who were eligible for the study and, who also agreed to participate. Frequency of treatment success, early treatment failure and late treatment failure in uncomplicated patients treated with chloroquine. Out of 63 cases enrolled and completely followed up, chloroquine treatment was effective in 54 cases (85.7%) and was not effective in nine cases (14.3%). All treatment failures were successfully treated with sulphadoxine + pyrimethamine (Fansidar) or quinine following the approved guidelines. Chloroquine remains highly effective in the treatment of malaria due to P. falciparum in the Zambezi Valley of Hurungwe district and therefore, has to remain the first line drug. Likewise, guidelines for the use of sulphadoxine + pyrimethamine (Fansidar) or quinine as second line drugs, are adequate to the local situation. Health workers directly supervised the patients when they were swallowing the tablets during the whole course, and this without doubt, indirectly increased the efficacy of chloroquine. It is vital to confirm the malaria diagnosis on the spot appointing microscopists or distributing a limited stock of Parasight-F test.

Therapeutic Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium falciparum in Haiti after Many Decades of its Use

PubMed Central

Okech, Bernard A.; Existe, Alexandre; Romain, Jean R.; Memnon, Gladys; Victor, Yves Saint; de Rochars, Madsen Beau; Fukuda, Mark

2015-01-01

Chloroquine (CQ) has been used for malaria treatment in Haiti for several decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a 42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was seasonal, with peak observations between October and January; 88% (107 of 121) of patients consented to participate. Sixty patients successfully completed the 42-day follow-up, whereas 47 patients withdrew consent or were lost to follow-up. The mean parasite density declined rapidly within the first few days after treatment. Seven patients did not clear their malaria infections and were clinically asymptomatic; therefore, they were considered late parasitological failures. About 90% (95% confidence interval = 84.20–97.90) of patients had no detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for recrudescence, reinfection, and CQ serum levels was not done in the seven patients, and therefore, their CQ resistance status is unresolved. CQ resistance surveillance by patient follow-up, in vitro drug sensitivity studies, and molecular markers is urgently needed in Haiti. PMID:25601993

Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests

PubMed Central

2012-01-01

Background Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR). Methods Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated. Results Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl. Conclusion Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs. PMID:22443344

Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests.

PubMed

Ratsimbasoa, Arsène; Ravony, Harintsoa; Vonimpaisomihanta, Jeanne-Aimée; Raherinjafy, Rogelin; Jahevitra, Martial; Rapelanoro, Rabenja; Rakotomanga, Jean De Dieu Marie; Malvy, Denis; Millet, Pascal; Ménard, Didier

2012-03-25

Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR). Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated. Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl. Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs.

Selection of Plasmodium falciparum Multidrug Resistance Gene 1 Alleles in Asexual Stages and Gametocytes by Artemether-Lumefantrine in Nigerian Children with Uncomplicated Falciparum Malaria ▿

PubMed Central

Happi, C. T.; Gbotosho, G. O.; Folarin, O. A.; Sowunmi, A.; Hudson, T.; O'Neil, M.; Milhous, W.; Wirth, D. F.; Oduola, A. M. J.

2009-01-01

We assessed Plasmodium falciparum mdr1 (Pfmdr1) gene polymorphisms and copy numbers as well as P. falciparum Ca2+ ATPase (PfATPase6) gene polymorphisms in 90 Nigerian children presenting with uncomplicated falciparum malaria and enrolled in a study of the efficacy of artemether-lumefantrine (AL). The nested PCR-restriction fragment length polymorphism and the quantitative real-time PCR methodologies were used to determine the alleles of the Pfmdr1 and PfATPase6 genes and the Pfmdr1 copy number variation, respectively, in patients samples collected prior to treatment and at the reoccurrence of parasites during a 42-day follow-up. The Pfmdr1 haplotype 86N-184F-1246D was significantly associated (P < 0.00001) with treatment failures and was selected for among posttreatment samples obtained from patients with newly acquired or recrudescing infections (P < 0.00001; χ2 = 36.5) and in gametocytes (log rank statistic = 5; P = 0.0253) after treatment with AL. All pre- and posttreatment samples as well as gametocytes harbored a single copy of the Pfmdr1 gene and the wild-type allele (L89) at codon 89 of the PfATPase6 gene. These findings suggest that polymorphisms in the Pfmdr1 gene are under AL selection pressure. Pfmdr1 polymorphisms may result in reduction in the therapeutic efficacy of this newly adopted combination treatment for uncomplicated falciparum malaria in Saharan countries of Africa. PMID:19075074

Selection of Plasmodium falciparum multidrug resistance gene 1 alleles in asexual stages and gametocytes by artemether-lumefantrine in Nigerian children with uncomplicated falciparum malaria.

PubMed

Happi, C T; Gbotosho, G O; Folarin, O A; Sowunmi, A; Hudson, T; O'Neil, M; Milhous, W; Wirth, D F; Oduola, A M J

2009-03-01

We assessed Plasmodium falciparum mdr1 (Pfmdr1) gene polymorphisms and copy numbers as well as P. falciparum Ca(2+) ATPase (PfATPase6) gene polymorphisms in 90 Nigerian children presenting with uncomplicated falciparum malaria and enrolled in a study of the efficacy of artemether-lumefantrine (AL). The nested PCR-restriction fragment length polymorphism and the quantitative real-time PCR methodologies were used to determine the alleles of the Pfmdr1 and PfATPase6 genes and the Pfmdr1 copy number variation, respectively, in patients samples collected prior to treatment and at the reoccurrence of parasites during a 42-day follow-up. The Pfmdr1 haplotype 86N-184F-1246D was significantly associated (P < 0.00001) with treatment failures and was selected for among posttreatment samples obtained from patients with newly acquired or recrudescing infections (P < 0.00001; chi(2) = 36.5) and in gametocytes (log rank statistic = 5; P = 0.0253) after treatment with AL. All pre- and posttreatment samples as well as gametocytes harbored a single copy of the Pfmdr1 gene and the wild-type allele (L89) at codon 89 of the PfATPase6 gene. These findings suggest that polymorphisms in the Pfmdr1 gene are under AL selection pressure. Pfmdr1 polymorphisms may result in reduction in the therapeutic efficacy of this newly adopted combination treatment for uncomplicated falciparum malaria in Saharan countries of Africa.

The complexities of malaria disease manifestations with a focus on asymptomatic malaria

PubMed Central

2012-01-01

Malaria is a serious parasitic disease in the developing world, causing high morbidity and mortality. The pathogenesis of malaria is complex, and the clinical presentation of disease ranges from severe and complicated, to mild and uncomplicated, to asymptomatic malaria. Despite a wealth of studies on the clinical severity of disease, asymptomatic malaria infections are still poorly understood. Asymptomatic malaria remains a challenge for malaria control programs as it significantly influences transmission dynamics. A thorough understanding of the interaction between hosts and parasites in the development of different clinical outcomes is required. In this review, the problems and obstacles to the study and control of asymptomatic malaria are discussed. The human and parasite factors associated with differential clinical outcomes are described and the management and treatment strategies for the control of the disease are outlined. Further, the crucial gaps in the knowledge of asymptomatic malaria that should be the focus of future research towards development of more effective malaria control strategies are highlighted. PMID:22289302

Hyperparasitaemia during clinical malaria episodes in infants aged 0-24 months and its association with in utero exposure to Plasmodium falciparum.

PubMed

Sylvester, Boniphace; Gasarasi, Dinah B; Aboud, Said; Tarimo, Donath; Massawe, Siriel; Mpembeni, Rose; Swedberg, Gote

2018-04-04

Existing information has shown that infants who are prenatally exposed to P. falciparum are susceptible to subsequent malaria infections. However, the effect of prenatal exposure to P. falciparum on parasite density during clinical malaria episodes has not been fully elucidated. This study is a component of a prospective cohort study for which initial results have been published. This component was designed to determine the effect of prenatal exposure to P. falciparum on parasite density during clinical malaria episodes in the first 24 months of life. A total of 215 infants were involved and monitored for clinical malaria episodes defined by fever (≥ 37 °C) and parasitaemia. The geometric mean parasite counts between exposed and unexposed infants were compared using independent samples t test. The effect of in utero exposure to P. falciparum on parasite density was assessed using binary logistic regression. The geometric mean parasite count per µl of blood during clinical malaria episodes in exposed infants was 24,889 (95% CI 18,286-31,490) while in unexposed infants it was 14,035 (95% CI 12,111-15,960), P < 0.05. Prenatal exposure to P. falciparum was associated with hyperparasitaemia during clinical malaria episodes (OR 7.04, 95% CI 2.31-21.74), while other factors were not significantly associated (P > 0.05).

Adherence to national guidelines for the diagnosis and management of severe malaria: a nationwide, cross-sectional survey in Malawi, 2012.

PubMed

Shah, Monica P; Briggs-Hagen, Melissa; Chinkhumba, Jobiba; Bauleni, Andy; Chalira, Alfred; Moyo, Dubulao; Dodoli, Wilfred; Luhanga, Misheck; Sande, John; Ali, Doreen; Gutman, Julie; Mathanga, Don P; Lindblade, Kim A

2016-07-19

Severe malaria has a case fatality rate of 10-20 %; however, few studies have addressed the quality of severe malaria case management. This study evaluated the diagnostic and treatment practices of malaria patients admitted to inpatient health facilities (HF) in Malawi. In July-August 2012, a nationwide, cross-sectional survey of severe malaria management was conducted in 36 HFs selected with equal probability from all eligible public sector HFs in Malawi. Patient records from all admissions during October 2011 and April 2012 (low and high season, respectively) were screened for an admission diagnosis of malaria or prescription of any anti-malarial. Eligible records were stratified by age (< 5 or ≥ 5 years). A maximum of eight records was randomly selected within each age and month stratum. Severe malaria was defined by admission diagnosis or documentation of at least one sign or symptom of severe malaria. Treatment with intravenous (IV) quinine or artesunate was considered correct. Patients without documentation of severe malaria were analysed as uncomplicated malaria patients; treatment with an artemisinin-based combination therapy (ACT) or oral quinine based on malaria test results was considered correct. All analyses accounted for HF level clustering and sampling weights. The analysis included 906 records from 35 HFs. Among these, 42 % (95 % confidence interval [CI] 35-49) had a severe malaria admission diagnosis and 50 % (95 % CI 44-57) had at least one severe malaria sign or symptom documented. Severe malaria patients defined by admission diagnosis (93, 95 % CI 86-99) were more likely to be treated correctly compared to patients defined by a severe sign (82, 95 % CI 75-89) (p < 0.0001). Among uncomplicated malaria patients, 26 % (95 % CI 18-35) were correctly treated and 53 % (95 % CI 42-64) were adequately treated with IV quinine alone or in combination with an ACT or oral quinine. A majority of patients diagnosed with severe malaria received the recommended IV therapy in accordance with national treatment guidelines. However, the inconsistencies between diagnosis of severe malaria and documentation of severe signs and symptoms highlight the need to improve healthcare worker recognition and documentation of severe signs and symptoms.

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya

PubMed Central

Thwing, J. I.; Odero, C. O.; Odhiambo, F. O.; Otieno, K. O.; Kariuki, S.; Ord, R.; Roper, C.; McMorrow, M.; Vulule, J.; Slutsker, L.; Newman, R. D.; Hamel, M. J.; Desai, M.

2018-01-01

Summary OBJECTIVES To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. METHODS Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6–59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. RESULTS The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrolment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. CONCLUSION Although artemether-lumefantrine (Coartem®) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem® in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardise the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy. PMID:19187521

Parasite burden and severity of malaria in Tanzanian children.

PubMed

Gonçalves, Bronner P; Huang, Chiung-Yu; Morrison, Robert; Holte, Sarah; Kabyemela, Edward; Prevots, D Rebecca; Fried, Michal; Duffy, Patrick E

2014-05-08

Severe Plasmodium falciparum malaria is a major cause of death in children. The contribution of the parasite burden to the pathogenesis of severe malaria has been controversial. We documented P. falciparum infection and disease in Tanzanian children followed from birth for an average of 2 years and for as long as 4 years. Of the 882 children in our study, 102 had severe malaria, but only 3 had more than two episodes. More than half of first episodes of severe malaria occurred after a second infection. Although parasite levels were higher on average when children had severe rather than mild disease, most children (67 of 102) had high-density infection (>2500 parasites per 200 white cells) with only mild symptoms before severe malaria, after severe malaria, or both. The incidence of severe malaria decreased considerably after infancy, whereas the incidence of high-density infection was similar among all age groups. Infections before and after episodes of severe malaria were associated with similar parasite densities. Nonuse of bed nets, placental malaria at the time of a woman's second or subsequent delivery, high-transmission season, and absence of the sickle cell trait increased severe-malaria risk and parasite density during infections. Resistance to severe malaria was not acquired after one or two mild infections. Although the parasite burden was higher on average during episodes of severe malaria, a high parasite burden was often insufficient to cause severe malaria even in children who later were susceptible. The diverging rates of severe disease and high-density infection after infancy, as well as the similar parasite burdens before and after severe malaria, indicate that naturally acquired resistance to severe malaria is not explained by improved control of parasite density. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Timing of Malaria Infection during Pregnancy Has Characteristic Maternal, Infant and Placental Outcomes

PubMed Central

Kalilani-Phiri, Linda; Thesing, Phillip C.; Nyirenda, Osward M.; Mawindo, Patricia; Madanitsa, Mwayi; Membe, Gladys; Wylie, Blair; Masonbrink, Abbey; Makwakwa, Kingsley; Kamiza, Steve; Muehlenbachs, Atis; Taylor, Terrie E.; Laufer, Miriam K.

2013-01-01

We conducted a clinical study of pregnant women in Blantyre, Malawi to determine the effect of the timing of malaria infection during pregnancy on maternal, infant and placental outcomes. Women were enrolled in their first or second trimester of their first or second pregnancy and followed every four weeks until delivery. Three doses of sulfadoxine-pyrimethamine were given for intermittent preventive treatment for malaria, and all episodes of parasitemia were treated according to the national guidelines. Placentas were collected at delivery and examined for malaria parasites and pigment by histology. Pregnant women had 0.6 episodes of malaria per person year of follow up. Almost all episodes of malaria were detected at enrollment and malaria infection during the follow up period was rare. Malaria and anemia at the first antenatal visit were independently associated with an increased risk of placental malaria detected at delivery. When all episodes of malaria were treated with effective antimalarial medication, only peripheral malaria infection at the time of delivery was associated with adverse maternal and infant outcomes. One quarter of the analyzed placentas had evidence of malaria infection. Placental histology was 78% sensitive and 89% specific for peripheral malaria infection during pregnancy. This study suggests that in this setting of high antifolate drug resistance, three doses of sulfadoxine-pyrimethamine maintain some efficacy in suppressing microscopically detectable parasitemia, although placental infection remains frequent. Even in this urban setting, a large proportion of women have malaria infection at the time of their first antenatal care visit. Interventions to control malaria early and aggressive case detection are required to limit the detrimental effects of pregnancy-associated malaria. PMID:24058614

Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study

PubMed Central

Manning, Laurens; Rarau, Patricia; Laman, Moses; Senn, Nicolas; Grimberg, Brian T.; Tavul, Livingstone; Stanisic, Danielle I.; Robinson, Leanne J.; Aponte, John J.; Dabod, Elijah; Reeder, John C.; Siba, Peter; Zimmerman, Peter A.; Davis, Timothy M. E.; King, Christopher L.; Michon, Pascal; Mueller, Ivo

2012-01-01

Background The erythrocyte polymorphism, Southeast Asian ovalocytosis (SAO) (which results from a 27-base pair deletion in the erythrocyte band 3 gene, SLC4A1Δ27) protects against cerebral malaria caused by Plasmodium falciparum; however, it is unknown whether this polymorphism also protects against P. vivax infection and disease. Methods and Findings The association between SAO and P. vivax infection was examined through genotyping of 1,975 children enrolled in three independent epidemiological studies conducted in the Madang area of Papua New Guinea. SAO was associated with a statistically significant 46% reduction in the incidence of clinical P. vivax episodes (adjusted incidence rate ratio [IRR] = 0.54, 95% CI 0.40–0.72, p<0.0001) in a cohort of infants aged 3–21 months and a significant 52% reduction in P. vivax (blood-stage) reinfection diagnosed by PCR (95% CI 22–71, p = 0.003) and 55% by light microscopy (95% CI 13–77, p = 0.014), respectively, in a cohort of children aged 5–14 years. SAO was also associated with a reduction in risk of P. vivax parasitaemia in children 3–21 months (1,111/µl versus 636/µl, p = 0.011) and prevalence of P. vivax infections in children 15–21 months (odds ratio [OR] = 0.39, 95% CI 0.23–0.67, p = 0.001). In a case-control study of children aged 0.5–10 years, no child with SAO was found among 27 cases with severe P. vivax or mixed P. falciparum/P. vivax malaria (OR = 0, 95% CI 0–1.56, p = 0.11). SAO was associated with protection against severe P. falciparum malaria (OR = 0.38, 95% CI 0.15–0.87, p = 0.014) but no effect was seen on either the risk of acquiring blood-stage infections or uncomplicated episodes with P. falciparum. Although Duffy antigen receptor expression and function were not affected on SAO erythrocytes compared to non-SAO children, high level (>90% binding inhibition) P. vivax Duffy binding protein–specific binding inhibitory antibodies were observed significantly more often in sera from SAO than non-SAO children (SAO, 22.2%; non-SAO, 6.7%; p = 0.008). Conclusions In three independent studies, we observed strong associations between SAO and protection against P. vivax malaria by a mechanism that is independent of the Duffy antigen. P. vivax malaria may have contributed to shaping the unique host genetic adaptations to malaria in Asian and Oceanic populations. Please see later in the article for the Editors' Summary. PMID:22973182

Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria.

PubMed

te Witt, René; van Wolfswinkel, Marlies E; Petit, Pieter L; van Hellemond, Jaap J; Koelewijn, Rob; van Belkum, Alex; van Genderen, Perry J J

2010-09-14

Most clinicians in developed, non-malaria endemic countries have limited or no experience in making clinical assessments of malaria disease severity and subsequent decisions regarding the need for parenteral therapy or high-level monitoring in febrile patients with imported malaria. In the present study, the diagnostic accuracy of plasma soluble Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), neopterin and procalcitonin levels as biomarkers for severe Plasmodium falciparum disease was evaluated in 104 travellers with imported malaria (26 patients with non-P. falciparum malaria, 64 patients with uncomplicated P. falciparum malaria and 14 patients with severe P. falciparum malaria). TREM-1, neopterin and procalcitonin were determined in serum using commercially available ELISA or EIA tests. The diagnostic performance of these biomarkers for severe disease was compared with plasma lactate, a well-validated parameter for disease severity in patients with malaria, as reference. Severe malaria was defined according to the modified WHO criteria. No significant differences in TREM-1 levels were detected between the different patient groups. Patients with severe P. falciparum malaria had significantly higher neopterin and procalcitonin levels on admission when compared to patients with uncomplicated P. falciparum malaria or non-P. falciparum malaria. Receiver Operating Characteristic (ROC) curve analysis showed that neopterin had the highest Area-Under-the-ROC curve (AUROC 0.85) compared with plasma lactate (AUROC 0.80) and procalcitonin (AUROC 0.78). At a cut-off point of 10.0 ng/ml, neopterin had a positive and negative predictive value of 0.38 and 0.98 whereas procalcitonin, at a cut-off point of 0.9 ng/ml, had a positive and negative predictive value of 0.30 and 1.00. Although the diagnostic value of neopterin and procalcitonin is limited, the high negative predictive value of both neopterin and procalcitonin may be helpful for a rapid exclusion of severe malaria disease on admission. This may be a valuable tool for physicians only occasionally dealing with ill-returned travellers from malaria-endemic regions and who need to decide on subsequent oral anti-malarial treatment or timely referral to a specialized centre for high-level monitoring and intensified parenteral treatment.

Novel anti-malarial combinations and their toxicity.

PubMed

Angus, Brian

2014-05-01

Artemisinin combination therapy for the treatment of uncomplicated malaria includes artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine and dihydroartemisinin plus piperaquine. These drugs are safe and efficacious at present. The emergence of artemisinin resistant parasites in SE Asia means that there is a need to optimise drug dosing and investigate novel therapies to maintain the impressive reduction in malaria mortality which has been seen in the past decade.

Platelet-mediated clumping of Plasmodium falciparum infected erythrocytes is associated with high parasitemia but not severe clinical manifestations of malaria in African children

PubMed Central

Arman, Mònica; Raza, Ahmed; Tempest, Louisa J.; Lyke, Kirsten E.; Thera, Mahamadou A.; Koné, Abdoulaye; Plowe, Christopher V.; Doumbo, Ogobara K.; Rowe, J. Alexandra

2009-01-01

Platelet-mediated clumping of Plasmodium falciparum infected erythrocytes is an adhesive phenotype commonly found in field isolates that has previously been associated with severe malaria. Here, clumping was assessed in 131 isolates from Malian children. The clumping phenotype was seen in 6% (n=51) of uncomplicated malaria, 24% (n=51) of severe malaria, and 45% (n=29) of high parasitemia non-severe malaria isolates. Multivariate analysis indicated that clumping was strongly positively associated with parasitemia (F1,122=24.1, p<0.001) but not with disease category (F2,122=1.8, p=0.17). Therefore platelet-mediated clumping in Malian P. falciparum isolates is primarily associated with high parasitemia and not with severe clinical manifestations of malaria. PMID:17984358

Quality of uncomplicated malaria case management in Ghana among insured and uninsured patients.

PubMed

Fenny, Ama P; Hansen, Kristian S; Enemark, Ulrika; Asante, Felix A

2014-07-24

The National Health Insurance Act, 2003 (Act 650) established the National Health Insurance Scheme (NHIS) in Ghana with the aim of increasing access to health care and improving the quality of basic health care services for all citizens. The main objective is to assess the effect of health insurance on the quality of case management for patients with uncomplicated malaria, ascertaining any significant differences in treatment between insured and non-insured patients. A structured questionnaire was used to collect data from 523 respondents diagnosed with malaria and prescribed malaria drugs from public and private health facilities in 3 districts across Ghana's three ecological zones. Collected information included initial examinations performed on patients (temperature, weight, age, blood pressure and pulse); observations of malaria symptoms by trained staff, laboratory tests conducted and type of drugs prescribed. Insurance status of patients, age, gender, education level and occupation were asked in the interviews. Of the 523 patients interviewed, only 40 (8%) were uninsured. Routine recording of the patients' age, weight, and temperature was high in all the facilities. In general, assessments needed to identify suspected malaria were low in all the facilities with hot body/fever and headache ranking the highest and convulsion ranking the lowest. Parasitological assessments in all the facilities were also very low. All patients interviewed were prescribed ACTs which is in adherence to the drug of choice for malaria treatment in Ghana. However, there were no significant differences in the quality of malaria treatment given to the uninsured and insured patients. Adherence to the standard protocol of malaria treatment is low. This is especially the case for parasitological confirmation of all suspected malaria patients before treatment with an antimalarial as currently recommended for the effective management of malaria in the country. The results show that about 16 percent of total sample were parasitologically tested. Effective management of the disease demands proper diagnosis and treatment and therefore facilities need to be adequately supplied with RDTs or be equipped with well functioning laboratories to provide adequate testing.

Quality of uncomplicated malaria case management in Ghana among insured and uninsured patients

PubMed Central

2014-01-01

Introduction The National Health Insurance Act, 2003 (Act 650) established the National Health Insurance Scheme (NHIS) in Ghana with the aim of increasing access to health care and improving the quality of basic health care services for all citizens. The main objective is to assess the effect of health insurance on the quality of case management for patients with uncomplicated malaria, ascertaining any significant differences in treatment between insured and non-insured patients. Method A structured questionnaire was used to collect data from 523 respondents diagnosed with malaria and prescribed malaria drugs from public and private health facilities in 3 districts across Ghana’s three ecological zones. Collected information included initial examinations performed on patients (temperature, weight, age, blood pressure and pulse); observations of malaria symptoms by trained staff, laboratory tests conducted and type of drugs prescribed. Insurance status of patients, age, gender, education level and occupation were asked in the interviews. Results Of the 523 patients interviewed, only 40 (8%) were uninsured. Routine recording of the patients’ age, weight, and temperature was high in all the facilities. In general, assessments needed to identify suspected malaria were low in all the facilities with hot body/fever and headache ranking the highest and convulsion ranking the lowest. Parasitological assessments in all the facilities were also very low. All patients interviewed were prescribed ACTs which is in adherence to the drug of choice for malaria treatment in Ghana. However, there were no significant differences in the quality of malaria treatment given to the uninsured and insured patients. Conclusion Adherence to the standard protocol of malaria treatment is low. This is especially the case for parasitological confirmation of all suspected malaria patients before treatment with an antimalarial as currently recommended for the effective management of malaria in the country. The results show that about 16 percent of total sample were parasitologically tested. Effective management of the disease demands proper diagnosis and treatment and therefore facilities need to be adequately supplied with RDTs or be equipped with well functioning laboratories to provide adequate testing. PMID:25056139

A Small Amount of Fat Does Not Affect Piperaquine Exposure in Patients with Malaria▿†

PubMed Central

Annerberg, Anna; Lwin, Khin Maung; Lindegardh, Niklas; Khrutsawadchai, Sakchai; Ashley, Elizabeth; Day, Nicholas P. J.; Singhasivanon, Pratap; Tarning, Joel; White, Nicholas J.; Nosten, François

2011-01-01

Dihydroartemisinin-piperaquine is a new, highly effective, and well-tolerated combination treatment for uncomplicated falciparum malaria. The lipophilic characteristic of piperaquine suggests that administration together with fat will increase the oral bioavailability of the drug, and this has been reported for healthy volunteers. This pharmacokinetic study monitored 30 adult patients with uncomplicated falciparum malaria for 4.5 months to evaluate the effects of the concomitant intake of fat on the total piperaquine exposure. The fixed-drug combination of dihydroartemisinin-piperaquine was given with water to fasting patients (n = 15) or was coadministered with 200 ml milk containing 6.4 g fat (n = 15). The drug combination was generally well tolerated, and there were no severe adverse effects reported for either group during the study. Total piperaquine exposure (area under the concentration-time curve from zero to infinity [AUC0-∞]; results are given as medians [ranges]) were not statistically different between fed (29.5 h · μg/ml [20.6 to 58.7 h · μg/ml]) and fasting (23.9 h · μg/ml [11.9 to 72.9 h · μg/ml]) patients, but the interindividual variation was reduced in the fed group. Overall, none of the pharmacokinetic parameters differed statistically between the groups. Total piperaquine exposure correlated well with the day 7 concentrations in the fasted group, but the fed group showed a poor correlation. In conclusion, the coadministration of 6.4 g fat did not have any significant effect on piperaquine pharmacokinetics in the treatment of uncomplicated malaria. PMID:21709087

Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali.

PubMed

Maiga, Bakary; Dolo, Amagana; Campino, Susana; Sepulveda, Nuno; Corran, Patrick; Rockett, Kirk A; Troye-Blomberg, Marita; Doumbo, Ogobara K; Clark, Taane G

2014-07-11

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (<1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males. The results highlight the need to consider markers in addition to G6PD202 in studies of deficiency. Further, large genetic epidemiological studies of multi-ethnic groups in West Africa across a spectrum of malaria severity phenotypes are required to establish who receives protection from G6PD deficiency.

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) in Treating Uncomplicated P. falciparum Malaria in Metehara, Eastern Ethiopia: Regulatory Clinical Study.

PubMed

Nega, Desalegn; Assefa, Ashenafi; Mohamed, Hussein; Solomon, Hiwot; Woyessa, Adugna; Assefa, Yibeltal; Kebede, Amha; Kassa, Moges

2016-01-01

As per the WHO recommendation, the development of resistance by P. falciparum to most artemisinin combination therapies (ACTs) triggered the need for routine monitoring of the efficacy of the drugs every two years in all malaria endemic countries. Hence, this study was carried out to assess the therapeutic efficacy of Artemether-Lumefantrine (Coartem®) in treating the uncomplicated falciparum malaria, after 9 years of its introduction in the Metehara, Eastern Ethiopia. This is part of the therapeutic efficacy studies by the Federal Ministry of Health Ethiopia, which were conducted in regionally representative sentinel sites in the country from October 2014 to January 2015. Based on the study criteria set by WHO, febrile and malaria suspected outpatients in the health center were consecutively recruited to study. A standard six-dose regimen of AL was administered over three days and followed up for measuring therapeutic responses over 28 days. Data entry and analysis was done by using the WHO designed Excel spreadsheet and SPSS version 20 for Windows. Statistical significant was considered for P-value less than 0.05. Of the 91 patients enrolled, the day-28 analysis showed 83 adequate clinical and parasitological responses (ACPRs). Per protocol analysis, PCR-uncorrected & corrected cure rates of Coartem® among the study participants were 97.6% (95%CI: 93.6-99.5) and 98.8% (CI: 93.5-100%), respectively. No parasite detected on day 3 and onwards. Fever clearance was above 91% on day-3. Mean hemoglobin was significantly increased (P<0.000) from 12.39 g/dl at day 0 to 13.45 g/dl on day 28. No serious adverse drug reactions were observed among the study participants. This study showed high efficacy of AL in the study area, which suggests the continuation of AL as first line drug for the treatment of uncomplicated P. falciparum malaria in the study area. This study recommends further studies on drug toxicity, particularly on repeated cough and oral ulceration.

Malaria and other febrile diseases among travellers: the experience of a reference centre located outside the Brazilian Amazon Region.

PubMed

Dotrário, Andréa Beltrami; Menon, Lucas José Bazzo; Bollela, Valdes Roberto; Martinez, Roberto; de Almeida E Araújo, Daniel Cardoso; da Fonseca, Benedito Antônio Lopes; Santana, Rodrigo de C

2016-05-26

Malaria is endemic in countries located in tropical and sub-tropical regions. The increasing flow of domestic and international travellers has made malaria a relevant health problem even in non-endemic regions. Malaria has been described as the main diagnosis among travellers presenting febrile diseases after returning from tropical countries. In Brazil, malaria transmission occurs mainly in the Amazon region. Outside this area, malaria transmission is of low magnitude. This cross-sectional study aimed to describe the experience in the diagnosis of malaria in a reference centre located outside the Brazilian Amazon Region, emphasizing the differences in clinical and laboratory markers between cases of malaria and those of other febrile diseases (OFD). Medical charts from adult patients (≥18 years) who underwent a thick smear test (TST) for malaria, between January 2001 and December 2014, were retrospectively reviewed. A total of 458 cases referred to perform the TST were included. Malaria was diagnosed in 193 (42 %) episodes. The remaining 265 episodes (58 %) were grouped as OFD. The majority of malaria episodes were acquired in the Brazilian Amazon Region. The median time between the onset of symptoms and the TST was 7 days. Only 53 (11.5 %) episodes were tested within the first 48 h after symptom onset. Comparing malaria with OFD, jaundice, nausea, vomiting, and reports of fever were more prevalent in the malaria group. Low platelet count and elevated bilirubin levels were also related to the diagnosis of malaria. The results indicate that outside the endemic area travellers presenting febrile disease suspected of being malaria underwent diagnostic test after considerable delay. The reporting of fever combined with a recent visit to an endemic area should promptly evoke the hypothesis of malaria. In these cases, specific diagnostic tests for malaria should be a priority. For cases that jump this step, the presence of elevated bilirubin or thrombocytopaenia should also indicate a diagnosis of malaria.

Pharmacokinetic considerations for use of artemisinin-based combination therapies against falciparum malaria in different ethnic populations.

PubMed

Sugiarto, Sri Riyati; Davis, Timothy M E; Salman, Sam

2017-11-01

Artemisinin-based combination therapy (ACT) is used extensively as first-line treatment for uncomplicated falciparum malaria. There has been no rigorous assessment of the potential for racial/ethnic differences in the pharmacokinetic properties of ACTs that might influence their efficacy. Areas covered: A comprehensive literature search was performed that identified 72 publications in which the geographical origin of the patients could be ascertained and the key pharmacokinetic parameters maximum drug concentration (C max ), area under the plasma concentration-time curve (AUC) and elimination half-life (t ½β ) were available for one or more of the five WHO-recommended ACTs (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine and artesunate-sulfadoxine-pyrimethamine). Comparisons of each of the three pharmacokinetic parameters of interest were made by drug (artemisinin derivative and long half-life partner), race/ethnicity (African, Asian, Caucasian, Melanesian, South American) and patient categories based on age and pregnancy status. Expert opinion: The review identified no evidence of a clinically significant influence of race/ethnicity on the pharmacokinetic properties of the nine component drugs in the five ACTs currently recommended by WHO for first-line treatment of uncomplicated falciparum malaria. This provides reassurance for health workers in malaria-endemic regions that ACTs can be given in recommended doses with the expectation of adequate blood concentrations regardless of race/ethnicity.

Effectiveness of Provider and Community Interventions to Improve Treatment of Uncomplicated Malaria in Nigeria: A Cluster Randomized Controlled Trial.

PubMed

Onwujekwe, Obinna; Mangham-Jefferies, Lindsay; Cundill, Bonnie; Alexander, Neal; Langham, Julia; Ibe, Ogochukwu; Uzochukwu, Benjamin; Wiseman, Virginia

2015-01-01

The World Health Organization recommends that malaria be confirmed by parasitological diagnosis before treatment using Artemisinin-based Combination Therapy (ACT). Despite this, many health workers in malaria endemic countries continue to diagnose malaria based on symptoms alone. This study evaluates interventions to help bridge this gap between guidelines and provider practice. A stratified cluster-randomized trial in 42 communities in Enugu state compared 3 scenarios: Rapid Diagnostic Tests (RDTs) with basic instruction (control); RDTs with provider training (provider arm); and RDTs with provider training plus a school-based community intervention (provider-school arm). The primary outcome was the proportion of patients treated according to guidelines, a composite indicator requiring patients to be tested for malaria and given treatment consistent with the test result. The primary outcome was evaluated among 4946 (93%) of the 5311 patients invited to participate. A total of 40 communities (12 in control, 14 per intervention arm) were included in the analysis. There was no evidence of differences between the three arms in terms of our composite indicator (p = 0.36): stratified risk difference was 14% (95% CI -8.3%, 35.8%; p = 0.26) in the provider arm and 1% (95% CI -21.1%, 22.9%; p = 0.19) in the provider-school arm, compared with control. The level of testing was low across all arms (34% in control; 48% provider arm; 37% provider-school arm; p = 0.47). Presumptive treatment of uncomplicated malaria remains an ingrained behaviour that is difficult to change. With or without extensive supporting interventions, levels of testing in this study remained critically low. Governments and researchers must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines. ClinicalTrials.gov NCT01350752.

Age-related pattern and monocyte-acquired haemozoin associated production of erythropoietin in children with severe malarial anaemia in Ghana.

PubMed

Abugri, James; Tetteh, John Kweku Amissah; Oseni, Lateef Adebayo; Mensah-Brown, Henrietta Esi; Delimini, Rupert Kantunye; Obuobi, David Osei; Akanmori, Bartholomew Dicky

2014-08-20

Malaria continues to be a global health challenge, affecting more than half the world's population and causing approximately 660,000 deaths annually. The majority of malaria cases are caused by Plasmodium falciparum and occur in sub-Saharan Africa. One of the major complications asscociated with malaria is severe anaemia, caused by a cycle of haemoglobin digestion by the parasite. Anaemia due to falciparum malaria in children has multifactorial pathogenesis, which includes suppression of bone marrow activity. Recent studies have shown that haemozoin, which is a by-product of parasite haemoglobin digestion, may play an important role in suppression of haemoglobin production, leading to anaemia. In this study we correlated the levels of erythropoietin (EPO), as an indicator of stimulation of haemoglobin production, to the levels of monocyte acquired haemozoin in children with both severe and uncomplicated malaria. There was a significantly negative correlation between levels of haemozoin-containing monocytes and EPO, which may suggest that haemozoin suppresses erythropoiesis in severe malaria. A multiple linear regression analysis and simple bar was used to investigate associations between various haematological parameters. To examine the levels of erythropoietin in the age categories, the levels of erythropoietin was measured using a commercial Enyme-Linked Immunosorbent Assay (ELISA). Giemsa-stained blood smears were used to determine percentage pigment containing monocytes. The haemozoin containing monocytes was expressed as a percentage of the total number of monocytes. To obtain the number of haemozoin containing monocytes/μL the percentage of haemozoin containing monocytes was multiplied by the absolute number of monocytes/μL from the automated haematology analyzer. The levels of erythropoietin in younger children (<3 years) was significantly higher than in older children with a similar degree of malaria anaemia (Hb levels) (p < 0.005). Haemozoin-containing monocytes were relatively higher in severe malaria anaemia patients compared to those with uncomplicated malaria (p < 0.001). Age purportedly has a direct effect on background levels of erythropoietin. With corresponding decreased levels of erythropoietin in older children with the same degree of severe malarial anaemia, conceivably, the bone marrows of younger children with acute malaria may be less sensitive to erythropoietin.

Seasonality in malaria transmission: implications for case-management with long-acting artemisinin combination therapy in sub-Saharan Africa.

PubMed

Cairns, Matthew E; Walker, Patrick G T; Okell, Lucy C; Griffin, Jamie T; Garske, Tini; Asante, Kwaku Poku; Owusu-Agyei, Seth; Diallo, Diadier; Dicko, Alassane; Cisse, Badara; Greenwood, Brian M; Chandramohan, Daniel; Ghani, Azra C; Milligan, Paul J

2015-08-19

Long-acting artemisinin-based combination therapy (LACT) offers the potential to prevent recurrent malaria attacks in highly exposed children. However, it is not clear where this advantage will be most important, and deployment of these drugs is not rationalized on this basis. To understand where post-treatment prophylaxis would be most beneficial, the relationship between seasonality, transmission intensity and the interval between malaria episodes was explored using data from six cohort studies in West Africa and an individual-based malaria transmission model. The total number of recurrent malaria cases per 1000 child-years at risk, and the fraction of the total annual burden that this represents were estimated for sub-Saharan Africa. In settings where prevalence is less than 10 %, repeat malaria episodes constitute a small fraction of the total burden, and few repeat episodes occur within the window of protection provided by currently available drugs. However, in higher transmission settings, and particularly in high transmission settings with highly seasonal transmission, repeat malaria becomes increasingly important, with up to 20 % of the total clinical burden in children estimated to be due to repeat episodes within 4 weeks of a prior attack. At a given level of transmission intensity and annual incidence, the concentration of repeat malaria episodes in time, and consequently the protection from LACT is highest in the most seasonal areas. As a result, the degree of seasonality, in addition to the overall intensity of transmission, should be considered by policy makers when deciding between ACT that differ in their duration of post-treatment prophylaxis.

An unrestricted diet for uncomplicated diverticulitis is safe: results of a prospective diverticulitis diet study.

PubMed

Stam, M A W; Draaisma, W A; van de Wall, B J M; Bolkenstein, H E; Consten, E C J; Broeders, I A M J

2017-04-01

The optimal diet for uncomplicated diverticulitis is unclear. Guidelines refrain from recommendation due to lack of objective information. The aim of the study was to determine whether an unrestricted diet during a first acute episode of uncomplicated diverticulitis is safe. A prospective cohort study was performed of patients diagnosed with diverticulitis for the first time between 2012 and 2014. Requirements for inclusion were radiologically proven modified Hinchey Ia/b diverticulitis, American Society of Anesthesiologists class I-III and the ability to tolerate an unrestricted diet. Exclusion criteria were the use of antibiotics and suspicion of inflammatory bowel disease or malignancy. All included patients were advised to take an unrestricted diet. The primary outcome parameter was morbidity. Secondary outcome measures were the development of recurrence and ongoing symptoms. There were 86 patients including 37 (43.0%) men. All patients were confirmed to have taken an unrestricted diet. There were nine adverse events in seven patients. These consisted of readmission for pain (five), recurrent diverticulitis (one) and surgery (three) for ongoing symptoms (two) and Hinchey Stage III (one). Seventeen (19.8%) patients experienced continuing symptoms 6 months after the initial episode and 4 (4.7%) experienced recurrent diverticulitis. The incidence of complications among patients taking an unrestricted diet during an initial acute uncomplicated episode of diverticulitis was in line with that reported in the literature. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study.

PubMed

Tiono, Alfred B; Guelbeogo, Moussa W; Sagnon, N Falé; Nébié, Issa; Sirima, Sodiomon B; Mukhopadhyay, Amitava; Hamed, Kamal

2013-11-12

In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes. Two studies were run in parallel in Burkina Faso to evaluate the impact of systematic identification and treatment of asymptomatic carriers of P. falciparum, detected by rapid diagnostic test, on disease transmission and susceptibility to clinical malaria episodes. A clinical study assessed the incidence of symptomatic malaria episodes with a parasite density >5,000/μL after three screening and treatment campaigns ~1 month apart before the rainy season; and an entomological study determined the effect of these campaigns on malaria transmission as measured by entomological inoculation rate. The intervention arm had lower prevalence of asymptomatic carriers of asexual parasites and lower prevalence of gametocyte carriers during campaigns 2 and 3 as compared to the control arm. During the entire follow-up period, out of 13,767 at-risk subjects, 2,516 subjects (intervention arm 1,332; control arm 1,184) had symptomatic malaria. Kaplan-Meier analysis of the incidence of first symptomatic malaria episode with a parasite density >5,000/μL showed that, in the total population, the two treatment arms were similar until Week 11-12 after campaign 3, corresponding with the beginning of the malaria transmission season, after which the probability of being free of symptomatic malaria was lower in the intervention arm (logrank p < 0.0001). Similar trends were observed in infants and children <5 years and in individuals ≥5 years of age. In infants and children <5 years old who experienced symptomatic malaria episodes, the geometric mean P. falciparum density was lower in the intervention arm than the control arm. This trend was not seen in those individuals aged ≥5 years. Over the year, monthly variation in mosquito density and entomological inoculation rate was comparable in both arms, with September peaks in both indices. Community screening and targeted treatment of asymptomatic carriers of P. falciparum had no effect on the dynamics of malaria transmission, but seemed to be associated with an increase in the treated community's susceptibility to symptomatic malaria episodes after the screening campaigns had finished. These results highlight the importance of further exploratory studies to better understand the dynamics of disease transmission in the context of malaria elimination.

Genetic Surveillance Detects Both Clonal and Epidemic Transmission of Malaria following Enhanced Intervention in Senegal

PubMed Central

Séne, Papa Diogoye; Park, Danny C.; Neafsey, Daniel E.; Schaffner, Stephen F.; Hamilton, Elizabeth J.; Lukens, Amanda K.; Van Tyne, Daria; Mboup, Souleymane; Sabeti, Pardis C.; Ndiaye, Daouda; Wirth, Dyann F.

2013-01-01

Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically identical parasite strains, coincident with increased deployment of malaria control interventions and decreased malaria deaths. Parasite genotypes in some cases persisted clonally across dry seasons. The increase in frequency of genetically identical parasite strains corresponded with decrease in the probability of multiple infections. Further, these observations support evidence of both clonal and epidemic population structures. These data provide the first evidence of a temporal correlation between the appearance of identical parasite types and increased malaria control efforts in Africa, which here included distribution of insecticide treated nets (ITNs), use of rapid diagnostic tests (RDTs) for malaria detection, and deployment of artemisinin combination therapy (ACT). Our results imply that genetic surveillance can be used to evaluate the effectiveness of disease control strategies and assist a rational global malaria eradication campaign. PMID:23593309

Genotypic and phenotypic characterization of G6PD deficiency in Bengali adults with severe and uncomplicated malaria.

PubMed

Plewes, Katherine; Soontarawirat, Ingfar; Ghose, Aniruddha; Bancone, Germana; Kingston, Hugh W F; Herdman, M Trent; Leopold, Stije J; Ishioka, Haruhiko; Faiz, Md Abul; Anstey, Nicholas M; Day, Nicholas P J; Hossain, Md Amir; Imwong, Mallika; Dondorp, Arjen M; Woodrow, Charles J

2017-03-29

Control of malaria increasingly involves administration of 8-aminoquinolines, with accompanying risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few data on the prevalence and genotypic basis of G6PD deficiency are available from Bangladesh, where malaria remains a major problem in the South (Chittagong Division). The aim of this study was to determine the prevalence of G6PD deficiency, and associated G6PD genotypes, in adults with falciparum malaria in southern Bangladesh. G6PD status was assessed via a combination of fluorescent spot testing (FST) and genotyping in 141 Bengali patients admitted with falciparum malaria to two centres in Chittagong Division from 2012 to 2014. In addition, an analysis of genomic data from 1000 Genomes Project was carried out among five healthy Indian subcontinent populations. One male patient with uncomplicated malaria was found to have G6PD deficiency on FST and a genotype associated with deficiency (hemizygous Orissa variant). In addition, there were two female patients heterozygous for deficiency variants (Orissa and Kerala-Kalyan). These three patients had a relatively long duration of symptoms prior to admission compared to G6PD normal cases, possibly suggesting an interaction with parasite multiplication rate. In addition, one of 27 healthy local controls was deficient on FST and hemizygous for the Mahidol variant of G6PD deficiency. Examination of 1000 Genomes Project sequencing data across the Indian subcontinent showed that 19/723 chromosomes (2.63%) carried a variant associated with deficiency. In the Bengali from Bangladesh 1000 Genomes population, three of 130 chromosomes (2.31%) carried deficient alleles; this included single chromosomes carrying the Kerala-Kalyan and Orissa variants. In line with other recent work, G6PD deficiency is uncommon in Bengalis in Bangladesh. Further studies of particular ethnic groups are needed to evaluate the potential risk of wide deployment of primaquine in malaria control efforts in Bangladesh.

Efficacy of Artesunate/Amodiaquine in the Treatment of Uncomplicated Malaria among Children in Ghana.

PubMed

Abuaku, Benjamin K; Mensah, Benedicta A; Ofori, Michael F; Myers-Hansen, James; Derkyi-Kwarteng, Abigail N; Essilfie, Felicia; Dokurugu, Moses; Amoakoh, Emmanuel; Koram, Kwadwo A; Ghansah, Anita

2017-09-01

The declining efficacy of chloroquine in the early 2000s in Ghana led to its replacement with artesunate/amodiaquine (AS/AQ) combination as first-line drug for treating uncomplicated malaria in 2005. Since then efficacy studies have been ongoing in the country to provide continuous data on the efficacy of AS/AQ and other alternative antimalarials (artemether/lumefantrine and dihyroartemisinin/piperaquine combinations) introduced in 2008. In vivo AS/AQ efficacy studies were conducted between June and October 2014 among children aged 6 months to 14 years, in two sentinel sites representing the forest and coastal zones of the country. The 2009 World Health Organization protocol for monitoring antimalarial drug efficacy was used in these studies. The studies showed an overall cumulative polymerase chain reaction-corrected day 28 cure rate of 97.2% (95% confidence interval [CI]: 93.6-99.1): 97.7% (95% CI: 92.0-99.7) within the forest zone and 96.7% (95% CI: 90.7-99.3) within the coastal zone ( P = 0.686). Prevalence of fever declined from 100% to < 4% after first day of treatment in both ecological zones. All children in the coastal zone had cleared parasites by day 2. Three children (3.2%) in the forest zone were parasitemic on day 2, whereas one child was parasitemic on day 3. Gametocytemia was absent in both zones after day 14, and mean hemoglobin concentration significantly increased from 10.3 g/dL (95% CI: 10.1-10.5) on day 0 to 11.8 g/dL (95% CI: 11.6-12.0) on day 28. We conclude that AS/AQ combination remains efficacious in the treatment of uncomplicated malaria in Ghana.

Household costs among patients hospitalized with malaria: evidence from a national survey in Malawi, 2012.

PubMed

Hennessee, Ian; Chinkhumba, Jobiba; Briggs-Hagen, Melissa; Bauleni, Andy; Shah, Monica P; Chalira, Alfred; Moyo, Dubulao; Dodoli, Wilfred; Luhanga, Misheck; Sande, John; Ali, Doreen; Gutman, Julie; Lindblade, Kim A; Njau, Joseph; Mathanga, Don P

2017-10-02

With 71% of Malawians living on < $1.90 a day, high household costs associated with severe malaria are likely a major economic burden for low income families and may constitute an important barrier to care seeking. Nevertheless, few efforts have been made to examine these costs. This paper describes household costs associated with seeking and receiving inpatient care for malaria in health facilities in Malawi. A cross-sectional survey was conducted in a representative nationwide sample of 36 health facilities providing inpatient treatment for malaria from June-August, 2012. Patients admitted at least 12 h before study team visits who had been prescribed an antimalarial after admission were eligible to provide cost information for their malaria episode, including care seeking at previous health facilities. An ingredients-based approach was used to estimate direct costs. Indirect costs were estimated using a human capital approach. Key drivers of total household costs for illness episodes resulting in malaria admission were assessed by fitting a generalized linear model, accounting for clustering at the health facility level. Out of 100 patients who met the eligibility criteria, 80 (80%) provided cost information for their entire illness episode to date and were included: 39% of patients were under 5 years old and 75% had sought care for the malaria episode at other facilities prior to coming to the current facility. Total household costs averaged $17.48 per patient; direct and indirect household costs averaged $7.59 and $9.90, respectively. Facility management type, household distance from the health facility, patient age, high household wealth, and duration of hospital stay were all significant drivers of overall costs. Although malaria treatment is supposed to be free in public health facilities, households in Malawi still incur high direct and indirect costs for malaria illness episodes that result in hospital admission. Finding ways to minimize the economic burden of inpatient malaria care is crucial to protect households from potentially catastrophic health expenditures.

Use of Antibiotics within the IMCI Guidelines in Outpatient Settings in Papua New Guinean Children: An Observational and Effectiveness Study

PubMed Central

Senn, Nicolas; Rarau, Patricia; Salib, Mary; Manong, Doris; Siba, Peter; Rogerson, Stephen

2014-01-01

Introduction There is a need to investigate the effectiveness and appropriateness of antibiotics prescription within the Integrated Management of Childhood Illness (IMCI) strategy in the context of routine outpatient clinics. Methods Making use of a passive case detection system established for a malaria prevention trial in outpatient clinics in Papua New Guinea, the appropriateness and effectiveness of the use of antibiotics within the IMCI was assessed in 1605 young children. Main outcomes were prescription of antibiotics and re-attendances within 14 days for mild pneumonia, mild diarrhoea and uncomplicated malaria whether they were managed with or without antibiotics (proxy of effectiveness). Appropriateness was assessed for both mild and severe cases, while effectiveness was assessed only for mild diseases. Results A total of 6975 illness episodes out of 8944 fulfilled inclusion criteria (no previous attendance <14 days+full medical records). Clinical incidence rates (episodes/child/year; 95% CI) were 0.85 (0.81–0.90) for pneumonia, 0.62 (0.58–0.66) for malaria and 0.72 (0.65–0.93) for diarrhoea. Fifty three percent of 6975 sick children were treated with antibiotics, 11% were not treated with antibiotics when they should have been and in 29% antibiotics were prescribed when they should not have been. Re-attendance rates within 14 days following clinical diagnosis of mild pneumonia were 9% (126/1401) when managed with antibiotics compared to 8% (56/701) when managed without (adjusted Hazard Ratio (aHR) = 1.00 (0.57–1.76), p = 0.98). Rates for mild diarrhoea were 8% (73/874) and 9% (79/866) respectively (aHR = 0.8 (0.42–1.57), p = 0.53). Conclusion Non-adherence to IMCI recommendations for prescription of antibiotics is common in routine settings in Papua New Guinea. Although recommended, the use of antibiotics in young children with mild pneumonia as defined by IMCI criteria did not impact on their outcome. Better tools and new strategies for the identification of bacterial infections that require antibiotics are urgently needed. PMID:24626194

Household level spatio-temporal analysis of Plasmodium falciparum and Plasmodium vivax malaria in Ethiopia.

PubMed

Seyoum, Dinberu; Yewhalaw, Delenasaw; Duchateau, Luc; Brandt, Patrick; Rosas-Aguirre, Angel; Speybroeck, Niko

2017-04-20

The global decline of malaria burden and goals for elimination has led to an increased interest in the fine-scale epidemiology of malaria. Micro-geographic heterogeneity of malaria infection could have implications for designing targeted small-area interventions. Two-year longitudinal cohort study data were used to explore the spatial and spatio-temporal distribution of malaria episodes in 2040 children aged < 10 years in 16 villages near the Gilgel-Gibe hydropower dam in Southwest Ethiopia. All selected households (HHs) were geo-referenced, and children were followed up through weekly house-to-house visits for two consecutive years to identify febrile episodes of P. falciparum and P. vivax infections. After confirming the spatial dependence of malaria episodes with Ripley's K function, SatScan TM was used to identify purely spatial and space-time clusters (hotspots) of annual malaria incidence for 2 years follow-up: year 1 (July 2008-June 2009) and year 2 (July 2009-June 2010). In total, 685 P. falciparum episodes (in 492 HHs) and 385 P. vivax episodes (in 290 HHs) were identified, representing respectively incidence rates of 14.6 (95% CI: 13.4-15.6) and 8.2 (95% CI: 7.3-9.1) per 1000 child-months at risk. In year 1, the most likely (128 HHs with 63 episodes, RR = 2.1) and secondary (15 HHs with 12 episodes, RR = 5.31) clusters of P. vivax incidence were found respectively in southern and north-western villages; while in year 2, the most likely cluster was located only in north-western villages (85 HHs with 16 episodes, RR = 4.4). Instead, most likely spatial clusters of P. falciparum incidence were consistently located in villages south of the dam in both years: year 1 (167 HHs with 81 episodes, RR = 1.8) and year 2 (133 HHs with 67 episodes, RR = 2.2). Space-time clusters in southern villages for P. vivax were found in August-November 2008 in year 1 and between November 2009 and February 2010 in year 2; while for P. falciparum, they were found in September-November 2008 in year 1 and October-November 2009 in year 2. Hotspots of P. falciparum incidence in children were more stable at the geographical level and over time compared to those of P. vivax incidence during the study period.

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

Shifting from presumptive to test-based management of malaria - technical basis and implications for malaria control in Ghana.

PubMed

Baiden, F; Malm, K; Bart-Plange, C; Hodgson, A; Chandramohan, D; Webster, J; Owusu-Agyei, S

2014-06-01

The presumptive approach was the World Health Organisation (WHO) recommended to the management of malaria for many years and this was incorporated into syndromic guidelines such as the Integrated Management of Childhood Illnesses (IMCI). In early 2010 however, WHO issued revised treatment guidelines that call for a shift from the presumptive to the test-based approach. Practically, this implies that in all suspected cases, the diagnosis of uncomplicated malaria should be confirmed using rapid test before treatment is initiated. This revision effectively brings to an end an era of clinical practice that span several years. Its implementation has important implications for the health systems in malaria-endemic countries. On the basis of research in Ghana and other countries, and evidence from program work, the Ghana National Malaria Control Program has issued revised national treatment guidelines that call for implementation of test-based management of malaria in all cases, and across all age groups. This article reviews the evidence and the technical basis for the shift to test-based management and examines the implications for malaria control in Ghana.

Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria.

PubMed

Lopera-Mesa, Tatiana M; Mita-Mendoza, Neida K; van de Hoef, Diana L; Doumbia, Saibou; Konaté, Drissa; Doumbouya, Mory; Gu, Wenjuan; Traoré, Karim; Diakité, Seidina A S; Remaley, Alan T; Anderson, Jennifer M; Rodriguez, Ana; Fay, Michael P; Long, Carole A; Diakité, Mahamadou; Fairhurst, Rick M

2012-01-01

Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA) precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs) and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of 'parasite-derived' UA stimulate immune cells to produce inflammatory cytokines in vitro. We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β) in 470 Malian children presenting with uncomplicated malaria (UM), non-cerebral severe malaria (NCSM) or cerebral malaria (CM). UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09-1.35, n = 23, p = 0.0007) and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97-1.41, n = 9, p = 0.0890) compared to those with UM (median 4.60 mg/dl, n = 438). In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001), IL-10 (r = 0.242, p<0.00001), sTNFRII (r = 0.221, p<0.00001), MCP-1 (r = 0.220, p<0.00001), IL-8 (r = 0.147, p = 0.002), TNFα (r = 0.132, p = 0.006) and IP-10 (r = 0.120, p = 0.012)]. In 39 children, UA levels were 1.49-fold (95% CI 1.34-1.65; p<0.0001) higher during their malaria episode [geometric mean titer (GMT) 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl). Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA and renal function may be involved. Defining pathogenic roles for parasite-derived UA precipitates, which we have not directly studied here, requires further investigation. ClinicalTrials.gov NCT00669084.

High Levels of Plasmodium falciparum Rosetting in All Clinical Forms of Severe Malaria in African Children

PubMed Central

Doumbo, Ogobara K.; Thera, Mahamadou A.; Koné, Abdoulaye K.; Raza, Ahmed; Tempest, Louisa J.; Lyke, Kirsten E.; Plowe, Christopher V.; Rowe, J. Alexandra

2010-01-01

Plasmodium falciparum rosetting (the spontaneous binding of infected erythrocytes to uninfected erythrocytes) is a well-recognized parasite virulence factor. However, it is currently unclear whether rosetting is associated with all clinical forms of severe malaria, or only with specific syndromes such as cerebral malaria. We investigated the relationship between rosetting and clinical malaria in 209 Malian children enrolled in a case-control study of severe malaria. Rosetting was significantly higher in parasite isolates from severe malaria cases compared with non-severe hyperparasitemia and uncomplicated malaria controls (F2,117 = 8.15, P < 0.001). Analysis of sub-categories of severe malaria (unrousable coma, severe anemia, non-comatose neurological impairment, repeated seizures or a small heterogeneous group with signs of renal failure or jaundice) showed high levels of rosetting in all sub-categories, and no statistically significant differences in rosetting between sub-categories (F4,67 = 1.28, P = 0.28). Thus rosetting may contribute to the pathogenesis of all severe malaria syndromes in African children, and interventions to disrupt rosetting could be potential adjunctive therapies for all forms of severe malaria in Africa. PMID:19996426

Artemisinin-based combination therapy in the treatment of uncomplicated malaria: review of recent regulatory experience at the European Medicines Agency

PubMed Central

Pelfrene, Eric; Pinheiro, Marie-Hélène; Cavaleri, Marco

2015-01-01

Malaria remains a major public health challenge with almost half of the world's population exposed to the risk of contracting the illness. Prompt, effective and well tolerated treatment remains one of the cornerstones in the disease management, with artemisinin-based combination therapy the recommended option for non-severe malaria in endemic areas with predominant Plasmodium falciparum infections. Recent experience has been obtained at the European Medicines Agency with regulatory approval of two such antimalarial fixed combination products. For these cases, two different regulatory pathways were applied. As such, the present contribution describes this experience, emphasising main differences and applicability offered by these regulatory choices. PMID:25855638

Clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among Afghan refugees in Pakistan.

PubMed

Howard, Natasha; Durrani, Naeem; Sanda, Sanda; Beshir, Khalid; Hallett, Rachel; Rowland, Mark

2011-06-23

Falciparum malaria is a significant problem for Afghan refugees in Pakistan. Refugee treatment guidelines recommended standard three-day chloroquine treatment (25 mg/kg) for first episodes and extended five-day treatment (40 mg/kg) for recrudescent infections, based on the assumption that a five-day course would more likely achieve a cure. An in-vivo randomized controlled trial was conducted among refugees with uncomplicated falciparum malaria to determine whether five-day treatment (CQ40) was more effective than standard treatment (CQ25). 142 falciparum patients were recruited into CQ25 or CQ40 treatment arms and followed up to 60 days with regular blood smears. The primary outcome was parasitological cure without recrudescence. Treatment failures were retreated with CQ40. PCR genotyping of 270 samples, from the same and nearby sites, was used to support interpretation of outcomes. 84% of CQ25 versus 51% of CQ40 patients experienced parasite recrudescence during follow-up (adjusted odds ratio 0.17, 95%CI 0.08-0.38). Cure rates were significantly improved with CQ40, particularly among adults. Fever clearance time, parasite clearance time, and proportions gametocytaemic post-treatment were similar between treatment groups. Second-line CQ40 treatment resulted in higher failure rates than first-line CQ40 treatment. CQ-resistance marker pfcrt 76T was found in all isolates analysed, while pfmdr1 86Y and 184Y were found in 18% and 37% of isolates respectively. CQ is not suitable for first-line falciparum treatment in Afghan refugee communities. The extended-dose CQ regimen can overcome 39% of resistant infections that would recrudesce under the standard regimen, but the high failure rate after directly observed treatment demonstrates its use is inappropriate.

School-based diagnosis and treatment of malaria by teachers using rapid diagnostic tests and artemisinin-based combination therapy: experiences and perceptions of users and implementers of the Learner Treatment Kit, southern Malawi.

PubMed

Mphwatiwa, Treza; Witek-McManus, Stefan; Mtali, Austin; Okello, George; Nguluwe, Paul; Chatsika, Hard; Roschnik, Natalie; Halliday, Katherine E; Brooker, Simon J; Mathanga, Don P

2017-08-07

Training teachers to diagnose uncomplicated malaria using malaria rapid diagnostic tests and treat with artemisinin-based combination therapy has the potential to improve the access of primary school children (6-14 years) to prompt and efficient treatment for malaria, but little is known about the acceptability of such an intervention. This qualitative study explored experiences and perceptions of users and implementers of a programme of school-based malaria case management via a first-aid kit-the Learner Treatment Kit (LTK)-implemented as part of a cluster-randomized controlled trial in Zomba district, Malawi. From 29 primary schools where teachers were trained to test and treat school children for malaria using the LTK, six schools were purposively selected on the basis of relative intervention usage (low, medium or high); school size and geographical location. In total eight focus group discussions were held with school children, parents and guardians, and teachers; and 20 in-depth interviews were conducted with key stakeholders at the school, district and national levels. Interviews were recorded, transcribed, and analysed using a thematic analysis approach. The LTK was widely perceived by respondents to be a worthwhile intervention, with the opinion that trained teachers were trusted providers of malaria testing and treatment to school children. Benefits of the programme included a perception of improved access to malaria treatment for school children; decreased school absenteeism; and that the programme supported broader national health and education policies. Potential barriers to successful implementation expressed included increased teacher workloads, a feeling of inadequate supervision from health workers, lack of incentives and concerns for the sustainability of the programme regarding the supply of drugs and commodities. Training teachers to test for and treat uncomplicated malaria in schools was well received by both users and implementers alike, and was perceived by the majority of stakeholders to be a valuable programme. Factors raised as critical to the success of such a programme included ensuring an effective supervisory system, a reliable supply chain, and the training of greater numbers of teachers per school to manage high consultation numbers, especially during the peak malaria transmission season.

The use and preference of artemether as a first-choice treatment for malaria: results from a cross-sectional survey in the Bata district, Equatorial Guinea.

PubMed

Romay-Barja, Maria; Ncogo, Policarpo; Nseng, Gloria; Santana-Morales, Maria A; Berzosa, Pedro; Herrador, Zaida; Valladares, Basilio; Riloha, Matilde; Benito, Agustin

2018-03-09

Malaria is endemic in Equatorial Guinea with stable transmission, and it remains a major cause of morbidity and mortality in children under 5 years of age. Adherence to artemisinin-based combination therapy (ACT) as a first-line treatment for uncomplicated malaria is critical to malaria control. Six years after the introduction of artesunate-amodiaquine (AS/AQ) therapy in Equatorial Guinea, adherence to the first-line treatment seems to be low in the Bata district. The factors associated with the choice of malaria treatment have not been studied previously in this area; therefore, this study aimed to analyse the preference and use of artemether as malaria treatment and its related factors in the Bata district of Equatorial Guinea. In 2013, a cross-sectional study was conducted in the Bata district, which involved 428 households. Bivariate and multivariate statistical analyses were conducted to determine the relevance of socio-economic, geographical, and behavioural factors that played a role in the preference and use of artemether as malaria treatment. Artemether was considered the best treatment for malaria by 110 caregivers (26%), and was the antimalarial most administrated in the Bata district. It was prescribed to 117 children (27.34%); while, only 6.78% were administered AS/AQ. Caregivers living ≤ 3 km from the nearest health facility were almost two times more likely to consider artemether as the best treatment than those living farther away (95% CI 0.31-0.86). Caregivers with at least a secondary school education were 2.7 times more likely to consider artemether as the best treatment than those less educated. Children whose caregivers considered artemether the best treatment against malaria were five times more likely to be treated with artemether than children with caregivers who did not consider it the best (OR 5.07, 95% CI 2.93-8.78). In contrast, children that reported weakness as a symptom were less likely to be treated with artemether than those with other symptoms (OR 0.47, 95% CI 0.28-0.78). Caregivers, public and private health staff, and drug sellers need to understand the importance of using ACT to treat uncomplicated malaria and the dangers of using artemisinin monotherapy.

Treatment for Uncomplicated Plasmodium falciparum Malaria in French Soldiers Deployed in Sub-Saharan Africa: Gaps Between Policy and Field Practice.

PubMed

Perisse, Anne; Velut, Guillaume; Javelle, Emilie; Loarer, Gwion; Michel, Remy; Simon, F

2018-02-07

Malaria prevention and treatment are big challenges for the French forces deployed in sub-Saharan Africa. Since December 2013, 1,800 French soldiers have been deployed at any one time in the Central African Republic in the framework of "Operation Sangaris" and European Union Force (EUFOR). Over the 2014-2015 period, about 500 cases of malaria were notified in these troops during the operation or after their return (annual incidence: 13.4 p.100 person-year). The recommendation to use dihydroartemisinin-piperaquine (DHA-PQ) as the first-line treatment for French soldiers suffering from uncomplicated Plasmodium falciparum malaria in endemic areas is not always followed in practice in the field by French military general practitioners (GPs). We conduced a retrospective Knowledge-Attitude-Practice study by self-administered questionnaire, to all military French doctors who were in mission in Central African Republic from January 2014 to July 2015 to try to understand what were the reasons for the GP not to prescribe DHA-PQ on the field. Thirty-six GPs (53%) answered to the questionnaire. Eighty-three percent of them knew about the recommendation to use DHA-PQ for un uncomplicated Pf malaria. Fifty-eight percent had a favorable attitude toward DHA-PQ. The factors associated with the prescription of another drug (Atovaquone-proguanil) were: the habit (odds ratio [OR] 0.1, confidence interval (CI) 0-0.6], the fact that Atovaquone-proguanil is more practical to use [OR 0.01, CI 0-0.1]. In practice, only 37.5% prescribed DHA-PQ the most of the time during their mission. Factors associated with a non-favorable attitude toward DHA-PQ were: the necessity to calculate a QTc interval during the treatment [OR 0.2, confidence interval 0-0.9], and the fact that DHA-PQ must be taken on an empty stomach [OR 0.3, CI 0.1-0.8]. GP who received a formation before their mission about malaria and treatment had a favorable attitude toward DHA-PQ. There is very satisfactory knowledge by the military GPs stationed in the Central African Republic on both the recommendations and prescription of antimalarial drugs. The present study highlights some difficulties in implementing the recommendations in an operational context, notably factors limiting the prescription of DHA-PQ during military deployment (need for ECG monitoring, empty stomach, and lack of habit). Proposals can be made to improve the efficacy, tolerance, and practicability of malaria treatment in the field. The main focus should be a more flexible application of the French DHA-PQ risk management plan in the field, specific training and communication about DHA-PQ use, the generalization of ECG printing equipment in the field, and the switch from DHA-PQ to an alternative artemisinin-based combination therapy during deployments in malaria-endemic areas. © Association of Military Surgeons of the United States 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study.

PubMed

Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N; Khan, Wasif Ali

2016-01-01

The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0-2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3) hours for P. falciparum, 20.0 (IQR: 9.5-22.7) hours for P. vivax and 16.6 (IQR: 10.0-46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10-60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather than primaquine administration. ClinicalTrials.gov NCT02389374.

Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda.

PubMed

Eziefula, Alice Chijioke; Staedke, Sarah G; Yeung, Shunmay; Webb, Emily; Kamya, Moses; White, Nicholas J; Bousema, Teun; Drakeley, Chris

2013-03-26

For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status. In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1-10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicated P falciparum malaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine. These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations.

Levels and interactions of plasma xanthine oxidase, catalase and liver function parameters in Nigerian children with Plasmodium falciparum infection.

PubMed

Iwalokun, B A; Bamiro, S B; Ogunledun, A

2006-12-01

Elevated plasma levels of xanthine oxidase and liver function parameters have been associated with inflammatory events in several human diseases. While xanthine oxidase provides in vitro protection against malaria, its pathophysiological functions in vivo and interactions with liver function parameters remain unclear. This study examined the interactions and plasma levels of xanthine oxidase (XO) and uric acid (UA), catalase (CAT) and liver function parameters GOT, GPT and bilirubin in asymptomatic (n=20), uncomplicated (n=32), and severe (n=18) falciparum malaria children aged 3-13 years. Compared to age-matched control (n=16), significant (p<0.05) elevation in xanthine oxidase by 100-550%, uric acid by 15.4-153.8%, GOT and GPT by 22.1-102.2%, and total bilirubin by 2.3-86% according to parasitaemia (geometric mean parasite density (GMPD)=850-87100 parasites/microL) was observed in the malarial children. Further comparison with control revealed higher CAT level (16.2+/-0.5 vs 14.6+/-0.4 U/L; p<0.05) lacking significant (p>0.05) correlation with XO, but lower CAT level (13.4-5.4 U/L) with improved correlations (r=-0.53 to -0.91; p<0.05) with XO among the asymptomatic and symptomatic malaria children studied. 75% of control, 45% of asymptomatic, 21.9% of uncomplicated, and none of severe malaria children had Hb level>11.0 g/dL. Multivariate analyses further revealed significant (p<0.05) correlations between liver function parameters and xanthine oxidase (r=0.57-0.64) only in the severe malaria group. We conclude that elevated levels of XO and liver enzymes are biochemical features of Plasmodium falciparum parasitaemia in Nigerian children, with both parameters interacting differently to modulate the catalase response in asymptomatic and symptomatic falciparum malaria.

Convalescent Plasmodium falciparum-specific seroreactivity does not correlate with paediatric malaria severity or Plasmodium antigen exposure.

PubMed

Kessler, Anne; Campo, Joseph J; Harawa, Visopo; Mandala, Wilson L; Rogerson, Stephen J; Mowrey, Wenzhu B; Seydel, Karl B; Kim, Kami

2018-04-25

Antibody immunity is thought to be essential to prevent severe Plasmodium falciparum infection, but the exact correlates of protection are unknown. Over time, children in endemic areas acquire non-sterile immunity to malaria that correlates with development of antibodies to merozoite invasion proteins and parasite proteins expressed on the surface of infected erythrocytes. A 1000 feature P. falciparum 3D7 protein microarray was used to compare P. falciparum-specific seroreactivity during acute infection and 30 days after infection in 23 children with uncomplicated malaria (UM) and 25 children with retinopathy-positive cerebral malaria (CM). All children had broad P. falciparum antibody reactivity during acute disease. IgM reactivity decreased and IgG reactivity increased in convalescence. Antibody reactivity to CIDR domains of "virulent" PfEMP1 proteins was low with robust reactivity to the highly conserved, intracellular ATS domain of PfEMP1 in both groups. Although children with UM and CM differed markedly in parasite burden and PfEMP1 exposure during acute disease, neither acute nor convalescent PfEMP1 seroreactivity differed between groups. Greater seroprevalence to a conserved Group A-associated ICAM binding extracellular domain was observed relative to linked extracellular CIDRα1 domains in both case groups. Pooled immune IgG from Malawian adults revealed greater reactivity to PfEMP1 than observed in children. Children with uncomplicated and cerebral malaria have similar breadth and magnitude of P. falciparum antibody reactivity. The utility of protein microarrays to measure serological recognition of polymorphic PfEMP1 antigens needs to be studied further, but the study findings support the hypothesis that conserved domains of PfEMP1 are more prominent targets of cross reactive antibodies than variable domains in children with symptomatic malaria. Protein microarrays represent an additional tool to identify cross-reactive Plasmodium antigens including PfEMP1 domains that can be investigated as strain-transcendent vaccine candidates.

Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria

PubMed Central

Kendjo, Eric; Augé-Courtoi, Claire; Cojean, Sandrine; Clain, Jérôme; Houzé, Pascal; Thellier, Marc; Hubert, Veronique; Deloron, Philippe; Houzé, Sandrine

2017-01-01

Objectives Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known. Methods From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology) associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants). Results Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host. Conclusions Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden. PMID:28410415

Malaria in Uganda: challenges to control on the long road to elimination. I. Epidemiology and current control efforts

PubMed Central

Yeka, Adoke; Gasasira, Anne; Mpimbaza, Arthur; Achan, Jane; Nankabirwa, Joaniter; Nsobya, Sam; Staedke, Sarah G.; Donnelly, Martin J.; Wabwire-Mangen, Fred; Talisuna, Ambrose; Dorsey, Grant; Kamya, Moses R.; Rosenthal, Philip J.

2011-01-01

Malaria remains one of the leading health problems of the developing world, and Uganda bears a particularly large burden from the disease. Our understanding is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality from severe malaria all remain very high. Uganda has made progress in implementing key malaria control measures, in particular distribution of insecticide impregnated bednets, indoor residual spraying of insecticides, utilization of artemisinin-based combination therapy to treat uncomplicated malaria, and provision of intermittent preventive therapy for pregnant women. However, despite enthusiasm regarding the potential for the elimination of malaria in other areas, there is no convincing evidence that the burden of malaria has decreased in Uganda in recent years. Major challenges to malaria control in Uganda include very high malaria transmission intensity, inadequate health care resources, a weak health system, inadequate understanding of malaria epidemiology and the impact of control interventions, increasing resistance of parasites to drugs and of mosquitoes to insecticides, inappropriate case management, inadequate utilization of drugs to prevent malaria, and inadequate epidemic preparedness and response. Despite these challenges, prospects for the control of malaria have improved, and with attention to underlying challenges, progress toward the control of malaria in Uganda can be expected. PMID:21420377

Additional Screening and Treatment of Malaria During Pregnancy Provides Further Protection Against Malaria and Nonmalarial Fevers During the First Year of Life.

PubMed

Natama, Hamtandi Magloire; Rovira-Vallbona, Eduard; Sorgho, Hermann; Somé, M Athanase; Traoré-Coulibaly, Maminata; Scott, Susana; Zango, Serge Henri; Sawadogo, Ousséni; Zongo, Sibiri Claude; Valéa, Innocent; Mens, Petra F; Schallig, Henk D F H; Kestens, Luc; Tinto, Halidou; Rosanas-Urgell, Anna

2018-05-25

Although consensus exists that malaria in pregnancy (MiP) increases the risk of malaria in infancy, and eventually nonmalarial fevers (NMFs), there is a lack of conclusive evidence of benefits of MiP preventive strategies in infants. In Burkina Faso, a birth cohort study was nested to a clinical trial assessing the effectiveness of a community-based scheduled screening and treatment of malaria in combination with intermittent preventive treatment with sulfadoxine-pyrimethamine (CSST/IPTp-SP) to prevent placental malaria. Clinical episodes and asymptomatic infections were monitored over 1 year of follow-up to compare the effect of CSST/IPTp-SP and standard IPTp-SP on malaria and NMFs. Infants born during low-transmission season from mothers receiving CSST/IPTp-SP had a 26% decreased risk of experiencing a first clinical episode (hazard ratio, 0.74 [95% confidence interval, .55-0.99]; P = .047). CSST/IPTp-SP interacted with birth season and gravidity to reduce the incidence of NMFs. No significant effects of CSST/IPTp-SP on the incidence of clinical episodes, parasite density, and Plasmodium falciparum infections were observed. Our findings indicate that CSST/IPTp-SP strategy may provide additional protection against both malaria and NMFs in infants during the first year of life, and suggest that malaria control interventions during pregnancy could have long-term benefits in infants.

Fever treatment in the absence of malaria transmission in an urban informal settlement in Nairobi, Kenya.

PubMed

Ye, Yazoume; Madise, Nyovani; Ndugwa, Robert; Ochola, Sam; Snow, Robert W

2009-07-15

In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%-20.5%) and higher among children below five years (20.1%, 95%CI:13.8%-27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%-62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria parasites to reduce the inappropriate exposure of poor communities to expensive anti-malarial drugs provided by clinical services and drug vendors, should be a priority for district planners.

Therapeutic assessment of chloroquine-primaquine combined regimen in adult cohort of Plasmodium vivax malaria from a tertiary care hospital in southwestern India.

PubMed

Rishikesh, Kumar; Kamath, Asha; Hande, Manjunatha H; Vidyasagar, Sudha; Acharya, Raviraja V; Acharya, Vasudeva; Belle, Jayaprakash; Shastry, Ananthakrishna B; Saravu, Kavitha

2015-08-11

Of late there have been accounts of therapeutic failure and chloroquine resistance in Plasmodium vivax malaria especially from Southeast Asian regions. The present study was conducted to assess the therapeutic efficacy of chloroquine-primaquine (CQ-PQ) combined regimen in a cohort of uncomplicated P. vivax mono-infection. A tertiary care hospital-based prospective study was conducted among adult cohort with mono-infection P. vivax malaria as per the World Health Organization's protocol of in vivo assessment of anti-malarial therapeutic efficacy. Participants were treated with CQ 25 mg/kg body weight divided over 3 days and PQ 0.25 mg/kg body weight daily for 2 weeks. Of a total of 125 participants recruited, 122 (97.6%) completed day 28 follow up, three (2.4%) participants were lost to follow-up. Eight patients (6.4%) were ascertained to have mixed P. vivax and Plasmodium falciparum infection by nested polymerase chain reaction test. The majority of subjects (56.8%, 71/125) became aparasitaemic on day 2 followed by 35.2% (44/125) on day 3, and 8% (10/125) on day 7, and remained so thereafter. Overall only one therapeutic failure (0.8%, 1/125) occurred on day 3 due to persistence of fever and parasitaemia. CQ-PQ combined regimen remains outstandingly effective for uncomplicated P. vivax malaria and should be retained as treatment of choice in the study region. One case of treatment failure indicates possible resistance which warrants constant vigilance and periodic surveillance.

Glucose-6-phosphate dehydrogenase deficient variants are associated with reduced susceptibility to malaria in the Brazilian Amazon.

PubMed

Santana, Marli S; Monteiro, Wuelton M; Siqueira, André M; Costa, Mônica F; Sampaio, Vanderson; Lacerda, Marcus V; Alecrim, Maria G

2013-05-01

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) has been shown to protect against malaria infection and severe manifestations in African and Asia, but there is a scarcity of studies in the Americas. This study aimed to study the prevalence of G6PDd and its association with malaria occurrence in the Brazilian Amazon. A cross-sectional study was conducted in the male population to estimate the prevalence of G6PDd and malaria infection. G6PD deficient samples were genotyped to identify the deficient variant. Number of previous malaria episodes and need for blood transfusion during malaria episodes were recorded by applying a standardized questionary. From a sample of 1478 male individuals, 66 were detected as G6PD deficient, resulting in a prevalence of of 4.5% (95% CI = 3.44-5.56%). Fifty six G6PD deficient individuals (3.8%; 95% CI = 2.82-4.77) presented the G6PD A-variant mutation, while 10 individuals (0.7%; 95% CI = 0.42-0.97) severely deficient were genotyped as carriers of the G6PD Mediterranean variant. After adjusting for age, G6PD deficient individuals were less likely to report the occurrence of malaria episodes, and the protective effect was related to the enzyme activity, with carriers of the GG6PD A-variant presenting a 88% reduction (AOR: 0.119; 95% CI = 0.057-0.252; p < 0.001) and carriers of the Meditarrenean variant presenting 99% lower risk (AOR: 0.010; 95% CI = 0.002-0.252; p < 0.001) when compared to non-deficient individuals. On the other hand, G6PD deficient subjects reported higher need of transfusion during malaria episodes (p < 0.001). G6PD enzyme activity was directly related to susceptibility to malaria in the Brazilian Amazon, where P. vivax predominates. Severe G6PDd was associated with considerable higher risk of malaria-related transfusions.

No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

PubMed Central

Maiga, Amelia W.; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Dara, Antoine; Traore, Oumar Bila; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Kone, Aminatou; Thera, Mahamadou A.; Plowe, Christopher V.; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

2012-01-01

Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa. PMID:22764287

Women's Access and Provider Practices for the Case Management of Malaria during Pregnancy: A Systematic Review and Meta-Analysis

PubMed Central

Hill, Jenny; D'Mello-Guyett, Lauren; Hoyt, Jenna; van Eijk, Anna M.; ter Kuile, Feiko O.; Webster, Jayne

2014-01-01

Background WHO recommends prompt diagnosis and quinine plus clindamycin for treatment of uncomplicated malaria in the first trimester and artemisinin-based combination therapies in subsequent trimesters. We undertook a systematic review of women's access to and healthcare provider adherence to WHO case management policy for malaria in pregnant women. Methods and Findings We searched the Malaria in Pregnancy Library, the Global Health Database, and the International Network for the Rational Use of Drugs Bibliography from 1 January 2006 to 3 April 2014, without language restriction. Data were appraised for quality and content. Frequencies of women's and healthcare providers' practices were explored using narrative synthesis and random effect meta-analysis. Barriers to women's access and providers' adherence to policy were explored by content analysis using NVivo. Determinants of women's access and providers' case management practices were extracted and compared across studies. We did not perform a meta-ethnography. Thirty-seven studies were included, conducted in Africa (30), Asia (4), Yemen (1), and Brazil (2). One- to three-quarters of women reported malaria episodes during pregnancy, of whom treatment was sought by >85%. Barriers to access among women included poor knowledge of drug safety, prohibitive costs, and self-treatment practices, used by 5%–40% of women. Determinants of women's treatment-seeking behaviour were education and previous experience of miscarriage and antenatal care. Healthcare provider reliance on clinical diagnosis and poor adherence to treatment policy, especially in first versus other trimesters (28%, 95% CI 14%–47%, versus 72%, 95% CI 39%–91%, p = 0.02), was consistently reported. Prescribing practices were driven by concerns over side effects and drug safety, patient preference, drug availability, and cost. Determinants of provider practices were access to training and facility type (public versus private). Findings were limited by the availability, quality, scope, and methodological inconsistencies of the included studies. Conclusions A systematic assessment of the extent of substandard case management practices of malaria in pregnancy is required, as well as quality improvement interventions that reach all providers administering antimalarial drugs in the community. Pregnant women need access to information on which anti-malarial drugs are safe to use at different stages of pregnancy. Please see later in the article for the Editors' Summary PMID:25093720

Women's access and provider practices for the case management of malaria during pregnancy: a systematic review and meta-analysis.

PubMed

Hill, Jenny; D'Mello-Guyett, Lauren; Hoyt, Jenna; van Eijk, Anna M; ter Kuile, Feiko O; Webster, Jayne

2014-08-01

WHO recommends prompt diagnosis and quinine plus clindamycin for treatment of uncomplicated malaria in the first trimester and artemisinin-based combination therapies in subsequent trimesters. We undertook a systematic review of women's access to and healthcare provider adherence to WHO case management policy for malaria in pregnant women. We searched the Malaria in Pregnancy Library, the Global Health Database, and the International Network for the Rational Use of Drugs Bibliography from 1 January 2006 to 3 April 2014, without language restriction. Data were appraised for quality and content. Frequencies of women's and healthcare providers' practices were explored using narrative synthesis and random effect meta-analysis. Barriers to women's access and providers' adherence to policy were explored by content analysis using NVivo. Determinants of women's access and providers' case management practices were extracted and compared across studies. We did not perform a meta-ethnography. Thirty-seven studies were included, conducted in Africa (30), Asia (4), Yemen (1), and Brazil (2). One- to three-quarters of women reported malaria episodes during pregnancy, of whom treatment was sought by >85%. Barriers to access among women included poor knowledge of drug safety, prohibitive costs, and self-treatment practices, used by 5%-40% of women. Determinants of women's treatment-seeking behaviour were education and previous experience of miscarriage and antenatal care. Healthcare provider reliance on clinical diagnosis and poor adherence to treatment policy, especially in first versus other trimesters (28%, 95% CI 14%-47%, versus 72%, 95% CI 39%-91%, p = 0.02), was consistently reported. Prescribing practices were driven by concerns over side effects and drug safety, patient preference, drug availability, and cost. Determinants of provider practices were access to training and facility type (public versus private). Findings were limited by the availability, quality, scope, and methodological inconsistencies of the included studies. A systematic assessment of the extent of substandard case management practices of malaria in pregnancy is required, as well as quality improvement interventions that reach all providers administering antimalarial drugs in the community. Pregnant women need access to information on which anti-malarial drugs are safe to use at different stages of pregnancy. Please see later in the article for the Editors' Summary.

Episodic Memory in Detoxified Alcoholics: Contribution of Grey Matter Microstructure Alteration

PubMed Central

Chanraud, Sandra; Leroy, Claire; Martelli, Catherine; Kostogianni, Nikoleta; Delain, Françoise; Aubin, Henri-Jean; Reynaud, Michel; Martinot, Jean-Luc

2009-01-01

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics. Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software. In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant. These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence. PMID:19707568

K13 Propeller Alleles, mdr1 Polymorphism, and Drug Effectiveness at Day 3 after Artemether-Lumefantrine Treatment for Plasmodium falciparum Malaria in Colombia, 2014-2015.

PubMed

Montenegro, Madeline; Neal, Aaron T; Posada, Maritza; De Las Salas, Briegel; Lopera-Mesa, Tatiana M; Fairhurst, Rick M; Tobon-Castaño, Alberto

2017-12-01

High treatment failure rates for Plasmodium falciparum malaria have been reported in Colombia for chloroquine, amodiaquine, and sulfadoxine-pyrimethamine. Artemisinin combination therapies were introduced in 2006 in Colombia, where artemether-lumefantrine (AL) is currently used to treat uncomplicated P. falciparum malaria. Artemisinin (ART) resistance was initially observed in Southeast Asia as an increased parasite clearance time, manifesting as a positive thick-blood smear on day 3 after treatment (D3 positivity). Recently, mutations in the propeller domain of the P. falciparum kelch13 gene ( K13 propeller) have been associated with ART resistance. In this study, we surveyed AL effectiveness at D3 and molecular markers of drug resistance among 187 uncomplicated P. falciparum cases in 4 regions of Colombia from June 2014 to July 2015. We found that 3.2% (4/125) of patients showed D3 positivity, 100% (163/163) of isolates carried wild-type K13 propeller alleles, 12.9% (23/178) of isolates had multiple copies of the multidrug resistance 1 gene ( mdr1 ), and 75.8% (113/149) of isolates harbored the double mutant N F S D D mdr1 haplotype (the underlining indicates mutant alleles). These data suggest that ART resistance is not currently suspected in Colombia but that monitoring for lumefantrine resistance and AL failures should continue. Copyright © 2017 American Society for Microbiology.

K13 Propeller Alleles, mdr1 Polymorphism, and Drug Effectiveness at Day 3 after Artemether-Lumefantrine Treatment for Plasmodium falciparum Malaria in Colombia, 2014-2015

PubMed Central

Montenegro, Madeline; Neal, Aaron T.; Posada, Maritza; De las Salas, Briegel; Lopera-Mesa, Tatiana M.

2017-01-01

ABSTRACT High treatment failure rates for Plasmodium falciparum malaria have been reported in Colombia for chloroquine, amodiaquine, and sulfadoxine-pyrimethamine. Artemisinin combination therapies were introduced in 2006 in Colombia, where artemether-lumefantrine (AL) is currently used to treat uncomplicated P. falciparum malaria. Artemisinin (ART) resistance was initially observed in Southeast Asia as an increased parasite clearance time, manifesting as a positive thick-blood smear on day 3 after treatment (D3 positivity). Recently, mutations in the propeller domain of the P. falciparum kelch13 gene (K13 propeller) have been associated with ART resistance. In this study, we surveyed AL effectiveness at D3 and molecular markers of drug resistance among 187 uncomplicated P. falciparum cases in 4 regions of Colombia from June 2014 to July 2015. We found that 3.2% (4/125) of patients showed D3 positivity, 100% (163/163) of isolates carried wild-type K13 propeller alleles, 12.9% (23/178) of isolates had multiple copies of the multidrug resistance 1 gene (mdr1), and 75.8% (113/149) of isolates harbored the double mutant NFSDD mdr1 haplotype (the underlining indicates mutant alleles). These data suggest that ART resistance is not currently suspected in Colombia but that monitoring for lumefantrine resistance and AL failures should continue. PMID:28947476

High prevalence of asymptomatic Plasmodium falciparum infection in Gabonese adults.

PubMed

Dal-Bianco, Matthias P; Köster, Kai B; Kombila, Ulrich D; Kun, Jürgen F J; Grobusch, Martin P; Ngoma, Ghyslain Mombo; Matsiegui, Pierre B; Supan, Christian; Salazar, Carmen L Ospina; Missinou, Michel A; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter

2007-11-01

Plasmodium falciparum, the most common malarial parasite in sub-Saharan Africa, accounts for a high number of deaths in children less than five years of age. In malaria-endemic countries with stable transmission, semi-immunity is usually acquired after childhood. For adults, severe malaria is rare. Infected adults have either uncomplicated malaria or asymptomatic parasitemia. During a period of one year, we screened 497 afebrile males to investigate the prevalence of asymptomatic P. falciparum parasitemia in villages near Lambaréné, Gabon by use of three different methods. A total of 52% of the individuals had parasites detected by a subtelomeric variable open reading frame polymerase chain reaction (stevor-PCR), 27% of the rapid diagnostic test results were positive, and 12% of the thick blood smears with low parasitemias had P. falciparum. Most positive cases were only detected by the stevor-PCR. Asymptomatic P. falciparum parasitemia in adults living in a malaria-endemic country is frequent.

Malaria, helminths, co-infection and anaemia in a cohort of children from Mutengene, south western Cameroon.

PubMed

Njua-Yafi, Clarisse; Achidi, Eric A; Anchang-Kimbi, Judith K; Apinjoh, Tobias O; Mugri, Regina N; Chi, Hanesh F; Tata, Rolland B; Njumkeng, Charles; Nkock, Emmanuel N; Nkuo-Akenji, Theresa

2016-02-06

Malaria and helminthiases frequently co-infect the same individuals in endemic zones. Plasmodium falciparum and helminth infections have long been recognized as major contributors to anaemia in endemic countries. Several studies have explored the influence of helminth infections on the course of malaria in humans but how these parasites interact within co-infected individuals remains controversial. In a community-based longitudinal study from March 2011 to February 2012, the clinical and malaria parasitaemia status of a cohort of 357 children aged 6 months to 10 years living in Mutengene, south-western region of Cameroon, was monitored. Following the determination of baseline malaria/helminths status and haemoglobin levels, the incidence of malaria and anaemia status was determined in a 12 months longitudinal study by both active and passive case detection. Among all the children who completed the study, 32.5 % (116/357) of them had at least one malaria episode. The mean (±SEM) number of malaria attacks per year was 1.44 ± 0.062 (range: 1-4 episodes) with the highest incidence of episodes occuring during the rainy season months of March-October. Children <5 years old were exposed to more malaria attacks [OR = 2.34, 95 % CI (1.15-4.75), p = 0.019] and were also more susceptible to anaemia [OR = 2.24, 95 % CI (1.85-4.23), p = 0.013] compared to older children (5-10 years old). Likewise children with malaria episodes [OR = 4.45, 95 % CI (1.66-11.94), p = 0.003] as well as those with asymptomatic parasitaemia [OR = 2.41, 95 % CI (1.58-3.69) p < 0.001] were susceptible to anaemia compared to their malaria parasitaemia negative counterparts. Considering children infected with Plasmodium alone as the reference, children infected with helminths alone were associated with protection from anaemia [OR = 0.357, 95 % CI (0.141-0.901), p = 0.029]. The mean haemoglobin level (g/dl) of participants co-infected with Plasmodium and helminths was higher (p = 0.006) compared to participants infected with Plasmodium or helminths alone. Children below 5 years of age were more susceptible to malaria and anaemia. The high prevalence of anaemia in this community was largely due to malaria parasitaemia. Malaria and helminths co-infection was protective against anaemia.

Uncomplicated Plasmodium vivax malaria in pregnancy associated with mortality from acute respiratory distress syndrome.

PubMed

McGready, Rose; Wongsaen, Klanarong; Chu, Cindy S; Tun, Nay Win; Chotivanich, Kesinee; White, Nicholas J; Nosten, François

2014-05-27

The association between severe malaria and Plasmodium vivax species is contentious. On the Thai-Myanmar border, all pregnant women are followed systematically with active weekly malaria screening. Over a 27-year period of providing antenatal care, 48,983 have been prospectively followed until pregnancy outcome (miscarriage or delivery) and 4,298 women have had P. vivax detected at least once. Reported here is the first known P. vivax-associated death amongst these women. The initial patient presentation was of uncomplicated P. vivax (0.5% parasitaemia) in a term, multigravida woman who responded rapidly to oral artesunate and mefloquine treatment, clearing her blood stage parasites within 48 hours. The patient appeared well, was ambulatory and due to be discharged but became unwell with acute respiratory distress syndrome (ARDS) requiring ventilation three days (67 hours) into treatment. Despite induction and delivery of a stillborn foetus, ventilatory requirements increased and the patient died on day 7. The patient had a low body mass index. Sensitive detection with nested PCR confirmed only the presence of P. vivax species and concomitant infections such as tuberculosis and human immunodeficiency virus (HIV) were also ruled out. The contemporaneous treatment of acute uncomplicated P. vivax and the onset of ARDS on day 3 in this patient implies a possible but unconfirmed association with death in this patient. Assuming this death was caused by P. vivax, the risk of ARDS-related maternal mortality in this setting did not differ significantly between Plasmodium falciparum and P. vivax (0.24 per 1,000 (1/4,158) versus 0.23 per 1,000 (1/4,298), contrary to the increased risk of maternal mortality from P. falciparum compared to P. vivax, 2.89 per 1,000 (12/4,158) versus 0.23 per 1,000 (1/4,298), P = 0.003.

Pharmacokinetic and pharmacodynamic characteristics of a new pediatric formulation of artemether-lumefantrine in African children with uncomplicated Plasmodium falciparum malaria.

PubMed

Djimdé, Abdoulaye A; Tekete, Mamadou; Abdulla, Salim; Lyimo, John; Bassat, Quique; Mandomando, Inacio; Lefèvre, Gilbert; Borrmann, Steffen

2011-09-01

The pharmacokinetic and pharmacodynamic properties of a new pediatric formulation of artemether-lumefantrine, dispersible tablet, were determined within the context of a multicenter, randomized, parallel-group study. In an exploratory approach, we compared a new pediatric formulation with the tablet formulation administered crushed in the treatment of African children with uncomplicated Plasmodium falciparum malaria. Patients were randomized to 3 different dosing groups (weights of 5 to <15 kg, 15 and <25 kg, and 25 to <35 kg). Treatment was administered twice daily over 3 days. Plasma concentrations of artemether and its active metabolite, dihydroartemisinin (DHA), were determined at 1 and 2 h after the first dose of dispersible (n = 91) and crushed (n = 93) tablets. A full pharmacokinetic profile of lumefantrine was reconstituted on the basis of 310 (dispersible tablet) and 315 (crushed tablet) plasma samples, collected at 6 different time points (1 sample per patient). Dispersible and crushed tablets showed similar artemether and DHA maximum concentrations in plasma (C(max)) for the different body weight groups, with overall means of 175 ± 168 and 190 ± 168 ng/ml, respectively, for artemether and 64.7 ± 58.1 and 63.7 ± 65.0 ng/ml, respectively, for DHA. For lumefantrine, the population C(max) were 6.3 μg/ml (dispersible tablet) and 7.7 μg/ml (crushed tablet), whereas the areas under the concentration-time curves from time zero to the time of the last quantifiable plasma concentration measured were 574 and 636 μg · h/ml, respectively. For both formulations, descriptive quintile analyses showed no apparent association between artemether/DHA C(max) and parasite clearance time or between the lumefantrine C(max) and the occurrence of adverse events or corrected QT interval changes. The results suggest that the dispersible tablet provides adequate systemic exposure to artemether, DHA, and lumefantrine in African children with uncomplicated P. falciparum malaria.

Multiplicity of Infection and Disease Severity in Plasmodium vivax

PubMed Central

Pacheco, M. Andreína; Lopez-Perez, Mary; Vallejo, Andrés F.; Herrera, Sócrates; Arévalo-Herrera, Myriam; Escalante, Ananias A.

2016-01-01

Background Multiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared. Methodology/Principal Findings As part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections. Conclusion The association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired immunity and exposure may have on multiclonal infections and their association with disease severity. PMID:26751811

Evidence for Dietary Fibre Modification in the Recovery and Prevention of Reoccurrence of Acute, Uncomplicated Diverticulitis: A Systematic Literature Review

PubMed Central

Dahl, Camilla; Crichton, Megan; Jenkins, Julie; Nucera, Romina; Mahoney, Sophie; Marx, Wolfgang

2018-01-01

In practice, nutrition recommendations vary widely for inpatient and discharge management of acute, uncomplicated diverticulitis. This systematic review aims to review the evidence and develop recommendations for dietary fibre modifications, either alone or alongside probiotics or antibiotics, versus any comparator in adults in any setting with or recently recovered from acute, uncomplicated diverticulitis. Intervention and observational studies in any language were located using four databases until March 2017. The Cochrane Risk of Bias tool and GRADE were used to evaluate the overall quality of the evidence and to develop recommendations. Eight studies were included. There was “very low” quality evidence for comparing a liberalised and restricted fibre diet for inpatient management to improve hospital length of stay, recovery, gastrointestinal symptoms and reoccurrence. There was “very low” quality of evidence for using a high dietary fibre diet as opposed to a standard or low dietary fibre diet following resolution of an acute episode, to improve reoccurrence and gastrointestinal symptoms. The results of this systematic review and GRADE assessment conditionally recommend the use of liberalised diets as opposed to dietary restrictions for adults with acute, uncomplicated diverticulitis. It also strongly recommends a high dietary fibre diet aligning with dietary guidelines, with or without dietary fibre supplementation, after the acute episode has resolved. PMID:29382074

Number of Diverticulitis Episodes Before Resection and Factors Associated With Earlier Interventions

PubMed Central

Simianu, Vlad V.; Fichera, Alessandro; Bastawrous, Amir L.; Davidson, Giana H.; Florence, Michael G.; Thirlby, Richard C.; Flum, David R.

2016-01-01

IMPORTANCE Despite professional recommendations to delay elective colon resection for patients with uncomplicated diverticulitis, early surgery (after <3 preceding episodes) appears to be common. Several factors have been suggested to contribute to early surgery, including increasing numbers of younger patients, a lower threshold to operate laparoscopically, and growing recognition of “smoldering” (or nonrecovering) diverticulitis episodes. However, the relevance of these factors in early surgery has not been well tested, and most prior studies have focused on hospitalizations, missing outpatient events and making it difficult to assess guideline adherence in earlier interventions. OBJECTIVE To describe patterns of episodes of diverticulitis before surgery and factors associated with earlier interventions using inpatient, outpatient, and antibiotic prescription claims. DESIGN, SETTING, AND PARTICIPANTS This investigation was a nationwide retrospective cohort study from January 1, 2009, to December 31, 2012. The dates of the analysis were July 2014 to May 2015. Participants were immunocompetent adult patients (age range, 18-64 years) with incident, uncomplicated diverticulitis. EXPOSURE Elective colectomy for diverticulitis. MAIN OUTCOMES AND MEASURES Inpatient, outpatient, and antibiotic prescription claims for diverticulitis captured in the MarketScan (Truven Health Analytics) databases. RESULTS Of 87 461 immunocompetent patients having at least 1 claim for diverticulitis, 6.4% (n = 5604) underwent a resection. The final study cohort comprised 3054 nonimmunocompromised patients who underwent elective resection for uncomplicated diverticulitis, of whom 55.6% (n = 1699) were male. Before elective surgery, they had a mean (SD) of 1.0 (0.9) inpatient claims, 1.5 (1.5) outpatient claims, and 0.5 (1.2) antibiotic prescription claims related to diverticulitis. Resection occurred after fewer than 3 episodes in 94.9% (2897 of 3054) of patients if counting inpatient claims only, in 80.5% (2459 of 3054) if counting inpatient and outpatient claims only, and in 56.3% (1720 of 3054) if counting all types of claims. Based on all types of claims, patients having surgery after fewer than 3 episodes were of similar mean age compared with patients having delayed surgery (both 47.7 years, P = .91), were less likely to undergo laparoscopy (65.1% [1120 of 1720] vs 70.8% [944 of 1334], P = .001), and had more time between the last 2 episodes preceding surgery (157 vs 96 days, P < .001). Patients with health maintenance organization or capitated insurance plans had lower rates of early surgery (50.1% [247 of 493] vs 57.4% [1429 of 2490], P = .01) than those with other insurance plan types. CONCLUSIONS AND RELEVANCE After considering all types of diverticulitis claims, 56.3% (1720 of 3054) of elective resections for uncomplicated diverticulitis occurred after fewer than 3 episodes. Earlier surgery was not explained by younger age, laparoscopy, time between the last 2 episodes preceding surgery, or financial risk-bearing for patients. In delivering value-added surgical care, factors driving early, elective resection for diverticulitis need to be determined. PMID:26864286

Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial.

PubMed

Mwaiswelo, Richard; Ngasala, Billy; Jovel, Irina; Aydin-Schmidt, Berit; Gosling, Roland; Premji, Zul; Mmbando, Bruno; Björkman, Anders; Mårtensson, Andreas

2016-08-26

The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission settings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged ≥1 year, with the exception of pregnant and lactating women, were enrolled and treated with AL plus a single PQ dose (0.25 mg/kg) or AL alone under supervision. PQ was administered together with the first AL dose. Clinical and laboratory assessments were performed at 0, 8, 24, 36, 48, 60, and 72 h and on days 7, 14, 21, and 28. The primary end-point was a polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) on day 28. Secondary outcomes included: fever and asexual parasitaemia clearance, proportion of patients with PCR-determined parasitaemia on day 3, and proportion of patients with Pfmdr1 N86Y and Pfcrt K76T on days 0, 3 and day of recurrent infection. Overall 220 patients were enrolled, 110 were allocated AL + PQ and AL, respectively. Parasite clearance by microscopy was fast, but PCR detectable parasitaemia on day 3 was 31/109 (28.4 %) and 29/108 (26.9 %) in patients treated with AL + PQ and AL, respectively (p = 0.79). Day 28 PCR-adjusted ACPR and re-infection rate was 105/105 (100 %) and 101/102 (99 %) (p = 0.31), and 5/107 (4.7 %) and 5/8 (4.8 %) (p = 0.95), in AL + PQ and AL arm, respectively. There was neither any statistically significant difference in the proportion of Pfmdr1 N86Y or Pfcrt K76T between treatment arms on days 0, 3 and day of recurrent infection, nor within treatment arms between days 0 and 3 or day 0 and day of recurrent infection. The new WHO recommendation of adding a single low-dose of PQ to AL did not compromise treatment outcome of uncomplicated P. falciparum malaria in Tanzania. Trial registration number NCT02090036.

The spectrum of retinopathy in adults with Plasmodium falciparum malaria.

PubMed

Maude, Richard J; Beare, Nicholas A V; Abu Sayeed, Abdullah; Chang, Christina C; Charunwatthana, Prakaykaew; Faiz, M Abul; Hossain, Amir; Yunus, Emran Bin; Hoque, M Gofranul; Hasan, Mahtab Uddin; White, Nicholas J; Day, Nicholas P J; Dondorp, Arjen M

2009-07-01

A specific retinopathy has been described in African children with cerebral malaria, but in adults this has not been extensively studied. Since the structure and function of the retinal vasculature greatly resembles the cerebral vasculature, study of retinal changes can reveal insights into the pathophysiology of cerebral malaria. A detailed observational study of malarial retinopathy in Bangladeshi adults was performed using high-definition portable retinal photography. Retinopathy was present in 17/27 adults (63%) with severe malaria and 14/20 adults (70%) with cerebral malaria. Moderate or severe retinopathy was more frequent in cerebral malaria (11/20, 55%) than in uncomplicated malaria (3/15, 20%; P=0.039), bacterial sepsis (0/5, 0%; P=0.038) or healthy controls (0/18, 0%; P<0.001). The spectrum of malarial retinopathy was similar to that previously described in African children, but no vessel discolouration was observed. The severity of retinal whitening correlated with admission venous plasma lactate (P=0.046), suggesting that retinal ischaemia represents systemic ischaemia. In conclusion, retinal changes related to microvascular obstruction were common in adults with severe falciparum malaria and correlated with disease severity and coma, suggesting that a compromised microcirculation has important pathophysiological significance in severe and cerebral malaria. Portable retinal photography has potential as a valuable tool to study malarial retinopathy.

Trends in malaria case management following changes in the treatment policy to artemisinin combination therapy at the Mbakong Health Centre, Cameroon 2006-2012: a retrospective study.

PubMed

Ndong, Ignatius C; Reenen, Mari van; Boakye, Daniel A; Mbacham, Wilfred F; Grobler, Anne F

2015-10-01

National malaria treatment policies are devised to guide health professionals and to facilitate diagnosis and case management. Following the recommendations of the WHO, Cameroon changed its malaria treatment policy from monotherapy to artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. We report an investigation into trends of case management following this change in policy. Data was collected retrospectively, through consultation and perusal of laboratory and prescription registers of the Mbakong Health Centre. Analysis of data was done using SPSS and SAS Statistics. Data presented herein demonstrate that from 2006 to 2012, a total of 2484 (58.7%) of the total prescriptions included an anti-malarial, 1989 (47.0%) included an antibiotic and 1935(45.7%) included an antipyretic. The anti-malarials prescribed were Anti-malaria combination therapy (ACT) - 1216 (47.6%), quinine 1044 (40.8%) or SP 296 (11.6%). Of the 1216 patients prescribed an ACT, 441(36.3%) had a positive malaria parasite confirmation, 746 (61.3%) were negative for plasmodium. Overall, 29 patients (2.4%) were treated either with an ACT without any test performed. Quinine intake was recorded in 566 (54.2%) patients positive for plasmodium. ACT prescription increased from 23% in 2007 to between 44 and 45% in 2008-2009. During this period there was a corresponding drop in the prescription of quinine from 38% in 2007 to 13% in 2009 (r=-0.43, p>0.05). Sulphadoxine-Pyrimethamine (SP) was restrictively prescribed to women of childbearing age (97.0%) after 2008. Antibiotics prescription dropped from 53.7% to 39.3% from 2010 to 2012. The odds of being prescribed an antibiotic was significantly higher in patients with a malaria negative result compared to malaria positive patients (OR=6.12, CI 4.74-7.91, p<0.00001). Overall, there is an over treatment of malaria, thus departing from the WHO guidelines of appropriate treatment. Although there is an overall increase in the prescription of ACT, less prescription of quinine and a noticeable restrain from prescription of SP to febrile cases, the old practice was still rampant. There is need for healthcare workers to adhere to guidelines in order to enhance the rational use of drugs to achieve appropriate treatment of uncomplicated malaria according to WHO guidelines. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia

PubMed Central

2012-01-01

Background A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN) with a three-day regimen of dihydroartemisinin-piperaquine (DHP), the existing programme drug, in adults with uncomplicated symptomatic malaria. Methods This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR) uncorrected and corrected. Results There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 ± 11.7 hours vs 25.5 ± 12.2 hours, p = 0.04). There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3–97.2) and 96.3% (95% Cl: 93.6–99.0) in AN, 96.3% (95% Cl: 93.5–99.0) and 97.3% (95% Cl: 95.0–99.6) in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality. Conclusion AN and DHP are confirmed very effective, safe and tolerate for treatment of any malaria. Both drugs are promising for multiple first-line therapy policies in Indonesia. PMID:22554203

The malaria testing and treatment landscape in Benin.

PubMed

Zinsou, Cyprien; Cherifath, Adjibabi Bello

2017-04-26

Since 2004, artemisinin-based combination therapy (ACT) has been the first-line treatment for uncomplicated malaria in Benin. In 2016, a medicine outlet survey was implemented to investigate the availability, price, and market share of anti-malarial treatment and malaria diagnostics. Results provide a timely and important benchmark to measure future interventions aimed at increasing access to quality malaria case management services. Between July 5th to August 6th 2016, a cross sectional, nationally-representative malaria outlet survey was conducted in Benin. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was implemented among 30 clusters (arrondissements). Outlets were eligible for inclusion in the study if they met at least one of three study criteria: (1) one or more anti-malarials reportedly in stock on the day of the survey; (2) one or more anti-malarials reportedly in stock within the 3 months preceding the survey; and/or (3) provided malaria blood testing. An audit was completed for all anti-malarials, malaria rapid diagnostic tests (RDT) and microscopy. 7260 outlets with the potential to sell or distribute anti-malarials were included in the census and 2966 were eligible and interviewed. A total of 17,669 anti-malarial and 494 RDT products were audited. Quality-assured ACT was available in 95.0% of all screened public health facilities and 59.4% of community health workers (CHW), and availability of malaria blood testing was 94.7 and 68.4% respectively. Sulfadoxine-pyrimethamine (SP) was available in 73.9% of public health facilities and not found among CHWs. Among private-sector outlets stocking at least one anti-malarial, non-artemisinin therapies were most commonly available (94.0% of outlets) as compared to quality-assured ACT (36.1%). 31.3% of the ACTs were marked with a "green leaf" logo, suggesting leakage of a co-paid ACT into Benin's unsubsidized ACT market from another country. 78.5% of the anti-malarials distributed were through the private sector, typically through general retailers (47.6% of all anti-malarial distribution). ACT comprised 44% of the private anti-malarial market share. Private-sector price of quality-assured ACT ($1.35) was three times more expensive than SP ($0.42) or chloroquine ($0.41). Non-artemisinin therapies were cited as the most effective treatment for uncomplicated malaria among general retailers and itinerant drug vendors. The ACTwatch data has shown the importance of the private sector in terms of access to malaria treatment for the majority of the population in Benin. These findings highlight the need for increased engagement with the private sector to improve malaria case management and an immediate need for a national ACT subsidy.

Artemisinin-based combination therapy in the treatment of uncomplicated malaria: review of recent regulatory experience at the European Medicines Agency.

PubMed

Pelfrene, Eric; Pinheiro, Marie-Hélène; Cavaleri, Marco

2015-07-01

Malaria remains a major public health challenge with almost half of the world's population exposed to the risk of contracting the illness. Prompt, effective and well tolerated treatment remains one of the cornerstones in the disease management, with artemisinin-based combination therapy the recommended option for non-severe malaria in endemic areas with predominant Plasmodium falciparum infections.Recent experience has been obtained at the European Medicines Agency with regulatory approval of two such antimalarial fixed combination products. For these cases, two different regulatory pathways were applied. As such, the present contribution describes this experience, emphasising main differences and applicability offered by these regulatory choices. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Plasma Uric Acid Levels Correlate with Inflammation and Disease Severity in Malian Children with Plasmodium falciparum Malaria

PubMed Central

Lopera-Mesa, Tatiana M.; Mita-Mendoza, Neida K.; van de Hoef, Diana L.; Doumbia, Saibou; Konaté, Drissa; Doumbouya, Mory; Gu, Wenjuan; Traoré, Karim; Diakité, Seidina A. S.; Remaley, Alan T.; Anderson, Jennifer M.; Rodriguez, Ana; Fay, Michael P.; Long, Carole A.; Diakité, Mahamadou; Fairhurst, Rick M.

2012-01-01

Background Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA) precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs) and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of ‘parasite-derived’ UA stimulate immune cells to produce inflammatory cytokines in vitro. Methods and Findings We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β) in 470 Malian children presenting with uncomplicated malaria (UM), non-cerebral severe malaria (NCSM) or cerebral malaria (CM). UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09–1.35, n = 23, p = 0.0007) and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97–1.41, n = 9, p = 0.0890) compared to those with UM (median 4.60 mg/dl, n = 438). In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001), IL-10 (r = 0.242, p<0.00001), sTNFRII (r = 0.221, p<0.00001), MCP-1 (r = 0.220, p<0.00001), IL-8 (r = 0.147, p = 0.002), TNFα (r = 0.132, p = 0.006) and IP-10 (r = 0.120, p = 0.012)]. In 39 children, UA levels were 1.49-fold (95% CI 1.34–1.65; p<0.0001) higher during their malaria episode [geometric mean titer (GMT) 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl). Conclusions Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA and renal function may be involved. Defining pathogenic roles for parasite-derived UA precipitates, which we have not directly studied here, requires further investigation. Trial Registration ClinicalTrials.gov NCT00669084 PMID:23071567

Efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy.

PubMed

Warsame, Marian; Hassan, Abdikarim Hussein; Hassan, Abdillahi Mohamed; Arale, Abdulkadir Mohamed; Jibril, Ali Mohamed; Mohamud, Said Abdulkadir; Barrette, Amy; Muse, Abdikarim Yusuf; Yusuf, Fahmi Essa; Nada, Rania A; Amran, Jamal Ghilan Hefzullah

2017-04-01

To determine the therapeutic efficacy of artesunate + sulphadoxine/pyrimethamine (AS + SP) and artemether + lumefantrine (AL), and to investigate the presence of molecular mutations associated with resistance, to inform national malaria treatment policy. One-arm prospective studies were conducted in three study sites in Somalia in 2013 and 2015 to evaluate the efficacy of AS + SP and AL among patients with uncomplicated falciparum malaria. Outcomes included clinical and parasitological response over 28 days, and the presence of dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) and mutations. Among patients treated with AS + SP, the PCR-corrected treatment failure rate was 12.3%. The majority of patients (89%) carried either the quintuple mutations (51I/108N + 437G/540E/581G or 51I/59R/108N + 437G/540E) or the quadruple mutation (51I/108N + 437G/540E). All patients who failed treatment with AS + SP carried the quintuple mutation (51I/108N + 437G/540E/581G). In the studies of AL, the PCR-corrected treatment failure rate was <6%. All patients in both treatment groups cleared their parasitaemia by day 3. The findings demonstrate a failing first-line treatment (AS + SP), with a failure rate above the threshold (10%) for policy change, and a high prevalence of quintuple mutations. In contrast, AL was highly efficacious. Based on these findings and the results from a previous AS + SP study, AL was selected to replace AS + SP as the first-line treatment for uncomplicated malaria in Somalia in 2016. Dihydroartemisinin + piperaquine (DHA + PPQ) has been recommended as the second-line treatment. Routine monitoring of recommended ACTs should continue to inform treatment policy. © 2017 John Wiley & Sons Ltd.

Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles.

PubMed

Warsame, Marian; Hassan, Abdillahi Mohamed; Barrette, Amy; Jibril, Ali Mohamed; Elmi, Husein Haji; Arale, Abdulkadir Mohamed; Mohammady, Hanan El; Nada, Rania A; Amran, Jamal Ghilan Hefzullah; Muse, Abdikarim; Yusuf, Fahmi Essa; Omar, Abdiqani Sheikh

2015-04-01

Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first-line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011. Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) genes. The proportion of PCR-corrected treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR = 5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96). The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy. © 2015 John Wiley & Sons Ltd.

Complement receptor 1 variants confer protection from severe malaria in Odisha, India.

PubMed

Panda, Aditya K; Panda, Madhumita; Tripathy, Rina; Pattanaik, Sarit S; Ravindran, Balachandran; Das, Bidyut K

2012-01-01

In Plasmodium falciparum infection, complement receptor-1 (CR1) on erythrocyte's surface and ABO blood group play important roles in formation of rosettes which are presumed to be contributory in the pathogenesis of severe malaria. Although several studies have attempted to determine the association of CR1 polymorphisms with severe malaria, observations remain inconsistent. Therefore, a case control study and meta-analysis was performed to address this issue. Common CR1 polymorphisms (intron 27 and exon 22) and blood group were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129 multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un-complicated malaria and 100 healthy controls from an endemic region of Odisha, India. Relevant publications for meta-analysis were searched from the database. The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG) and alleles (T and G) that are associated with low expression of CR1 on red blood cells, conferred significant protection against CM, MOD and malaria deaths. Combined analysis showed significant association of blood group B/intron 27-AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that the CR1 exon 22 low expression polymorphism is significantly associated with protection against severe malaria. The results of the present study demonstrate that common CR1 variants significantly protect against severe malaria in an endemic area.

The economic costs of malaria in children in three sub-Saharan countries: Ghana, Tanzania and Kenya

PubMed Central

2013-01-01

Background Malaria causes significant mortality and morbidity in sub-Saharan Africa (SSA), especially among children less than five years of age (U5 children). Although the economic burden of malaria in this region has been assessed previously, the extent and variation of this burden remains unclear. This study aimed to estimate the economic costs of malaria in U5 children in three countries (Ghana, Tanzania and Kenya). Methods Health system and household costs previously estimated were integrated with costs associated with co-morbidities, complications and productivity losses due to death. Several models were developed to estimate the expected treatment cost per episode per child, across different age groups, by level of severity and with or without controlling for treatment-seeking behaviour. Total annual costs (2009) were calculated by multiplying the treatment cost per episode according to severity by the number of episodes. Annual health system prevention costs were added to this estimate. Results Household and health system costs per malaria episode ranged from approximately US$ 5 for non-complicated malaria in Tanzania to US$ 288 for cerebral malaria with neurological sequelae in Kenya. On average, up to 55% of these costs in Ghana and Tanzania and 70% in Kenya were assumed by the household, and of these costs 46% in Ghana and 85% in Tanzania and Kenya were indirect costs. Expected values of potential future earnings (in thousands) lost due to premature death of children aged 0–1 and 1–4 years were US$ 11.8 and US$ 13.8 in Ghana, US$ 6.9 and US$ 8.1 in Tanzania, and US$ 7.6 and US$ 8.9 in Kenya, respectively. The expected treatment costs per episode per child ranged from a minimum of US$ 1.29 for children aged 2–11 months in Tanzania to a maximum of US$ 22.9 for children aged 0–24 months in Kenya. The total annual costs (in millions) were estimated at US$ 37.8, US$ 131.9 and US$ 109.0 nationwide in Ghana, Tanzania and Kenya and included average treatment costs per case of US$ 11.99, US$ 6.79 and US$ 20.54, respectively. Conclusion This study provides important insight into the economic burden of malaria in SSA that may assist policy makers when designing future malaria control interventions. PMID:24004482

[Malaria and HIV infection: clinical and biological aspects at Donka National Hospital in Conakry, Guinea].

PubMed

Bald, I; Camara, A; Baldé, O; Magassouba, N F; Bah, M S; Makanéra, A; Gamy, E P

2010-08-01

Malaria and HIV/AIDS are two of the most widespread infectious diseases encountered in sub-Saharan Africa. Even minor interactions between these two diseases could have substantial effects on public health. The purpose of this study was to investigate associations between malaria and HIV infection. Study was carried out over an 8-month period (April 1, 2003 to November 30, 2003) in the Tropical and Infectious Diseases Department of the Donka National Hospital in Conakry, Guinea. A total of 89 malaria patients including 41 cases with HIV infection and 48 controls without HIV infection were included. All patients were hospitalized during the study and provided informed consent. Results showed that malaria affected all age groups in the same proportion. Mean patient age was 34 years (range, 15 and 76 years). Males were more frequently infected with a sex ratio of 1.05. The average number of malaria episodes was higher in cases (malaria with HIV-infection than in controls (malaria without HIV infection). Hyperthermia was observed in most cases (68.29%) and controls (77.08%). Severe anemia was observed in 26.82% of cases versus 10.41% of controls. Low parasite density was observed in 73.17% of cases as compared to 68.75% of controls. The recovery rate was higher in the control group than in case group: 27.08% versus 14.63%. The death rate was higher in the case group than in the control group: 21.95% versus 6.25%. These findings demonstrate a link between malaria and HIV. The frequency of malaria episodes was higher in patients with HIV infection than patients without HIV infection and the outcome of malarial episodes was better in patients without HIV infection.

Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana.

PubMed

Abuaku, Benjamin; Duah, Nancy; Quaye, Lydia; Quashie, Neils; Koram, Kwadwo

2012-11-22

In 2008, artemether - lumefantrine (AL) and dihydroartemisinin - piperaquine (DHAP) were added to artesunate - amodiaquine (AS-AQ) as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest zone and 93.8% (95% CI: 77.8, 98.9) in the coastal zone (P = 0.017). Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences. The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite clearance observed in the zone.

[Practices of caregivers and national recommendations for treatment of malaria in Benin in 2009].

PubMed

Robin, S; Bruneton, C; Guévart, E

2017-08-01

New treatments against malaria (artemisinin-based combination therapies, ACT) resulted in profound changes in the therapeutic behaviours in Africa. This study aims to evaluate the practices adaptation to the new strategies in Benin in 2009. In three southern areas of the country, 14 private pharmacies, 10 public health centers and 10 private health centers were audited. Between July and October 2009, 36 providers and 93 prescribers were interviewed, 127 dispensations for self-medication were observed, 210 prescriptions were analyzed according to the WHO recommendations, 251 patients with complaints of malaria and 50 healthy women were interviewed and 34 physical inventories were conducted in pharmacies. Knowledge and trainings were inadequate, especially in the private sector and for the providers, as 41.6% of requests for antimalarial drugs were without prescription in private pharmacies. Only 28% of prescribers and 47% of providers knew the national recommendations of 1st line treatment for uncomplicated malaria. 53% of prescribers treated patients by ACT without prior parasitological examination in the case of uncomplicated malaria and no Rapid Diagnostic Test (RDT) was carried out or requested during the dispensation. Pharmaceutical advices were absent in 78.7% of cases and population acknowledged a lack of knowledge about use of the treatment. Private pharmacies were structures where the variability of available antimalarial drugs was the largest, up to 70 different specialities and where unit prices were highest, up to 7.7 times those charged in public health centers. In the field, the difficulties of application of recommendations, given at the scientific or political level, show the necessity of accompanying policy change by prior training activities of all health stakeholders and of adapting the previous regulations to facilitate implementation of the new rules. The number of authorizations issued for the ACT should be limited; authorization to chloroquine and oral formulations of artemisinin monotherapy should be removed. Since the private sector is actually involved in the fight against malaria, one should provide in this sector ACT and rapid diagnostic tests at subsidized prices.

Haemoglobin dynamics in Papuan and non-Papuan adults in northeast Papua, Indonesia, with acute, uncomplicated vivax or falciparum malaria

PubMed Central

2013-01-01

Background Haemoglobin (Hb) recovers slowly in malaria and may be influenced by naturally acquired immunity. Hb recovery was compared in malaria immune, indigenous Papuan and non-Papuan adults with limited malaria exposure. Methods Hb concentrations were measured on Days (D) 0, 3, 7, and 28 in 57 Papuans and 105 non-Papuans treated with chloroquine, doxycycline or both drugs for acute, uncomplicated Plasmodium vivax (n?=?64) or Plasmodium falciparum (n?=?98). Results Mean (SD, range) D0 Hb was 12.7 (2.2, 7–21.3) g/dL and was similar in P. falciparum infected Papuans and non-Papuans: 12.2 vs. 12.8 g/dL (P?=?0.15) but significantly lower in: (i) P. vivax-infected Papuans vs. P. vivax-infected non-Papuans: 11.4 vs. 13.47 g/dL [∆?=?−2.07 (95% CI: –3.3 – –0.8), P?=?0.0018], (ii) all patients with splenomegaly (vs. those without splenomegaly): 12.16 vs. 13.01 g/dL [∆?=?−0.85 (−1.6– –0.085), P?=?0.029], and (iii) all females vs. all males: 10.18 vs. 13.01 g/dL [∆?=?−2.82 (−3.97 – –1.67), P?

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia.

PubMed

Opoka, Robert O; Ndugwa, Christopher M; Latham, Teresa S; Lane, Adam; Hume, Heather A; Kasirye, Phillip; Hodges, James S; Ware, Russell E; John, Chandy C

2017-12-14

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416. © 2017 by The American Society of Hematology.

Current management and prevention of malaria in pregnancy: a review.

PubMed

Agboghoroma, C O

2014-01-01

Pregnant women suffer more frequent and severe malaria than non-pregnant women. Malaria in pregnancy contributes to the high maternal and perinatal morbidity and mortality in Africa. To review the burden and highlight the current management and prevention strategies for control of malaria in pregnancy in Africa. Papers for this review were identified by searches of PubMed and Google, and references from relevant articles. Search terms were "malaria", "malaria in pregnancy", "Malaria during pregnancy" and "antimalarial drug". Only papers published in English between 1983 and 2013 were included. In malarial endemic areas, acquired partial malarial immunity is not effective during pregnancy. Pregnant women are prone to frequent malaria infections which may be severe or asymptomatic but associated with placental parasitization. Malaria contributes 2-15% to maternal anaemia, 13-70% to intrauterine growth restriction, 8-14% to low birth weight, 8-36% to prematurity, 3-8% to infant deaths and 2.9-17.6% to maternal mortality. The control of malaria in pregnancy is currently predicated on three main strategies: 1) Prompt and effective case management of malaria; 2).Use of Insecticide-treated nets; and 3).Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine. Artemisinin-based combined therapy is the recommended treatment for uncomplicated malaria in the second and third trimesters of pregnancy, while quinine is used in the first trimester and for severe cases of malaria at any gestational age. The control of malaria during pregnancy should be an integral part of efforts to reduce maternal and perinatal morbidity and mortality in Africa.

Socio-Demographics and the Development of Malaria Elimination Strategies in the Low Transmission Setting

PubMed Central

Chuquiyauri, Raul; Paredes, Maribel; Peñataro, Pablo; Torres, Sonia; Marin, Silvia; Tenorio, Alexander; Brouwer, Kimberly C.; Abeles, Shira; Llanos-Cuentas, Alejandro; Gilman, Robert H.; Kosek, Margaret; Vinetz, Joseph M.

2011-01-01

This analysis presents a comprehensive description of malaria burden and risk factors in Peruvian Amazon villages where malaria transmission is hypoendemic. More than 9,000 subjects were studied in contrasting village settings within the Department of Loreto, Peru, where most malaria occurs in the country. Plasmodium vivax is responsible for more than 75% of malaria cases; severe disease from any form of malaria is uncommon and death rare. The association between lifetime malaria episodes and individual and household covariates was studied using polychotomous logistic regression analysis, assessing effects on odds of some vs. no lifetime malaria episodes. Malaria morbidity during lifetime was strongly associated with age, logging, farming, travel history, and living with a logger or agriculturist. Select groups of adults, particularly loggers and agriculturists acquire multiple malaria infections in transmission settings outside of the main domicile, and may be mobile human reservoirs by which malaria parasites move within and between micro-regions within malaria endemic settings. For example, such individuals might well be reservoirs of transmission by introducing or reintroducing malaria into their home villages and their own households, depending on vector ecology and the local village setting. Therefore, socio-demographic studies can identify people with the epidemiological characteristic of transmission risk, and these individuals would be prime targets against which to deploy transmission blocking strategies along with insecticide treated bednets and chemoprophylaxis. PMID:22100446

Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection

PubMed Central

Chuquiyauri, Raul; Molina, Douglas M.; Moss, Eli L.; Wang, Ruobing; Gardner, Malcolm J.; Brouwer, Kimberly C.; Torres, Sonia; Gilman, Robert H.; Llanos-Cuentas, Alejandro; Neafsey, Daniel E.; Felgner, Philip; Liang, Xiaowu; Vinetz, Joseph M.

2015-01-01

Large scale antibody responses in Plasmodium vivax malaria remains unexplored in the endemic setting. Protein microarray analysis of asexual-stage P. vivax was used to identify antigens recognized in sera from residents of hypoendemic Peruvian Amazon. Over 24 months, of 106 participants, 91 had two symptomatic P. vivax malaria episodes, 11 had three episodes, 3 had four episodes, and 1 had five episodes. Plasmodium vivax relapse was distinguished from reinfection by a merozoite surface protein-3α restriction fragment length polymorphism polymerase chain reaction (MSP3α PCR-RFLP) assay. Notably, P. vivax reinfection subjects did not have higher reactivity to the entire set of recognized P. vivax blood-stage antigens than relapse subjects, regardless of the number of malaria episodes. The most highly recognized P. vivax proteins were MSP 4, 7, 8, and 10 (PVX_003775, PVX_082650, PVX_097625, and PVX_114145); sexual-stage antigen s16 (PVX_000930); early transcribed membrane protein (PVX_090230); tryptophan-rich antigen (Pv-fam-a) (PVX_092995); apical merozoite antigen 1 (PVX_092275); and proteins of unknown function (PVX_081830, PVX_117680, PVX_118705, PVX_121935, PVX_097730, PVX_110935, PVX_115450, and PVX_082475). Genes encoding reactive proteins exhibited a significant enrichment of non-synonymous nucleotide variation, an observation suggesting immune selection. These data identify candidates for seroepidemiological tools to support malaria elimination efforts in P. vivax-endemic regions. PMID:26149860

The spectrum of retinopathy in adults with Plasmodium falciparum malaria

PubMed Central

Maude, Richard J.; Beare, Nicholas A.V.; Sayeed, Abdullah Abu; Chang, Christina C.; Charunwatthana, Prakaykaew; Faiz, M. Abul; Hossain, Amir; Yunus, Emran Bin; Hoque, M. Gofranul; Hasan, Mahtab Uddin; White, Nicholas J.; Day, Nicholas P.J.; Dondorp, Arjen M.

2009-01-01

Summary A specific retinopathy has been described in African children with cerebral malaria, but in adults this has not been extensively studied. Since the structure and function of the retinal vasculature greatly resembles the cerebral vasculature, study of retinal changes can reveal insights into the pathophysiology of cerebral malaria. A detailed observational study of malarial retinopathy in Bangladeshi adults was performed using high-definition portable retinal photography. Retinopathy was present in 17/27 adults (63%) with severe malaria and 14/20 adults (70%) with cerebral malaria. Moderate or severe retinopathy was more frequent in cerebral malaria (11/20, 55%) than in uncomplicated malaria (3/15, 20%; P = 0.039), bacterial sepsis (0/5, 0%; P = 0.038) or healthy controls (0/18, 0%; P < 0.001). The spectrum of malarial retinopathy was similar to that previously described in African children, but no vessel discolouration was observed. The severity of retinal whitening correlated with admission venous plasma lactate (P = 0.046), suggesting that retinal ischaemia represents systemic ischaemia. In conclusion, retinal changes related to microvascular obstruction were common in adults with severe falciparum malaria and correlated with disease severity and coma, suggesting that a compromised microcirculation has important pathophysiological significance in severe and cerebral malaria. Portable retinal photography has potential as a valuable tool to study malarial retinopathy. PMID:19344925

Anaemia following Artemisinin-Based Combination Treatments of Uncomplicated Plasmodium falciparum Malaria in Children: Temporal Patterns of Haematocrit and the Use of Uncomplicated Hyperparasitaemia as a Model for Evaluating Late-Appearing Anaemia.

PubMed

Sowunmi, Akin; Akano, Kazeem; Ntadom, Godwin; Ayede, Adejumoke; Oguche, Stephen; Agomo, Chimere; Okafor, Henrietta; Watila, Ismaila; Meremikwu, Martin; Ogala, William; Agomo, Philip; Adowoye, Elsie; Fatunmbi, Bayo; Aderoyeje, Temitope; Happi, Christian; Gbotosho, Grace; Folarin, Onikepe

2017-01-01

In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia. The frequency of anaemia (haematocrit <30%), and temporal changes in haematocrit were evaluated in 1,191 malarious children following ACTs. "Haematocrit conservation" was evaluated by using the fall in haematocrit/1,000 asexual parasites cleared from the peripheral blood (FIH/1,000 asexual parasites cpb), and the ratio of the average haematocrit (on the first 3 days of starting treatment):total parasitaemia cleared. The frequency of anaemia decreased significantly following treatment. FIH/1,000 asexual parasites cpb, average haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks after treatment began were significantly lower in hyperparasitaemic children than in children without hyperparasitaemia, suggesting haematocrit conservation during treatment followed later by a loss of haematocrit. Asymptomatic late-appearing anaemia occurred in 6% of the children. Artesunate-amodiaquine and artemether-lumefantrine contribute to haematocrit conservation at high parasitaemias but may cause late-appearing anaemia. © 2017 S. Karger AG, Basel.

Efficacy and Effectiveness of Mefloquine and Artesunate Combination Therapy for Uncomplicated Plasmodium falciparum Malaria in the Peruvian Amazon

PubMed Central

de Oliveira, Alexandre Macedo; Chavez, Jorge; de Leon, Gabriel Ponce; Durand, Salomon; Arrospide, Nancy; Roberts, Jacquelin; Cabezas, Cesar; Marquiño, Wilmer

2011-01-01

We evaluated the efficacy and effectiveness of mefloquine (MQ) plus artesunate (AS) to treat patients with uncomplicated malaria in the Peruvian Amazon Basin in April 2005–March 2006. Patients ≥ 1 year of age with fever (axillary temperature ≥ 37.5°C) or history of fever and Plasmodium falciparum monoinfection were included. Patients received antimalarial treatment with MQ (12.5 mg/kg/day for two days) and AS (4.0 mg/kg/day for three days) either by directly observed therapy or without directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed on the basis of clinical and parasitologic outcomes. Ninety-six patients were enrolled in each study group; nine patients were lost to follow-up. All patients, except for one in the observed group, demonstrated adequate clinical and parasitologic response; none had detectable parasitemia on day 3. The efficacy of MQ + AS efficacy was 98.9% (95% confidence interval = 94.1–100.0%) and the effectiveness was 100.0% (95% confidence interval = 95.9–100.0%). Our study shows that MQ + AS is highly efficacious in the Peruvian Amazon. PMID:21896825

The effects of house spraying with DDT or lambda-cyhalothrin against Anopheles arabiensis on measures of malarial morbidity in children in Tanzania.

PubMed

Mnzava, A E; Rwegoshora, R T; Tanner, M; Msuya, F H; Curtis, C F; Irare, S G

1993-08-01

The effects of house spraying of DDT and lambda-cyhalothrin against populations of Anopheles arabiensis were assessed in children aged between 1 and 10 years with regard to fever episodes and parasite prevalences. DDT and lambda-cyhalothrin treatment did not reduce the prevalence of malaria episodes as defined by fever (temperatures > or = 37.4 degrees C and/or fever reported) combined with high parasitaemia (> or = 100 parasites/200 leucocytes). However, the prevalence of malaria parasitaemia, of the episodes of fever with any level of malaria parasitaemia and of high parasitaemia alone were significantly reduced. Furthermore, the reduction in mean parasite densities was greater in children of the 1-2 years age group for both insecticides and also for children of 3-5 years age group with lambda-cyhalothrin. Measured and/or reported fever and high parasitaemia were correlated and the data indicated that most of the fevers in these children could be attributed to malaria. Using this criterion it is concluded that the population of An. arabiensis responded to both DDT and lambda-cyhalothrin house spraying which in turn also reduced malaria-related morbidity.

Implementation of Home based management of malaria in children reduces the work load for peripheral health facilities in a rural district of Burkina Faso.

PubMed

Tiono, Alfred B; Kaboré, Youssouf; Traoré, Abdoulaye; Convelbo, Nathalie; Pagnoni, Franco; Sirima, Sodiomon B

2008-10-03

Home Management of Malaria (HMM) is one of the key strategies to reduce the burden of malaria for vulnerable population in endemic countries. It is based on the evidence that well-trained communities health workers can provide prompt and adequate care to patients close to their homes. The strategy has been shown to reduce malaria mortality and severe morbidity and has been adopted by the World Health Organization as a cornerstone of malaria control in Africa. However, the potential fall-out of this community-based strategy on the work burden at the peripheral health facilities level has never been investigated. A two-arm interventional study was conducted in a rural health district of Burkina Faso. The HMM strategy has been implemented in seven community clinics catchment's area (intervention arm). For the other seven community clinics in the control arm, no HMM intervention was implemented. In each of the study arms, presumptive treatment was provided for episodes of fevers/malaria (defined operationally as malaria). The study drug was artemether-lumefantrine, which was sold at a subsidized price by community health workers/Key opinion leaders at the community level and by the pharmacists at the health facility level. The outcome measured was the proportion of malaria cases among all health facility attendance (all causes diseases) in both arms throughout the high transmission season. A total of 7,621 children were enrolled in the intervention arm and 7,605 in the control arm. During the study period, the proportions of malaria cases among all health facility attendance (all causes diseases) were 21.0%, (445/2,111, 95% CI [19.3%-22.7%]) and 70.7% (2,595/3,671, 95% CI 68.5%-71.5%), respectively in the intervention and control arms (p < 0.0001). The relative risk ratio for a fever/malaria episode to be treated at the HF level was 30% (0.30 < RR < 0.32). The number of malaria episodes treated in the intervention arm was much higher than in the control arm (6,661 vs. 2,595), with malaria accounting for 87.4% of all disease episodes recorded in the intervention area and for 34.1% in the control area (P < 0.0001). Of all the malaria cases treated in the intervention arm, only 6.7% were treated at the health facility level. These findings suggest that implementation of HMM, by reducing the workload in health facilities, might contributes to an overall increase of the performance of the peripheral health facilities.

A public-private partnership for malaria control: lessons from the Malarone Donation Programme.

PubMed Central

Oyediran, A. B. O. Olukayode; Ddumba, Edward M.; Ochola, Samuel A.; Lucas, Adetokunbo O.; Koporc, Kim; Dowdle, Walter R.

2002-01-01

In 1996, Glaxo Wellcome offered to donate up to a million treatment courses annually of Malarone, a new antimalarial, with a view to reducing the global burden of malaria. The Malarone Donation Programme (MDP) was established the following year. Eight pilot sites were selected in Kenya and Uganda to develop and evaluate an effective, locally sustainable donation strategy that ensured controlled and appropriate use of Malarone. The pilot programme targeted individuals who had acute uncomplicated Plasmodium falciparum malaria that had not responded to first-line treatments with chloroquine or sulfadoxine-pyrimethamine. Of the 161 079 patients clinically diagnosed at the pilot sites as having malaria, 1101 (0.68%) met all the conditions for participation and received directly observed treatment with Malarone. MDP had a positive effect at the pilot sites by improving the diagnosis and management of malaria. However, the provision of Malarone as a second-line drug at the district hospital level was not an efficient and effective use of resources. The number of deaths among children and adults ineligible for MDP at the pilot sites suggested that high priority should be given to meeting the challenges of malaria treatment at the community level. PMID:12471403

Artemisinin-Naphthoquine versus Artemether-Lumefantrine for Uncomplicated Malaria in Papua New Guinean Children: An Open-Label Randomized Trial

PubMed Central

Laman, Moses; Moore, Brioni R.; Benjamin, John M.; Yadi, Gumul; Bona, Cathy; Warrel, Jonathan; Kattenberg, Johanna H.; Koleala, Tamarah; Manning, Laurens; Kasian, Bernadine; Robinson, Leanne J.; Sambale, Naomi; Lorry, Lina; Karl, Stephan; Davis, Wendy A.; Rosanas-Urgell, Anna; Mueller, Ivo; Siba, Peter M.; Betuela, Inoni; Davis, Timothy M. E.

2014-01-01

Background Artemisinin combination therapies (ACTs) with broad efficacy are needed where multiple Plasmodium species are transmitted, especially in children, who bear the brunt of infection in endemic areas. In Papua New Guinea (PNG), artemether-lumefantrine is the first-line treatment for uncomplicated malaria, but it has limited efficacy against P. vivax. Artemisinin-naphthoquine should have greater activity in vivax malaria because the elimination of naphthoquine is slower than that of lumefantrine. In this study, the efficacy, tolerability, and safety of these ACTs were assessed in PNG children aged 0.5–5 y. Methods and Findings An open-label, randomized, parallel-group trial of artemether-lumefantrine (six doses over 3 d) and artemisinin-naphthoquine (three daily doses) was conducted between 28 March 2011 and 22 April 2013. Parasitologic outcomes were assessed without knowledge of treatment allocation. Primary endpoints were the 42-d P. falciparum PCR-corrected adequate clinical and parasitologic response (ACPR) and the P. vivax PCR-uncorrected 42-d ACPR. Non-inferiority and superiority designs were used for falciparum and vivax malaria, respectively. Because the artemisinin-naphthoquine regimen involved three doses rather than the manufacturer-specified single dose, the first 188 children underwent detailed safety monitoring. Of 2,542 febrile children screened, 267 were randomized, and 186 with falciparum and 47 with vivax malaria completed the 42-d follow-up. Both ACTs were safe and well tolerated. P. falciparum ACPRs were 97.8% and 100.0% in artemether-lumefantrine and artemisinin-naphthoquine-treated patients, respectively (difference 2.2% [95% CI −3.0% to 8.4%] versus −5.0% non-inferiority margin, p = 0.24), and P. vivax ACPRs were 30.0% and 100.0%, respectively (difference 70.0% [95% CI 40.9%–87.2%], p<0.001). Limitations included the exclusion of 11% of randomized patients with sub-threshold parasitemias on confirmatory microscopy and direct observation of only morning artemether-lumefantrine dosing. Conclusions Artemisinin-naphthoquine is non-inferior to artemether-lumefantrine in PNG children with falciparum malaria but has greater efficacy against vivax malaria, findings with implications in similar geo-epidemiologic settings within and beyond Oceania. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12610000913077 Please see later in the article for the Editors' Summary PMID:25549086

Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children.

PubMed

Boivin, Michael J; Sikorskii, Alla; Familiar-Lopez, Itziar; Ruiseñor-Escudero, Horacio; Muhindo, Mary; Kapisi, James; Bigira, Victor; Bass, Judy K; Opoka, Robert O; Nakasujja, Noeline; Kamya, Moses; Dorsey, Grant

2016-04-14

Asymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda. Infants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim-sulfamethoxazole, monthly sulfadoxine-pyrimethamine, or monthly dihydroartemisinin-piperaquine (DP), to be given between enrollment (4-6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb < 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU). DP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01). Malaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings.

UK malaria treatment guidelines 2016.

PubMed

Lalloo, David G; Shingadia, Delane; Bell, David J; Beeching, Nicholas J; Whitty, Christopher J M; Chiodini, Peter L

2016-06-01

1.Malaria is the tropical disease most commonly imported into the UK, with 1300-1800 cases reported each year, and 2-11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9. Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet(®)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone-proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram-negative bacteraemia/septicaemia. 14. Children with severe malaria should also be treated with empirical broad spectrum antibiotics until bacterial infection can be excluded (Grade 1B). 15. Haemolysis occurs in approximately 10-15% patients following intravenous artesunate treatment. Haemoglobin concentrations should be checked approximately 14 days following treatment in those treated with IV artemisinins (Grade 2C). 16. Falciparum malaria in pregnancy is more likely to be complicated: the placenta contains high levels of parasites, stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. 17. Uncomplicated falciparum malaria in the second and third trimester of pregnancy should be treated with artemether-lumefantrine (Grade 2B). Uncomplicated falciparum malaria in the first trimester of pregnancy should usually be treated with quinine and clindamycin but specialist advice should be sought. Severe malaria in any trimester of pregnancy should be treated as for any other patient with artesunate preferred over quinine (Grade 1C). 18. Children with uncomplicated malaria should be treated with an ACT (artemether-lumefantrine or dihydroartemisinin-piperaquine) as first line treatment (Grade 1A). Quinine with doxycycline or clindamycin, or atovaquone-proguanil at appropriate doses for weight can also be used. Doxycycline should not be given to children under 12 years. 19. Either an oral ACT or chloroquine can be used for the treatment of non-falciparum malaria. An oral ACT is preferred for a mixed infection, if there is uncertainty about the infecting species, or for P. vivax infection from areas where chloroquine resistance is common (Grade 1B). 20. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine (1A). Primaquine is more effective at preventing relapse if taken at the same time as chloroquine (Grade 1C). 21. Primaquine should be avoided or given with caution under expert supervision in patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. 22. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy and when breastfeeding (until the G6PD status of child is known); after initial treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery or cessation of breastfeeding when hypnozoite eradication can be considered. 23. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

TLR9 Polymorphisms Are Associated with Altered IFN-γ Levels in Children with Cerebral Malaria

PubMed Central

Sam-Agudu, Nadia A.; Greene, Jennifer A.; Opoka, Robert O.; Kazura, James W.; Boivin, Michael J.; Zimmerman, Peter A.; Riedesel, Melissa A.; Bergemann, Tracy L.; Schimmenti, Lisa A.; John, Chandy C.

2010-01-01

Toll-like receptor (TLR) polymorphisms have been associated with disease severity in malaria infection, but mechanisms for this association have not been characterized. The TLR2, 4, and 9 single nucleotide polymorphism (SNP) frequencies and serum interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels were assessed in Ugandan children with cerebral malaria (CM, N = 65) and uncomplicated malaria (UM, N = 52). The TLR9 C allele at −1237 and G allele at 1174 were strongly linked, and among children with CM, those with the C allele at −1237 or the G allele at 1174 had higher levels of IFN-γ than those without these alleles (P = 0.03 and 0.008, respectively). The TLR9 SNPs were not associated with altered IFN-γ levels in children with UM or altered TNF-α levels in either group. We present the first human data that TLR SNPs are associated with altered cytokine production in parasitic infection. PMID:20348497

Specific Receptor Usage in Plasmodium falciparum Cytoadherence Is Associated with Disease Outcome

PubMed Central

Ochola, Lucy B.; Siddondo, Bethsheba R.; Ocholla, Harold; Nkya, Siana; Kimani, Eva N.; Williams, Thomas N.; Makale, Johnstone O.; Liljander, Anne; Urban, Britta C.; Bull, Pete C.; Szestak, Tadge; Marsh, Kevin; Craig, Alister G.

2011-01-01

Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving several host receptors and a major parasite-derived variant antigen (PfEMP1) expressed on the surface of the infected erythrocyte membrane. Previous studies have suggested a role for ICAM-1 in the pathology of cerebral malaria, although these have been inconclusive. In this study we have examined the cytoadherence patterns of 101 patient isolates from varying clinical syndromes to CD36 and ICAM-1, and have used variant ICAM-1 proteins to further characterise this adhesive phenotype. Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases. PMID:21390226

Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis

PubMed Central

Okell, Lucy C.; Cairns, Matthew; Griffin, Jamie T.; Ferguson, Neil M.; Tarning, Joel; Jagoe, George; Hugo, Pierre; Baker, Mark; D’Alessandro, Umberto; Bousema, Teun; Ubben, David; Ghani, Azra C.

2014-01-01

There are currently several recommended drug regimens for uncomplicated falciparum malaria in Africa. Each has different properties that determine its impact on disease burden. Two major antimalarial policy options are artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA–PQP). Clinical trial data show that DHA–PQP provides longer protection against reinfection, while AL is better at reducing patient infectiousness. Here we incorporate pharmacokinetic-pharmacodynamic factors, transmission-reducing effects and cost into a mathematical model and simulate malaria transmission and treatment in Africa, using geographically explicit data on transmission intensity and seasonality, population density, treatment access and outpatient costs. DHA–PQP has a modestly higher estimated impact than AL in 64% of the population at risk. Given current higher cost estimates for DHA–PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large. We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden. PMID:25425081

Rational case management of malaria with a rapid diagnostic test, Paracheck Pf®, in antenatal health care in Bangui, Central African Republic.

PubMed

Manirakiza, Alexandre; Serdouma, Eugène; Heredeïbona, Luc Salva; Djalle, Djibrine; Madji, Nestor; Moyen, Methode; Soula, Georges; Le Faou, Alain; Delmont, Jean

2012-06-26

Both treatment and prevention strategies are recommended by the World Health Organization for the control of malaria during pregnancy in tropical areas. The aim of this study was to assess use of a rapid diagnostic test for prompt management of malaria in pregnancy in Bangui, Central African Republic. A cohort of 76 pregnant women was screened systematically for malaria with ParacheckPf® at each antenatal visit. The usefulness of the method was analysed by comparing the number of malaria episodes requiring treatment in the cohort with the number of prescriptions received by another group of pregnant women followed-up in routine antenatal care. In the cohort group, the proportion of positive ParacheckPf® episodes during antenatal clinics visits was 13.8%, while episodes of antimalarial prescriptions in the group which was followed-up routinely by antenatal personnel was estimated at 26.3%. Hence, the relative risk of the cohort for being prescribed an antimalarial drug was 0.53. Therefore, the attributable fraction of presumptive treatment avoided by systematic screening with ParacheckPf® was 47%. Use of a rapid diagnostic test is useful, affordable and easy for adequate treatment of malaria in pregnant women. More powerful studies of the usefulness of introducing the test into antenatal care are needed in all heath centres in the country and in other tropical areas.

Therapeutic efficacy and effects of artesunate-amodiaquine and artemether-lumefantrine on malaria-associated anaemia in Nigerian children aged two years and under.

PubMed

Sowunmi, Akintunde; Akano, Kazeem; Ayede, Adejumoke I; Ntadom, Godwin; Adewoye, Elsie O; Fatunmbi, Bayo; Aderoyeje, Temitope

2016-07-06

Artemisinin-based combination therapies are recommended as first-line treatments for uncomplicated falciparum malaria, but there is little evaluation of their efficacy and effects on uncomplicated malaria-associated anaemia in children aged 2 years and under. Parasitological efficacy and effects on malaria-associated anaemia were evaluated in 250 malarious children aged 2 years and under, and efficacy was evaluated in 603 malarious children older than two but younger than 5 years of age following treatment with artesunate-amodiaquine (AA) or artemether-lumefantrine (AL). Kinetics of the disposition of parasitaemia following treatment were evaluated using a non-compartment model. Late-appearing anaemia (LAA) was diagnosed using the following criteria: clearance of parasitaemia, fever and other symptoms occurring within 7 days of starting treatment, adequate clinical and parasitological response on days 28-42, haematocrit (HCT) ≥ 30 % at 1 and/or 2 weeks, a fall in HCT to < 30 % occurring at 3-6 weeks, absence of concomitant illness at 1-6 weeks, and absence of asexual parasitaemia detected using both microscopy and polymerase chain reaction (PCR) at 1-6 weeks. Overall, in children aged 2 years and under, the PCR-corrected parasitological efficacy was 97.2 % (95 % CI 92.8-101.6), which was similar for both treatments. In children older than 2 years, parasitological efficacy was also similar for both treatments, but parasite prevalence 1 day after treatment began was significantly higher, and fever and parasite clearance times were significantly faster in the AA-treated children compared with the AL-treated children. Declines in parasitaemia were monoexponential with an estimated elimination half-time of 1 h. Elimination half-times were similar for both treatments. In children aged 2 years and under who were anaemic at presentation, the mean anaemia recovery time was 12.1 days (95 % CI 10.6-13.6, n = 127), which was similar for both treatments. Relatively asymptomatic LAA occurred in 11 children (4.4 %) aged 2 years and under, the recovery from which was uneventful. This study showed that AA and AL are efficacious treatments for uncomplicated falciparum malaria in Nigerian children aged 2 years and under, and that AA clears parasitaemia and fever significantly faster than AL in children older than 2 years. Both treatments may cause a relatively asymptomatic LAA with uneventful recovery in a small proportion of children aged 2 years and under. Pan African Clinical Trial Registry PACTR201508001188143, 3 July 2015; PACTR201510001189370, 3 July 2015; PACTR201508001191898, 7 July 2015 and PACTR201508001193368, 8 July 2015  http://www.pactr.org .

Modelling recurrent events: comparison of statistical models with continuous and discontinuous risk intervals on recurrent malaria episodes data

PubMed Central

2014-01-01

Background Recurrent events data analysis is common in biomedicine. Literature review indicates that most statistical models used for such data are often based on time to the first event or consider events within a subject as independent. Even when taking into account the non-independence of recurrent events within subjects, data analyses are mostly done with continuous risk interval models, which may not be appropriate for treatments with sustained effects (e.g., drug treatments of malaria patients). Furthermore, results can be biased in cases of a confounding factor implying different risk exposure, e.g. in malaria transmission: if subjects are located at zones showing different environmental factors implying different risk exposures. Methods This work aimed to compare four different approaches by analysing recurrent malaria episodes from a clinical trial assessing the effectiveness of three malaria treatments [artesunate + amodiaquine (AS + AQ), artesunate + sulphadoxine-pyrimethamine (AS + SP) or artemether-lumefantrine (AL)], with continuous and discontinuous risk intervals: Andersen-Gill counting process (AG-CP), Prentice-Williams-Peterson counting process (PWP-CP), a shared gamma frailty model, and Generalized Estimating Equations model (GEE) using Poisson distribution. Simulations were also made to analyse the impact of the addition of a confounding factor on malaria recurrent episodes. Results Using the discontinuous interval analysis, AG-CP and Shared gamma frailty models provided similar estimations of treatment effect on malaria recurrent episodes when adjusted on age category. The patients had significant decreased risk of recurrent malaria episodes when treated with AS + AQ or AS + SP arms compared to AL arm; Relative Risks were: 0.75 (95% CI (Confidence Interval): 0.62-0.89), 0.74 (95% CI: 0.62-0.88) respectively for AG-CP model and 0.76 (95% CI: 0.64-0.89), 0.74 (95% CI: 0.62-0.87) for the Shared gamma frailty model. With both discontinuous and continuous risk intervals analysis, GEE Poisson distribution models failed to detect the effect of AS + AQ arm compared to AL arm when adjusted for age category. The discontinuous risk interval analysis was found to be the more appropriate approach. Conclusion Repeated event in infectious diseases such as malaria can be analysed with appropriate existing models that account for the correlation between multiple events within subjects with common statistical software packages, after properly setting up the data structures. PMID:25073652

The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen–encoding var genes

PubMed Central

Tonkin-Hill, Gerry Q.; Trianty, Leily; Noviyanti, Rintis; Nguyen, Hanh H. T.; Sebayang, Boni F.; Lampah, Daniel A.; Marfurt, Jutta; Cobbold, Simon A.; Rambhatla, Janavi S.; McConville, Malcolm J.; Rogerson, Stephen J.; Brown, Graham V.; Day, Karen P.; Price, Ric N.; Anstey, Nicholas M.

2018-01-01

Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to—or is selected by—this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients. The transcriptomes of 19 parasite isolates associated with severe malaria indicated that these parasites had decreased glycolysis without activation of compensatory pathways; altered chromatin structure and probably transcriptional regulation through decreased histone methylation; reduced surface expression of PfEMP1; and down-regulated expression of multiple chaperone proteins. Our RNAseq also identified novel associations between disease severity and PfEMP1 transcripts, domains, and smaller sequence segments and also confirmed all previously reported associations between expressed PfEMP1 sequences and severe disease. These findings will inform efforts to identify vaccine targets for severe malaria and also indicate how parasites adapt to—or are selected by—the host environment in severe malaria. PMID:29529020

The cost of uncomplicated childhood fevers to Kenyan households: implications for reaching international access targets

PubMed Central

Larson, Bruce A; Amin, Abdinasir A; Noor, Abdisalan M; Zurovac, Dejan; Snow, Robert W

2006-01-01

Background Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services. Methods We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset. Results 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF), and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time) of an uncomplicated childhood fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug within 24 hours of fever onset, while 17.5% were treated within 48 hours at a HCF. To achieve an increase from 17.5% to 33% of fevers treated with an antimalarial drug within 48 hours at a HCF (Scenario 1), children already being taken to a HCF would need to be taken earlier. Under this scenario, direct cash expenditures would not change, and total household costs would fall slightly to $1.86 because caretakers also save time with prompt treatment if the child has malaria. Conclusion The management of uncomplicated childhood fevers imposes substantial costs on Kenyan households. Achieving substantial improvements in the numbers of fevers treated within 48 hours at a HCF with an effective antimalarial drug (Scenario 1) will not impose additional costs on households. Achieving additional improvements in fevers treated promptly at a HCF (Scenario 2) will impose additional costs on some households roughly equal to average cash expenses for transportation to a HCF. Additional financing mechanisms that further reduce the costs of accessing care at a HCF and/or that make artemisinin-based combination therapies (ACTs) accessible for home management need to be developed and evaluated as a top priority. PMID:17196105

The cost of uncomplicated childhood fevers to Kenyan households: implications for reaching international access targets.

PubMed

Larson, Bruce A; Amin, Abdinasir A; Noor, Abdisalan M; Zurovac, Dejan; Snow, Robert W

2006-12-29

Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services. We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset. 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF), and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time) of an uncomplicated childhood fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug within 24 hours of fever onset, while 17.5% were treated within 48 hours at a HCF. To achieve an increase from 17.5% to 33% of fevers treated with an antimalarial drug within 48 hours at a HCF (Scenario 1), children already being taken to a HCF would need to be taken earlier. Under this scenario, direct cash expenditures would not change, and total household costs would fall slightly to $1.86 because caretakers also save time with prompt treatment if the child has malaria. The management of uncomplicated childhood fevers imposes substantial costs on Kenyan households. Achieving substantial improvements in the numbers of fevers treated within 48 hours at a HCF with an effective antimalarial drug (Scenario 1) will not impose additional costs on households. Achieving additional improvements in fevers treated promptly at a HCF (Scenario 2) will impose additional costs on some households roughly equal to average cash expenses for transportation to a HCF. Additional financing mechanisms that further reduce the costs of accessing care at a HCF and/or that make artemisinin-based combination therapies (ACTs) accessible for home management need to be developed and evaluated as a top priority.

Tumor necrosis factor -α, interleukin-10, intercellular and vascular adhesion molecules are possible biomarkers of disease severity in complicated Plasmodium vivax isolates from Pakistan.

PubMed

Raza, Afsheen; Ghanchi, Najia K; Sarwar Zubairi, Ali bin; Raheem, Ahmed; Nizami, Sobia; Beg, Mohammad Asim

2013-01-01

Cytokine-mediated endothelial activation pathway is a known mechanism of pathogenesis employed by Plasmodium falciparum to induce severe disease symptoms in human host. Though considered benign, complicated cases of Plasmodium vivax are being reported worldwide and from Pakistan. It has been hypothesized that P.vivax utilizes similar mechanism of pathogenesis, as that of P.falciparum for manifestations of severe malaria. Therefore, the main objective of this study was to characterize the role of cytokines and endothelial activation markers in complicated Plasmodium vivax isolates from Pakistan. A case control study using plasma samples from well-characterized groups suffering from P.vivax infection including uncomplicated cases (n=100), complicated cases (n=82) and healthy controls (n=100) were investigated. Base line levels of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Intercellular adhesion molecule-1 (ICAM-1), Vascular adhesion molecule-1(VCAM-1) and E-selectin were measured by ELISA. Correlation of cytokines and endothelial activation markers was done using Spearman's correlation analysis. Furthermore, significance of these biomarkers as indicators of disease severity was also analyzed. The results showed that TNF-α, IL-10, ICAM-1and VCAM-1 were 3-fold, 3.7 fold and 2 fold increased between uncomplicated and complicated cases. Comparison of healthy controls with uncomplicated cases showed no significant difference in TNF-α concentrations while IL-6, IL-10, ICAM-1, VCAM-1 and E-selectin were found to be elevated respectively. In addition, significant positive correlation was observed between TNF-α and IL-10/ ICAM-1, IL-6 and IL-10, ICAM-1 and VCAM-1.A Receiver operating curve (ROC) was generated which showed that TNF-α, IL-10, ICAM-1 and VCAM-1 were the best individual predictors of complicated P.vivax malaria. The results suggest that though endothelial adhesion molecules are inducible by pro-inflammatory cytokine TNF-α, however, cytokine-mediated endothelial activation pathway is not clearly demonstrated as a mechanism of pathogenesis in complicated P.vivax malaria cases from Pakistan.

Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection.

PubMed

Chuquiyauri, Raul; Molina, Douglas M; Moss, Eli L; Wang, Ruobing; Gardner, Malcolm J; Brouwer, Kimberly C; Torres, Sonia; Gilman, Robert H; Llanos-Cuentas, Alejandro; Neafsey, Daniel E; Felgner, Philip; Liang, Xiaowu; Vinetz, Joseph M

2015-10-01

Large scale antibody responses in Plasmodium vivax malaria remains unexplored in the endemic setting. Protein microarray analysis of asexual-stage P. vivax was used to identify antigens recognized in sera from residents of hypoendemic Peruvian Amazon. Over 24 months, of 106 participants, 91 had two symptomatic P. vivax malaria episodes, 11 had three episodes, 3 had four episodes, and 1 had five episodes. Plasmodium vivax relapse was distinguished from reinfection by a merozoite surface protein-3α restriction fragment length polymorphism polymerase chain reaction (MSP3α PCR-RFLP) assay. Notably, P. vivax reinfection subjects did not have higher reactivity to the entire set of recognized P. vivax blood-stage antigens than relapse subjects, regardless of the number of malaria episodes. The most highly recognized P. vivax proteins were MSP 4, 7, 8, and 10 (PVX_003775, PVX_082650, PVX_097625, and PVX_114145); sexual-stage antigen s16 (PVX_000930); early transcribed membrane protein (PVX_090230); tryptophan-rich antigen (Pv-fam-a) (PVX_092995); apical merozoite antigen 1 (PVX_092275); and proteins of unknown function (PVX_081830, PVX_117680, PVX_118705, PVX_121935, PVX_097730, PVX_110935, PVX_115450, and PVX_082475). Genes encoding reactive proteins exhibited a significant enrichment of non-synonymous nucleotide variation, an observation suggesting immune selection. These data identify candidates for seroepidemiological tools to support malaria elimination efforts in P. vivax-endemic regions. © The American Society of Tropical Medicine and Hygiene.

Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study.

PubMed

McGready, R; Lee, S J; Wiladphaingern, J; Ashley, E A; Rijken, M J; Boel, M; Simpson, J A; Paw, M K; Pimanpanarak, M; Mu, Oh; Singhasivanon, P; White, N J; Nosten, F H

2012-05-01

The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed first-trimester pregnancies of women from the Thai-Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Of 48,426 pregnant women, 17,613 (36%) met the inclusion criteria: 16,668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04-3·59) and symptomatic malaria (3·99, 3·10-5·13), and were similar for Plasmodium falciparum and Plasmodium vivax. Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15-11·46) and parasitaemia (1·49, 1·25-1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81-0·91). The risk of miscarriage was similar for women treated with chloroquine (92 [26%] of 354), quinine (95 [27%) of 355), or artesunate (20 [31%] of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects associated with artesunate treatment occurred in early pregnancy. Prospective studies should now be done to assess the safety and efficacy of artemisinin combination treatments in early pregnancy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Spatio-temporal heterogeneity of malaria morbidity in Ghana: Analysis of routine health facility data

PubMed Central

Malm, Keziah; Peprah, Nana Yaw; Silal, Sheetal P.

2018-01-01

Background Malaria incidence is largely influenced by vector abundance. Among the many interconnected factors relating to malaria transmission, weather conditions such as rainfall and temperature are known to create suitable environmental conditions that sustain reproduction and propagation of anopheles mosquitoes and malaria parasites. In Ghana, climatic conditions vary across the country. Understanding the heterogeneity of malaria morbidity using data sourced from a recently setup data repository for routine health facility data could support planning. Methods Monthly aggregated confirmed uncomplicated malaria cases from the District Health Information Management System and average monthly rainfall and temperature records obtained from the Ghana Meteorological Agency from 2008 to 2016 were analysed. Univariate time series models were fitted to the malaria, rainfall and temperature data series. After pre-whitening the morbidity data, cross correlation analyses were performed. Subsequently, transfer function models were developed for the relationship between malaria morbidity and rainfall and temperature. Results Malaria morbidity patterns vary across zones. In the Guinea savannah, morbidity peaks once in the year and twice in both the Transitional forest and Coastal savannah, following similar patterns of rainfall at the zonal level. While the effects of rainfall on malaria morbidity are delayed by a month in the Guinea savannah and Transitional Forest zones those of temperature are delayed by two months in the Transitional forest zone. In the Coastal savannah however, incidence of malaria is significantly associated with two months lead in rainfall and temperature. Conclusion Data captured on the District Health Information Management System has been used to demonstrate heterogeneity in the dynamics of malaria morbidity across the country. Timing of these variations could guide the deployment of interventions such as indoor residual spraying, Seasonal Malaria Chemoprevention or vaccines to optimise effectiveness on zonal basis. PMID:29377908

Spatio-temporal heterogeneity of malaria morbidity in Ghana: Analysis of routine health facility data.

PubMed

Awine, Timothy; Malm, Keziah; Peprah, Nana Yaw; Silal, Sheetal P

2018-01-01

Malaria incidence is largely influenced by vector abundance. Among the many interconnected factors relating to malaria transmission, weather conditions such as rainfall and temperature are known to create suitable environmental conditions that sustain reproduction and propagation of anopheles mosquitoes and malaria parasites. In Ghana, climatic conditions vary across the country. Understanding the heterogeneity of malaria morbidity using data sourced from a recently setup data repository for routine health facility data could support planning. Monthly aggregated confirmed uncomplicated malaria cases from the District Health Information Management System and average monthly rainfall and temperature records obtained from the Ghana Meteorological Agency from 2008 to 2016 were analysed. Univariate time series models were fitted to the malaria, rainfall and temperature data series. After pre-whitening the morbidity data, cross correlation analyses were performed. Subsequently, transfer function models were developed for the relationship between malaria morbidity and rainfall and temperature. Malaria morbidity patterns vary across zones. In the Guinea savannah, morbidity peaks once in the year and twice in both the Transitional forest and Coastal savannah, following similar patterns of rainfall at the zonal level. While the effects of rainfall on malaria morbidity are delayed by a month in the Guinea savannah and Transitional Forest zones those of temperature are delayed by two months in the Transitional forest zone. In the Coastal savannah however, incidence of malaria is significantly associated with two months lead in rainfall and temperature. Data captured on the District Health Information Management System has been used to demonstrate heterogeneity in the dynamics of malaria morbidity across the country. Timing of these variations could guide the deployment of interventions such as indoor residual spraying, Seasonal Malaria Chemoprevention or vaccines to optimise effectiveness on zonal basis.

Retinal Changes in Uncomplicated and Severe Plasmodium knowlesi Malaria.

PubMed

Govindasamy, Gayathri; Barber, Bridget E; Ghani, Shuaibah A; William, Timothy; Grigg, Matthew J; Borooah, Shyamanga; Dhillon, Bal; Dondorp, Arjen M; Yeo, Tsin W; Anstey, Nicholas M; Maude, Richard J

2016-05-01

Plasmodium knowlesi causes severe malaria, but its pathogenesis is poorly understood. Retinal changes provide insights into falciparum malaria pathogenesis but have not been studied in knowlesi malaria. An observational study was conducted in Malaysian adults hospitalized with severe (n = 20) and nonsevere (n = 24) knowlesi malaria using indirect ophthalmoscopy (n = 44) and fundus photography (n = 29). The patients' median age was 44 years (range, 18-74 years). No coma or deaths occurred. Photography detected retinal changes in 11 of 12 patients (92%) with severe and 14 of 17 (82%) with nonsevere knowlesi malaria. Nonspecific retinal whitening occurred in 3 (35%) and 5 (29%) patients with severe and nonsevere disease, respectively; hemorrhages in 2 (17%) and 3 (18%); loss of retinal pigment epithelium in 1 (8%) and 4 (24%); and drusen in 9 (71%) and 12 (75%). All changes were mild, with no significant differences between severe and nonsevere disease. Patients with retinal hemorrhages had lower platelet counts than those without (median, 22 vs 43 × 10(9)/L; P= .04). The paucity of specific retinal findings associated with disease severity in knowlesi malaria contrasts with the retinopathy of severe adult falciparum malaria with and without coma, suggesting that falciparum-like microvascular sequestration in the brain is not a major component in severe knowlesi malaria pathogenesis. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Baseline in vivo, ex vivo and molecular responses of Plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in Colombia.

PubMed

Aponte, Samanda; Guerra, Ángela Patricia; Álvarez-Larrotta, Catalina; Bernal, Sindy Durley; Restrepo, César; González, Camila; Yasnot, María Fernanda; Knudson-Ospina, Angélica

2017-02-01

Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed. From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found. This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine combined with primaquine for radical treatment of vivax malaria in Sumatera, Indonesia.

PubMed

Pasaribu, Ayodhia Pitaloka; Chokejindachai, Watcharee; Sirivichayakul, Chukiat; Tanomsing, Naowarat; Chavez, Irwin; Tjitra, Emiliana; Pasaribu, Syahril; Imwong, Mallika; White, Nicholas J; Dondorp, Arjen M

2013-12-01

A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established. We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year. Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ. In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated. NCT01288820.

Phase 2a, Open-Label, 4-Escalating-Dose, Randomized Multicenter Study Evaluating the Safety and Activity of Ferroquine (SSR97193) Plus Artesunate, versus Amodiaquine Plus Artesunate, in African Adult Men with Uncomplicated Plasmodium falciparum Malaria.

PubMed

Supan, Christian; Mombo-Ngoma, Ghyslain; Kombila, Maryvonne; Ospina Salazar, Carmen L; Held, Jana; Lell, Bertrand; Cantalloube, Cathy; Djeriou, Elhadj; Ogutu, Bernhards; Waitumbi, John; Otsula, Nekoye; Apollo, Duncan; Polhemus, Mark E; Kremsner, Peter G; Walsh, Douglas S

2017-08-01

Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator. After a 2:1 randomization (block size three, equating to N = 12 for each ferroquine dose and N = 6 for each of four amodiaquine comparator groups) patients received daily for three consecutive days, either ferroquine + AS (200 mg/day) or amodiaquine (612 mg/day) + AS (200 mg/day). Safety, electrocardiograms, parasite clearance times, efficacy, and pharmacokinetics were assessed to day 28. Seventy-two patients were randomized. Ferroquine + AS showed generally mild increases (Grade 1 toxicity) in alanine aminotransferase (ALT) levels with a dose trend starting at 400 mg. There were two Grade 2 ALT events: one patient receiving 200 mg (3.8 upper limit of normal [ULN], day 7) and one receiving 600 mg (3.3 ULN, day 14), both without increased bilirubin. One ferroquine 100 mg + AS patient after one dose was withdrawn after developing a QTcF interval prolongation > 60 milliseconds over baseline. Parasitemias in all patients cleared quickly, with no recurrence through day 28. Hepatic, as well as cardiac, profiles should be monitored closely in future trials. (ClinicalTrials.gov: NCT00563914).

Application of loop-mediated isothermal amplification for malaria diagnosis during a follow-up study in São Tomé.

PubMed

Lee, Pei-Wen; Ji, Dar-Der; Liu, Chia-Tai; Rampao, Herodes S; do Rosario, Virgilio E; Lin, I-Feng; Shaio, Men-Fang

2012-12-06

A reliable and simple test for the detection of malaria parasite is crucial in providing effective treatment and therapeutic follow-up, especially in malaria elimination programmes. A comparison of four methods, including nested polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) were used for the malaria diagnosis and treatment follow-up in São Tomé and Príncipe, during a successful pre-elimination campaign. During the period September to November 2009, blood samples from 128 children (five to 14 years old) with temperature ≥38°C (tympanic) in the District of Agua Grande were examined using four different methods, i.e., histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (HRP-2-RDTs), optical microscopy, nested PCR, and LAMP. First-line treatment with artesunate-amodiaquine was given for uncomplicated malaria and intravenous quinine was given for complicated malaria. Children with persistent positivity for malaria by microscopy, or either by nested PCR, or by LAMP on day 7 were given second-line treatment with artemether-lumefantrine. Treatment follow-up was made weekly, for up to four weeks. On day 0, positive results for HRP-2-RDTs, microscopy, nested PCR, and LAMP, were 68(53%), 47(37%), 64(50%), and 65(51%), respectively. When nested PCR was used as a reference standard, only LAMP was comparable; both HRP-2-RDTs and microscopy had moderate sensitivity; HRP-2-RDTs had poor positive predictive value (PPV) and a moderate negative predictive value (NPV) for the treatment follow-up. Seventy-one children with uncomplicated malaria and eight children with complicated falciparum malaria were diagnosed based on at least one positive result from the four tests as well as clinical criteria. Twelve of the 79 children receiving first-line treatment had positive results by nested PCR on day 7 (nested PCR-corrected day 7 cure rate was 85%). After the second-line treatment, nested PCR/LAMP-corrected day 28 cure rate was 83% for these 12 children. HRP-2-RDTs have similar sensitivity as microscopy but less specificity. However, as compared to nested PCR, the poor sensitivity of HRP-2-RDTs indicates that low parasitaemia may not be detected after treatment, as well as the low specificity of HRP-2-RDTs indicates it cannot be applied for treatment follow-up. LAMP has similar sensitivity and specificity to nested PCR. With high PPV and NPV, LAMP is simpler and faster as compared to nested PCR with the advantage of detecting low parasitaemia becoming a potential point-of-care test for treatment follow-up.

Application of loop-mediated isothermal amplification for malaria diagnosis during a follow-up study in São Tomé

PubMed Central

2012-01-01

Background A reliable and simple test for the detection of malaria parasite is crucial in providing effective treatment and therapeutic follow-up, especially in malaria elimination programmes. A comparison of four methods, including nested polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) were used for the malaria diagnosis and treatment follow-up in São Tomé and Príncipe, during a successful pre-elimination campaign. Method During the period September to November 2009, blood samples from 128 children (five to 14 years old) with temperature ≥38°C (tympanic) in the District of Agua Grande were examined using four different methods, i.e., histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (HRP-2-RDTs), optical microscopy, nested PCR, and LAMP. First-line treatment with artesunate-amodiaquine was given for uncomplicated malaria and intravenous quinine was given for complicated malaria. Children with persistent positivity for malaria by microscopy, or either by nested PCR, or by LAMP on day 7 were given second-line treatment with artemether-lumefantrine. Treatment follow-up was made weekly, for up to four weeks. Results On day 0, positive results for HRP-2-RDTs, microscopy, nested PCR, and LAMP, were 68(53%), 47(37%), 64(50%), and 65(51%), respectively. When nested PCR was used as a reference standard, only LAMP was comparable; both HRP-2-RDTs and microscopy had moderate sensitivity; HRP-2-RDTs had poor positive predictive value (PPV) and a moderate negative predictive value (NPV) for the treatment follow-up. Seventy-one children with uncomplicated malaria and eight children with complicated falciparum malaria were diagnosed based on at least one positive result from the four tests as well as clinical criteria. Twelve of the 79 children receiving first-line treatment had positive results by nested PCR on day 7 (nested PCR-corrected day 7 cure rate was 85%). After the second-line treatment, nested PCR/LAMP-corrected day 28 cure rate was 83% for these 12 children. Conclusions HRP-2-RDTs have similar sensitivity as microscopy but less specificity. However, as compared to nested PCR, the poor sensitivity of HRP-2-RDTs indicates that low parasitaemia may not be detected after treatment, as well as the low specificity of HRP-2-RDTs indicates it cannot be applied for treatment follow-up. LAMP has similar sensitivity and specificity to nested PCR. With high PPV and NPV, LAMP is simpler and faster as compared to nested PCR with the advantage of detecting low parasitaemia becoming a potential point-of-care test for treatment follow-up. PMID:23217163

Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

PubMed Central

2012-01-01

Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to <25 kg, with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria. Patients were randomized (2:1) to pyronaridine-artesunate granules (60/20 mg) once daily or artemether-lumefantrine crushed tablets (20/120 mg) twice daily, both dosed by bodyweight, orally (liquid suspension) for three days. Results Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR), corrected for re-infection using polymerase chain reaction (PCR) genotyping (per-protocol population) was 97.1% (329/339; 95% CI 94.6, 98.6) for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9) for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P < .0001). Pyronaridine-artesunate was non-inferior to artemether-lumefantrine: treatment difference -1.8% (95% CI -4.3 to 1.6). The incidence of drug-related adverse events was 37.2% (132/355) with pyronaridine-artesunate, 44.4% (80/180) with artemether-lumefantrine. Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups. From day 3 until study completion, one patient in each treatment group had peak alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. Trial registration ClinicalTrials.gov: identifier NCT00541385 PMID:23113947

Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya.

PubMed

Rusk, Andria; Smith, Nathan; Menya, Diana; Obala, Andrew; Simiyu, Chrispinus; Khwa-Otsyula, Barasa; O'Meara, Wendy

2012-08-06

Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Most of the medicine retailers surveyed (65%) were able to identify artemether-lumefantrine (AL) as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could not is still too high. Furthermore, knowing the MOH recommended anti-malarial medication does not always ensure it is recommended or dispensed to customers. Retailer training and education are both areas that could be improved. Considering the influence that patient demand has on retailer behaviour, future interventions focusing on community education may positively influence appropriate dispensing of anti-malarials.

Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya

PubMed Central

2012-01-01

Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65%) were able to identify artemether-lumefantrine (AL) as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could not is still too high. Furthermore, knowing the MOH recommended anti-malarial medication does not always ensure it is recommended or dispensed to customers. Retailer training and education are both areas that could be improved. Considering the influence that patient demand has on retailer behaviour, future interventions focusing on community education may positively influence appropriate dispensing of anti-malarials. PMID:22866866

Identification of immune signatures predictive of clinical protection from malaria.

PubMed

Valletta, John Joseph; Recker, Mario

2017-10-01

Antibodies are thought to play an essential role in naturally acquired immunity to malaria. Prospective cohort studies have frequently shown how continuous exposure to the malaria parasite Plasmodium falciparum cause an accumulation of specific responses against various antigens that correlate with a decreased risk of clinical malaria episodes. However, small effect sizes and the often polymorphic nature of immunogenic parasite proteins make the robust identification of the true targets of protective immunity ambiguous. Furthermore, the degree of individual-level protection conferred by elevated responses to these antigens has not yet been explored. Here we applied a machine learning approach to identify immune signatures predictive of individual-level protection against clinical disease. We find that commonly assumed immune correlates are poor predictors of clinical protection in children. On the other hand, antibody profiles predictive of an individual's malaria protective status can be found in data comprising responses to a large set of diverse parasite proteins. We show that this pattern emerges only after years of continuous exposure to the malaria parasite, whereas susceptibility to clinical episodes in young hosts (< 10 years) cannot be ascertained by measured antibody responses alone.

Rational case management of malaria with a rapid diagnostic test, Paracheck Pf®, in antenatal health care in Bangui, Central African Republic

PubMed Central

2012-01-01

Background Both treatment and prevention strategies are recommended by the World Health Organization for the control of malaria during pregnancy in tropical areas. The aim of this study was to assess use of a rapid diagnostic test for prompt management of malaria in pregnancy in Bangui, Central African Republic. Methods A cohort of 76 pregnant women was screened systematically for malaria with ParacheckPf® at each antenatal visit. The usefulness of the method was analysed by comparing the number of malaria episodes requiring treatment in the cohort with the number of prescriptions received by another group of pregnant women followed-up in routine antenatal care. Results In the cohort group, the proportion of positive ParacheckPf® episodes during antenatal clinics visits was 13.8%, while episodes of antimalarial prescriptions in the group which was followed-up routinely by antenatal personnel was estimated at 26.3%. Hence, the relative risk of the cohort for being prescribed an antimalarial drug was 0.53. Therefore, the attributable fraction of presumptive treatment avoided by systematic screening with ParacheckPf® was 47%. Conclusions Use of a rapid diagnostic test is useful, affordable and easy for adequate treatment of malaria in pregnant women. More powerful studies of the usefulness of introducing the test into antenatal care are needed in all heath centres in the country and in other tropical areas. PMID:22734602

A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes

PubMed Central

Vos, Martijn W.; Stone, Will J. R.; Koolen, Karin M.; van Gemert, Geert-Jan; van Schaijk, Ben; Leroy, Didier; Sauerwein, Robert W.; Bousema, Teun; Dechering, Koen J.

2015-01-01

Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic Plasmodium falciparum reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening. Analyses of sixty-five compounds from the Medicines for Malaria Venture validation and malaria boxes identified 37 compounds with high levels of TRA (>80%); different assay modes allowed discrimination between gametocytocidal and downstream modes of action. Comparison of SMFA data to published assay formats for predicting parasite infectivity indicated that individual in vitro screens show substantial numbers of false negatives. These results highlight the importance of the SMFA in the screening pipeline for transmission reducing compounds and present a rapid and objective method. In addition we present sixteen diverse chemical scaffolds from the malaria box that may serve as a starting point for further discovery and development of malaria transmission blocking drugs. PMID:26687564

Artesunate-mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial.

PubMed

Grigg, Matthew J; William, Timothy; Menon, Jayaram; Dhanaraj, Prabakaran; Barber, Bridget E; Wilkes, Christopher S; von Seidlein, Lorenz; Rajahram, Giri S; Pasay, Cielo; McCarthy, James S; Price, Ric N; Anstey, Nicholas M; Yeo, Tsin W

2016-02-01

The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate-mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876. Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate-mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76-91]) of 115 patients in the artesunate-mefloquine group versus 61 (55% [45-64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0-40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate-mefloquine than in those given chloroquine (18·0 h [range 6·0-48·0] vs 24·0 h [6·0-60·0]; p<0·0001), with faster clearance of ring stages in the artesunate-mefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9-9·4] vs 13·8 h [12·1-15·4]; p<0·0001). Risk of anaemia within 28 days was lower in patients in the artesunate-mefloquine group (71 [62%; 95% CI 52·2-70·6]) than in those in the chloroquine group (83 [75%; 65·6-82·5]; p=0·035). Gametocytaemia as detected by PCR for pks25 was present in 44 (86%) of 51 patients in the artesunate-mefloquine group and 41 (84%) of 49 patients in the chloroquine group at baseline, and in three (6%) of 49 patients and two (4%) of 48 patients, respectively, at day 7. Fever clearance was faster in the artesunate-mefloquine group (mean 11·5 h [95% CI 8·3-14·6]) than in the chloroquine group (14·8 h [11·7-17·8]; p=0·034). Bed occupancy was 2426 days per 1000 patients in the artesunate-mefloquine group versus 2828 days per 1000 patients in the chloroquine group (incidence rate ratio 0·858 [95% CI 0·812-0·906]; p<0·0001). One (<1%) patient in the artesunate-mefloquine group had a serious neuropsychiatric event regarded as probably related to study drug. Artesunate-mefloquine is highly efficacious for treatment of uncomplicated P knowlesi malaria. The rapid therapeutic response of the drug offers significant advantages compared with chloroquine monotherapy and supports a unified treatment policy for artemisinin-based combination therapy for all Plasmodium species in co-endemic areas. Malaysian Ministry of Health, Australian National Health and Medical Research Council, and Asia Pacific Malaria Elimination Network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial

PubMed Central

Veenemans, Jacobien; Milligan, Paul; Prentice, Andrew M.; Schouten, Laura R. A.; Inja, Nienke; van der Heijden, Aafke C.; de Boer, Linsey C. C.; Jansen, Esther J. S.; Koopmans, Anna E.; Enthoven, Wendy T. M.; Kraaijenhagen, Rob J.; Demir, Ayse Y.; Uges, Donald R. A.; Mbugi, Erasto V.; Savelkoul, Huub F. J.; Verhoef, Hans

2011-01-01

Background It is uncertain to what extent oral supplementation with zinc can reduce episodes of malaria in endemic areas. Protection may depend on other nutrients. We measured the effect of supplementation with zinc and other nutrients on malaria rates. Methods and Findings In a 2×2 factorial trial, 612 rural Tanzanian children aged 6–60 months in an area with intense malaria transmission and with height-for-age z-score≤−1.5 SD were randomized to receive daily oral supplementation with either zinc alone (10 mg), multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Intervention group was indicated by colour code, but neither participants, researchers, nor field staff knew who received what intervention. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. The primary outcome, an episode of malaria, was assessed among children reported sick at a primary care clinic, and pre-defined as current Plasmodium infection with an inflammatory response, shown by axillary temperature ≥37.5°C or whole blood C-reactive protein concentration ≥8 mg/L. Nutritional indicators were assessed at baseline and at 251 days (median; 95% reference range: 191–296 days). In the primary intention-to-treat analysis, we adjusted for pre-specified baseline factors, using Cox regression models that accounted for multiple episodes per child. 592 children completed the study. The primary analysis included 1,572 malaria episodes during 526 child-years of observation (median follow-up: 331 days). Malaria incidence in groups receiving zinc, multi-nutrients without zinc, multi-nutrients with zinc and placebo was 2.89/child-year, 2.95/child-year, 3.26/child-year, and 2.87/child-year, respectively. There was no evidence that multi-nutrients influenced the effect of zinc (or vice versa). Neither zinc nor multi-nutrients influenced malaria rates (marginal analysis; adjusted HR, 95% CI: 1.04, 0.93–1.18 and 1.10, 0.97–1.24 respectively). The prevalence of zinc deficiency (plasma zinc concentration <9.9 µmol/L) was high at baseline (67% overall; 60% in those without inflammation) and strongly reduced by zinc supplementation. Conclusions We found no evidence from this trial that zinc supplementation protected against malaria. Trial Registration ClinicalTrials.gov NCT00623857 Please see later in the article for the Editors' Summary. PMID:22131908

Investigating payment coping mechanisms used for the treatment of uncomplicated malaria to different socio-economic groups in Nigeria.

PubMed

Etiaba, Enyi; Onwujekwe, Obinna; Uzochukwu, Benjamin; Adjagba, Alex

2015-03-01

Given the enormous economic burden of malaria in Nigeria and in sub-Saharan Africa, it is important to determine how different population groups cope with payment for malaria treatment. This paper provides new information about the differences in household coping mechanisms for expenditures on malaria treatment. The study was undertaken in two communities in Southeast Nigeria. A total of 200 exit interviews were conducted with patients and their care givers after consultation and treatment for malaria. The methods that were used to cope with payments for malaria treatment expenditures were determined. The coping mechanisms were disaggregated by socio-economic status (SES). The average expenditure to treat malaria was $22.9, which was all incurred through out-of- pocket payments. Some households used more than one coping method but none reported using health insurance. It was found that use of household savings (79.5%) followed by reduction in other household expenses (22.5%) were the most common coping methods. The reduction of other household expenses was significantly more prevalent with the average (Q4) SES group (p<0.05). . People used different coping strategies to take care of their malaria expenditures, which are mostly paid out-of-pocket. The average socio-economic household had to forego other basic household expenditures in order to cope with malaria illness; otherwise there were no other significant differences in the coping mechanisms across the different SES groups. This could be indicative of the catastrophic nature of malaria treatment expenditures. Interventions that will reduce the burden of malaria expenditures on all households, within the context of Universal Health Coverage are needed so as to decrease the economic burden of malaria on households.

Traditional healers in Nigeria: perception of cause, treatment and referral practices for severe malaria.

PubMed

Okeke, T A; Okafor, H U; Uzochukwu, B S C

2006-07-01

Malaria remains one of the main causes of mortality among young children in sub-Saharan Africa. In Nigeria traditional healers play an important role in health care delivery and the majority of the population depend on them for most of their ailments. The aim of this study was to investigate the perceptions of traditional healers regarding causes, symptoms, treatment of uncomplicated malaria and referral practices for severe malaria with a view to developing appropriate intervention strategies aimed at improving referral practices for severe malaria. A qualitative study was carried out in Ugwogo-Nike, a rural community in south-east Nigeria, which included in-depth interviews with 23 traditional healers. The traditional healers believed that the treatment of severe malaria, especially convulsions, with herbal remedies was very effective. Some traditional healers were familiar with the signs and symptoms of malaria, but malaria was perceived as an environmentally related disease caused by heat from the scorching sun. The majority of traditional healers believed that convulsions are inherited from parents, while a minority attributed them to evil spirits. Most (16/23) will not refer cases to a health facility because they believe in the efficacy of their herbal remedies. The few that did refer did so after several stages of traditional treatment, which resulted in long delays of about two weeks before appropriate treatment was received. The fact that traditional healers are important providers of treatment for severe malaria, especially convulsions, underlines the need to enlist their support in efforts to improve referral practices for severe malaria.

Design, implementation and evaluation of a training programme for school teachers in the use of malaria rapid diagnostic tests as part of a basic first aid kit in southern Malawi.

PubMed

Witek-McManus, Stefan; Mathanga, Don P; Verney, Allison; Mtali, Austin; Ali, Doreen; Sande, John; Mwenda, Reuben; Ndau, Saidi; Mazinga, Charles; Phondiwa, Emmanuel; Chimuna, Tiyese; Melody, David; Roschnik, Natalie; Brooker, Simon J; Halliday, Katherine E

2015-09-17

With increasing levels of enrolment, primary schools present a pragmatic opportunity to improve the access of school children to timely diagnosis and treatment of malaria, increasingly recognised as a major health problem within this age group. The expanded use of malaria rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT) by community health workers (CHWs) has raised the prospect of whether teachers can provide similar services for school children. We describe and evaluate the training of primary school teachers to use a first aid kit containing malaria RDTs and ACT for the diagnosis and treament of uncomplicated malaria in school children in southern Malawi. We outline the development of the intervention as: (1) conception and design, (2) pilot training, (3) final training, and (4) 7-month follow up. The training materials were piloted at a four-day workshop in July 2013 following their design at national stakeholders meetings. The evaluation of the pilot training and materials were assessed in relation to increased knowledge and skill sets using checklist evaluations and questionnaires, the results of which informed the design of a final seven-day training programme held in December 2013. A follow up of trained teachers was carried out in July 2014 following 7 months of routine implementation. A total of 15 teachers were evaluated at four stages: pilot training, two weeks following pilot, final training and seven months following final training. A total of 15 and 92 teachers were trained at the pilot and final training respectively. An average of 93 % of the total steps required to use RDTs were completed correctly at the final training, declining to 87 % after 7 months. All teachers were observed correctly undertaking safe blood collection and handling, accurate RDT interpretation, and correct dispensing of ACT. The most commonly observed errors were a failure to wait 20 minutes before reading the test result, and adding an incorrect volume of buffer to the test cassette. Following training, teachers are able to competently use RDTs and ACTs test and treat children at school for uncomplicated malaria safely and accurately. Teachers demonstrate a comparable level of RDT use relative to non-health professional users of RDTs, and sustain this competency over a period of seven months during routine implementation.

Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants

PubMed Central

Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel

2017-01-01

ABSTRACT Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences (P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.) PMID:29061746

Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants.

PubMed

Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel; Bassat, Quique

2018-01-01

Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences ( P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.). Copyright © 2017 Gargano et al.

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

PubMed Central

Baker, Virginia S; Imade, Godwin E; Molta, Norman B; Tawde, Pallavi; Pam, Sunday D; Obadofin, Michael O; Sagay, Soloman A; Egah, Daniel Z; Iya, Daniel; Afolabi, Bangmboye B; Baker, Murray; Ford, Karen; Ford, Robert; Roux, Kenneth H; Keller, Thomas CS

2008-01-01

Background In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Methods Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. Results The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. Conclusion The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed. PMID:18312656

Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria.

PubMed

Tun, Thein; Tint, Hla Soe; Lin, Khin; Kyaw, Thar Tun; Myint, Moe Kyaw; Khaing, Win; Tun, Zaw Win

2009-09-01

All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine+1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2+/-8.6 h and 34.6+/-14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment.

Phase II trial in China of a new, rapidly-acting and effective oral antimalarial, CGP 56697, for the treatment of Plasmodium falciparum malaria.

PubMed

Jiao, X; Liu, G Y; Shan, C O; Zhao, X; Li, X W; Gathmann, I; Royce, C

1997-09-01

One hundred and two Chinese out-patients with naturally acquired, previously untreated, falciparum malaria were selected to evaluate the efficacy of a new combination anti-malaria therapy, CGP 56697 (artemether plus benflumetol). In this open non-comparative trial each patient received a combination of 80 mg artemether and 480 mg benflumetol given orally at 0, 8, 24 and 48 hours (total: 320 mg artemether, 1,920 mg benflumetol). Patients were kept for 28 days in a transmission-free hospital in an area with chloroquine resistant falciparum malaria to prevent reinfection and to aid diagnosis of recrudescence. Progress and possible adverse effects were monitored by blood film parasitology, blood biochemistry assays, urinalysis, ECG and X-ray. Ninety-eight of the 102 patients were shown to be free of infection at 28 days, a 96.1% cure rate. Parasite reduction at 24 hours was 99.4%. Time to effect complete parasite clearance ranged from 24 to 54 hours (median 30 hours). Time for fever clearance ranged from 6 to 78 hours (median 18 hours). Recrudescence was low (3.9%). No significant adverse side-effects were encountered. It is concluded that CGP 56697, a combination anti-malaria therapy of artemether with benflumetol, offered a rapid and highly effective treatment for acute uncomplicated falciparum malaria in an area of chloroquine-resistant malaria in China.

Argemone mexicana decoction versus artesunate-amodiaquine for the management of malaria in Mali: policy and public-health implications.

PubMed

Graz, Bertrand; Willcox, Merlin L; Diakite, Chiaka; Falquet, Jacques; Dackuo, Florent; Sidibe, Oumar; Giani, Sergio; Diallo, Drissa

2010-01-01

A classic way of delaying drug resistance is to use an alternative when possible. We tested the malaria treatment Argemone mexicana decoction (AM), a validated self-prepared traditional medicine made with one widely available plant and safe across wide dose variations. In an attempt to reflect the real situation in the home-based management of malaria in a remote Malian village, 301 patients with presumed uncomplicated malaria (median age 5 years) were randomly assigned to receive AM or artesunate-amodiaquine [artemisinin combination therapy (ACT)] as first-line treatment. Both treatments were well tolerated. Over 28 days, second-line treatment was not required for 89% (95% CI 84.1-93.2) of patients on AM, versus 95% (95% CI 88.8-98.3) on ACT. Deterioration to severe malaria was 1.9% in both groups in children aged 5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a first-line complement to standard modern drugs in high-transmission areas, in order to reduce the drug pressure for development of resistance to ACT, in the management of malaria. In view of the low rate of severe malaria and good tolerability, AM may also constitute a first-aid treatment when access to other antimalarials is delayed.

Extended Safety, Immunogenicity and Efficacy of a Blood-Stage Malaria Vaccine in Malian Children: 24-Month Follow-Up of a Randomized, Double-Blinded Phase 2 Trial

PubMed Central

Laurens, Matthew B.; Thera, Mahamadou A.; Coulibaly, Drissa; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Bennett, Jason W.; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.; Doumbo, Ogobara K.

2013-01-01

Background The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1–6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season. Trial Registration Clinicaltrials.gov NCT00460525 NCT00460525 PMID:24260195

Quality of Malaria Case Management in Malawi: Results from a Nationally Representative Health Facility Survey

PubMed Central

Steinhardt, Laura C.; Chinkhumba, Jobiba; Wolkon, Adam; Luka, Madalitso; Luhanga, Misheck; Sande, John; Oyugi, Jessica; Ali, Doreen; Mathanga, Don; Skarbinski, Jacek

2014-01-01

Background Malaria is endemic throughout Malawi, but little is known about quality of malaria case management at publicly-funded health facilities, which are the major source of care for febrile patients. Methods In April–May 2011, we conducted a nationwide, geographically-stratified health facility survey to assess the quality of outpatient malaria diagnosis and treatment. We enrolled patients presenting for care and conducted exit interviews and re-examinations, including reference blood smears. Moreover, we assessed health worker readiness (e.g., training, supervision) and health facility capacity (e.g. availability of diagnostics and antimalarials) to provide malaria case management. All analyses accounted for clustering and unequal selection probabilities. We also used survey weights to produce estimates of national caseloads. Results At the 107 facilities surveyed, most of the 136 health workers interviewed (83%) had received training on malaria case management. However, only 24% of facilities had functional microscopy, 15% lacked a thermometer, and 19% did not have the first-line artemisinin-based combination therapy (ACT), artemether-lumefantrine, in stock. Of 2,019 participating patients, 34% had clinical malaria (measured fever or self-reported history of fever plus a positive reference blood smear). Only 67% (95% confidence interval (CI): 59%, 76%) of patients with malaria were correctly prescribed an ACT, primarily due to missed malaria diagnosis. Among patients without clinical malaria, 31% (95% CI: 24%, 39%) were prescribed an ACT. By our estimates, 1.5 million of the 4.4 million malaria patients seen in public facilities annually did not receive correct treatment, and 2.7 million patients without clinical malaria were inappropriately given an ACT. Conclusions Malawi has a high burden of uncomplicated malaria but nearly one-third of all patients receive incorrect malaria treatment, including under- and over-treatment. To improve malaria case management, facilities must at minimum have basic case management tools, and health worker performance in diagnosing malaria must be improved. PMID:24586497

Quality of malaria case management in Malawi: results from a nationally representative health facility survey.

PubMed

Steinhardt, Laura C; Chinkhumba, Jobiba; Wolkon, Adam; Luka, Madalitso; Luhanga, Misheck; Sande, John; Oyugi, Jessica; Ali, Doreen; Mathanga, Don; Skarbinski, Jacek

2014-01-01

Malaria is endemic throughout Malawi, but little is known about quality of malaria case management at publicly-funded health facilities, which are the major source of care for febrile patients. In April-May 2011, we conducted a nationwide, geographically-stratified health facility survey to assess the quality of outpatient malaria diagnosis and treatment. We enrolled patients presenting for care and conducted exit interviews and re-examinations, including reference blood smears. Moreover, we assessed health worker readiness (e.g., training, supervision) and health facility capacity (e.g. availability of diagnostics and antimalarials) to provide malaria case management. All analyses accounted for clustering and unequal selection probabilities. We also used survey weights to produce estimates of national caseloads. At the 107 facilities surveyed, most of the 136 health workers interviewed (83%) had received training on malaria case management. However, only 24% of facilities had functional microscopy, 15% lacked a thermometer, and 19% did not have the first-line artemisinin-based combination therapy (ACT), artemether-lumefantrine, in stock. Of 2,019 participating patients, 34% had clinical malaria (measured fever or self-reported history of fever plus a positive reference blood smear). Only 67% (95% confidence interval (CI): 59%, 76%) of patients with malaria were correctly prescribed an ACT, primarily due to missed malaria diagnosis. Among patients without clinical malaria, 31% (95% CI: 24%, 39%) were prescribed an ACT. By our estimates, 1.5 million of the 4.4 million malaria patients seen in public facilities annually did not receive correct treatment, and 2.7 million patients without clinical malaria were inappropriately given an ACT. Malawi has a high burden of uncomplicated malaria but nearly one-third of all patients receive incorrect malaria treatment, including under- and over-treatment. To improve malaria case management, facilities must at minimum have basic case management tools, and health worker performance in diagnosing malaria must be improved.

Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial

PubMed Central

Yeboah-Antwi, Kojo; Pilingana, Portipher; Macleod, William B.; Semrau, Katherine; Siazeele, Kazungu; Kalesha, Penelope; Hamainza, Busiku; Seidenberg, Phil; Mazimba, Arthur; Sabin, Lora; Kamholz, Karen; Thea, Donald M.; Hamer, Davidson H.

2010-01-01

Background Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs). Methods and Findings Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14–0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19–8.94). There were two deaths in the intervention and one in the control arm. Conclusions The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia. Trial registration ClinicalTrials.gov NCT00513500 Please see later in the article for the Editors' Summary PMID:20877714

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

PubMed Central

Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

2010-01-01

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

Malarial Retinopathy in Bangladeshi Adults

PubMed Central

Sayeed, Abdullah Abu; Maude, Richard J.; Hasan, Mahtab Uddin; Mohammed, Noor; Hoque, M. Gofranul; Dondorp, Arjen M.; Faiz, M. Abul

2011-01-01

To establish if assessment of malarial retinopathy in adult malaria using ophthalmoscopy by non-ophthalmologists has clinical and prognostic significance, 210 Bangladeshi adults were assessed by both direct and indirect ophthalmoscopy; 20 of 20 healthy subjects and 20 of 20 patients with vivax malaria showed no retinal changes, whereas in patients with falciparum malaria, indirect ophthalmoscopy revealed malarial retinopathy (predominantly retinal hemorrhages) in 18 of 21 (86%) fatal, 31 of 75 (41%) cerebral, 16 of 64 (25%) non-cerebral but severe, and 1 of 31 (3%) uncomplicated cases. Direct ophthalmoscopy missed retinopathy in one of these cases and found fewer retinal hemorrhages (mean difference = 3.09; 95% confidence interval = 1.50–4.68; P < 0.0001). Severity of retinopathy increased with severity of disease (P for trend < 0.0001), and renal failure, acidosis, and moderate/severe retinopathy were independent predictors of mortality by both ophthalmoscopic techniques. Direct ophthalmoscopy by non-ophthalmologists is an important clinical tool to aid diagnosis and prognosis in adults with severe malaria, and indirect ophthalmoscopy by non-ophthalmologists, although more sensitive, provides minimal additional prognostic information. PMID:21212217

Factors associated with chloroquine-induced pruritus during malaria treatment in Mozambican university students.

PubMed

Gama, Helena; Ismael, Aldo; Sitoi, Felicidade; Matola, André; Barros, Henrique; Lunet, Nuno

2009-01-01

It has been suggested that reductions in chloroquine use may be followed by a resurgence of chloroquine-susceptible falciparum malaria, and chloroquine might once again be an effective treatment choice, which renews the importance of aspects related to its use and misuse. Therefore, we aimed to estimate the prevalence of chloroquine-induced pruritus and to identify risk factors for its occurrence in Mozambican University students. A cross-sectional study was conducted at a private University in Maputo. Students were approached in the classrooms to complete a self-administered questionnaire covering sociodemographic characteristics, number of previous malaria episodes, utilization of antimalarial drugs, and life prevalence of chloroquine induced pruritus. Among 795 respondents, 77.4% (601/777) reported at least one malaria episode and 73.2% (542/740) had used chloroquine before. The life-prevalence of chloroquine-induced pruritus was 30.1% (158/525). Pruritus tended to be more frequent when chloroquine was used for treatment compared with prophylaxis only (31.2% vs. 10.3%, p<0.05), and chloroquine use in the last malaria episode was less frequent in participants recalling chloroquine-induced pruritus (52.3% vs. 65.1%, p<0.05). About one third of the black population using chloroquine experienced chloroquine-induced pruritus at least once. This adverse reaction tended to be less frequent when lower doses of chloroquine were used and to influence future anti-malarial therapeutic choices.

Procalcitonin as a biomarker for severe Plasmodium falciparum disease: a critical appraisal of a semi-quantitative point-of-care test in a cohort of travellers with imported malaria.

PubMed

Hesselink, Dennis A; Burgerhart, Jan-Steven; Bosmans-Timmerarends, Hanna; Petit, Pieter; van Genderen, Perry J J

2009-09-01

Imported malaria occurs as a relatively rare event in developed countries. As a consequence, most clinicians have little experience in making clinical assessments of disease severity and decisions regarding the need for parenteral therapy or high-level monitoring. In this study, the diagnostic accuracy of procalcitonin (PCT) for severe Plasmodium falciparum disease was assessed in a cohort of 100 consecutive travellers with various species of imported malaria. In all patients, PCT was measured on admission with a semi-quantitative 'point-of-care' test. Patients with severe P. falciparum malaria had significantly higher median PCT levels on admission as compared with patients with uncomplicated P. falciparum disease. In addition, PCT levels in patients with non-falciparum malaria were also higher compared with patients with non-severe falciparum malaria but lower compared with severe P. falciparum malaria. At a cut-off point of 10 ng/mL, PCT had a sensitivity of 0,67 and a specificity of 0,94 for severe falciparum disease. However, at lower cut-off points the specificity and positive predictive value were rather poor although the sensitivity and negative predictive value remained high. Potential drawbacks in the interpretation of elevated PCT levels on admission may be caused by infections with non-falciparum species and by concomitant bacterial infections. Semi-quantitative determination of PCT on admission is of limited use in the initial clinical assessment of disease severity in travellers with imported malaria, especially in settings with limited experience with the treatment of malaria.

Micronutrient Deficiencies and Plasmodium vivax Malaria among Children in the Brazilian Amazon

PubMed Central

Benzecry, Silvana Gomes; Alexandre, Márcia Almeida; Vítor-Silva, Sheila; Salinas, Jorge Luis; de Melo, Gisely Cardoso; Marinho, Helyde Albuquerque; Paes, Ângela Tavares; de Siqueira, André Machado; Monteiro, Wuelton Marcelo; Lacerda, Marcus Vinícius Guimarães; Leite, Heitor Pons

2016-01-01

Background There is a growing body of evidence linking micronutrient deficiencies and malaria incidence arising mostly from P. falciparum endemic areas. We assessed the impact of micronutrient deficiencies on malaria incidence and vice versa in the Brazilian state of Amazonas. Methodology/Principal Findings We evaluated children <10 years old living in rural communities in the state of Amazonas, Brazil, from May 2010 to May 2011. All children were assessed for sociodemographic, anthropometric and laboratory parameters, including vitamin A, beta-carotene, zinc and iron serum levels at the beginning of the study (May 2010) and one year later (May 2011). Children were followed in between using passive surveillance for detection of symptomatic malaria. Those living in the study area at the completion of the observation period were reassessed for micronutrient levels. Univariate Cox-proportional Hazards models were used to assess whether micronutrient deficiencies had an impact on time to first P. vivax malaria episode. We included 95 children median age 4.8 years (interquartile range [IQR]: 2.3–6.6), mostly males (60.0%) and with high maternal illiteracy (72.6%). Vitamin A deficiencies were found in 36% of children, beta-carotene deficiency in 63%, zinc deficiency in 61% and iron deficiency in 51%. Most children (80%) had at least one intestinal parasite. During follow-up, 16 cases of vivax malaria were diagnosed amongst 13 individuals. Micronutrient deficiencies were not associated with increased malaria incidence: vitamin A deficiency [Hazard ratio (HR): 1.51; P-value: 0.45]; beta-carotene [HR: 0.47; P-value: 0.19]; zinc [HR: 1.41; P-value: 0.57] and iron [HR: 2.31; P-value: 0.16]). Upon reevaluation, children with al least one episode of malaria did not present significant changes in micronutrient levels. Conclusion Micronutrient serum levels were not associated with a higher malaria incidence nor the malaria episode influenced micronutrient levels. Future studies targeting larger populations to assess micronutrients levels in P. vivax endemic areas are warranted in order to validate these results. PMID:26963624

Glucose-6-phosphate dehydrogenase status and risk of hemolysis in Plasmodium falciparum-infected African children receiving single-dose primaquine.

PubMed

Eziefula, Alice C; Pett, Helmi; Grignard, Lynn; Opus, Salome; Kiggundu, Moses; Kamya, Moses R; Yeung, Shunmay; Staedke, Sarah G; Bousema, Teun; Drakeley, Chris

2014-08-01

Glucose-6-phosphate dehydrogenase (G6PD) enzyme function and genotype were determined in Ugandan children with uncomplicated falciparum malaria enrolled in a primaquine trial after exclusion of severe G6PD deficiency by fluorescent spot test. G6PD A- heterozygotes and hemizygotes/homozygotes experienced dose-dependent lower hemoglobin concentrations after treatment. No severe anemia was observed. Copyright © 2014, Eziefula et al.

Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana.

PubMed

Abuaku, Benjamin; Duah, Nancy; Quaye, Lydia; Quashie, Neils; Malm, Keziah; Bart-Plange, Constance; Koram, Kwadwo

2016-01-05

Case management based on prompt diagnosis and adequate treatment using artemisinin-based combination therapy (ACT) remains the main focus of malaria control in Ghana. As part of routine surveillance on the therapeutic efficacy of ACT in Ghana, the efficacy of amodiaquine-artesunate (AS-AQ) and artemether-lumefantrine (AL) were studied in six sentinel sites representing the forest and savannah zones of the country. Three sites representing the two ecological zones studied AS-AQ whilst the other three sites studied AL. In each site, the study was a one-arm prospective evaluation of the clinical, parasitological, and haematological responses to directly observed therapy for uncomplicated malaria with either AS-AQ or AL among children aged 6 months and 9 years. The WHO 2009 protocol for monitoring anti-malarial drug efficacy was used for the study between July 2013 and March 2014. Per-protocol analyses on day 28 showed an overall PCR-corrected cure rate of 100% for AS-AQ and 97.6% (95% CI 93.1, 99.5) for AL: 97.2% (95% CI 92.0, 99.4) in the forest zone and 100% in the savannah zone. Kaplan-Meier survival analysis showed similar outcomes. Prevalence of fever decreased by about 75% after the first day of treatment with each ACT in the two ecological zones. No child studied was parasitaemic on day 3, and gametocytaemia was generally maintained at low levels (<5%). Post-treatment mean haemoglobin concentrations significantly increased in the two ecological zones. Therapeutic efficacy of AS-AQ and AL remains over 90% in the forest and savannah zones of Ghana. Additionally, post-treatment parasitaemia on day 3 is rare suggesting that artemisinin is still efficacious in Ghana.

A Phase 3, Double-Blind, Randomized Study of Arterolane Maleate–Piperaquine Phosphate vs Artemether–Lumefantrine for Falciparum Malaria in Adolescent and Adult Patients in Asia and Africa

PubMed Central

Toure, Offianan Andre; Valecha, Neena; Tshefu, Antoinette K.; Thompson, Ricardo; Krudsood, Srivicha; Gaye, Oumar; Rao, Bappanaidu Hoigegudde Krishnamurthy; Sagara, Issaka; Bose, Tarit Kumar; Mohanty, Sanjib; Rao, Ballamudi Srinivas; Anvikar, Anupkumar R.; Mwapasa, Victor; Noedl, Harald; Arora, Sudershan; Roy, Arjun; Iyer, Sunil S.; Sharma, Pradeep; Saha, Nilanjan; Jalali, Rajinder K.

2016-01-01

Background. Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicated Plasmodium falciparum malaria. Methods. In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12–65 years with P. falciparum monoinfection received either AM–PQP (714 patients) once daily or artemether–lumefantrine (A–L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. Results. Of the 714 patients in the AM–PQP group, 638 (89.4%) completed the study; of the 358 patients in the A–L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR–corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. Conclusions. AM–PQP showed comparable efficacy and safety to A–L in the treatment of uncomplicated P. falciparum malaria in adolescent and adult patients. AM–PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. Clinical Trials Registration. India. CTRI/2009/091/000101. PMID:26908796

Malaria research and its influence on anti-malarial drug policy in Malawi: a case study.

PubMed

Mwendera, Chikondi; de Jager, Christiaan; Longwe, Herbert; Phiri, Kamija; Hongoro, Charles; Mutero, Clifford M

2016-06-01

In 1993, Malawi changed its first-line anti-malarial treatment for uncomplicated malaria from chloroquine to sulfadoxine-pyrimethamine (SP), and in 2007, it changed from SP to lumefantrine-artemether. The change in 1993 raised concerns about whether it had occurred timely and whether it had potentially led to early development of Plasmodium falciparum resistance to SP. This case study examined evidence from Malawi in order to assess if the policy changes were justifiable and supported by evidence. A systematic review of documents and published evidence between 1984 and 1993, when chloroquine was the first-line drug, and 1994 and 2007, when SP was the first-line drug, was conducted herein. The review was accompanied with key informant interviews. A total of 1287 publications related to malaria drug policy changes in sub-Saharan Africa were identified. Using the inclusion criteria, four articles from 1984 to 1993 and eight articles from 1994 to 2007 were reviewed. Between 1984 and 1993, three studies reported on chloroquine poor efficacy prompting policy change according to WHO's recommendation. From 1994 to 2007, four studies conducted in the early years of policy change reported a high SP efficacy of above 80%, retaining it as a first-line drug. Unpublished sentinel site studies between 2005 and 2007 showed a reduced efficacy of SP, influencing policy change to lumefantrine-artemether. The views of key informants indicate that the switch from chloroquine to SP was justified based on local evidence despite unavailability of WHO's policy recommendations, while the switch to lumefantrine-artemether was uncomplicated as the country was following the recommendations from WHO. Ample evidence from Malawi influenced and justified the policy changes. Therefore, locally generated evidence is vital for decision making during policy change.

Impact of Pregnancy-Associated Malaria on Infant Malaria Infection in Southern Benin

PubMed Central

Borgella, Sophie; Fievet, Nadine; Huynh, Bich-Tram; Ibitokou, Samad; Hounguevou, Gbetognon; Affedjou, Jacqueline; Sagbo, Jean-Claude; Houngbegnon, Parfait; Guezo-Mévo, Blaise; Massougbodji, Achille; Luty, Adrian J. F.

2013-01-01

Background Infants of mothers with placental Plasmodium falciparum infections at delivery are themselves more susceptible to malaria attacks or to infection in early life. Methodology/ Principal Findings To assess the impact of either the timing or the number of pregnancy-associated malaria (PAM) infections on the incidence of parasitemia or malaria attacks in infancy, we followed 218 mothers through pregnancy (monthly visits) up to delivery and their infants from birth to 12 months of age (fortnightly visits), collecting detailed clinical and parasitological data. After adjustment on location, mother’s age, birth season, bed net use, and placental malaria, infants born to a mother with PAM during the third trimester of pregnancy had a significantly increased risk of infection (OR [95% CI]: 4.2 [1.6; 10.5], p = 0.003) or of malaria attack (4.6 [1.7; 12.5], p = 0.003). PAM during the first and second trimesters had no such impact. Similarly significant results were found for the effect of the overall number of PAM episodes on the time to first parasitemia and first malaria attack (HR [95% CI]: 2.95 [1.58; 5.50], p = 0.001 and 3.19 [1.59; 6.38], p = 0.001) respectively. Conclusions/ Significance This study highlights the importance of protecting newborns by preventing repeated episodes of PAM in their mothers. PMID:24236190

High risk of Plasmodium vivax malaria following splenectomy in Papua, Indonesia.

PubMed

Kho, Steven; Andries, Benediktus; Poespoprodjo, Jeanne R; Commons, Robert J; Shanti, Putu A I; Kenangalem, Enny; Douglas, Nicholas M; Simpson, Julie A; Sugiarto, Paulus; Anstey, Nicholas M; Price, Ric N

2018-05-16

Splenectomy increase the risk of severe and fatal infections, however the risk of Plasmodium vivax malaria is unknown. We quantified the Plasmodium species-specific risks of malaria and other outcomes following splenectomy in patients attending a hospital in Papua, Indonesia. Records of all patients attending Mitra-Masyarakat Hospital 2004-2013 were reviewed, identifying those who underwent splenectomy. Subsequent risks of specific clinical outcomes within 12 months for splenectomized patients were compared to non-splenectomized patients from their first recorded hospital admission. In addition, patients splenectomized for trauma between 2015-2016 were followed prospectively for 14 months. Of the 10,774 non-pregnant patients aged 12-60 years hospitalized during 2004-2013, 67 underwent splenectomy. Compared to non-splenectomized inpatients, patients undergoing splenectomy had a 5-fold higher rate of malaria presentation within 12 months (Adjusted Hazard Ratio (AHR)=5.0 [95%CI:3.4-7.3], p<0.001). The rate was greater for P. vivax (AHR=7.8 [95%CI:5.0-12.3], p<0.001) compared to P. falciparum (AHR=3.0 [95%CI:1.7-5.4], p<0.001). Splenectomized patients had greater risk of being hospitalized for any cause (AHR=1.8 [95%CI:1.0-3.0], p=0.037) and, diarrheal illness (AHR=3.5 [95%CI:1.3-9.6], p=0.016). In the prospective cohort, 8 of 11 splenectomized patients had 18 episodes of malaria over 14 months, 12 episodes of P. vivax in 8 patients and 6 episodes of P. falciparum in 6 patients. Splenectomy is associated with a high risk of malaria, greater for P. vivax than P. falciparum. Eradication of P. vivax hypnozoites using primaquine (radical cure) and subsequent malaria prophylaxis is warranted in patients following splenectomy in malaria-endemic areas, particularly in the early post-operative period.

Identification of immune signatures predictive of clinical protection from malaria

PubMed Central

2017-01-01

Antibodies are thought to play an essential role in naturally acquired immunity to malaria. Prospective cohort studies have frequently shown how continuous exposure to the malaria parasite Plasmodium falciparum cause an accumulation of specific responses against various antigens that correlate with a decreased risk of clinical malaria episodes. However, small effect sizes and the often polymorphic nature of immunogenic parasite proteins make the robust identification of the true targets of protective immunity ambiguous. Furthermore, the degree of individual-level protection conferred by elevated responses to these antigens has not yet been explored. Here we applied a machine learning approach to identify immune signatures predictive of individual-level protection against clinical disease. We find that commonly assumed immune correlates are poor predictors of clinical protection in children. On the other hand, antibody profiles predictive of an individual’s malaria protective status can be found in data comprising responses to a large set of diverse parasite proteins. We show that this pattern emerges only after years of continuous exposure to the malaria parasite, whereas susceptibility to clinical episodes in young hosts (< 10 years) cannot be ascertained by measured antibody responses alone. PMID:29065113

Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon.

PubMed

Lell, Bertrand; Mordmüller, Benjamin; Dejon Agobe, Jean-Claude; Honkpehedji, Josiane; Zinsou, Jeannot; Mengue, Juliana Boex; Loembe, Marguerite Massinga; Adegnika, Ayola Akim; Held, Jana; Lalremruata, Albert; Nguyen, The Trong; Esen, Meral; Kc, Natasha; Ruben, Adam J; Chakravarty, Sumana; Lee Sim, B Kim; Billingsley, Peter F; James, Eric R; Richie, Thomas L; Hoffman, Stephen L; Kremsner, Peter G

2018-02-01

Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria-exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers ( P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms ( P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria.

Knowledge and Adherence to the National Guidelines for Malaria Diagnosis in Pregnancy among Health-Care Providers and Drug-Outlet Dispensers in Rural Western Kenya.

PubMed

Riley, Christina; Dellicour, Stephanie; Ouma, Peter; Kioko, Urbanus; Omar, Ahmeddin; Kariuki, Simon; Ng'ang'a, Zipporah; Desai, Meghna; Buff, Ann M; Gutman, Julie R

2018-05-01

Prompt diagnosis and effective treatment of acute malaria in pregnancy (MiP) is important for the mother and fetus; data on health-care provider adherence to diagnostic guidelines in pregnancy are limited. From September to November 2013, a cross-sectional survey was conducted in 51 health facilities and 39 drug outlets in Western Kenya. Provider knowledge of national diagnostic guidelines for uncomplicated MiP were assessed using standardized questionnaires. The use of parasitologic testing was assessed in health facilities via exit interviews with febrile women of childbearing age and in drug outlets via simulated-client scenarios, posing as pregnant women or their spouses. Overall, 93% of providers tested for malaria or accurately described signs and symptoms consistent with clinical malaria. Malaria was parasitologically confirmed in 77% of all patients presenting with febrile illness at health facilities and 5% of simulated clients at drug outlets. Parasitological testing was available in 80% of health facilities; 92% of patients evaluated at these facilities were tested. Only 23% of drug outlets had malaria rapid diagnostic tests (RDTs); at these outlets, RDTs were offered in 17% of client simulations. No differences were observed in testing rates by pregnancy trimester. The study highlights gaps among health providers in diagnostic knowledge and practice related to MiP, and the lack of malaria diagnostic capacity, particularly in drug outlets. The most important factor associated with malaria testing of pregnant women was the availability of diagnostics at the point of service. Interventions that increase the availability of malaria diagnostic services might improve malaria case management in pregnant women.

Gender roles and perceptions of malaria risk in agricultural communities of Mwea Division in Central Kenya.

PubMed

Woldu, Dawit Okubatsion; Haile, Zelalem Teka

2015-01-01

We examined gender differences in the perception of high malaria risk in women and factors associated with a high number of malaria episodes in the Mwea Division of Central Kenya. Ethnographic and successive free listing interviews (an open-ended data collection technique used to show the relation of items in a given domain) with 53 key informants and structured interviews conducted from June to October 2010 with 250 respondents who represented the socioeconomic and geographical diversity of the area were analyzed. Qualitative text analysis and inferential statistics were employed. While a greater proportion of men (51.6%) attributed women's high malaria risk to their "biological weakness," most women believed that their high malaria risk was related to their role in the agricultural fields (43.6%) and to their household responsibilities (23.1%). Compared to men, women were more likely to work in wet aspects of agricultural activities (χ(2) (2, N = 153) = 13.47, p < .01). Women were nearly twice as likely as men to report high episodes of malaria (adjusted odds ratio: 2.54; 95% confidence interval: 1.05-6.15). Culturally prescribed gender roles in agricultural communities in Mwea may play an important role in explaining disparity in reported malaria incidence. While identification of ecological and economic determinants of malaria is important, gender-based research can make a significant contribution to the development of effective and sustainable malaria reduction strategies.

Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination.

PubMed

Ouji, Manel; Augereau, Jean-Michel; Paloque, Lucie; Benoit-Vical, Françoise

2018-01-01

The use of artemisinin-based combination therapies (ACTs), which combine an artemisinin derivative with a partner drug, in the treatment of uncomplicated malaria has largely been responsible for the significant reduction in malaria-related mortality in tropical and subtropical regions. ACTs have also played a significant role in the 18% decline in the incidence of malaria cases from 2010 to 2016. However, this progress is seriously threatened by the reduced clinical efficacy of artemisinins, which is characterised by delayed parasitic clearance and a high rate of recrudescence, as reported in 2008 in Western Cambodia. Resistance to artemisinins has already spread to several countries in Southeast Asia. Furthermore, resistance to partner drugs has been shown in some instances to be facilitated by pre-existing decreased susceptibility to the artemisinin component of the ACT. A major concern is not only the spread of these multidrug-resistant parasites to the rest of Asia but also their possible appearance in Sub-Saharan Africa, the continent most affected by malaria, as has been the case in the past with parasite resistance to other antimalarial treatments. It is therefore essential to understand the acquisition of resistance to artemisinins by Plasmodium falciparum to adapt malaria treatment policies and to propose new therapeutic solutions. © M. Ouji et al., published by EDP Sciences, 2018.

Paradoxical associations between soil-transmitted helminths and Plasmodium falciparum infection.

PubMed

Fernández-Niño, Julián A; Idrovo, Alvaro J; Cucunubá, Zulma M; Reyes-Harker, Patricia; Guerra, Ángela P; Moncada, Ligia I; López, Myriam C; Barrera, Sandra M; Cortés, Liliana J; Olivera, Mario; Nicholls, Rubén S

2012-11-01

Evidence on the comorbidity between soil-transmitted helminth infections and malaria is scarce and divergent. This study explored the interactions between soil-transmitted helminth infections and uncomplicated falciparum malaria in an endemic area of Colombia. A paired case-control study matched by sex, age and location in Tierralta, Cordoba, was done between January and September 2010. The incident cases were 68 patients with falciparum malaria and 178 asymptomatic controls. A questionnaire was used to gather information on sociodemographic variables. Additionally physical examinations were carried out, stool samples were analysed for intestinal parasites and blood samples for Ig E concentrations. We found associations between infection with hookworm (OR: 4.21; 95% CI: 1.68-11.31) and Ascaris lumbricoides (OR 0.43; 95% CI: 0.18-1.04) and the occurrence of falciparum malaria. The effects of soil-transmitted helminths on the occurrence of malaria were found to be paradoxical. While hookworm is a risk factor, A. lumbricoides has a protective effect. The findings suggest that, in addition to the comorbidity, the presence of common determinants of soil-transmitted helminth infections and malaria could also exist. While the biological mechanisms involved are not clear, public health policies aimed at the control of their common social and environmental determinants are suggested. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

PubMed Central

Mbabazi, Phoebe; Hopkins, Heidi; Osilo, Emmanuel; Kalungu, Michael; Byakika-Kibwika, Pauline; Kamya, Moses R.

2015-01-01

Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high-transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria. PMID:25624399

Spatio-Temporal Dynamics of Asymptomatic Malaria: Bridging the Gap Between Annual Malaria Resurgences in a Sahelian Environment.

PubMed

Coulibaly, Drissa; Travassos, Mark A; Tolo, Youssouf; Laurens, Matthew B; Kone, Abdoulaye K; Traore, Karim; Sissoko, Mody; Niangaly, Amadou; Diarra, Issa; Daou, Modibo; Guindo, Boureima; Rebaudet, Stanislas; Kouriba, Bourema; Dessay, Nadine; Piarroux, Renaud; Plowe, Christopher V; Doumbo, Ogobara K; Thera, Mahamadou A; Gaudart, Jean

2017-12-01

In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009-2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.

Impact of malaria interventions on child mortality in endemic African settings: comparison and alignment between LiST and Spectrum-Malaria model.

PubMed

Korenromp, Eline; Hamilton, Matthew; Sanders, Rachel; Mahiané, Guy; Briët, Olivier J T; Smith, Thomas; Winfrey, William; Walker, Neff; Stover, John

2017-11-07

In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030. Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST. Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival.

Use of artemether-lumefantrine to treat malaria during pregnancy: what do we know and need to know?

PubMed

Mutabingwa, Theonest K; Adam, Ishag

2013-02-01

Artemether-lumefantrine is a fixed-dose combination containing 20 mg artemether/120 mg lumefantrine per tablet, used for treating uncomplicated malaria in patients weighing ≥5 kg. It is the first artemisinin-based combination registered in some European countries and in the USA. It is marketed in Europe as Riamet(®) (Novartis, Basel, Switzerland) and in malaria-endemic countries as Coartem(®) (Novartis). Safety concerns prevent early pregnancy usage, while limited postmarketing surveillance has delayed safety assessment and policy development. Large clinical studies, postmarketing surveillance and pharmacovigillance ongoing in some countries may soon bridge safety issues. Fatty diet requirements for optimal absorption, pregnancy-induced changes in pharmacokinetics, pregnancy-related anorexia and food taboos, and emerging reduced parasite sensitivity to artemisinin, challenges optimal artemether-lumefantrine dosing and efficacy during pregnancy. This evaluation addresses drug usage, safety concerns following early exposure, implications for changed pharmacokinetics and reduced parasite susceptibility. Clinical-use updates and strategies to address some knowledge gaps including key operational research are discussed.

Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria

PubMed Central

Woodberry, Tonia; Kienzle, Vivian; McPhun, Virginia; Minigo, Gabriela; Lampah, Daniel A.; Kenangalem, Enny; Engwerda, Christian; López, J. Alejandro; Anstey, Nicholas M.

2013-01-01

Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC’s immunotherapeutic potential. PMID:23835848

Malaria in rural Burkina Faso: local illness concepts, patterns of traditional treatment and influence on health-seeking behaviour.

PubMed

Beiersmann, Claudia; Sanou, Aboubakary; Wladarsch, Evelyn; De Allegri, Manuela; Kouyaté, Bocar; Müller, Olaf

2007-08-08

The literature on health care seeking behaviour in sub-Saharan Africa for children suffering from malaria is quite extensive. This literature, however, is predominantly quantitative and, inevitably, fails to explore how the local concepts of illness may affect people's choices. Understanding local concepts of illness and their influence on health care-seeking behaviour can complement existing knowledge and lead to the development of more effective malaria control interventions. In a rural area of Burkina Faso, four local concepts of illness resembling the biomedical picture of malaria were described according to symptoms, aetiology, and treatment. Data were collected through eight focus group discussions, 17 semi-structured interviews with key informants, and through the analysis of 100 verbal autopsy questionnaires of children under-five diagnosed with malaria. Sumaya, dusukun yelema, kono, and djoliban were identified as the four main local illness concepts resembling respectively uncomplicated malaria, respiratory distress syndrome, cerebral malaria, and severe anaemia. The local disease categorization was found to affect both treatment and provider choice. While sumaya is usually treated by a mix of traditional and modern methods, dusukun yelema and kono are preferably treated by traditional healers, and djoliban is preferably treated in modern health facilities. Besides the conceptualization of illness, poverty was found to be another important influencing factor of health care-seeking behaviour. The findings complement previous evidence on health care-seeking behaviour, by showing how local concepts of illness strongly influence treatment and choice of provider. Local concepts of illness need to be considered when developing specific malaria control programmes.

N-Acetylcysteine as adjunctive treatment in severe malaria: A randomized double blinded placebo controlled clinical trial

PubMed Central

Charunwatthana, Prakaykaew; Faiz, M. Abul; Ruangveerayut, Ronnatrai; Maude, Richard; Rahman, M. Ridwanur; Roberts, L. Jackson; Moore, Kevin; Yunus, Emran Bin; Hoque, M. Gofranul; Hasan, Mahatab Uddin; Lee, Sue J.; Pukrittayakamee, Sasithon; Newton, Paul N.; White, Nicholas J.; Day, Nicholas P.J.; Dondorp, Arjen M.

2009-01-01

Objective Markers of oxidative stress are reported to be increased in severe malaria. It has been suggested that the antioxidant N-acetylcysteine (NAC) may be beneficial in treatment. We studied the efficacy and safety of parenteral N-acetylcysteine as an adjunct to artesunate treatment of severe falciparum malaria. Design A randomized double-blind placebo controlled trial on the use of high dose intravenous NAC as adjunctive treatment to artesunate. Setting A provincial hospital in Western Thailand and a tertiary referral hospital in Chittagong, Bangladesh. Patients One hundred and eight adult patients with severe falciparum malaria. Interventions Patients were randomized to receive N-acetylcysteine or placebo as adjunctive treatment to intravenous artesunate. Measurements and main results A total of 56 patients were treated with NAC and 52 received placebo. NAC had no significant effect on mortality, lactate clearance times (p=0.74) or coma recovery times (p=0.46). Parasite clearance time was increased from 30h (range 6h to 144h) to 36h (range 6h to 120h) (p=0.03), but this could be explained by differences in admission parasitemia. Urinary F2-isoprostane metabolites, measured as a marker of oxidative stress, were increased in severe malaria compared to patients with uncomplicated malaria and healthy volunteers. Admission red cell rigidity correlated with mortality, but did not improve with NAC. Conclusion Systemic oxidative stress is increased in severe malaria. Treatment with N-acetylcysteine had no effect on outcome in patients with severe falciparum malaria in this setting. PMID:19114891

Recurrent Fever in Children

PubMed Central

Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

2016-01-01

Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time. PMID:27023528

Recurrent Fever in Children.

PubMed

Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

2016-03-25

Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.

No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate–Mefloquine in Northwestern Brazil

PubMed Central

Ladeia-Andrade, Simone; de Melo, Gladson Naber P.; de Souza-Lima, Rita de Cássia; Salla, Laís C.; Bastos, Melissa S.; Rodrigues, Priscila T.; Luz, Francisco das Chagas O.; Ferreira, Marcelo U.

2016-01-01

We evaluated the clinical efficacy of artesunate–mefloquine (ASMQ) fixed-dose combination to treat uncomplicated malaria in Juruá Valley, the main Plasmodium falciparum transmission hotspot in Brazil. Between November 2010 and February 2013, we enrolled 162 patients aged 4–73 years, with fever or a history of fever, and a single-species P. falciparum infection confirmed by microscopy and polymerase chain reaction (PCR). All 154 patients who completed the 42-day follow-up presented an adequate clinical and parasitologic response. ASMQ was well tolerated and no adverse event caused treatment interruption. Gametocytes were detected in 46.3% patients; 35.2% had gametocytes at enrollment, whereas others developed patent gametocytemia 1–14 days after starting ASMQ. By day 3 of treatment, all subjects had cleared asexual parasitemia, but parasite DNA remained PCR detectable in 37.6% of them. Day-3 PCR positivity was associated with prolonged gametocyte carriage. We found no molecular evidence of resistance to either MQ (pfmdr1 gene amplification) or AS (mutations in selected kelch13 gene domains known to be associated with AS resistance) in the local P. falciparum population. These results strongly support the use of ASMQ as a first-line regimen to treat uncomplicated P. falciparum malaria in northwestern Brazil, but underscore the need for gametocytocidal drugs to reduce the transmission potential of ASMQ-treated patients (ClinicalTrials.gov number NCT01144702). PMID:27068396

Clinical characteristics and disposition kinetics of the hepatomegaly associated with acute, uncomplicated, Plasmodium falciparum malaria in children.

PubMed

Sowunmi, A; Adedeji, A A; Sowunmi, C O; Falade, C O; Falade, A G; Ohaeri, B; Happi, T C; Oduola, A M

2001-01-01

The clinical characteristics and the kinetics of the disposition of the hepatomegaly associated with acute, uncomplicated Plasmodium falciparum malaria were investigated in 162 children in an endemic area of Nigeria. Hepatomegaly was significantly more common in the younger than in the older children. Complete resolution occurred in 48% following antimalarial chemotherapy. In the children in whom hepatomegaly did not resolve, a reduction in liver size of < 17% by the time parasitaemia was cleared (usually on day 3) was associated with non-resolution of hepatomegaly by days 7 or 14 of follow-up. An increase in liver size to at least 125% of the baseline value by day 4 or 5 was associated with a lack of therapeutic response, providing the child involved was aged < 5 years. In the children who had complete clearance of parasitaemia and resolution of hepatomegaly, there was no significant relationship between the parasitaemia-derived conventional indices of therapeutic response [i.e. time to clearance of 50% (PC50) or 90% (PC90) of the parasitaemia, and the parasite-clearance time (PCT)] and the corresponding parameters derived from measurement of liver size [i.e. time for resolution of 50% (HR50) or 90% (HR90) of the hepatomegaly and the hepatomegaly-resolution time (HRT)] in the same patients. However, as the HR50:PC50, HR90:PC90 and HRT:PCT ratios were similar (range = 1.6-2.1), the liver parameters may have therapeutic application. In the children with drug-sensitive P. falciparum infections and in whom hepatomegaly completely resolved, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUChp) increased in proportion to the liver size below the costal margin (P = 0.02, from analysis of variance), but there was no significant difference in the half-lives of hepatomegaly (t1/2hp) or in the ratios of liver size to AUChp, indicating that the kinetics of the resolution of hepatomegaly were linear in the range examined. Comparison of the kinetic indices of hepatomegaly and parasitaemia showed that, although the half-lives of parasitaemia and hepatomegaly and the corresponding clearance values were similar, there was no correlation between these parameters among those in whom hepatomegaly completely resolved and parasitaemia completely cleared. These results indicate that routine clinical measurement of the liver size in children with hepatomegaly during acute, uncomplicated, P. falciparum malaria may have some use in evaluating and monitoring the therapeutic responses of infections. The resolution of hepatomegaly, a reflection of pathological changes, lags behind clearance of parasitaemia in children with P. falciparum malaria, and supports the use of the liver 'rate' as a malariometric index for assessing the intensity of transmission in endemic areas.

A cost-effectiveness analysis of provider and community interventions to improve the treatment of uncomplicated malaria in Nigeria: study protocol for a randomized controlled trial.

PubMed

Wiseman, Virginia; Ogochukwu, Ezeoke; Emmanuel, Nwala; Lindsay J, Mangham; Bonnie, Cundill; Jane, Enemuo; Eloka, Uchegbu; Benjamin, Uzochukwu; Obinna, Onwujekwe

2012-06-09

There is mounting evidence of poor adherence by health service personnel to clinical guidelines for malaria following a symptomatic diagnosis. In response to this, the World Health Organization (WHO) recommends that in all settings clinical suspicion of malaria should be confirmed by parasitological diagnosis using microscopy or Rapid Diagnostic Test (RDT). The Government of Nigeria plans to introduce RDTs in public health facilities over the coming year. In this context, we will evaluate the effectiveness and cost-effectiveness of two interventions designed to support the roll-out of RDTs and improve the rational use of ACTs. It is feared that without supporting interventions, non-adherence will remain a serious impediment to implementing malaria treatment guidelines. A three-arm stratified cluster randomized trial is used to compare the effectiveness and cost-effectiveness of: (1) provider malaria training intervention versus expected standard practice in malaria diagnosis and treatment; (2) provider malaria training intervention plus school-based intervention versus expected standard practice; and (3) the combined provider plus school-based intervention versus provider intervention alone. RDTs will be introduced in all arms of the trial. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit primary health centers, pharmacies, and patent medicine dealers. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider and community knowledge. Costs will be estimated from both a societal and provider perspective using standard economic evaluation methodologies. Clinicaltrials.gov NCT01350752.

Demographic, Socioeconomic, and Geographic Factors Leading to Severe Malaria and Delayed Care Seeking in Ugandan Children: A Case-Control Study.

PubMed

Mpimbaza, Arthur; Ndeezi, Grace; Katahoire, Anne; Rosenthal, Philip J; Karamagi, Charles

2017-11-01

We studied associations between delayed care seeking, demographic, socioeconomic, and geographic factors and likelihood of severe malaria in Ugandan children. The study was based at Jinja Hospital, Uganda. We enrolled 325 severe malaria cases and 325 uncomplicated malaria controls matched by age and residence. Patient details, an itinerary of events in response to illness, household information, and location of participants' residences were captured. Conditional logistic regression was used to determine risk factors for severe malaria and delayed care seeking. Delayed care seeking (≥ 24 hours after fever onset; odds ratio [OR] 5.50; 95% confidence interval [CI] 2.70, 11.1), seeking care at a drug shop as the initial response to illness (OR 3.62; 95% CI 1.86, 7.03), and increasing distance from place of residence to the nearest health center (OR 1.45; 95% CI 1.17, 1.79) were independent risk factors for severe malaria. On subgroup analysis, delayed care seeking was a significant risk factor in children with severe malaria attributable to severe anemia (OR 15.6; 95% CI 3.02, 80.6), but not unconsciousness (OR 1.13; 95% CI 0.30, 4.28). Seeking care at a drug shop (OR 2.84; 95% CI 1.12, 7.21) and increasing distance to the nearest health center (OR 1.18; 95% CI 1.01, 1.37) were independent risk factors for delayed care seeking. Delayed care seeking and seeking care at a drug shop were risk factors for severe malaria. Seeking care at a drug shop was also a predictor of delayed care seeking. The role of drug shops in contributing to delayed care and risk of severe malaria requires further study.

Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria

PubMed Central

Machado, Patrícia; Manco, Licínio; Gomes, Cláudia; Mendes, Cristina; Fernandes, Natércia; Salomé, Graça; Sitoe, Luis; Chibute, Sérgio; Langa, José; Ribeiro, Letícia; Miranda, Juliana; Cano, Jorge; Pinto, João; Amorim, António; do Rosário, Virgílio E.; Arez, Ana Paula

2012-01-01

Background Pyruvate kinase (PK) deficiency, causing hemolytic anemia, has been associated to malaria protection and its prevalence in sub-Saharan Africa is not known so far. This work shows the results of a study undertaken to determine PK deficiency occurrence in some sub-Saharan African countries, as well as finding a prevalent PK variant underlying this deficiency. Materials and Methods Blood samples of individuals from four malaria endemic countries (Mozambique, Angola, Equatorial Guinea and Sao Tome and Principe) were analyzed in order to determine PK deficiency occurrence and detect any possible high frequent PK variant mutation. The association between this mutation and malaria was ascertained through association studies involving sample groups from individuals showing different malaria infection and outcome status. Results The percentage of individuals showing a reduced PK activity in Maputo was 4.1% and the missense mutation G829A (Glu277Lys) in the PKLR gene (only identified in three individuals worldwide to date) was identified in a high frequency. Heterozygous carrier frequency was between 6.7% and 2.6%. A significant association was not detected between either PK reduced activity or allele 829A frequency and malaria infection and outcome, although the variant was more frequent among individuals with uncomplicated malaria. Conclusions This was the first study on the occurrence of PK deficiency in several areas of Africa. A common PKLR mutation G829A (Glu277Lys) was identified. A global geographical co-distribution between malaria and high frequency of PK deficiency seems to occur suggesting that malaria may be a selective force raising the frequency of this 277Lys variant. PMID:23082140

Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review.

PubMed

Visser, Benjamin J; Wieten, Rosanne W; Kroon, Daniëlle; Nagel, Ingeborg M; Bélard, Sabine; van Vugt, Michèle; Grobusch, Martin P

2014-11-26

Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike. A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014. The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi. ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority. CRD42014009103.

Helminth Infection and Eosinophilia and the Risk of Plasmodium falciparum Malaria in 1- to 6-Year-Old Children in a Malaria Endemic Area

PubMed Central

Bejon, Philip; Mwangi, Tabitha W.; Lowe, Brett; Peshu, Norbert; Hill, Adrian V. S.; Marsh, Kevin

2008-01-01

Background Helminth infection is common in malaria endemic areas, and an interaction between the two would be of considerable public health importance. Animal models suggest that helminth infections may increase susceptibility to malaria, but epidemiological data has been limited and contradictory. Methodology/Principal Findings In a vaccine trial, we studied 387 one- to six-year-old children for the effect of helminth infections on febrile Plasmodium falciparum malaria episodes. Gastrointestinal helminth infection and eosinophilia were prevalent (25% and 50% respectively), but did not influence susceptibility to malaria. Hazard ratios were 1 for gastrointestinal helminth infection (95% CI 0.6–1.6) and 0.85 and 0.85 for mild and marked eosinophilia, respectively (95% CI 0.56–1.76 and 0.69–1.96). Incident rate ratios for multiple episodes were 0.83 for gastro-intestinal helminth infection (95% CI 0.5–1.33) and 0.86 and 0.98 for mild and marked eosinophilia (95% CI 0.5–1.4 and 0.6–1.5). Conclusions/Significance There was no evidence that infection with gastrointestinal helminths or urinary schistosomiasis increased susceptibility to Plasmodium falciparum malaria in this study. Larger studies including populations with a greater prevalence of helminth infection should be undertaken. PMID:18265875

IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients.

PubMed

Kumsiri, Ratchanok; Troye-Blomberg, Marita; Pattanapanyasat, Kovit; Krudsood, Srivicha; Maneerat, Yaowapa

2016-02-01

Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-α and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-α levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p=0.011) and S groups (p=0.025) were significantly higher than those in C group. In contrast the TNF-α levels tended to be higher in the UC than those in the S (p=0.343) and significantly higher than those in C (p=0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p<0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r=-0.762, p=0.028), and TNF-α and IgE-IgG complexes (r=-0.715, p=0.002). Significant positive correlations between levels of specific IgE and TNF-α (r=0.575, p=0.010); and sCD23 (r=0.597, p=0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-α and the malaria-specific IgG may correlate with protection against falciparum malaria. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women.

PubMed

Mutagonda, Ritah F; Kamuhabwa, Appolinary A R; Minzi, Omary M S; Massawe, Siriel N; Asghar, Muhammad; Homann, Manijeh V; Färnert, Anna; Aklillu, Eleni

2017-07-03

Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania. Day-7 LF plasma concentration and genotyping forCYP2B6 (c.516G>T, c.983T>C), CYP3A4*1B, CYP3A5 (*3, *6, *7) and ABCB1 c.4036A4G were determined. Blood smear for parasite quantification by microscopy, and dried blood spot for parasite screening and genotyping using qPCR and nested PCR were collected at enrolment up to day 28 to differentiate between reinfection from recrudescence. Treatment response was recorded following the WHO protocol. In total, 92 pregnant women in their second and third trimester were included in the study and 424 samples were screened for presence of P. falciparum. Parasites were detected during the follow up period in 11 (12%) women between day 7 and 28 after treatment and PCR genotyping confirmed recrudescent infection in 7 (63.3%) women. The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4-17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in pregnant women followed up for 28 days (P = 0.018). Genetic variations in CYP3A4 and CYP3A5may influence LF pharmacokinetics and treatment outcome in pregnant women.

Household responses to malaria and their costs: a study from rural Sri Lanka.

PubMed

Konradsen, F; van der Hoek, W; Amerasinghe, P H; Amerasinghe, F P; Fonseka, K T

1997-01-01

A study of the cost of malaria at the household level, community perceptions, preventive measures and illness behaviour linked to the disease was undertaken in 5 villages in the dry zone of Sri Lanka. The surveyed community had a high knowledge of malaria, although side effects of antimalarial drugs were often confused with symptoms of the disease. The community sought prompt diagnosis and treatment at 'western-type' facilities, with 84% making use of government facilities as their first choice and 16% preferring private facilities. The preventive measures used were burning coils (54% of families) and special leaves (69% of families), and 93% of the families had their houses sprayed with insecticides. Average direct expenditure on a single malaria episode was $3 US, with some families spending more than 10% of the annual household net income per episode. The highest expenditure was on special diets for the sick person, to neutralize the perceived heating effect of the disease and its treatment.

Impact of Improving Community-Based Access to Malaria Diagnosis and Treatment on Household Costs.

PubMed

Castellani, Joëlle; Nsungwa-Sabiiti, Jesca; Mihaylova, Borislava; Ajayi, IkeOluwapo O; Siribié, Mohamadou; Afonne, Chinenye; Balyeku, Andrew; Sermé, Luc; Sanou, Armande K; Sombié, Benjamin S; Tiono, Alfred B; Sirima, Sodiomon B; Kabarungi, Vanessa; Falade, Catherine O; Kyaligonza, Josephine; Evers, Silvia M A A; Paulus, Aggie T G; Petzold, Max; Singlovic, Jan; Gomes, Melba

2016-12-15

 Community health workers (CHWs) were trained in Burkina Faso, Nigeria, and Uganda to diagnose febrile children using malaria rapid diagnostic tests, and treat positive malaria cases with artemisinin-based combination therapy (ACT) and those who could not take oral medicines with rectal artesunate. We quantified the impact of this intervention on private household costs for childhood febrile illness.  Households with recent febrile illness in a young child in previous 2 weeks were selected randomly before and during the intervention and data obtained on household costs for the illness episode. Household costs included consultation fees, registration costs, user fees, diagnosis, bed, drugs, food, and transport costs. Private household costs per episode before and during the intervention were compared. The intervention's impact on household costs per episode was calculated and projected to districtwide impacts on household costs.  Use of CHWs increased from 35% of illness episodes before the intervention to 50% during the intervention (P < .0001), and total household costs per episode decreased significantly in each country: from US Dollars (USD) $4.36 to USD $1.54 in Burkina Faso, from USD $3.90 to USD $2.04 in Nigeria, and from USD $4.46 to USD $1.42 in Uganda (all P < .0001). There was no difference in the time used by the child's caregiver to care for a sick child (59% before intervention vs 51% during intervention spent ≤2 days). Using the most recent population figures for each study district, we estimate that the intervention could save households a total of USD $29 965, USD $254 268, and USD $303 467, respectively, in the study districts in Burkina Faso, Nigeria, and Uganda.  Improving access to malaria diagnostics and treatments in malaria-endemic areas substantially reduces private household costs. The key challenge is to develop and strengthen community human resources to deliver the intervention, and ensure adequate supplies of commodities and supervision. We demonstrate feasibility and benefit to populations living in difficult circumstances.  ISRCTN13858170. © 2016 World Health Organization; licensee Oxford Journals.

Spatio-temporal analysis of malaria within a transmission season in Bandiagara, Mali.

PubMed

Coulibaly, Drissa; Rebaudet, Stanislas; Travassos, Mark; Tolo, Youssouf; Laurens, Matthew; Kone, Abdoulaye K; Traore, Karim; Guindo, Ando; Diarra, Issa; Niangaly, Amadou; Daou, Modibo; Dembele, Ahmadou; Sissoko, Mody; Kouriba, Bourema; Dessay, Nadine; Gaudart, Jean; Piarroux, Renaud; Thera, Mahamadou A; Plowe, Christopher V; Doumbo, Ogobara K

2013-03-01

Heterogeneous patterns of malaria transmission are thought to be driven by factors including host genetics, distance to mosquito breeding sites, housing construction, and socio-behavioural characteristics. Evaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) techniques has been a major asset to this approach. To assess time and space distribution of malaria disease in Bandiagara, Mali, within a transmission season, data were used from an ongoing malaria incidence study that enrolled 300 participants aged under six years old". Children's households were georeferenced using a handheld global position system. Clinical malaria was defined as a positive blood slide for Plasmodium falciparum asexual stages associated with at least one of the following signs: headache, body aches, fever, chills and weakness. Daily rainfall was measured at the local weather station.Landscape features of Bandiagara were obtained from satellite images and field survey. QGIS™ software was used to map malaria cases, affected and non-affected children, and the number of malaria episodes per child in each block of Bandiagara. Clusters of high or low risk were identified under SaTScan(®) software according to a Bernoulli model. From June 2009 to May 2010, 296 clinical malaria cases were recorded. Though clearly temporally related to the rains, Plasmodium falciparum occurrence persisted late in the dry season. Two "hot spots" of malaria transmission also found, notably along the Yamé River, characterized by higher than expected numbers of malaria cases, and high numbers of clinical episodes per child. Conversely, the north-eastern sector of the town had fewer cases despite its proximity to a large body of standing water which was mosquito habitat. These results confirm the existence of a marked spatial heterogeneity of malaria transmission in Bandiagara, providing support for implementation of targeted interventions.

A 14-Year Experience in the Management of Patients with Acquired Immune Thrombotic Thrombocytopenic Purpura in Northern Israel.

PubMed

Rinott, Nadav; Mashiach, Tatiana; Horowitz, Netanel A; Schliamser, Liliana; Sarig, Galit; Keren-Politansky, Anat; Dann, Eldad J

2015-01-01

Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life-threatening microangiopathic disorder usually treated with therapeutic plasma exchange (TPE). The current study assessed the role of rituximab in the treatment of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP patients treated with TPE and a cohort of refractory or relapsed patients who also received rituximab. This retrospective evaluation included 45 I-TTP patients, treated between January 2000 and October 2013, who underwent at least 3 TPE procedures and were followed up until December 2013 or death. Thirty-one patients with an uncomplicated course received TPE only. Fourteen patients had a complicated course due to either a primary refractory/exacerbated disease (n = 5) or relapse (n = 9) and received rituximab together with TPE. The median number of TPE procedures performed in the first TTP episode in the uncomplicated cohort and groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively. The relapse rates per follow-up year in the uncomplicated I-TTP, primary refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes, respectively. After rituximab therapy this rate dropped to 0.2 per year in the relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a complicated course and experienced a major benefit from rituximab in terms of effectiveness and safety. © 2015 S. Karger AG, Basel.

Impact of Artemisinin-Based Combination Therapy and Insecticide-Treated Nets on Malaria Burden in Zanzibar

PubMed Central

Bhattarai, Achuyt; Ali, Abdullah S; Kachur, S. Patrick; Mårtensson, Andreas; Abbas, Ali K; Khatib, Rashid; Al-mafazy, Abdul-wahiyd; Ramsan, Mahdi; Rotllant, Guida; Gerstenmaier, Jan F; Molteni, Fabrizio; Abdulla, Salim; Montgomery, Scott M; Kaneko, Akira; Björkman, Anders

2007-01-01

Background The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar. Methods and Findings Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period. Conclusions Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions. PMID:17988171

Unit-dose packaged drugs for treating malaria.

PubMed

Orton, L; Barnish, G

2005-04-18

Unit-dose packaging of antimalarial drugs may improve malaria cure by making it easier for patients to take their treatment correctly. To summarize the effects of unit-dose packaged treatment on cure and treatment adherence in people with uncomplicated malaria. We searched the Cochrane Infectious Diseases Group Specialized Register (November 2004), CENTRAL (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), LILACS (November 2004), conference proceedings, and reference lists of articles. We also contacted pharmaceutical companies, organizations, and researchers in the field. Randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and controlled before-and-after studies of unit-dose packaged drugs for treating uncomplicated malaria. We independently assessed study eligibility and methodological quality, and extracted data for an intention to treat analysis, where possible. We combined binary data using relative risk (RR) and the fixed-effect model, and presented them with 95% confidence intervals (CI). We attempted to contact study authors for additional information. Three quasi-RCTs (895 participants) and one cluster-RCT (6 health facilities) met the inclusion criteria. Trials were of poor methodological quality, and none adequately assessed treatment failure. Unit-dose packaged drugs (in conjunction with prescriber training and patient information) appeared to be associated with higher participant-reported treatment adherence in all trials.A meta-analysis of two trials (596 participants) showed that participant-reported treatment adherence was higher with blister-packed tablets compared with tablets in paper envelopes (RR 1.18, 1.12 to 1.25). Two trials using tablets in sectioned polythene bags as the intervention also noted an increase in participant-reported treatment adherence: the cluster-RCT (6 clusters) compared it with tablets in paper envelopes, and the other trial compared it with syrup in bottles (RR 2.15, 1.76 to 2.61; 299 participants). There is insufficient evidence to determine the effect of unit-dose packaged antimalarial drugs on treatment failure. Unit-dose packaging supported by prescriber training and patient information appears to improve participant-reported treatment adherence, but these data come from trials with methodological limitations.

Prescription practices and availability of artemisinin monotherapy in India: where do we stand?

PubMed Central

2011-01-01

Background The World Health Organization has urged all member states to deploy artemisinin-based combination therapy and progressively withdraw oral artemisinin monotherapies from the market due to their high recrudescence rates and to reduce the risk of drug resistance. Prescription practices by physicians and the availability of oral artemisinin monotherapies with pharmacists directly affect the pattern of their use. Thus, treatment practices for malaria, with special reference to artemisinin monotherapy prescription, in selected states of India were evaluated. Methods Structured, tested questionnaires were used to conduct convenience surveys of physicians and pharmacists in eleven purposively selected districts across six states in 2008. In addition, exit interviews of patients with a diagnosis of uncomplicated malaria or a prescription for an anti-malarial drug were also performed. Logistic regression was used to determine patient clinical care, and institutional factors associated with artemisinin monotherapy prescription. Results Five hundred and eleven physicians from 196 health facilities, 530 pharmacists, and 1, 832 patients were interviewed. Artemisinin monotherapy was available in 72.6% of pharmacies and was prescribed by physicians for uncomplicated malaria in all study states. Exit interviews among patients confirmed the high rate of use of artemisinin monotherapy with 14.8% receiving such a prescription. Case management, i.e. method of diagnosis and overall treatment, varied by state and public or private sector. Treatment in the private sector (OR 8.0, 95%CI: 3.8, 17) was the strongest predictor of artemisinin monotherapy prescription when accounting for other factors. Use of the combination therapy recommended by the national drug policy, artesunate + sulphadoxine-pyrimethamine, was minimal (4.9%), with the exception of one state. Conclusions Artemisinin monotherapy use was widespread across India in 2008. The accessible sale of oral artemisinin monotherapy in retail market and an inadequate supply of recommended drugs in the public sector health facilities promoted its prescription. This study resulted in notifications to all state drug controllers in India to withdraw the oral artemisinin formulations from the market. In 2010, artesunate + sulphadoxine-pyrimethamine became the universal first-line treatment for confirmed Plasmodium falciparum malaria and was deployed at full scale. PMID:22166073

How Do Korsakoff Patients Learn New Concepts?

ERIC Educational Resources Information Center

Pitel, Anne Lise; Beaunieux, Helene; Guillery-Girard, Berengere; Witkowski, Thomas; de la Sayette, Vincent; Viader, Fausto; Desgranges, Beatrice; Eustache, Francis

2009-01-01

The goal of the present investigation was to assess semantic learning in Korsakoff patients (KS), compared with uncomplicated alcoholics (AL) and control subjects (CS), taking the nature of the information to-be-learned and the episodic memory profiles of the three groups into account. Ten new complex concepts, each illustrated by a photo and…

Efficacy and Tolerability of Artesunate Plus Sulfadoxine-Pyrimethamine and Sulfadoxine-Pyrimethamine Alone for the Treatment of Uncomplicated Plasmodium Falciparium Malaria in Peru

DTIC Science & Technology

2005-01-01

Combinations of artemisinin drugs with mefloquine have al- ready proven to be highly efficacious in Southeast Asia and there is suggestive evidence...4 Artemisinin and its derivatives produce more rapid resolution of fever and parasitemia than any other antima- larial agent due to their rapid...virtue of their activity against the gametocyte stage of the parasite.6 Other promising candidates for combination therapy with an artemisinin drug

Costs Associated with Malaria in Pregnancy in the Brazilian Amazon, a Low Endemic Area Where Plasmodium vivax Predominates

PubMed Central

Bôtto-Menezes, Camila; Bardají, Azucena; dos Santos Campos, Giselane; Fernandes, Silke; Hanson, Kara; Martínez-Espinosa, Flor Ernestina; Menéndez, Clara; Sicuri, Elisa

2016-01-01

Background Information on costs associated with malaria in pregnancy (MiP) in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon. Methods/Principal Findings Between January 2011 and March 2012 patient costs for the treatment of MiP were collected through an exit survey at a tertiary referral hospital and at a primary health care centre in the Manaus metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with malaria were interviewed after an outpatient consultation or at discharge after admission. Seventy-three interviews were included in the analysis. Ninety-six percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In 2010, the total median costs from the patient perspective were estimated at US $45.91 and US $216.29 for an outpatient consultation and an admission, respectively. When multiple P. vivax infections during the same pregnancy were considered, patient costs increased up to US $335.85, representing the costs of an admission plus an outpatient consultation. Provider direct and overhead cost data were obtained from several sources. The provider cost associated with an outpatient case, which includes several consultations at the tertiary hospital was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum malaria episode. The cost of an inpatient day and average admission of 3 days was US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis and treatment of all malaria cases reported in pregnant women in Manaus in 2010 (N = 364) were US $17,038.50, of which 92.4% (US$ 15,741.14) due to P. vivax infection. Conclusion Despite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P. falciparum. The information generated may help health policy decisions for the current control and future elimination of malaria in the area. PMID:27031515

Economic burden of malaria and predictors of cost variability to rural households in south-central Ethiopia

PubMed Central

Lindtjørn, Bernt; Deressa, Wakgari; Gari, Taye; Loha, Eskindir; Robberstad, Bjarne

2017-01-01

Background While recognizing the recent remarkable achievement in the global malaria reduction, the disease remains a challenge to the malaria endemic countries in Africa. Beyond the huge health consequence of malaria, policymakers need to be informed about the economic burden of the disease to the households. However, evidence on the economic burden of malaria in Ethiopia is scanty. The aims of this study were to estimate the economic burden of malaria episode and to identify predictors of cost variability to the rural households. Methods A prospective costing approach from a household perspective was employed. A total of 190 malaria patients were enrolled to the study from three health centers and nine health posts in Adami Tullu district in south-central Ethiopia, in 2015. Primary data were collected on expenditures due to malaria, forgone working days because of illness, socioeconomic and demographic situation, and households’ assets. Quantile regression was applied to predict factors associated with the cost variation. Socioeconomic related inequality was measured using concentration index and concentration curve. Results The median cost of malaria per episode to the household was USD 5.06 (IQR: 2.98–8.10). The direct cost accounted for 39%, while the indirect counterpart accounted for 61%. The history of malaria in the last six months and the level of the facility visited in the health system predominantly influenced the direct cost. The indirect cost was mainly influenced by the availability of antimalarial drugs in the health facility. The concentration curve and the concentration index for direct cost indicate significant pro-rich inequality. Plasmodium falciparum is significantly more costly for households compared to Plasmodium vivax. Conclusion The economic burden of malaria to the rural households in Ethiopia was substantial—mainly to the poor—indicating that reducing malaria burden could contribute to the poverty reduction as well. PMID:29020063

Prolonged Neutrophil Dysfunction Following Plasmodium falciparum Malaria is Related to Hemolysis and Heme Oxygenase-1 Induction1

PubMed Central

Cunnington, Aubrey J.; Njie, Madi; Correa, Simon; Takem, Ebako N.; Riley, Eleanor M.; Walther, Michael

2012-01-01

It is not known why people are more susceptible to bacterial infections such as non-Typhoid Salmonella (NTS) during and after a malaria infection but, in mice, malarial hemolysis impairs resistance to NTS by impairing the neutrophil oxidative burst. This acquired neutrophil dysfunction is a consequence of induction of the cytoprotective, heme degrading enzyme heme oxygenase-1 (HO-1) in neutrophil progenitors in bone marrow. In this study, we assessed whether neutrophil dysfunction occurs in humans with malaria and how this relates to hemolysis. We evaluated neutrophil function in 58 Gambian children with Plasmodium falciparum malaria (55 (95%) with uncomplicated disease), and examined associations with erythrocyte count, haptoglobin, hemopexin, plasma heme, expression of receptors for heme uptake, and HO-1 induction. Malaria caused the appearance of a dominant population of neutrophils with reduced oxidative burst activity, which gradually normalized over 8 weeks of follow-up. The degree of neutrophil impairment correlated significantly with markers of hemolysis and HO-1 induction. HO-1 expression was increased in blood during acute malaria, but at a cellular level HO-1 expression was modulated by changes in surface expression of the haptoglobin receptor (CD163). These findings demonstrate that neutrophil dysfunction occurs in P. falciparum malaria and support the relevance of the mechanistic studies in mice. Furthermore, they suggest the presence of a regulatory pathway to limit HO-1 induction by hemolysis in the context of infection, and indicate new targets for therapeutic intervention to abrogate the susceptibility to bacterial infection in the context of hemolysis in humans. PMID:23100518

A systematic review of randomized clinical trials published in Malaria Journal between 2008 and 2013.

PubMed

Martínez-Alonso, E; Ramos, J M

2016-06-01

Randomized controlled trials (RCT) are a key component in clinical research and they provide the highest quality clinical results. The objective of this study was to describe the main characteristics of RCTs published in Malaria Journal, including research topics, study population and design, funding sources and collaboration between institutions. This may help researchers and funders define future research priorities in this field. A retrospective analysis was performed on the RCTs published in Malaria Journal between January 1, 2008 and December 31, 2013. A key-word search by "Randomized controlled trial" or "Random*" was carried out in PubMed. RCT indexed to MEDLINE were selected for the analysis. A total of 108 published articles containing RCTs were analysed. Treatment of uncomplicated Plasmodium falciparum malaria (n=45, 41.6%), especially the efficacy and safety of antimalarial drugs, and malaria prevention (n=34, 31.5%) were the two main research topics. The majority of trials were conducted in Africa (62.2%) and Asia (27%) and received external funding (private, 42.3% and/or public, 38.6%). Paediatric population was the primary study group (n=63, 58.3%), followed by adults (n=29, 26.9%). Pregnant women (n=7) and geriatric population (n=1) remain underrepresented. Nearly 75% of trials were conducted in individual subjects and 25% in groups of subjects (cluster RCTs). A considerable collaboration between researchers and institutions is noteworthy. RCTs published in Malaria Journal address a wide range of research topics. Paediatric trials conducted in Africa and Asia are frequently performed, and a significant worldwide collaboration to fight against malaria has been identified.

Promoter polymorphisms in the ATP binding cassette transporter gene influence production of cell-derived microparticles and are highly associated with susceptibility to severe malaria in humans.

PubMed

Sahu, Upasana; Mohapatra, Biranchi N; Kar, Shantanu K; Ranjit, Manoranjan

2013-04-01

Microparticle (MP) efflux is known to be mediated by the ABCA1 protein, and the plasma level of these cell-derived MPs is elevated considerably during human malarial infection. Therefore, two polymorphisms at positions -477 and -320 in the promoter of the ABCA1 gene were genotyped and tested for association with the plasma MP level in four groups of malaria patients segregated according to the clinical severity, i.e., cerebral malaria (CM), multiorgan dysfunction (MOD), noncerebral severe malaria, and uncomplicated malaria (UM). The TruCount tube-based flow cytometric method was used for the exact quantification of different cell-derived MPs in patients. Polymorphisms in the ABCA1 gene promoter were analyzed by use of the PCR/two-primer-pair method, followed by restriction fragment length polymorphism, in 428 malaria patients. The level of circulating plasma MPs was significantly higher in febrile patients with Plasmodium falciparum infection, especially in CM patients compared to healthy individuals. The homozygous wild-type -477 and -320 genotype was observed to be significantly higher in patients with severe malaria. These patients also showed marked increases in the plasma MP numbers compared to UM patients. We report here for the first time an association of ABCA1 promoter polymorphisms with susceptibility to severe malaria, especially to CM and MOD, indicating the protective effect of the mutant variant of the polymorphism. We hypothesize that the -477T and -320G polymorphisms affect the downregulation of MP efflux and may be a predictor of organ complication during P. falciparum malarial infections.

Malaria in selected non-Amazonian countries of Latin America.

PubMed

Arevalo-Herrera, Myriam; Quiñones, Martha Lucia; Guerra, Carlos; Céspedes, Nora; Giron, Sandra; Ahumada, Martha; Piñeros, Juan Gabriel; Padilla, Norma; Terrientes, Zilka; Rosas, Angel; Padilla, Julio Cesar; Escalante, Ananias A; Beier, John C; Herrera, Socrates

2012-03-01

Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent's contribution to the global malaria burden is small, at least 1-1.2 million malaria cases are reported annually. Sixty percent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2%) followed by P. falciparum (25.7%) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA) (sponsored by the Pan American Health Organization/World Health Organization (PAHO/WHO) and several other partners), have made great investments for malaria control in the region. We describe here the current status of malaria in a non-Amazonian region comprising several countries of South and Central America participating in the Centro Latino Americano de Investigación en Malaria (CLAIM), an International Center of Excellence for Malaria Research (ICEMR) sponsored by the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID). Copyright © 2011 Elsevier B.V. All rights reserved.

Malaria in selected non-Amazonian countries of Latin America

PubMed Central

Arevalo-Herrera, Myriam; Quiñones, Martha Lucia; Guerra, Carlos; Céspedes, Nora; Giron, Sandra; Ahumada, Martha; Piñeros, Juan Gabriel; Padilla, Norma; Terrientes, Zilka; Rosas, Ángel; Padilla, Julio Cesar; Escalante, Ananias A.; Beier, John C.; Herrera, Socrates

2011-01-01

Approximately 170 million inhabitants of the American continent live at risk of malaria transmission. Although the continent’s contribution to the global malaria burden is small, at least 1 to 1.2 million malaria cases are reported annually. Sixty per cent of the malaria cases occur in Brazil and the other 40% are distributed in 20 other countries of Central and South America. Plasmodium vivax is the predominant species (74.2 %) followed by P. falciparum (25.7 %) and P. malariae (0.1%), and no less than 10 Anopheles species have been identified as primary or secondary malaria vectors. Rapid deforestation and agricultural practices are directly related to increases in Anopheles species diversity and abundance, as well as in the number of malaria cases. Additionally, climate changes profoundly affect malaria transmission and are responsible for malaria epidemics in some regions of South America. Parasite drug resistance is increasing, but due to bio-geographic barriers there is extraordinary genetic differentiation of parasites with limited dispersion. Although the clinical spectrum ranges from uncomplicated to severe malaria cases, due to the generally low to middle transmission intensity, features such as severe anemia, cerebral malaria and other complications appear to be less frequent than in other endemic regions and asymptomatic infections are a common feature. Although the National Malaria Control Programs (NMCP) of different countries differ in their control activities these are all directed to reduce morbidity and mortality by using strategies like health promotion, vector control and impregnate bed nets among others. Recently, international initiatives such as the Malaria Control Program in Andean-country Border Regions (PAMAFRO) (implemented by the Andean Organism for Health (ORAS) and sponsored by The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)) and The Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA) (sponsored by the Pan American Health Organization/World Health Organization (PAHO/WHO) and several other partners), have made great investments for malaria control in the region. We describe here the current status of malaria in a non-Amazonian region comprising several countries of South and Central America participating in the Centro Latino Americano de Investigación en Malaria (CLAIM), an International Center of Excellence for Malaria Research (ICEMR) sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). PMID:21741349

Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study.

PubMed

Kasirye, Ronnie; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy

2016-07-15

The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX). This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use. 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30. The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.

Declining Transmission and Immunity to Malaria and Emerging Artemisinin Resistance in Thailand: A Longitudinal Study.

PubMed

Ataíde, Ricardo; Powell, Rosanna; Moore, Kerryn; McLean, Alistair; Phyo, Aung Pyae; Nair, Shalini; White, Marina; Anderson, Tim J; Beeson, James G; Simpson, Julie A; Nosten, Francois; Fowkes, Freya J I

2017-09-15

Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time. Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time. Immunity to P. falciparum declined prior to 2004, preceding the emergence of artemisinin resistance-associated genotypes and phenotypes (maximum mean change in antibody level per year: anti-MSP142 = -0.17; 95% confidence interval [CI] = -.31 to -.04; P = .01). In this period of declining immunity, and in the absence of kelch13 mutations, PCt½ increased. Between 2007 and 2011, levels of antibodies fluctuated, and higher antibody levels were associated with faster PCt½ (maximum yearly change in PCt½, in hours: EBA140rII = -0.39; 95% CI = -.61 to -.17; P < .001). Understanding the impact of changing transmission and immunity on the emergence of artemisinin resistance is important particularly as increased malaria control and elimination activities may enhance immunological conditions for the expansion of artemisinin-resistant P. falciparum. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Health, human rights, and malaria control: historical background and current challenges.

PubMed

Brentlinger, Paula E

2006-01-01

Malaria, a parasitic infection, causes hundreds of millions of disease episodes and more than a million deaths every year, nearly all of them occurring in the poorer and more vulnerable sectors of the world's developing countries. In spite of the great burden of suffering caused by malaria, the human rights implications of this disease have not been well described. This article summarizes important associations between the spread of malaria and human rights abuses (such as those associated with slavery and armed conflict) and between poverty, socio-economic inequity, and access to malaria-control measures. The author concludes that malaria control merits inclusion as a core element in global strategies to achieve progressive realization of the right to health.

Malaria, Epstein-Barr virus infection and the pathogenesis of Burkitt's lymphoma.

PubMed

Mawson, Anthony R; Majumdar, Suvankar

2017-11-01

A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR, Path Global Health 2013;107(3):122-9). Repeated episodes of malaria would therefore be expected to expose the tissues of affected individuals to potentially toxic doses of vitamin A. It is proposed that such episodes activate latent EBV infection, which in turn activates retinoid-responsive genes. Expression of these genes enhances viral replication and induces germinal center (GC) B cell expansion, activation-induced cytidine deaminase (AID) expression, and c-myc translocation, which in turn predisposes to BL. Thus, an endogenous form of retinoid toxicity related to malaria infection may be the common factor linking frequent malaria, EBV infection and BL, whereby prolonged exposure of lymphatic tissues to high concentrations of retinoids may combine to induce B-cell translocation and increase the risk of Burkitt's lymphoma. © 2017 UICC.

Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests in returning travellers and migrants: a retrospective study

PubMed Central

2012-01-01

Background Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis and prompt treatment. Validation of their usefulness in travellers with fever was needed. The safety of a strategy to diagnose falciparum malaria based on RDT followed by immediate or delayed microscopy reading at first attendance was evaluated in one referral hospital in Switzerland. Methods A retrospective study was conducted in the outpatient clinic and emergency ward of University Hospital, covering a period of eight years (1999–2007). The study was conducted in the outpatient clinic and emergency ward of University Hospital. All adults suspected of malaria with a diagnostic test performed were included. RDT and microscopy as immediate tests were performed during working hours, and RDT as immediate test and delayed microscopy reading out of laboratory working hours. The main outcome measure was occurrence of specific complications in RDT negative and RDT positive adults. Results 2,139 patients were recruited. 1987 had both initial RDT and blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed uncomplicated malaria with both RDT and BS positive on day 1 and day 6 respectively. Among the 152 patients initially malaria positive, 137 had both RDT and BS positive, four only BS positive and five only RDT positive (PCR confirmed) (six had only one test performed). None of the four initially RDT negative/BS positive and none of the five initially BS negative/RDT positive developed severe malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a reduction of a median of 2.1 hours to get a first malaria test result. Conclusions A malaria diagnostic strategy based on RDTs and a delayed BS is safe in non-immune populations, and shortens the time to first malaria test result. PMID:23158019

Prevalence of Malaria Parasitemia and Purchase of Artemisinin-Based Combination Therapies (ACTs) among Drug Shop Clients in Two Regions in Tanzania with ACT Subsidies

PubMed Central

Briggs, Melissa A.; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S. Patrick

2014-01-01

Background Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. Method and Findings A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6–18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9–11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2–6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5–7.4). Conclusion Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops. PMID:24732258

Prevalence of malaria parasitemia and purchase of artemisinin-based combination therapies (ACTs) among drug shop clients in two regions in Tanzania with ACT subsidies.

PubMed

Briggs, Melissa A; Kalolella, Admirabilis; Bruxvoort, Katia; Wiegand, Ryan; Lopez, Gerard; Festo, Charles; Lyaruu, Pierre; Kenani, Mitya; Abdulla, Salim; Goodman, Catherine; Kachur, S Patrick

2014-01-01

Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6-18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9-11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2-6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5-7.4). Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops.

Management of imported malaria in Europe

PubMed Central

2012-01-01

In this position paper, the European Society for Clinical Microbiology and Infectious Diseases, Study Group on Clinical Parasitology, summarizes main issues regarding the management of imported malaria cases. Malaria is a rare diagnosis in Europe, but it is a medical emergency. A travel history is the key to suspecting malaria and is mandatory in patients with fever. There are no specific clinical signs or symptoms of malaria although fever is seen in almost all non-immune patients. Migrants from malaria endemic areas may have few symptoms. Malaria diagnostics should be performed immediately on suspicion of malaria and the gold- standard is microscopy of Giemsa-stained thick and thin blood films. A Rapid Diagnostic Test (RDT) may be used as an initial screening tool, but does not replace urgent microscopy which should be done in parallel. Delays in microscopy, however, should not lead to delayed initiation of appropriate treatment. Patients diagnosed with malaria should usually be hospitalized. If outpatient management is preferred, as is the practice in some European centres, patients must usually be followed closely (at least daily) until clinical and parasitological cure. Treatment of uncomplicated Plasmodium falciparum malaria is either with oral artemisinin combination therapy (ACT) or with the combination atovaquone/proguanil. Two forms of ACT are available in Europe: artemether/lumefantrine and dihydroartemisinin/piperaquine. ACT is also effective against Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi, but these species can be treated with chloroquine. Treatment of persistent liver forms in P. vivax and P. ovale with primaquine is indicated after excluding glucose 6 phosphate dehydrogenase deficiency. There are modified schedules and drug options for the treatment of malaria in special patient groups, such as children and pregnant women. The potential for drug interactions and the role of food in the absorption of anti-malarials are important considerations in the choice of treatment. Complicated malaria is treated with intravenous artesunate resulting in a much more rapid decrease in parasite density compared to quinine. Patients treated with intravenous artesunate should be closely monitored for haemolysis for four weeks after treatment. There is a concern in some countries about the lack of artesunate produced according to Good Manufacturing Practice (GMP). PMID:22985344

Prescriptions for uncomplicated malaria treatment among pregnant women in the Brazilian Amazon: evidences from the Mafalda Project.

PubMed

Luz, Tatiana Chama Borges; Miranda, Elaine Silva; Freitas, Letícia Figueira; Osório-de-Castro, Claudia Garcia Serpa

2013-06-01

To evaluate antimalarial prescriptions according to quality indicators and to describe adverse events reports among pregnant women with uncomplicated malaria. Descriptive study of medical files of pregnant women 15 years and older, residents in high-risk municipalities in the Brazilian Amazon. Antimalarial medicines were characterized by frequency of prescription, type of plasmodium and health care facilities where prescribing took place, and by possible adverse events. Variables were compared by Pearson's chi-square. A total of 262 medical files were evaluated. Most patients were diagnosed for Plasmodium vivax 71,2%. Chloroquine was the commonest prescribed antimalarial (65.6%). Of P. vivax prescriptions, 9.0%, and 16.2% of P. falciparum prescriptions presented antimalarials not recommended in the official protocol. Prescriptions for P. falciparum , in significantly higher proportion, did not adhere to the official protocol in regard to type of antimalarial and dose/duration of treatment (p = 0,001). They also lacked information on dose and dosing interval (p = 0,004). There were no significant differences among reference centers and basic health care units in respect to the prescribed antimalarials, to prescriptions containing antimalarials not recommended in the official protocol or in respect to lack of dosing information. Chloroquine was the antimalarial most related to the occurrence of adverse events. THE findings indicate that there are flaws in antimalarial prescribing for pregnant women, especially in respect to their adequacy to the official protocol.

Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon.

PubMed

Hill, N; Lenglet, A; Arnéz, A M; Carneiro, I

2007-11-17

To determine the effectiveness in reducing malaria of combining an insect repellent with insecticide treated bed nets compared with the nets alone in an area where vector mosquitoes feed in the early evening. A double blind, placebo controlled cluster-randomised clinical study. Rural villages and peri-urban districts in the Bolivian Amazon. 4008 individuals in 860 households. All individuals slept under treated nets; one group also used a plant based insect repellent each evening, a second group used placebo. Episodes of Plasmodium falciparum or P vivax malaria confirmed by rapid diagnostic test or blood slide, respectively. We analysed 15,174 person months at risk and found a highly significant 80% reduction in episodes of P vivax in the group that used treated nets and repellent (incidence rate ratio 0.20, 95% confidence interval 0.11 to 0.38, P<0.001). Numbers of P falciparum cases during the study were small and, after adjustment for age, an 82% protective effect was observed, although this was not significant (0.18, 0.02 to 1.40, P=0.10). Reported episodes of fever with any cause were reduced by 58% in the group that used repellent (0.42, 0.31 to 0.56, P<0.001). Insect repellents can provide protection against malaria. In areas where vectors feed in the early evening, effectiveness of treated nets can be significantly increased by using repellent between dusk and bedtime. This has important implications in malaria vector control programmes outside Africa and shows that the combined use of treated nets and insect repellents, as advocated for most tourists travelling to high risk areas, is fully justified. NCT 00144716.

Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria.

PubMed

Wattanakoon, Yupaporn; Chittamas, Sunee; Pornkulprasit, Vichitra; Kanda, Tozo; Thimasarn, Krongthong; Rojanawatsirivej, Chaiporn; Looareesuwan, Sornchai; Bunnag, Danai

2003-09-01

Plasmodium falciparum in Thailand is multi-drug resistant. In a previous study it was shown that artesunate and mefloquine were effective, as follow up, we monitored the efficacy of this regimen for six years. During 1997-2002, 516 adult male volunteer patients in Chanthaburi Province were enrolled (50 patients in the first year, 400 patients in 1998-2001 and 66 patients in 2002). The symptom complex and parasite count (thick blood film) were monitored on days 0, 1, 2, 7, 14, 21, 28, 35 and 42. The dosages used were artesunate (ATS) 150 mg and mefloquine (M) 750 mg at hour 0 and ATS 100 mg and M 500 mg at hour 24. Their ages ranged from 30-35 years and their mean body weights were 54-56 kg. The presenting symptoms were fever 100%, headache 97-100%, anorexia 78-90%, and nausea 28-40%. The geometric mean of parasitemia ranged from 7,357-12,750/mm3. Defervescence in one day was found in 42-76% of patients and 85-100% in 2 days. The sensitivity (S) ranged from 87-94% and RI resistance (recrudescence) ranged from 6-13%. Forty patients demonstrated RI type of response, 37 were cured after being retreated with the same dosage and another 3 patients were cured after the third course of treatment. The aggravated adverse effects included vomiting (8-20%), anorexia (1-41%) and diarrhea (0-16%). These side effects were mild and transient. The efficacy of the artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria was high. The RI type of response was possibly due to re-infection or multiple broods and not to drug resistance. The adverse effects of anorexia, nausea, vomiting and diarrhea were mild and transient for mefloquine. The combination can be used as stand by treatment in areas of multi-drug resistant falciparum malaria.

A randomized trial on effectiveness of artemether-lumefantrine versus artesunate plus amodiaquine for unsupervised treatment of uncomplicated Plasmodium falciparum malaria in Ghanaian children

PubMed Central

Kobbe, Robin; Klein, Philipp; Adjei, Samuel; Amemasor, Solomon; Thompson, William Nana; Heidemann, Hanna; Nielsen, Maja V; Vohwinkel, Julia; Hogan, Benedikt; Kreuels, Benno; Bührlen, Martina; Loag, Wibke; Ansong, Daniel; May, Jürgen

2008-01-01

Background Numerous trials have demonstrated high efficacy and safety of artemisinin-based combination therapy (ACT) under supervised treatment. In contrast, effectiveness studies comparing different types of ACT applied unsupervised are scarce. The aim of this study was to compare effectiveness, tolerability and acceptance of artesunate plus amodiaquine (ASAQ) against that of artemether-lumefantrine (AL) in Ghanaian children with uncomplicated Plasmodium falciparum malaria. Methods A randomized open-label trial was conducted at two district hospitals in the Ashanti region, Ghana, an area of intense malaria transmission. A total of 246 children under five years of age were randomly assigned to either ASAQ (Arsucam®) or AL (Coartem®). Study participants received their first weight-adjusted dose under supervision. After the parent/guardian was advised of times and mode of administration the respective three-day treatment course was completed unobserved at home. Follow-up visits were performed on days 3, 7, 14 and 28 to evaluate clinical and parasitological outcomes, adverse events, and haematological recovery. Length polymorphisms of variable regions of msp1 and msp2 were determined to differentiate recrudescences from reinfections. Acceptance levels of both treatment regimens were assessed by means of standardized interviews. Results Adequate clinical and parasitological responses after AL and ASAQ treatment were similar (88.3% and 91.7%, respectively). Interestingly, more late clinical failures until day 28 occurred in AL-treated children than in those who received ASAQ (17.5% and 7.3%, respectively; Hazard Ratio 2.41, 95% CI 1.00–5.79, p < 0.05). Haematological recovery and drug tolerability were not found to be significantly different in both study arms. The acceptance of treatment with ASAQ was higher than that with AL (rank-scores 10.6 and 10.3, respectively; p < 0.05). Conclusion Unobserved AL and ASAQ treatment showed high adequate clinical and parasitological responses, though AL was inferior in preventing late clinical failures. PMID:19099594

Malaria in rural Mozambique. Part I: Children attending the outpatient clinic

PubMed Central

Guinovart, Caterina; Bassat, Quique; Sigaúque, Betuel; Aide, Pedro; Sacarlal, Jahit; Nhampossa, Tacilta; Bardají, Azucena; Nhacolo, Ariel; Macete, Eusébio; Mandomando, Inácio; Aponte, John J; Menéndez, Clara; Alonso, Pedro L

2008-01-01

Background Malaria represents a huge burden for the health care services across Africa. Describing malaria attending health services contributes to quantify the burden and describe the epidemiology and clinical presentation. Methods Retrospective analysis of data collected through the Manhiça morbidity surveillance system (Mozambique) on all paediatric visits (<15 years) to the outpatient clinic from June 2003 to May 2005. Age-specific minimum community-based incidence rates (MCBIRs) of malaria were calculated using demographic surveillance system data. Malaria was defined as fever or history of fever in the preceding 24 hours with asexual Plasmodium falciparum parasitaemia of any density in the blood smear. Results A total of 94,941 outpatient visits were seen during the study period, of which 30.5% had malaria. Children younger than three years accounted for almost half of the total malaria cases and children aged ≥ 5 years represented 36.4% of the cases. Among children who presented with malaria, 56.7% had fever and among children who presented with fever or a history of fever only 37.2% had malaria. The geometric mean parasitaemia in malaria cases was 8582.2 parasites/μL, peaking in children aged two to three years. 13% of malaria cases had a PCV<25% and the mean PCV in malaria cases increased gradually with age, ranging from 27.8% in children aged 2–12 months to 34.4% in ≥ 5 years. The percentage of cases admitted or transferred showed a clear decreasing trend with age. MCBIRs of outpatient malaria per 1,000 child years at risk for the whole study period were of 394 in infants, 630 in children aged 1 to <5 years and 237 in children aged five years or more. A clustering of the cases was observed, whereby most children never had malaria, some had a few episodes and very few had many episodes. Conclusion Preventive measures should be targeted at children younger than three years, as they carry the highest burden of malaria. Children aged 5–15 years represent around a third of the malaria cases and should also be included in control programmes. Concern should be raised about presumptive treatment of fever cases with artemisinin-combination therapies, as many children will, according to IMCI guidelines, receive treatment unnecessarily. PMID:18302770

Malaria in rural Mozambique. Part I: children attending the outpatient clinic.

PubMed

Guinovart, Caterina; Bassat, Quique; Sigaúque, Betuel; Aide, Pedro; Sacarlal, Jahit; Nhampossa, Tacilta; Bardají, Azucena; Nhacolo, Ariel; Macete, Eusébio; Mandomando, Inácio; Aponte, John J; Menéndez, Clara; Alonso, Pedro L

2008-02-26

Malaria represents a huge burden for the health care services across Africa. Describing malaria attending health services contributes to quantify the burden and describe the epidemiology and clinical presentation. Retrospective analysis of data collected through the Manhiça morbidity surveillance system (Mozambique) on all paediatric visits (<15 years) to the outpatient clinic from June 2003 to May 2005. Age-specific minimum community-based incidence rates (MCBIRs) of malaria were calculated using demographic surveillance system data. Malaria was defined as fever or history of fever in the preceding 24 hours with asexual Plasmodium falciparum parasitaemia of any density in the blood smear. A total of 94,941 outpatient visits were seen during the study period, of which 30.5% had malaria. Children younger than three years accounted for almost half of the total malaria cases and children aged > or = 5 years represented 36.4% of the cases. Among children who presented with malaria, 56.7% had fever and among children who presented with fever or a history of fever only 37.2% had malaria. The geometric mean parasitaemia in malaria cases was 8582.2 parasites/muL, peaking in children aged two to three years. 13% of malaria cases had a PCV<25% and the mean PCV in malaria cases increased gradually with age, ranging from 27.8% in children aged 2-12 months to 34.4% in > or = 5 years. The percentage of cases admitted or transferred showed a clear decreasing trend with age. MCBIRs of outpatient malaria per 1,000 child years at risk for the whole study period were of 394 in infants, 630 in children aged 1 to <5 years and 237 in children aged five years or more. A clustering of the cases was observed, whereby most children never had malaria, some had a few episodes and very few had many episodes. Preventive measures should be targeted at children younger than three years, as they carry the highest burden of malaria. Children aged 5-15 years represent around a third of the malaria cases and should also be included in control programmes. Concern should be raised about presumptive treatment of fever cases with artemisinin-combination therapies, as many children will, according to IMCI guidelines, receive treatment unnecessarily.

Use of buffy coat thick films in detecting malaria parasites in patients with negative conventional thick films.

PubMed

Duangdee, Chatnapa; Tangpukdee, Noppadon; Krudsood, Srivicha; Wilairatana, Polrat

2012-04-01

To determine the frequency of malaria parasite detection from the buffy coat blood films by using capillary tube in falciparum malaria patients with negative conventional thick films. Thirty six uncomplicated falciparum malaria patients confirmed by conventional thick and thin films were included in the study. The patients were treated with artemisinin combination therapy at Hospital for Tropical Diseases, Bangkok, Thailand for 28 day. Fingerpricks for conventional blood films were conducted every 6 hours until negative parasitemia, then daily fingerpricks for parasite checks were conducted until the patients were discharged from hospital. Blood samples were also concurrently collected in 3 heparinized capillary tubes at the same time of fingerpricks for conventional blood films when the prior parasitemia was negative on thin films and parasitemia was lower than 50 parasites/200 white blood cells by thick film. The first negative conventional thick films were compared with buffy coat thick films for parasite identification. Out of 36 patients with thick films showing negative for asexual forms of parasites, buffy coat films could detect remaining 10 patients (27.8%) with asexual forms of Plasmodium falciparum. The study shows that buffy coat thick films are useful and can detect malarial parasites in 27.8% of patients whose conventional thick films show negative parasitemia.

Evaluating malaria case management at public health facilities in two provinces in Angola.

PubMed

Plucinski, Mateusz M; Ferreira, Manzambi; Ferreira, Carolina Miguel; Burns, Jordan; Gaparayi, Patrick; João, Lubaki; da Costa, Olinda; Gill, Parambir; Samutondo, Claudete; Quivinja, Joltim; Mbounga, Eliane; de León, Gabriel Ponce; Halsey, Eric S; Dimbu, Pedro Rafael; Fortes, Filomeno

2017-05-03

Malaria accounts for the largest portion of healthcare demand in Angola. A pillar of malaria control in Angola is the appropriate management of malaria illness, including testing of suspect cases with rapid diagnostic tests (RDTs) and treatment of confirmed cases with artemisinin-based combination therapy (ACT). Periodic systematic evaluations of malaria case management are recommended to measure health facility readiness and adherence to national case management guidelines. Cross-sectional health facility surveys were performed in low-transmission Huambo and high-transmission Uíge Provinces in early 2016. In each province, 45 health facilities were randomly selected from among all public health facilities stratified by level of care. Survey teams performed inventories of malaria commodities and conducted exit interviews and re-examinations, including RDT testing, of a random selection of all patients completing outpatient consultations. Key health facility readiness and case management indicators were calculated adjusting for the cluster sampling design and utilization. Availability of RDTs or microscopy on the day of the survey was 71% (54-83) in Huambo and 85% (67-94) in Uíge. At least one unit dose pack of one formulation of an ACT (usually artemether-lumefantrine) was available in 83% (66-92) of health facilities in Huambo and 79% (61-90) of health facilities in Uíge. Testing rates of suspect malaria cases in Huambo were 30% (23-38) versus 69% (53-81) in Uíge. Overall, 28% (13-49) of patients with uncomplicated malaria, as determined during the re-examination, were appropriately treated with an ACT with the correct dose in Huambo, compared to 60% (42-75) in Uíge. Incorrect case management of suspect malaria cases was associated with lack of healthcare worker training in Huambo and ACT stock-outs in Uíge. The results reveal important differences between provinces. Despite similar availability of testing and ACT, testing and treatment rates were lower in Huambo compared to Uíge. A majority of true malaria cases seeking care in health facilities in Huambo were not appropriately treated with anti-malarials, highlighting the importance of continued training and supervision of healthcare workers in malaria case management, particularly in areas with decreased malaria transmission.

X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria.

PubMed

Guindo, Aldiouma; Fairhurst, Rick M; Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

2007-03-01

Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A- form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. We conducted large case-control studies of the A- form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. The A- form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females. Although these conclusions are consistent with data from at least one previous study, they have not heretofore been realized to our knowledge, and they therefore give fresh perspectives on malaria protection by G6PD deficiency as an X-linked trait.

Incidence and admission rates for severe malaria and their impact on mortality in Africa.

PubMed

Camponovo, Flavia; Bever, Caitlin A; Galactionova, Katya; Smith, Thomas; Penny, Melissa A

2017-01-03

Appropriate treatment of life-threatening Plasmodium falciparum malaria requires in-patient care. Although the proportion of severe cases accessing in-patient care in endemic settings strongly affects overall case fatality rates and thus disease burden, this proportion is generally unknown. At present, estimates of malaria mortality are driven by prevalence or overall clinical incidence data, ignoring differences in case fatality resulting from variations in access. Consequently, the overall impact of preventive interventions on disease burden have not been validly compared with those of improvements in access to case management or its quality. Using a simulation-based approach, severe malaria admission rates and the subsequent severe malaria disease and mortality rates for 41 malaria endemic countries of sub-Saharan Africa were estimated. Country differences in transmission and health care settings were captured by use of high spatial resolution data on demographics and falciparum malaria prevalence, as well as national level estimates of effective coverage of treatment for uncomplicated malaria. Reported and modelled estimates of cases, admissions and malaria deaths from the World Malaria Report, along with predicted burden from simulations, were combined to provide revised estimates of access to in-patient care and case fatality rates. There is substantial variation between countries' in-patient admission rates and estimated levels of case fatality rates. It was found that for many African countries, most patients admitted for in-patient treatment would not meet strict criteria for severe disease and that for some countries only a small proportion of the total severe cases are admitted. Estimates are highly sensitive to the assumed community case fatality rates. Re-estimation of national level malaria mortality rates suggests that there is substantial burden attributable to inefficient in-patient access and treatment of severe disease. The model-based methods proposed here offer a standardized approach to estimate the numbers of severe malaria cases and deaths based on national level reporting, allowing for coverage of both curative and preventive interventions. This makes possible direct comparisons of the potential benefits of scaling-up either category of interventions. The profound uncertainties around these estimates highlight the need for better data.

X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria

PubMed Central

Doumbo, Ogobara K; Wellems, Thomas E; Diallo, Dapa A

2007-01-01

Background Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X-linked deficiency states associated with protection against malaria, notably in Africa where the A− form of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. Methods and Findings We conducted large case-control studies of the A− form of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life-threatening malaria in these studies. Conclusions The A− form of G6PD deficiency in Africa is under strong natural selection from the preferential protection it provides to hemizygous males against life-threatening malaria. Little or no such protection is present among heterozygous females. Although these conclusions are consistent with data from at least one previous study, they have not heretofore been realized to our knowledge, and they therefore give fresh perspectives on malaria protection by G6PD deficiency as an X-linked trait. PMID:17355169

The Hidden Burden of Plasmodium vivax Malaria in Pregnancy in the Amazon: An Observational Study in northwestern Brazil.

PubMed

Pincelli, Anaclara; Neves, Paulo A R; Lourenço, Barbara H; Corder, Rodrigo M; Malta, Maíra B; Sampaio-Silva, Juliana; de Souza, Rodrigo M; Cardoso, Marly A; Castro, Marcia C; Ferreira, Marcelo U; For The Mina Brazil Working Group

2018-05-07

We measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax , were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z -scores of 0.35 (95% confidence interval [CI] = 0.14-0.57) and in birth length z -scores of 0.31 (95% CI = 0.08-0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05-0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite's DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.

Toll-like receptor polymorphisms in malaria-endemic populations

PubMed Central

Greene, Jennifer A; Moormann, Ann M; Vulule, John; Bockarie, Moses J; Zimmerman, Peter A; Kazura, James W

2009-01-01

Background Toll-like receptors (TLR) and related downstream signaling pathways of innate immunity have been implicated in the pathogenesis of Plasmodium falciparum malaria. Because of their potential role in malaria pathogenesis, polymorphisms in these genes may be under selective pressure in populations where this infectious disease is endemic. Methods A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA) was developed to determine the frequencies of TLR2, TLR4, TLR9, MyD88-Adaptor Like Protein (MAL) single nucleotide polymorphisms (SNPs), and TLR2 length polymorphisms in 170 residents of two regions of Kenya where malaria transmission is stable and high (holoendemic) or episodic and low, 346 residents of a malaria holoendemic region of Papua New Guinea, and 261 residents of North America of self-identified ethnicity. Results The difference in historical malaria exposure between the two Kenyan sites has significantly increased the frequency of malaria protective alleles glucose-6-phoshpate dehydrogenase (G6PD) and Hemoglobin S (HbS) in the holoendemic site compared to the episodic transmission site. However, this study detected no such difference in the TLR2, TLR4, TLR9, and MAL allele frequencies between the two study sites. All polymorphisms were in Hardy Weinberg Equilibrium in the Kenyan and Papua New Guinean populations. TLR9 SNPs and length polymorphisms within the TLR2 5' untranslated region were the only mutant alleles present at a frequency greater than 10% in all populations. Conclusion Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms in populations with different histories of malaria exposure suggest that these innate immune pathways have not been under strong selective pressure by malaria. Genotype frequencies are consistent with Hardy-Weinberg Equilibrium and the Neutral Theory, suggesting that genetic drift has influenced allele frequencies to a greater extent than selective pressure from malaria or any other infectious agents in these populations. PMID:19317913

Reducing microscopy-based malaria misdiagnosis in a low-resource area of Tanzania.

PubMed

Allen, Lisa K; Hatfield, Jennifer M; Manyama, Mange

2013-01-01

Misdiagnosis of malaria is a major problem in Africa leading not only to incorrect individual level treatment, but potentially the acceleration of the spread of drug resistance in low-transmission areas. In this paper we report on the outcomes of a simple intervention that utilized a social entrepreneurship approach (SEA) to reduce misdiagnosis associated with hospital-based microscopy of malaria in a low-transmission area of rural Tanzania. A pre-post assessment was conducted on patients presenting to the hospital outpatient department with malaria and non-malaria like symptoms in January 2009 (pre-intervention) and June 2009 (post-intervention). All participants were asked a health seeking behavior questionnaire and blood samples were taken for local and quality control microscopy. Multivariate logistic regression was conducted to determine magnitude of misdiagnosis with local microscopy pre- versus- post intervention. Local microscopy pre-intervention specificity was 29.5% (95% CI = 21.6% - 38.4%) whereas the post intervention specificity was 68.6% (95% CI = 60.2% - 76.2%). Both pre and post intervention sensitivity were difficult to determine due to an unexpected low number of true positive cases. The proportion of participants misdiagnosed pre-intervention was 70.2% (95%CI = 61.3%-78.0%) as compared to 30.6% (95%CI = 23.2%-38.8%) post-intervention. This resulted in a 39.6% reduction in misdiagnosis of malaria at the local hospital. The magnitude of misdiagnosis for the pre-intervention participants was 5.3 (95%CI = 3.1-9.3) that of the post-intervention participants. In conclusion, this study provides evidence that a simple intervention can meaningfully reduce the magnitude of microscopy-based misdiagnosis of malaria for those individuals seeking treatment for uncomplicated malaria. We anticipate that this intervention will facilitate a valuable and sustainable change in malaria diagnosis at the local hospital.

Spectrum-Malaria: a user-friendly projection tool for health impact assessment and strategic planning by malaria control programmes in sub-Saharan Africa.

PubMed

Hamilton, Matthew; Mahiane, Guy; Werst, Elric; Sanders, Rachel; Briët, Olivier; Smith, Thomas; Cibulskis, Richard; Cameron, Ewan; Bhatt, Samir; Weiss, Daniel J; Gething, Peter W; Pretorius, Carel; Korenromp, Eline L

2017-02-10

Scale-up of malaria prevention and treatment needs to continue but national strategies and budget allocations are not always evidence-based. This article presents a new modelling tool projecting malaria infection, cases and deaths to support impact evaluation, target setting and strategic planning. Nested in the Spectrum suite of programme planning tools, the model includes historic estimates of case incidence and deaths in groups aged up to 4, 5-14, and 15+ years, and prevalence of Plasmodium falciparum infection (PfPR) among children 2-9 years, for 43 sub-Saharan African countries and their 602 provinces, from the WHO and malaria atlas project. Impacts over 2016-2030 are projected for insecticide-treated nets (ITNs), indoor residual spraying (IRS), seasonal malaria chemoprevention (SMC), and effective management of uncomplicated cases (CMU) and severe cases (CMS), using statistical functions fitted to proportional burden reductions simulated in the P. falciparum dynamic transmission model OpenMalaria. In projections for Nigeria, ITNs, IRS, CMU, and CMS scale-up reduced health burdens in all age groups, with largest proportional and especially absolute reductions in children up to 4 years old. Impacts increased from 8 to 10 years following scale-up, reflecting dynamic effects. For scale-up of each intervention to 80% effective coverage, CMU had the largest impacts across all health outcomes, followed by ITNs and IRS; CMS and SMC conferred additional small but rapid mortality impacts. Spectrum-Malaria's user-friendly interface and intuitive display of baseline data and scenario projections holds promise to facilitate capacity building and policy dialogue in malaria programme prioritization. The module's linking to the OneHealth Tool for costing will support use of the software for strategic budget allocation. In settings with moderately low coverage levels, such as Nigeria, improving case management and achieving universal coverage with ITNs could achieve considerable burden reductions. Projections remain to be refined and validated with local expert input data and actual policy scenarios.

Evaluation of a PfHRP2 and a pLDH-based Rapid Diagnostic Test for the Diagnosis of Severe Malaria in 2 Populations of African Children

PubMed Central

Hendriksen, Ilse C. E.; Mtove, George; Pedro, Alínia José; Gomes, Ermelinda; Silamut, Kamolrat; Lee, Sue J.; Mwambuli, Abraham; Gesase, Samwel; Reyburn, Hugh; Day, Nicholas P. J.; White, Nicholas J.; von Seidlein, Lorenz

2011-01-01

Background. Rapid diagnostic tests (RDTs) now play an important role in the diagnosis of falciparum malaria in many countries where the disease is endemic. Although these tests have been extensively evaluated in uncomplicated falciparum malaria, reliable data on their performance for diagnosing potentially lethal severe malaria is lacking. Methods. We compared a Plasmodium falciparum histidine-rich-protein2 (PfHRP2)–based RDT and a Plasmodium lactate dehydrogenase (pLDH)–based RDT with routine microscopy of a peripheral blood slide and expert microscopy as a reference standard for the diagnosis of severe malaria in 1898 children who presented with severe febrile illness at 2 centers in Mozambique and Tanzania. Results. The overall sensitivity, specificity, positive predictive value, and negative predictive values of the PfHRP2-based test were 94.0%, 70.9%, 85.4%, and 86.8%, respectively, and for the pLDH-based test, the values were 88.0%, 88.3%, 93.2%, and 80.3%, respectively. At parasite counts <1000 parasites/μL (n = 173), sensitivity of the pLDH-based test was low (45.7%), compared with that of the PfHRP2-based test (69.9%). Both RDTs performed better than did the routine slide reading in a clinical laboratory as assessed in 1 of the centers. Conclusion. The evaluated PfHRP2-based RDT is an acceptable alternative to routine microscopy for diagnosing severe malaria in African children and performed better than did the evaluated pLDH-based RDT. PMID:21467015

Malaria and severe anemia over eight years at Gambo Rural Hospital, southern Ethiopia.

PubMed

Barreiro, Pablo; Tiziano, Gebre; Fano, Haji; Yohannes, Tafesse; Gosa, Ashenafi; Reyes, Francisco; Tesfamariam, Abraham; Górgolas, Miguel; Ramos, José M

2017-06-01

Evolution of incident malaria and frequency of anemia were analyzed over eight years in a rural hospital in southern Ethiopia. Capillary blood samples were tested for hemoglobin concentration, and in some instances for malaria parasites, at Gambo Rural General Hospital between January 2007 and September 2014, and the results recorded. Main demographic data were also recorded in subjects with Plasmodium sp. infections. Of a total of 54,493 blood samples taken from 45,096 different patients, 21,723 (39.9%) samples from 19,173 (42.5%) patients were tested for malaria parasites. Malaria was diagnosed in 825 (3.79%, 95% CI 3.55%, 4.06%) instances (58.3% P. vivax and 41.7% P. falciparum; one episode in 575 patients and two episodes in 125 patients). A sustained decrease in yearly incidence of malaria was observed between 2011 (6.1%) and 2014 (2.4%) (p < 0.01). Of all the malaria patients, those with hemoglobin levels less than 8 g/dL, were younger compared to those with levels of 8 g/dL or more (median age of 5 years vs. 18 years; p < 0.01) and more commonly infected with P. falciparum (57.1% vs. 34.8%; p < 0.001). In multivariate analysis, severe anemia (hemoglobin <8 g/dL) in the context of anemia was associated with P falciparum infection (adjusted odd ratio [OR] 2.48, 95% confidence interval [CI] 1.68, 3.65) and younger age (OR 1.06, 95% CI 1.04, 1.07).

Placental malaria and the risk of malaria in infants in a high malaria transmission area in ghana: a prospective cohort study.

PubMed

Asante, Kwaku Poku; Owusu-Agyei, Seth; Cairns, Matthew; Dodoo, Daniel; Boamah, Ellen Abrafi; Gyasi, Richard; Adjei, George; Gyan, Ben; Agyeman-Budu, Akua; Dodoo, Theophilus; Mahama, Emmanuel; Amoako, Nicholas; Dosoo, David Kwame; Koram, Kwadwo; Greenwood, Brian; Chandramohan, Daniel

2013-11-01

Whether the risk of malaria is increased in infants born to mothers who experience malaria during pregnancy is uncertain.  We investigated malaria incidence among an infant cohort born to 355 primigravidae and 1500 multigravidae with or without placental malaria (PM) in a high malaria transmission area of Ghana. PM was assessed using placental histology. The incidence of all episodes of malaria parasitemia or clinical malaria was very similar among 3 groups of infants: those born to multigravidae without PM, multigravidae with PM, and primigravidae with PM. Infants born to primigravidae without PM experienced a lower incidence of malaria parasitemia or clinical malaria than the other 3 groups: adjusted hazard ratio, 0.64 (95% confidence interval [CI], .48-.86, P < .01) and 0.60 (95% CI, .43-.84, P < .01), respectively. The incidence of malaria parasitemia or clinical malaria was about 2 times higher in most poor infants compared to least poor infants. There was no suggestion that exposure to PM directly increased incidence of malaria among infants of multigravidae. In our study area, absence of placental malaria in primigravidae is a marker of low exposure, and this probably explains the lower incidence of malaria-related outcomes among infants of PM-negative primigravidae.

Malaria infection and disease in an area with pyrethroid-resistant vectors in southern Benin

PubMed Central

2010-01-01

Background This study aimed to investigate baseline data on malaria before the evaluation of new vector control strategies in an area of pyrethroid-resistance of vectors. The burden of malaria was estimated in terms of infection (prevalence and parasite density) and of clinical episodes. Methods Between December 2007 and December 2008 in the health district of Ouidah - Kpomassè - Tori Bossito (southern Benin), a descriptive epidemiological survey of malaria was conducted. From 28 selected villages, seven were randomized from which a total of 440 children aged 0 to 5 years were randomly selected. Clinical and parasitological information was obtained by active case detection of malaria episodes carried out during eight periods of six consecutive days scheduled at six weekly intervals and by cross-sectional surveys of asymptomatic infection. Entomological information was also collected. The ownership, the use and the correct use of long-lasting insecticide-treated nets (LLINs) were checked over weekly-survey by unannounced visits at home in the late evening. Results Mean parasite density in asymptomatic children was 586 P. falciparum asexual forms per μL of blood (95%CI 504-680). Pyrogenic parasite cut-off was estimated 2,000 P. falciparum asexual blood forms per μL. The clinical incidence of malaria was 1.5 episodes per child per year (95%CI 1.2-1.9). Parasitological and clinical variables did not vary with season. Anopheles gambiae s.l. was the principal vector closely followed by Anopheles funestus. Entomological inoculation rate was 5.3 (95%CI 1.1-25.9) infective bites per human per year. Frequency of the L1014F kdr (West) allele was around 50%. Annual prevalence rate of Plasmodium falciparum asymptomatic infection was 21.8% (95%CI 19.1-24.4) and increased according to age. Mean rates of ownership and use of LLINs were 92% and 70% respectively. The only correct use of LLINs (63%) conferred 26% individual protection against only infection (OR = 0.74 (95%IC 0.62-0.87), p = 0.005). Conclusion The health district of Ouidah-Kpomassè-Tori Bossito is a mesoendemic area with a moderate level of pyrethroid-resistance of vectors. The used LLINs rate was high and only the correct use of LLINs was found to reduce malaria infection without influencing malaria morbidity. PMID:21194470

Sulfadoxine-Pyrimethamine-Based Intermittent Preventive Treatment, Bed Net Use, and Antenatal Care during Pregnancy: Demographic Trends and Impact on the Health of Newborns in the Kassena Nankana District, Northeastern Ghana

DTIC Science & Technology

2010-01-01

treatment for uncomplicated malaria, whether confirmed, or suspected, in 2004 and SIP- based IPTp was introduced in 2005.1•3 Indoor residual spray - ing...emigrations recorded. Although many women may have been using long - lasting ITNs during pregnancy, this quality of the bed nets could not be determined with...care, provision and wide use of insecticide -treated bed nets (ITNs), and intensified health education. Ghana readily adopted and began implementa

Current clinical efficacy of chloroquine for the treatment of Plasmodium falciparum infections in urban Dar es Salaam, United Republic of Tanzania.

PubMed Central

Premji, Z.; Makwaya, C.; Minjas, J. N.

1999-01-01

Reported is the use of a 14-day WHO protocol, which takes into account the clinical, parasitological and haematological responses to antimalarial drugs, to determine the efficacy of chloroquine in the treatment of uncomplicated malaria in young children (n = 200) in urban Dar es Salaam. Chloroquine failure was found in 43% of the children. Of these, 12.5% were considered to be early treatment failures and were given a single dose of sulfadoxine-pyrimethamine. Fever subsided in all children treated with sulfadoxine-pyrimethamine and there were no parasitological failures. In addition, children treated with sulfadoxine-pyrimethamine because of early treatment failure with chloroquine had better haematological recovery than the chloroquine-sensitive group. It is concluded that chloroquine can no longer be considered an effective therapy for P. falciparum malaria in young children in Dar es Salaam. PMID:10534897

Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial.

PubMed

Asante, Kwaku Poku; Abdulla, Salim; Agnandji, Selidji; Lyimo, John; Vekemans, Johan; Soulanoudjingar, Solange; Owusu, Ruth; Shomari, Mwanajaa; Leach, Amanda; Jongert, Erik; Salim, Nahya; Fernandes, Jose F; Dosoo, David; Chikawe, Maria; Issifou, Saadou; Osei-Kwakye, Kingsley; Lievens, Marc; Paricek, Maria; Möller, Tina; Apanga, Stephen; Mwangoka, Grace; Dubois, Marie-Claude; Madi, Tigani; Kwara, Evans; Minja, Rose; Hounkpatin, Aurore B; Boahen, Owusu; Kayan, Kingsley; Adjei, George; Chandramohan, Daniel; Carter, Terrell; Vansadia, Preeti; Sillman, Marla; Savarese, Barbara; Loucq, Christian; Lapierre, Didier; Greenwood, Brian; Cohen, Joe; Kremsner, Peter; Owusu-Agyei, Seth; Tanner, Marcel; Lell, Bertrand

2011-10-01

The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI). 8 month follow-up data have been reported for safety and immunogenicity of RTS,S/AS01(E) when integrated into the EPI. We report extended follow-up to 19 months, including efficacy results. We did a randomised, open-label, phase 2 trial of safety and efficacy of the RTS,S/AS01(E) candidate malaria vaccine given with EPI vaccines between April 30, 2007, and Oct 7, 2009, in Ghana, Tanzania, and Gabon. Eligible children were 6-10 weeks of age at first vaccination, without serious acute or chronic illness. All children received the EPI diphtheria, tetanus, pertussis (inactivated whole-cell), and hepatitis-B vaccines, Haemophilus influenzae type b vaccine, and oral polio vaccine at study months 0, 1, and 2, and measles vaccine and yellow fever vaccines at study month 7. Participants were randomly assigned (1:1:1) to receive three doses of RTS,S/AS01(E) at 6, 10, and 14 weeks (0, 1, 2 month schedule) or at 6 weeks, 10 weeks, and 9 months (0, 2, 7 month schedule) or placebo. Randomisation was according to a predefined block list with a computer-generated randomisation code. Detection of serious adverse events and malaria was by passive case detection. Antibodies against Plasmodium falciparum circumsporozoite protein and HBsAg were monitored for 19 months. This study is registered with ClinicalTrials.gov, number NCT00436007. 511 children were enrolled. Serious adverse events occurred in 57 participants in the RTS,S/AS01(E) 0, 1, 2 month group (34%, 95% CI 27-41), 47 in the 0, 1, 7 month group (28%, 21-35), and 49 (29%, 22-36) in the control group; none were judged to be related to study vaccination. At month 19, anticircumsporozoite immune responses were significantly higher in the RTS,S/AS01(E) groups than in the control group. Vaccine efficacy for the 0, 1, 2 month schedule (2 weeks after dose three to month 19, site-adjusted according-to-protocol analysis) was 53% (95% CI 26-70; p=0·0012) against first malaria episodes and 59% (36-74; p=0·0001) against all malaria episodes. For the entire study period, (total vaccinated cohort) vaccine efficacy against all malaria episodes was higher with the 0, 1, 2 month schedule (57%, 95% CI 33-73; p=0·0002) than with the 0, 1, 7 month schedule (32% CI 16-45; p=0·0003). 1 year after dose three, vaccine efficacy against first malaria episodes was similar for both schedules (0, 1, 2 month group, 61·6% [95% CI 35·6-77·1], p<0·001; 0, 1, 7 month group, 63·8% [40·4-78·0], p<0·001, according-to-protocol cohort). Vaccine efficacy was consistent with the target put forward by the WHO-sponsored malaria vaccine technology roadmap for a first-generation malaria vaccine. The 0, 1, 2 month vaccine schedule has been selected for phase 3 candidate vaccine assessment. Program for Appropriate Technology in Health Malaria Vaccine Initiative; GlaxoSmithKline Biologicals. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prevention of recurrent urinary tract infections in women.

PubMed

2013-06-01

Around 40-50% of women experience at least one urinary tract infection (UTI) during their lifetime and 20-30% of these have a recurrence within 3-4 months of the initial infection.¹ Recurrent UTI (usually defined as three episodes in the last 12 months or two episodes in the last 6 months) can have a considerable impact on a woman's quality of life. Each episode of acute UTI in young women is typically associated with about 6 days of symptoms, 2.4 days of restricted activities and 0.4 days of bed rest.¹ Antibacterial prophylaxis is effective in preventing recurrent episodes, but at the expense of unwanted effects and a risk of promoting bacterial resistance. Here we assess the efficacy of different antibacterial regimens and non-antibacterial alternatives (cranberry, probiotics, oestrogens, immunostimulation, hyaluronic acid and chondroitin, acupuncture and herbs) in the prevention of recurrent uncomplicated UTIs in women.

Randomized Controlled Trial of Levamisole Hydrochloride as Adjunctive Therapy in Severe Falciparum Malaria With High Parasitemia

PubMed Central

Maude, Richard J.; Silamut, Kamolrat; Plewes, Katherine; Charunwatthana, Prakaykaew; Ho, May; Abul Faiz, M.; Rahman, Ridwanur; Hossain, Md Amir; Hassan, Mahtab U.; Bin Yunus, Emran; Hoque, Gofranul; Islam, Faridul; Ghose, Aniruddha; Hanson, Josh; Schlatter, Joel; Lacey, Rachel; Eastaugh, Alison; Tarning, Joel; Lee, Sue J.; White, Nicholas J.; Chotivanich, Kesinee; Day, Nicholas P. J.; Dondorp, Arjen M.

2014-01-01

Background. Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine. Methods. Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate. Results. Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0–28 025) parasites/µL × hour in patients treated with levamisole and 5489 (IQR, 192–25 848) parasites/µL × hour in controls (P = .25). The “sequestration ratios” at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P > .40). The median time to normalization of plasma lactate (<2 mmol/L) was 24 (IQR, 12–30) hours with levamisole vs 28 (IQR, 12–36) hours without levamisole (P = .15). Conclusions. There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole. PMID:23943850

Feasibility and implementation of community-based malaria case management with integrated vector control in the Democratic Republic of Congo.

PubMed

Swana, Edouard Kawawa; Makan, Ghislain Yav; Mukeng, Clarence Kaut; Mupumba, Henriette Ilunga; Kalaba, Gabriel Mutabusha; Luboya, Oscar Numbi; Bangs, Michael J

2016-08-15

Malaria prevalence in the Mulumbu Health Area in Lualaba Province, Democratic Republic of the Congo has remained high (>70 %) despite repeated vector control (indoor residual spray) and mass insecticide-treated bed net coverage. Therefore, a pilot study was implemented to attack the parasite directly and demonstrate the feasibility and acceptability of community case management of malaria (CCMm) using trained community health workers (CHWs). A 13 month prospective evaluation of CCMm was undertaken in 14 rural villages. Focus group discussions and structured interviews were conducted in pre- and post-intervention periods to assess community acceptability of CCMm. Weekly data collected by CHWs assessed program impact over time, matched with malaria school-based prevalence surveys (MSPS) in the Mulumbu Health Area (CCMm study arm) compared to a comparison (non-CCMm) arm in the Mpala Health Area approximately 25 km apart. Overall population perception of the CCMm was highly positive. 6619 community contacts were managed by CHWs from which 1433 (21.6 %) were malaria positive by rapid detection tests during the 10 month intervention. Among the malaria infected, 94.7 % (1358) were recorded as 'uncomplicated' infections with 99.7 % provided full course of treatment. CHWs referred 278 (4.2 %) patients deemed 'complicated' to a designated primary health center for advanced care. While pre-intervention MSPS data revealed significantly higher (p = 0.0135) malaria in the CCMm area compared to the non-CCMm area, at post-intervention there was no statistical difference (p = 0.562) between the two areas. Notably, for the first time, no malaria-related deaths were recorded in the 14 CCMm intervention villages during observation. Community case management of malaria was shown to be an effective and promising strategy for prompt and effective management of malaria. It was well accepted by the community and showed evidence of a reduction in malaria morbidity and mortality. Further refinement of CCMm implementation, cost implications and sustainability is advised before expanding the programme.

Factors associated with contracting malaria in Ward 29 of Shamva District, Zimbabwe, 2014.

PubMed

Muchena, Gladwin; Gombe, Notion; Takundwa, Lucia; Tshimanga, Mufuta; Bangure, Donewell; Masuka, Nyasha; Juru, Tsitsi

2017-04-25

Malaria cases at Wadzanayi Clinic in Shamva District, Zimbabwe, increased drastically, surpassing the epidemic threshold, in week four of December 2013. This rise was sustained, which necessitated an investigation of the outbreak. To identify risk factors and system weaknesses to improve epidemic preparedness and response. An unmatched 1:1 case-control study was conducted in Ward 29 of Shamva District in Zimbabwe. Epidemic preparedness and response were assessed using the Zimbabwean epidemic preparedness and response guidelines. The sociodemographic characteristics of all participants were similar, except for gender. The risk factors for contracting malaria were performing early morning chores (odds ratio (OR) 2.75; 95% confidence interval (CI) 1.20 - 6.32), having a body of water near the home (OR 3.41; 95% CI 1.62 - 7.20) and having long grass near the home (OR 2.61; 95% CI 1.10 - 6.37). Protective factors were staying indoors at night (OR 0.13; 95% CI 0.06 - 0.28) and staying in a sprayed home (OR 0.36; 95% CI 0.21 - 0.92). All cases were diagnosed with a malaria rapid diagnostic test. All complicated cases were treated with quinine. Four out of 58 uncomplicated cases were treated with quinine. The rest were treated with co-artemether. There was no documentation of the outbreak response by the district health executive. Respraying (indoor residual spraying) was carried out, with a coverage of 78% of rooms sprayed. One nurse out of seven at Wadzanayi Clinic was trained in integrated disease surveillance and response, and malaria case management. District malaria thresholds were outdated. Malaria commodities such as drugs and sprays did not have reorder limits. This study re-emphasises the importance of environmental- and personal-level factors as determinants of malaria. Poor out-break preparedness and response may have propagated the malaria outbreak in this setting. Health education and the use of mosquito repellants should be emphasised. Larvicide may reduce the malaria burden. Epidemic preparedness and response need to be strengthened. Outbreak investigation remains important. This study emphasises the need for malaria interventions to be tailored to locally prevailing determinants to avert outbreaks.

Haemoglobin changes and risk of anaemia following treatment for uncomplicated falciparum malaria in sub-Saharan Africa.

PubMed

Zwang, Julien; D'Alessandro, Umberto; Ndiaye, Jean-Louis; Djimdé, Abdoulaye A; Dorsey, Grant; Mårtensson, Andreas A; Karema, Corine; Olliaro, Piero L

2017-06-23

Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop of -12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15's, the mean Hb decline between day 0-3 was -4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline. Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28. There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia. On presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1-2, followed by a linear increase through follow-up. The degree of the early Hb dip is determined by pre-treatment parasitaemia and parasite clearance rates. Hb trends and rick of anaemia are independent of treatment.

In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene

PubMed Central

2013-01-01

Background Dihydroartemisinin-piperaquine is a new ACT that is administered as single daily dose for three days and has been demonstrated to be tolerated and highly effective for the treatment of uncomplicated Plasmodium falciparum malaria. Piperaquine was used alone to replace chloroquine as the first-line treatment for uncomplicated malaria in China in response to increasing chloroquine resistance in the 1970s. However, the rapid emergence of piperaquine-resistant strains that resulted in the cessation of its use in China in the 1980s, suggests that there is cross-resistance between piperaquine and chloroquine. Very few data are available on cross-resistance between piperaquine and chloroquine, and the data that do exist are often contradictory. Methods In total, 280 P. falciparum isolates, collected between April 2008 and June 2012 from patients hospitalized in France with imported malaria from a malaria-endemic country, were assessed ex vivo for piperaquine and chloroquine susceptibilities by using the standard 42-hour 3H-hypoxanthine uptake inhibition method. The chloroquine resistance-associated mutation K76T in pfcrt was also investigated for the 280 isolates. Results The IC50 for piperaquine ranged from 9.8 nM to 217.3 nM (mean = 81.3 nM. The IC50 for chloroquine ranged from 5.0 nM to 1,918 nM (mean = 83.6 nM. A significant but low correlation was observed between the Log IC50 values for piperaquine and chloroquine (r = 0.145, p < 0.001). However, the coefficient of determination of 0.021 indicates that only 2.1% of the variation in the response to piperaquine is explained by the variation in the response to chloroquine. The mean value for piperaquine was 74.0 nM in the Pfcrt K76 wild-type group (no = 125) and 87.7 nM in the 76 T mutant group (no = 155). This difference was not significant (p = 0.875, Mann Whitney U test). Conclusions The present work demonstrates that there was no cross-resistance between piperaquine and chloroquine among 280 P. falciparum isolates and that piperaquine susceptibility is not associated with pfcrt, the gene involved in chloroquine resistance. These results confirm the efficacy of piperaquine in association with dihydroartemisinin and support its use in areas in which parasites are resistant to chloroquine. PMID:24274185

Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone.

PubMed

Smith, Samuel J; Kamara, Anitta R Y; Sahr, Foday; Samai, Mohamed; Swaray, Alpha S; Menard, Didier; Warsame, Marian

2018-06-19

Currently, the national malaria control programme (NMCP) of Sierra Leone recommends artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as first- and second-line treatment for uncomplicated malaria, respectively, and artesunate + sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment during pregnancy and for infants. In 2016, the NMCP conducted a study to assess the clinical and parasitological responses of children under five years to ASAQ, AL and dihydroartemisinin-piperaquine (DHA/PPQ) according to the WHO protocol. Day-0 samples were tested for mutations in the Kelch 13 gene (pfk13) and dihydrofolate reductase/dihydropteroate synthase (dhfr/dhps) genes associated with artemisinin and SP resistance, respectively, and amplification in the Pfplasmepsin2 gene for piperaquine resistance. A total of 295 (ASAQ = 128, AL = 64 and DHA/PPQ = 103) eligible children were enrolled at three sites. PCR-corrected 100% adequate clinical and parasitological response and no parasitaemia on day-3 were observed for all patients in each treatment group. Of the 278 samples with interpretable molecular data, only 2.2% carried non-synonymous pfk13 mutants (A578S, I646T), which are not associated with artemisinin resistance. None of the 103 day-0 samples from the DAH/PPQ group had Pfplasmepsin2 gene amplification, confirming the absence of piperaquine resistance. The prevalence of the triple pfdhfr mutant (N51I/C59R/S108N) was close to or reached fixation (97.4-100%). For combined pfdhfr/pfdhps mutation, 55-71% carried the quadruple (N51I/C59R/S108N+A437G) mutant and about 10% the quintuple mutant N51I/C59R/S108N+A437G/K540E. Our findings confirm that ASAQ, AL and DHA/PPQ were highly effective for the treatment of uncomplicated malaria in the study areas, and neither pfk13 validated mutations nor Pfplasmepsin2 multiple copies were found. The very low prevalence of the quintuple mutant in this study supports the NMCP's decision to introduce intermittent preventive treatment for infants with SP in the districts with high malaria transmission. Copyright © 2018. Published by Elsevier B.V.

Medical Surveillance Monthly Report. Volume 23, Number 1, January 2016

DTIC Science & Technology

2016-01-01

Volume 23 Number 1 P A G E 2 Update: Malaria , U.S. Armed Forces, 2015 P A G E 7 Durations of service until first and recurrent episodes of...of special surveillance interest CDC/James Gathany MSMR Vol. 23 No. 1 January 2016 Page 2 U.S. service members are at risk of acquiring malaria ...personal travel. Th e num- ber of malaria cases among U.S. military service members in 2015 (n=30) was the lowest annual count in at least 20 years and

Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

PubMed

White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

2016-09-22

KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01753323 .).

Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria.

PubMed

Jamsen, Kris M; Duffull, Stephen B; Tarning, Joel; Lindegardh, Niklas; White, Nicholas J; Simpson, Julie A

2012-07-11

Artemisinin-based combination therapy (ACT) is currently recommended as first-line treatment for uncomplicated malaria, but of concern, it has been observed that the effectiveness of the main artemisinin derivative, artesunate, has been diminished due to parasite resistance. This reduction in effect highlights the importance of the partner drugs in ACT and provides motivation to gain more knowledge of their pharmacokinetic (PK) properties via population PK studies. Optimal design methodology has been developed for population PK studies, which analytically determines a sampling schedule that is clinically feasible and yields precise estimation of model parameters. In this work, optimal design methodology was used to determine sampling designs for typical future population PK studies of the partner drugs (mefloquine, lumefantrine, piperaquine and amodiaquine) co-administered with artemisinin derivatives. The optimal designs were determined using freely available software and were based on structural PK models from the literature and the key specifications of 100 patients with five samples per patient, with one sample taken on the seventh day of treatment. The derived optimal designs were then evaluated via a simulation-estimation procedure. For all partner drugs, designs consisting of two sampling schedules (50 patients per schedule) with five samples per patient resulted in acceptable precision of the model parameter estimates. The sampling schedules proposed in this paper should be considered in future population pharmacokinetic studies where intensive sampling over many days or weeks of follow-up is not possible due to either ethical, logistic or economical reasons.

Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania

PubMed Central

Saulo, Eleonor C; Forsberg, Birger C; Premji, Zul; Montgomery, Scott M; Björkman, Anders

2008-01-01

Background The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored. Methods Structured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors. Results Among 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care. "Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug. Conclusion WTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded. PMID:18976453

Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania.

PubMed

Saulo, Eleonor C; Forsberg, Birger C; Premji, Zul; Montgomery, Scott M; Björkman, Anders

2008-10-31

The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored. Structured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors. Among 265 mothers and household heads, 244 (92%, CI = 88%-95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%-61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2-3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug. WTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem fully at governmental health care facilities and at a consumer price of TSh 300-500 (US$ 0.28-0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.

Artemisinin resistance--modelling the potential human and economic costs.

PubMed

Lubell, Yoel; Dondorp, Arjen; Guérin, Philippe J; Drake, Tom; Meek, Sylvia; Ashley, Elizabeth; Day, Nicholas P J; White, Nicholas J; White, Lisa J

2014-11-23

Artemisinin combination therapy is recommended as first-line treatment for falciparum malaria across the endemic world and is increasingly relied upon for treating vivax malaria where chloroquine is failing. Artemisinin resistance was first detected in western Cambodia in 2007, and is now confirmed in the Greater Mekong region, raising the spectre of a malaria resurgence that could undo a decade of progress in control, and threaten the feasibility of elimination. The magnitude of this threat has not been quantified. This analysis compares the health and economic consequences of two future scenarios occurring once artemisinin-based treatments are available with high coverage. In the first scenario, artemisinin combination therapy (ACT) is largely effective in the management of uncomplicated malaria and severe malaria is treated with artesunate, while in the second scenario ACT are failing at a rate of 30%, and treatment of severe malaria reverts to quinine. The model is applied to all malaria-endemic countries using their specific estimates for malaria incidence, transmission intensity and GDP. The model describes the direct medical costs for repeated diagnosis and retreatment of clinical failures as well as admission costs for severe malaria. For productivity losses, the conservative friction costing method is used, which assumes a limited economic impact for individuals that are no longer economically active until they are replaced from the unemployment pool. Using conservative assumptions and parameter estimates, the model projects an excess of 116,000 deaths annually in the scenario of widespread artemisinin resistance. The predicted medical costs for retreatment of clinical failures and for management of severe malaria exceed US$32 million per year. Productivity losses resulting from excess morbidity and mortality were estimated at US$385 million for each year during which failing ACT remained in use as first-line treatment. These 'ballpark' figures for the magnitude of the health and economic threat posed by artemisinin resistance add weight to the call for urgent action to detect the emergence of resistance as early as possible and contain its spread from known locations in the Mekong region to elsewhere in the endemic world.

[Imported malaria in University Hospital Center of Bordeaux, France, 2000-2007. A comparison study with the French national epidemiological data].

PubMed

Pistone, T; Diallo, A; Receveur, M C; Mansour, R; Roger-Schmeltz, J; Millet, P; Malvy, D

2010-05-01

In Western countries, France accounts for the most concerned by imported malaria. The objective of the present study was to describe the epidemiological and clinical features of imported malaria in adults attending the University Hospital Center (UHC) ofBordeaux and to compare these findings with the French national epidemiological data. A retrospective analysis of all patients aged over 15 years with parasitologically confirmed malaria in patients recruited between January 1, 2000 and December 31, 2007 has been performed. A total of 526 cases fitted the inclusion criteria with two-thirds of males and a mean age of 37 years. Patients were less frequently native from sub-Saharan Africa (SA), Madagascar, and Comoros than those from the French national data register (29 versus 72%). Hence, SA was the main destination (2/3 travelling to Western Africa and 1/3 to Central Africa). The recourse to an adequate chemoprophylaxis (CPL) for stays in areas of chemoresistance had been reported in about one-third of the patients. From these, two thirds were noncompliant. The recourse to chloroquine less frequent (6 versus 24%) among patients from Bordeaux compared to those from the national data register whereas the recourse to mosquito net use more frequent in patients from Bordeaux (36 versus 3%). Plasmodium falciparum was the main infective species.Malaria was more frequently associated with hospitalization (89 versus 71%) and with severe disease (9 versus 4%) in Bordeaux than in national data register. Two deaths were declared. Atovaquone-proguanil (AP) combination therapy wasmore frequently used in Bordeaux compared to the national data (64 versus 20%). This AP combination treatment was the most frequently prescribed for uncomplicated malaria, whereas intravenous quinine was mainly used for complicated malaria and for patients with vomiting. The lack of CPL, the diagnosis or therapeutic delay, and the lethality of malaria among travellers infected by malaria imported from SA argue for the implementation of continuing medical training and health education targeted at travellers from France to high malaria-endemic areas such as SA, Madagascar, and Comoros.

Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian children.

PubMed

Arama, Charles; Diarra, Issa; Kouriba, Bourèma; Sirois, Francine; Fedoryak, Olesya; Thera, Mahamadou A; Coulibaly, Drissa; Lyke, Kirsten E; Plowe, Christopher V; Chrétien, Michel; Doumbo, Ogobara K; Mbikay, Majambu

2018-01-01

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a hepatic secretory protein which promotes the degradation of low-density lipoprotein receptors leading to reduced hepatic uptake of plasma cholesterol. Non-synonymous single-nucleotide polymorphisms in its gene have been linked to hypo- or hyper- cholesterolemia, depending on whether they decrease or increase PCSK9 activity, respectively. Since the proliferation and the infectivity of Plasmodium spp. partially depend on cholesterol from the host, we hypothesize that these PCSK9 genetic polymorphisms could influence the course of malaria infection in individuals who carry them. Here we examined the frequency distribution of one dominant (C679X) and two recessive (A443T, I474V) hypocholesterolemic polymorphisms as well as that of one recessive hypercholesterolemic polymorphism (E670G) among healthy and malaria-infected Malian children. Dried blood spots were collected in Bandiagara, Mali, from 752 age, residence and ethnicity-matched children: 253 healthy controls, 246 uncomplicated malaria patients and 253 severe malaria patients. Their genomic DNA was extracted and genotyped for the above PCSK9 polymorphisms using Taqman assays. Associations of genotype distributions and allele frequencies with malaria were evaluated. The minor allele frequency of the A443T, I474V, E670G, and C679X polymorphisms in the study population sample was 0.12, 0.20, 0.26, and 0.02, respectively. For each polymorphism, the genotype distribution among the three health conditions was statistically insignificant, but for the hypercholesterolemic E670G polymorphism, a trend towards association of the minor allele with malaria severity was observed (P = 0.035). The association proved to be stronger when allele frequencies between healthy controls and severe malaria cases were compared (Odd Ratio: 1.34; 95% Confidence Intervals: 1.04-1.83); P = 0.031). Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible to severe malaria. Further investigation of the cholesterol regulating function of PCSK9 in the pathophysiology of malaria is needed.

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study

PubMed Central

Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

2015-01-01

Summary Background The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. Methods We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3–12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. Findings 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70–0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99–1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22–2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86–1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82–1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. Interpretation Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. Funding Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative). PMID:26686045

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study.

PubMed

Uyoga, Sophie; Ndila, Carolyne M; Macharia, Alex W; Nyutu, Gideon; Shah, Shivang; Peshu, Norbert; Clarke, Geraldine M; Kwiatkowski, Dominic P; Rockett, Kirk A; Williams, Thomas N

2015-10-01

The global prevalence of X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is thought to be a result of selection by malaria, but epidemiological studies have yielded confusing results. We investigated the relationships between G6PD deficiency and both malaria and non-malarial illnesses among children in Kenya. We did this study in Kilifi County, Kenya, where the G6PD c.202T allele is the only significant cause of G6PD deficiency. We tested the associations between G6PD deficiency and severe and complicated Plasmodium falciparum malaria through a case-control study of 2220 case and 3940 control children. Cases were children aged younger than 14 years, who visited the high dependency ward of Kilifi County Hospital with severe malaria between March 1, 1998, and Feb 28, 2010. Controls were children aged between 3-12 months who were born within the same study area between August 2006, and September 2010. We assessed the association between G6PD deficiency and both uncomplicated malaria and other common diseases of childhood in a cohort study of 752 children aged younger than 10 years. Participants of this study were recruited from a representative sample of households within the Ngerenya and Chonyi areas of Kilifi County between Aug 1, 1998, and July 31, 2001. The primary outcome measure for the case-control study was the odds ratio for hospital admission with severe malaria (computed by logistic regression) while for the cohort study it was the incidence rate ratio for uncomplicated malaria and non-malaria illnesses (computed by Poisson regression), by G6PD deficiency category. 2863 (73%) children in the control group versus 1643 (74%) in the case group had the G6PD normal genotype, 639 (16%) versus 306 (14%) were girls heterozygous for G6PD c.202T, and 438 (11%) versus 271 (12%) children were either homozygous girls or hemizygous boys. Compared with boys and girls without G6PD deficiency, we found significant protection from severe malaria (odds ratio [OR] 0·82, 95% CI 0·70-0·97; p=0·020) among G6PD c.202T heterozygous girls but no evidence for protection among G6PD c.202T hemizygous boys and homozygous girls (OR 1·18, 0·99-1·40; p=0·056). Median follow-up for the mild disease cohort study was 2·24 years (IQR 2·22-2·85). G6PD c.202T had no effect on other common diseases of childhood in heterozygous girls (incidence rate ratio 0·98, 95% CI 0·86-1·11; p=0·82) or homozygous girls or hemizygous boys (0·93, 0·82-1·04; p=0·25), with the sole exception of a marginally significant increase in the incidence of helminth infections among heterozygous girls. Heterozygous girls might be the driving force for the positive selection of G6PD deficiency alleles. Further studies are needed to definitively establish the mechanisms by which G6PD deficiency confers an advantage against malaria in heterozygous individuals. Such studies could lead to the development of new treatments. Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health (as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative). Copyright © 2015 Uyoga et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines.

PubMed

Fowkes, Freya J I; Simpson, Julie A; Beeson, James G

2013-10-30

Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

Clinical and molecular surveillance of drug resistant vivax malaria in Myanmar (2009-2016).

PubMed

Nyunt, Myat Htut; Han, Jin-Hee; Wang, Bo; Aye, Khin Myo; Aye, Kyin Hla; Lee, Seong-Kyun; Htut, Ye; Kyaw, Myat Phone; Han, Kay Thwe; Han, Eun-Taek

2017-03-16

One of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance. While epidemiology and surveillance of the drug resistance in falciparum malaria is being explored globally, there are few studies on drug resistance vivax malaria. To assess the spread of drug-resistant vivax malaria in Myanmar, a multisite, prospective, longitudinal study with retrospective analysis of previous therapeutic efficacy studies, was conducted. A total of 906 from nine study sites were included in retrospective analysis and 208 from three study sites in prospective study. Uncomplicated vivax mono-infected patients were recruited and monitored with longitudinal follow-up until day 28 after treatment with chloroquine. Amplification and sequence analysis of molecular markers, such as mutations in pvcrt-O, pvmdr1, pvdhps and pvdhfr, were done in day-0 samples in prospective study. Clinical failure cases were found only in Kawthaung, southern Myanmar and western Myanmar sites within 2009-2016. Chloroquine resistance markers, pvcrt-O 'AAG' insertion and pvmdr1 mutation (Y976F) showed higher mutant rate in southern and central Myanmar than western site: 66.7, 72.7 vs 48.3% and 26.7, 17.0 vs 1.7%, respectively. A similar pattern of significantly higher mutant rate of antifolate resistance markers, pvdhps (S382A, K512M, A553G) and pvdhfr (F57L/I, S58R, T61M, S117T/N) were noted. Although clinical failure rate was low, widespread distribution of chloroquine and antifolate resistance molecular makers alert to the emergence and spread of drug resistance vivax malaria in Myanmar. Proper strategy and action plan to eliminate and contain the resistant strain strengthened together with clinical and molecular surveillance on drug resistance vivax is recommended.

Cost–effectiveness of artemisinin combination therapy for uncomplicated malaria in children: data from Papua New Guinea

PubMed Central

Davis, Wendy A; Clarke, Philip M; Siba, Peter M; Karunajeewa, Harin A; Davy, Carol; Mueller, Ivo

2011-01-01

Abstract Objective To compare the cost–effectiveness of conventional antimalarial therapy with that of three artemisinin combination treatment regimens in children from Papua New Guinea aged 6 to 60 months. Methods An incremental cost–effectiveness analysis was performed using data from 656 children with Plasmodium falciparum and/or P. vivax malaria who participated in a large intervention trial in two clinics in northern Papua New Guinea. The children were randomized to one of the following groups: (i) conventional treatment with chloroquine plus sulfadoxine plus pyrimethamine (CQ+S+P); (ii) artesunate plus S plus P; (iii) dihydroartemisinin plus piperaquine (DHA+PQ); and (iv) artemether plus lumefantrine (A+L). For treatment outcomes, World Health Organization definitions were used. The cost of transport between home and the clinic plus direct health-care costs served as a basis for determining each regimen’s incremental cost per incremental treatment success relative to CQ+S+P by day 42 and its cost per life year saved. Findings A+L proved to be the most effective regimen against P. falciparum malaria and was highly cost-effective at 6.97 United States dollars (US$) per treatment success (about US$ 58 per life year saved). DHA+PQ was the most effective regimen against P. vivax malaria and was more cost-effective than CQ+S+P. Conclusion A+L and DHA+PQ are highly cost-effective regimens for the treatment of paediatric P. falciparum and P. vivax malaria, respectively, in parts of Papua New Guinea. Future research will be required to determine if these findings hold true for other territories in Asia and Oceania with similar malaria epidemiology. PMID:21379417

Direct observation of outpatient management of malaria in a rural Ghanaian district.

PubMed

Ameme, Donne Kofi; Afari, Edwin Andrews; Nyarko, Kofi Mensah; Malm, Keziah Laurencia; Sackey, Samuel; Wurapa, Fred

2014-01-01

In Ghana, malaria continues to top outpatient morbidities; accounting for about 40% of all attendances. Effective case-management is key to its control. We evaluated case-management practices of uncomplicated malaria in Kwahu South District (KSD) health facilities to determine their conformity to guidelines. We conducted a cross sectional survey at all public health facilities in three randomly selected sub-districts in KSD. A non-participatory observation of suspected malaria consultations was conducted. Suspected malaria was defined as any person with fever (by history or measured axillary temperature > or equal 37.5 oC) presenting at the selected health facilities between 19th and 29th April 2013. Findings were expressed as frequencies, relative frequencies, mean (± standard deviation) and median. Of 70 clinical observations involving 10 prescribers in six health facilities, 40 (57.1%) were females and 16 (22.9%) were below five years. Median age was 18 years (interquartile range: 5-33). Overall, 63 (90.0%) suspected case-patients had diagnostic tests. Two (3.6%) were treated presumptively. All 31 confirmed and 10 (33.3%) of the test negative case-patients received Artemisinin-based Combination Therapies (ACTs). However, only 12 (27.9%) of the 43 case-patients treated with ACT received Artesunate-Amodiaquine (AA). Only three (18.8%) of the under-fives were examined for non-malarial causes of fever. Mean number of drugs per patient was 3.7 drugs (± 1.1). Only 45 (64.3%) patients received at least one counseling message. Conformity of malaria case-management practices to guidelines in KSD was suboptimal. Apart from high rate of diagnostic testing and ACT use, prescription of AA, physical examination and counseling needed improvement.

Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children.

PubMed

Guiyedi, Vincent; Chanseaud, Youri; Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-04-25

Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFalpha), with the manifestation of CM in Gabonese children. To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFalpha concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFalpha concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

PubMed Central

Fesel, Constantin; Snounou, Georges; Rousselle, Jean-Claude; Lim, Pharat; Koko, Jean; Namane, Abdelkader; Cazenave, Pierre-André; Kombila, Maryvonne; Pied, Sylviane

2007-01-01

Background Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. Methodology To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. Results/Conclusion The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM. PMID:17460756

Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria Transmission Areas of Kenya.

PubMed

de Laurent, Zaydah R; Chebon, Lorna J; Ingasia, Luicer A; Akala, Hoseah M; Andagalu, Ben; Ochola-Oyier, Lynette Isabella; Kamau, Edwin

2018-05-01

The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller domain have been useful in identifying ART resistance in SEA. ART combination therapy (ACT) remains highly efficacious in the treatment of uncomplicated malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of ACT is closely monitored. Toward this effort, this study profiled the prevalence of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and in different time periods, before (pre) and after (post) the introduction of ACT as the first-line treatment of malaria. Nineteen nonsynonymous mutations were present in the pre-ACT samples ( N = 64) compared with 22 in the post-ACT samples ( N = 251). Eight of these mutations were present in both pre- and post-ACT parasites. Interestingly, seven of the shared single-nucleotide polymorphisms were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S mutation reported in SSA and the V568G mutation reported in SEA were found in both pre- and post-ACT parasites, with their frequencies declining post-ACT. D584Y and R539K mutations were found only in post-ACT parasites; changes in these codons have also been reported in SEA with different amino acids. The N585K mutation described for the first time in this study was present only in post-ACT parasites, and it was the most prevalent mutation at a frequency of 5.2%. This study showed the type, prevalence, and frequency of K13 mutations that varied based on the malaria ecological zones and also between the pre- and post-ACT time periods.

Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria.

PubMed

Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

2014-03-04

The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. To evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria. We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; ClinicalTrials.gov; the metaRegister of Controlled Trials (mRCT); and the WHO International Clinical Trials Search Portal up to 16 January 2014. We searched reference lists and conference abstracts, and contacted experts for information about ongoing and unpublished trials. Randomized controlled trials of artesunate-pyronaridine versus other ACTs in adults and children with uncomplicated P. falciparum malaria.For the safety analysis, we also included adverse events data from trials comparing any treatment regimen containing pyronaridine with regimens not containing pyronaridine. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence. We included six randomized controlled trials enrolling 3718 children and adults. Artesunate-pyronaridine versus artemether-lumefantrineIn two multicentre trials, enrolling mainly older children and adults from west and south-central Africa, both artesunate-pyronaridine and artemether-lumefantrine had fewer than 5% PCR adjusted treatment failures during 42 days of follow-up, with no differences between groups (two trials, 1472 participants, low quality evidence). There were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.60, 95% CI 0.40 to 0.90, two trials, 1720 participants, moderate quality evidence), but no difference was detected over the whole 42 day follow-up (two trials, 1691 participants, moderate quality evidence). Artesunate-pyronaridine versus artesunate plus mefloquineIn one multicentre trial, enrolling mainly older children and adults from South East Asia, both artesunate-pyronaridine and artesunate plus mefloquine had fewer than 5% PCR adjusted treatment failures during 28 days follow-up (one trial, 1187 participants, moderate quality evidence). PCR-adjusted treatment failures were 6% by day 42 for these treated with artesunate-pyronaridine, and 4% for those with artesunate-mefloquine (RR 1.64, 95% CI 0.89 to 3.00, one trial, 1116 participants, low quality evidence). Again, there were fewer new infections during the first 28 days in those given artesunate-pyronaridine (PCR-unadjusted treatment failure: RR 0.35, 95% CI 0.17 to 0.73, one trial, 1720 participants, moderate quality evidence), but no differences were detected over the whole 42 days (one trial, 1146 participants, low quality evidence). Adverse effectsSerious adverse events were uncommon in these trials, with no difference detected between artesunate-pyronaridine and comparator ACTs. The analysis of liver function tests showed biochemical elevation were four times more frequent with artesunate-pyronaridine than with the other antimalarials (RR 4.17, 95% CI 1.38 to 12.62, four trials, 3523 participants, moderate quality evidence). Artesunate-pyronaridine performed well in these trials compared to artemether-lumefantrine and artesunate plus mefloquine, with PCR-adjusted treatment failure at day 28 below the 5% standard set by the WHO. Further efficacy and safety studies in African and Asian children are required to clarify whether this combination is an option for first-line treatment.

Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial

PubMed Central

Stanisic, Danielle I.; Robinson, Leanne; Barnadas, Céline; Manong, Doris; Salib, Mary; Iga, Jonah; Tarongka, Nandao; Ley, Serej; Rosanas-Urgell, Anna; Aponte, John J.; Zimmerman, Peter A.; Beeson, James G.; Schofield, Louis; Siba, Peter; Rogerson, Stephen J.; Reeder, John C.; Mueller, Ivo

2012-01-01

Background Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv). Methods and Findings In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention. Conclusions IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv. Trial registration ClinicalTrials.gov NCT00285662 Please see later in the article for the Editors' Summary PMID:22479155

CYP2D6 activity and the risk of recurrence of Plasmodium vivax malaria in the Brazilian Amazon: a prospective cohort study.

PubMed

Brasil, Larissa W; Rodrigues-Soares, Fernanda; Santoro, Ana B; Almeida, Anne C G; Kühn, Andrea; Ramasawmy, Rajendranath; Lacerda, Marcus V G; Monteiro, Wuelton M; Suarez-Kurtz, Guilherme

2018-02-01

CYP2D6 pathway mediates the activation of primaquine into active metabolite(s) in hepatocytes. CYP2D6 is highly polymorphic, encoding CYP2D6 isoforms with normal, reduced, null or increased activity. It is hypothesized that Plasmodium vivax malaria patients with defective CYP2D6 function would be at increased risk for primaquine failure to prevent recurrence. The aim of this study was to investigate the association of CYP2D6 polymorphisms and inferred CYP2D6 phenotypes with malaria recurrence in patients from the Western Brazilian Amazon, following chloroquine/primaquine combined therapy. The prospective cohort consisted of P. vivax malaria patients who were followed for 6 months after completion of the chloroquine/primaquine therapy. Recurrence was defined as one or more malaria episodes, 28-180 days after the initial episode. Genotyping for nine CYP2D6 SNPs and copy number variation was performed using TaqMan assays in a Fast 7500 Real-Time System. CYP2D6 star alleles (haplotypes), diplotypes and CYP2D6 phenotypes were inferred, and the activity score system was used to define the functionality of the CYP2D6 diplotypes. CYP2D6 activity scores (AS) were dichotomized at ≤ 1 (gPM, gIM and gNM-S phenotypes) and ≥ 1.5 (gNM-F and gUM phenotypes). Genotyping was successfully performed in 190 patients (44 with recurrence and 146 without recurrences). Recurrence incidence was higher in individuals presenting reduced activity CYP2D6 phenotypes (adjusted relative risk = 1.89, 95% CI 1.01-3.70; p = 0.049). Attributable risk and population attributable fraction were 11.5 and 9.9%, respectively. The time elapsed from the first P. vivax malaria episode until the recurrence did not differ between patients with AS of ≤ 1 versus ≥ 1.5 (p = 0.917). The results suggest that CYP2D6 polymorphisms are associated with increased risk of recurrence of vivax malaria, following chloroquine-primaquine combined therapy. This association is interpreted as the result of reduced conversion of primaquine into its active metabolites in patients with reduced CYP2D6 enzymatic activity.

Impact of climate variability on the transmission risk of malaria in northern Côte d'Ivoire.

PubMed

M'Bra, Richard K; Kone, Brama; Soro, Dramane P; N'krumah, Raymond T A S; Soro, Nagnin; Ndione, Jacques A; Sy, Ibrahima; Ceccato, Pietro; Ebi, Kristie L; Utzinger, Jürg; Schindler, Christian; Cissé, Guéladio

2018-01-01

Since the 1970s, the northern part of Côte d'Ivoire has experienced considerable fluctuation in its meteorology including a general decrease of rainfall and increase of temperature from 1970 to 2000, a slight increase of rainfall since 2000, a severe drought in 2004-2005 and flooding in 2006-2007. Such changing climate patterns might affect the transmission of malaria. The purpose of this study was to analyze climate and environmental parameters associated with malaria transmission in Korhogo, a city in northern Côte d'Ivoire. All data were collected over a 10-year period (2004-2013). Rainfall, temperature and Normalized Difference Vegetation Index (NDVI) were the climate and environmental variables considered. Association between these variables and clinical malaria data was determined, using negative binomial regression models. From 2004 to 2013, there was an increase in the annual average precipitation (1100.3-1376.5 mm) and the average temperature (27.2°C-27.5°C). The NDVI decreased from 0.42 to 0.40. We observed a strong seasonality in these climatic variables, which resembled the seasonality in clinical malaria. An incremental increase of 10 mm of monthly precipitation was, on average, associated with a 1% (95% Confidence interval (CI): 0.7 to 1.2%) and a 1.2% (95% CI: 0.9 to 1.5%) increase in the number of clinical malaria episodes one and two months later respectively. A 1°C increase in average monthly temperature was, on average, associated with a decline of a 3.5% (95% CI: 0.1 to 6.7%) in clinical malaria episodes. A 0.1 unit increase in monthly NDVI was associated with a 7.3% (95% CI: 0.8 to 14.1%) increase in the monthly malaria count. There was a similar increase for the preceding-month lag (6.7% (95% CI: 2.3% to 11.2%)). The study results can be used to establish a malaria early warning system in Korhogo to prepare for outbreaks of malaria, which would increase community resilience no matter the magnitude and pattern of climate change.

Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children.

PubMed

Olotu, Ally; Fegan, Gregory; Wambua, Juliana; Nyangweso, George; Leach, Amanda; Lievens, Marc; Kaslow, David C; Njuguna, Patricia; Marsh, Kevin; Bejon, Philip

2016-06-30

The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group. Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P=0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P=0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P=0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P=0.008]). A three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.).

Emerging concepts in T follicular helper cell responses to malaria.

PubMed

Hansen, Diana S; Obeng-Adjei, Nyamekye; Ly, Ann; Ioannidis, Lisa J; Crompton, Peter D

2017-02-01

Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (T FH ) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced T H1 cytokines are associated with the activation of (i) T-like memory T FH cells with impaired B cell helper function, and (ii) pre-T FH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional T FH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses. Deeper knowledge of T FH cells in malaria could illuminate strategies to improve vaccines through modulating T FH cell responses. This review summarizes emerging concepts in T FH cell responses to malaria. Copyright © 2016. Published by Elsevier Ltd.

The malaria testing and treatment landscape in Kenya: results from a nationally representative survey among the public and private sector in 2016.

PubMed

Musuva, Anne; Ejersa, Waqo; Kiptui, Rebecca; Memusi, Dorothy; Abwao, Edward

2017-12-21

Since 2004, Kenya's national malaria treatment guidelines have stipulated artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria, and since 2014, confirmatory diagnosis of malaria in all cases before treatment has been recommended. A number of strategies to support national guidelines have been implemented in the public and private sectors in recent years. A nationally-representative malaria outlet survey, implemented across four epidemiological zones, was conducted between June and August 2016 to provide practical evidence to inform strategies and policies in Kenya towards achieving national malaria control goals. A total of 17,852 outlets were screened and 2271 outlets were eligible and interviewed. 78.3% of all screened public health facilities stocked both malaria diagnostic testing and quality-assured ACT (QAACT). Sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy was available in 70% of public health facilities in endemic areas where it is recommended for treatment. SP was rarely found in the public sector outside of the endemic areas (< 0.5%). The anti-malaria stocking private sector had lower levels of QAACT (46.7%) and malaria blood testing (20.8%) availability but accounted for majority of anti-malarial distribution (70.6% of the national market share). More than 40% of anti-malarials were distributed by unregistered pharmacies (37.3%) and general retailers (7.1%). QAACT accounted for 58.2% of the total anti-malarial market share, while market share for non-QAACT was 15.8% and for SP, 24.8%. In endemic areas, 74.9% of anti-malarials distributed were QAACT. Elsewhere, QAACT market share was 49.4% in the endemic-prone areas, 33.2% in seasonal-transmission areas and 37.9% in low-risk areas. Although public sector availability of QAACT and malaria diagnosis is relatively high, there is a gap in availability of both testing and treatment that must be addressed. The private sector in Kenya, where the majority of anti-malarials are distributed, is also critical for achieving universal coverage with appropriate malaria case management. There is need for a renewed commitment and effective strategies to ensure access to affordable QAACT and confirmatory testing in the private sector, and should consider how to address malaria case management among informal providers responsible for a substantial proportion of the anti-malarial market share.

Evaluation of case management of uncomplicated malaria in Haiti: a national health facility survey, 2012.

PubMed

Landman, Keren Z; Jean, Samuel E; Existe, Alexandre; Akom, Eniko E; Chang, Michelle A; Lemoine, Jean Frantz; Mace, Kimberly E

2015-10-09

Malaria is a public health concern in Haiti, although there are limited data on its burden and case management. National malaria guidelines updated in 2012 recommend treatment with chloroquine and primaquine. In December 2012, a nationally-representative cross-sectional survey of health facilities (HFs) was conducted to determine malaria prevalence among febrile outpatients and malaria case management quality at baseline before scale-up of diagnostics and case management training. Among all 833 HFs nationwide, 30 were selected randomly, in proportion to total HFs per region, for 2-day evaluations. Survey teams inventoried HF material and human resources. Outpatients of all ages were screened for temperature >37.5 °C or history of fever; those without severe symptoms were consented and enrolled. Providers evaluated and treated enrolled patients according to HF standards; the survey teams documented provider-ordered diagnostic tests and treatment decisions. Facility-based test results [microscopy and malaria rapid diagnostic tests (RDTs)] were collected from HF laboratories. Blood smears for gold-standard microscopy, and dried blood spots for polymerase chain reaction (PCR) were obtained. Malaria diagnostic capacity, defined as completing a test for an enrolled patient or having adequate resources for RDTs or microscopy, was present in 11 (37 %) HFs. Among 459 outpatients screened, 257 (56 %) were febrile, of which 193 (75 %) were eligible, and 153 (80 %) were enrolled. Among 39 patients with facility-level malaria test results available on the survey day, 11 (28 %) were positive, of whom 6 (55 %) were treated with an anti-malarial. Twenty-seven (95 %) of the 28 patients testing negative were not treated with an anti-malarial. Of 114 patients without test results available, 35 (31 %) were presumptively treated for malaria. Altogether, 42 patients were treated with an anti-malarial, one (2 %) according to Haiti's 2012 guidelines. Of 140 gold-standard smears, none were positive, although one patient tested positive by PCR, a more sensitive technique. The national prevalence of malaria among febrile outpatients is estimated to be 0.5 % (95 % confidence interval 0-1.7 %). Malaria is an uncommon cause of fever in Haitian outpatients, and limited, often inaccurate, diagnostic capacity at baseline contributes to over diagnosis. Scale-up of diagnostics and training on new guidelines should improve malaria diagnosis and treatment in Haiti.

Comparison of apoptosis in human primary pulmonary endothelial cells and a brain microvascular endothelial cell line co-cultured with Plasmodium falciparum field isolates.

PubMed

Essone, Jean Claude Biteghe Bi; N'Dilimabaka, Nadine; Ondzaga, Julien; Lekana-Douki, Jean Bernard; Mba, Dieudonné Nkoghe; Deloron, Philippe; Mazier, Dominique; Gay, Frédrérick; Touré Ndouo, Fousseyni S

2017-06-27

Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of malaria remain elusive. The cerebral microvascular endothelial cells-D3 and lung endothelial cells both from human were cultured separately and challenged with P. falciparum field isolates taken directly from malaria patients or 3D7 strain (in vitro maintained culture). The capacity of these P. falciparum isolates to induce endothelial cell apoptosis via cytoadherence or not was then assessed. Overall, 27 P. falciparum isolates were collected from patients with uncomplicated malaria (n = 25) or severe malaria (n = 2). About half the isolates (n = 17) were able to bind brain endothelial cells (12 isolates, 44%) or lung endothelial cells (17 isolates, 63%) or both (12 isolates, 44%). Sixteen (59%) of the 27 isolates were apoptogenic for brain and/or lung endothelial cells. The apoptosis stimulus could be cytoadherence, direct cell-cell contact without cytoadherence, or diffusible soluble factors. While some of the apoptogenic isolates used two stimuli (direct contact with or without cytoadherence, plus soluble factors) to induce apoptosis, others used only one. Among the 16 apoptogenic isolates, eight specifically targeted brain endothelial cells, one lung endothelial cells, and seven both. These results indicate that the brain microvascular cell line was more susceptible to apoptosis triggered by P. falciparum than the primary pulmonary endothelial cells and may have relevance to host-parasite interaction.

The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of var Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1.

PubMed

Mkumbaye, Sixbert I; Wang, Christian W; Lyimo, Eric; Jespersen, Jakob S; Manjurano, Alphaxard; Mosha, Jacklin; Kavishe, Reginald A; Mwakalinga, Steven B; Minja, Daniel T R; Lusingu, John P; Theander, Thor G; Lavstsen, Thomas

2017-04-01

By attaching infected erythrocytes to the vascular lining, Plasmodium falciparum parasites leave blood circulation and avoid splenic clearance. This sequestration is central to pathogenesis. Severe malaria is associated with parasites expressing an antigenically distinct P. falciparum erythrocyte membrane protein 1 (PfEMP1) subset mediating binding to endothelial receptors. Previous studies indicate that PfEMP1 adhesins with so-called CIDRα1 domains capable of binding endothelial protein C receptor (EPCR) constitute the PfEMP1 subset associated with severe pediatric malaria. To analyze the relative importance of different subtypes of CIDRα1 domains, we compared Pf emp1 transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria ( n = 42), children with mild malaria not requiring hospitalization ( n = 10), and children with parasitemia and no ongoing fever ( n = 12). High levels of transcripts encoding EPCR-binding PfEMP1 were found in patients with symptomatic infections, and the abundance of these transcripts increased with disease severity. The compositions of CIDRα1 subtype transcripts varied markedly between patients, and none of the subtypes were dominant. Transcript-level analyses targeting other domain types indicated that subtypes of DBLβ or DBLζ domains might mediate binding phenomena that, in conjunction with EPCR binding, could contribute to pathogenesis. These observations strengthen the rationale for targeting the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDRα1 subtypes. Copyright © 2017 American Society for Microbiology.

Drugs in Development for Malaria.

PubMed

Ashley, Elizabeth A; Phyo, Aung Pyae

2018-05-25

The last two decades have seen a surge in antimalarial drug development with product development partnerships taking a leading role. Resistance of Plasmodium falciparum to the artemisinin derivatives, piperaquine and mefloquine in Southeast Asia means new antimalarials are needed with some urgency. There are at least 13 agents in clinical development. Most of these are blood schizonticides for the treatment of uncomplicated falciparum malaria, under evaluation either singly or as part of two-drug combinations. Leading candidates progressing through the pipeline are artefenomel-ferroquine and lumefantrine-KAF156, both in Phase 2b. Treatment of severe malaria continues to rely on two parenteral drugs with ancient forebears: artesunate and quinine, with sevuparin being evaluated as an adjuvant therapy. Tafenoquine is under review by stringent regulatory authorities for approval as a single-dose treatment for Plasmodium vivax relapse prevention. This represents an advance over standard 14-day primaquine regimens; however, the risk of acute haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency remains. For disease prevention, several of the newer agents show potential but are unlikely to be recommended for use in the main target groups of pregnant women and young children for some years. Latest predictions are that the malaria burden will continue to be high in the coming decades. This fact, coupled with the repeated loss of antimalarials to resistance, indicates that new antimalarials will be needed for years to come. Failure of the artemisinin-based combinations in Southeast Asia has stimulated a reappraisal of current approaches to combination therapy for malaria with incorporation of three or more drugs in a single treatment under consideration.

Comparative feasibility of implementing rapid diagnostic test and microscopy for parasitological diagnosis of malaria in Uganda.

PubMed

Batwala, Vincent; Magnussen, Pascal; Nuwaha, Fred

2011-12-19

In Uganda, parasite-based diagnosis is recommended for every patient suspected to have malaria before prescribing anti-malarials. However, the majority of patients are still treated presumptively especially in low-level health units. The feasibility of implementing parasite-based diagnosis for uncomplicated malaria in rural health centres (HCs) was investigated with a view to recommending measures for scaling up the policy. Thirty HCs were randomized to implement parasite-based diagnosis based on rapid diagnostic tests [RDTs] (n = 10), blood microscopy (n = 10) and presumptive diagnosis (control arm) (n = 10). Feasibility was assessed by comparing the proportion of patients who received parasite-based diagnosis; with a positive malaria parasite-based diagnosis who received artemether-lumefantrine (AL); with a negative malaria parasite-based diagnosis who received AL; and patient waiting time. Clinicaltrials.gov: NCT00565071. 102, 087 outpatients were enrolled. Patients were more likely to be tested in the RDT 44, 565 (96.6%) than in microscopy arm 19, 545 (60.9%) [RR: 1.59]. RDTs reduced patient waiting time compared to microscopy and were more convenient to health workers and patients. Majority 23, 804 (99.7%) in presumptive arm were prescribed AL. All (100%) of patients who tested positive for malaria in RDT and microscopy arms were prescribed anti-malarials. Parasitological-based diagnosis significantly reduced AL prescription in RDT arm [RR: 0.62] and microscopy arm [RR: 0.72] compared to presumptive treatment. Among patients not tested in the two intervention arms, 12, 044 (96.1%) in microscopy and 965 (61.6%) in RDT arm were treated with AL [RR: 1.56]. Overall 10, 558 (29.4%) with negative results [5, 110 (23.4%) in RDT and 5, 448 (39.0%) in microscopy arms] were prescribed AL. It was more feasible to implement parasite-based diagnosis for malaria using RDT than with microscopy. A high proportion of patients with negative malaria results are still prescribed anti-malarials. There is need to increase access to parasite-based diagnosis where microscopy is used. In order to fully harness the benefits of parasitological confirmation of malaria, it is necessary to reduce the prescription of anti-malarials in negative patients.

Consensus document of the Spanish Urological Association on the management of uncomplicated recurrent urinary tract infections.

PubMed

Prieto, L; Esteban, M; Salinas, J; Adot, J M; Arlandis, S; Peri, L; Cozar, J M

2015-01-01

The clinical manifestations of urinary infections, commonly mild and uncomplicated, have resulted in a generally empirical therapeutic decision-making process, which does not help fight resistances to antibacterial agents, thus causing a high rate of recurrence. This study seeks to reduce the clinical variability in the diagnosis and treatment of uncomplicated recurrent urinary tract infections (RUTIs). The consensus document was developed using a nominal group methodology, using scientific evidence on RUTIs extracted from a systematic (noncomprehensive) literature review, along with the expert judgment of specialists and their experience in clinical practice. RUTIs are considered the manifestation of at least 3 episodes of uncomplicated infection, with a positive culture in the past 12 months, in addition to (for men) the absence of structural or functional abnormalities. We maintain that the treatment should be empiric when suspecting RUTIs (prior to obtaining a urine sample for culture) in those patients who have a high probability of recurrence, associated risk factors and/or urinary or general symptoms, such as fever and chills. Homogeneous criteria are recommended for the diagnosis and treatment in order to fight the increased rates of resistance that the microorganisms develop against antimicrobial agents. Imprecision in the identification of the infection requires a search for agreements on homogenized criteria and decision algorithms that guide the management of these patients. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

PubMed Central

2013-01-01

Background Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. Discussion The Malaria Vaccine Technology Roadmap’s goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%’. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Conclusions Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine. PMID:24228861

Patterns and predictors of malaria care-seeking, diagnostic testing, and artemisinin-based combination therapy for children under five with fever in Northern Nigeria: a cross-sectional study.

PubMed

Millar, Kathryn R; McCutcheon, Jennifer; Coakley, Eugenie H; Brieger, William; Ibrahim, Mohammed A; Mohammed, Zainab; Bassi, Amos; Sambisa, William

2014-11-21

Despite recent improvements in malaria prevention strategies, malaria case management remains a weakness in Northern Nigeria, which is underserved and suffers the country's highest rates of under-five child mortality. Understanding malaria care-seeking patterns and comparing case management outcomes to World Health Organization (WHO) and Nigeria's National Malaria Control Programme (NMCP) guidelines are necessary to identify where policy and programmatic strategies should focus to prevent malaria mortality and morbidity. A cross-sectional survey based on lot quality assurance sampling was used to collect data on malaria care-seeking for children under five with fever in the last two weeks throughout Sokoto and Bauchi States. The survey assessed if the child received NMCP/WHO recommended case management: prompt treatment, a diagnostic blood test, and artemisinin-based combination therapy (ACT). Deviations from this pathway and location of treatment were also assessed. Lastly, logistic regression was used to assess predictors of seeking treatment. Overall, 76.7% of children were brought to treatment-45.5% to a patent medicine vendor and 43.8% to a health facility. Of children brought to treatment, 61.5% sought treatment promptly, but only 9.8% received a diagnostic blood test and 7.2% received a prompt ACT. When assessing adherence to the complete case management pathway, only 1.0% of children received NMCP/WHO recommended treatment. When compared to other treatment locations, health facilities provided the greatest proportion of children with NMCP/WHO recommended treatment. Lastly, children 7-59 months old were at 1.74 (p = 0.003) greater odds of receiving treatment than children ≤6 months. Northern Nigeria's coverage rates of NMCP/WHO standard malaria case management for children under five with fever fall short of the NMCP goal of 80% coverage by 2010 and universal coverage thereafter. Given the ability to treat a child with malaria differs greatly between treatment locations, policy and logistics planning should address the shortages of essential malaria supplies in recommended and frequently accessed treatment locations. Particular emphasis should be placed on integrating the private sector into standardized care and educating caregivers on the necessity for testing before treatment and the availability of free ACT in public health facilities for uncomplicated malaria.

The use of paediatric artemisinin combinations in sub-Saharan Africa: a snapshot questionnaire survey of health care personnel

PubMed Central

2011-01-01

Background Paediatric drug formulations for artemisinin combination therapy (P-ACT) have been developed over the past few years and have been shown to improve the therapeutic management of young children with uncomplicated falciparum malaria. This process was however not equally paralleled by a timely adoption of P-ACT in national and international treatment recommendations. National malaria programmes in sub-Saharan Africa have not yet widely embraced this new therapeutic tool. To which extent P-ACT is used in the field in sub-Saharan Africa is not known to date. Methods This snapshot questionnaire survey aimed to provide an overview on the current routine practices for the availability and use of P-ACT as anti-malarial treatment for young children in sub-Saharan Africa. Health care personnel in seven countries in West-, Central, and East-Africa were invited to answer a structured questionnaire assessing use and availability of P-ACT. Results A total of 71 respondents including doctors, nurses and pharmacy personnel responsible for the anti-malarial treatment of young children were interviewed. P-ACT was used by 83% (95% confidence interval: 73-90%; n = 59) as first-line treatment for young children. Use of 15 different P-ACT products was reported among which only two have received WHO prequalification status and approval by a stringent registration authority. Use of a specific P-ACT product was not linked to consumer prices or availability of supporting clinical trial data, but may depend more on the marketing capacity of the manufacturer. Major differences in frequency and dosing of anti-malarial regimens with identical anti-malarial compounds and the marketing of loose combinations were recorded. Conclusion Paediatric ACT is widely used for the treatment of uncomplicated malaria in young children. However, the majority of P-ACT formulations in use do not meet highest international quality standards evoking concerns for patients' safety and the induction of drug resistance. Improving the quality of currently marketed P-ACT should constitute a public health priority besides their adoption into official treatment recommendations. PMID:22168234

Working towards consensus on methods used to elicit participant-reported safety data in uncomplicated malaria clinical drug studies: a Delphi technique study.

PubMed

Mandimika, Nyaradzo; Barnes, Karen I; Chandler, Clare I R; Pace, Cheryl; Allen, Elizabeth N

2017-01-28

Eliciting adverse event (AE) and non-study medication data reports from clinical research participants is integral to evaluating drug safety. However, using different methods to question participants yields inconsistent results, compromising the interpretation, comparison and pooling of data across studies. This is particularly important given the widespread use of anti-malarials in vulnerable populations, and their increasing use in healthy, but at-risk individuals, as preventive treatment or to reduce malaria transmission. Experienced and knowledgeable anti-malarial drug clinical researchers were invited to participate in a Delphi technique study, to facilitate consensus on what are considered optimal (relevant, important and feasible) methods, tools, and approaches for detecting participant-reported AE and non-study medication data in uncomplicated malaria treatment studies. Of 72 invited, 25, 16 and 10 panellists responded to the first, second and third rounds of the Delphi, respectively. Overall, 68% (68/100) of all questioning items presented for rating achieved consensus. When asking general questions about health, panellists agreed on the utility of a question/concept about any change in health, taking care to ensure that such questions/concepts do not imply causality. Eighty-nine percent (39/44) of specific signs and symptoms questions were rated as optimal. For non-study medications, a general question and most structured questioning items were considered an optimal approach. The use of mobile phones, patient diaries, rating scales as well as openly engaging with participants to discuss concerns were also considered optimal complementary data-elicitation tools. This study succeeded in reaching consensus within a section of the anti-malarial drug clinical research community about using a general question concept, and structured questions for eliciting data about AEs and non-study medication reports. The concepts and items considered in this Delphi to be relevant, important and feasible should be further investigated for potential inclusion in a harmonized approach to collect participant-elicited anti-malarial drug safety data. This, in turn, should improve understanding of anti-malarial drug safety.

Dynamics of Malaria Drug Resistance Patterns in the Amazon Basin Region following Changes in Peruvian National Treatment Policy for Uncomplicated Malaria▿ †

PubMed Central

Bacon, David J.; McCollum, Andrea M.; Griffing, Sean M.; Salas, Carola; Soberon, Valeria; Santolalla, Meddly; Haley, Ryan; Tsukayama, Pablo; Lucas, Carmen; Escalante, Ananias A.; Udhayakumar, Venkatachalam

2009-01-01

Monitoring changes in the frequencies of drug-resistant and -sensitive genotypes can facilitate in vivo clinical trials to assess the efficacy of drugs before complete failure occurs. Peru changed its national treatment policy for uncomplicated malaria to artesunate (ART)-plus-mefloquine (MQ) combination therapy in the Amazon basin in 2001. We genotyped isolates collected in 1999 and isolates collected in 2006 to 2007 for mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, multidrug resistance gene 1 (Pfmdr-1), the chloroquine (CQ) resistance transporter gene (Pfcrt), and the Ca2+ ATPase gene (PfATP6); these have been shown to be involved in resistance to sulfadoxine-pyrimethamine (SP), MQ, CQ, and possibly ART, respectively. Microsatellite haplotypes around the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr-1 loci were also determined. There was a significant decline in the highly SP resistant Pfdhfr and Pfdhps genotypes from 1999 to 2006. In contrast, a CQ-resistant Pfcrt genotype increased in frequency during the same period. Among five different Pfmdr-1 allelic forms noted in 1999, two genotypes increased in frequency while one genotype decreased by 2006. We also noted previously undescribed polymorphisms in the PfATP6 gene as well as an increase in the frequency of a deletion mutant during this period. In addition, microsatellite analysis revealed that the resistant Pfdhfr, Pfdhps, and Pfcrt genotypes have each evolved from a single founder haplotype, while Pfmdr-1 genotypes have evolved from at least two independent haplotypes. Importantly, this study demonstrates that the Peruvian triple mutant Pfdhps genotypes are very similar to those found in other parts of South America. PMID:19258269

Gametocyte clearance dynamics following oral artesunate treatment of uncomplicated falciparum malaria in Malian children.

PubMed

Djimde, Abdoulaye A; Maiga, Amelia W; Ouologuem, Dinkorma; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Doumbo, Ogobara K

2016-01-01

Artemisinin-based combination therapies decrease Plasmodium gametocyte carriage. However, the role of artesunate in monotherapy in vivo, the mechanisms involved, and the utility of gametocyte carriage as a potential tool for the surveillance of antimalarial resistance are poorly understood. In 2010-2011, we conducted an open-label, prospective efficacy study of artesunate as monotherapy in children 1-10 years of age with uncomplicated falciparum malaria in Bougoula-Hameau, Mali. Standard oral doses of artesunate were administered for 7 days and patients were followed up for 28 days. The data were compared to a similar study conducted in 2002-2004. Of 100 children enrolled in the 2010-2011 study, 92 were analyzed and compared to 217 children enrolled in the 2002-2004 study. The proportion of gametocyte carriers was unchanged at the end of treatment (23% at baseline vs. 24% on day 7, p = 1.0) and did not significantly decline until day 21 of follow-up (23% vs. 6%, p = 0.003). The mean gametocyte density at inclusion remained unchanged at the end of treatment (12 gametocytes/μL vs. 16 gametocytes/μL, p = 0.6). Overall, 46% of the 71 initial non-carriers had gametocytes detected by day 7. Similar results were found in the 2002-2004 study. In both studies, although gametocyte carriage significantly decreased by the end of the 28-day follow-up, artesunate did not clear mature gametocytes during treatment and did not prevent the appearance of new stage V gametocytes as assessed by light microscopy. Baseline gametocyte carriage was significantly higher 6 years after the deployment of artemisinin-based combination therapies in this setting. © A.A. Djimde et al., published by EDP Sciences, 2016.

Adherence to malaria diagnosis and treatment guidelines among healthcare workers in Ogun State, Nigeria.

PubMed

Bamiselu, Oluyomi F; Ajayi, IkeOluwapo; Fawole, Olufunmilayo; Dairo, David; Ajumobi, Olufemi; Oladimeji, Abisola; Steven, Yoon

2016-08-19

Malaria case management remains a vital component of malaria control strategies. Despite the introduction of national malaria treatment guidelines and scale-up of malaria control interventions in Nigeria, anecdotal evidence shows some deviations from the guidelines in malaria case management. This study assessed factors influencing adherence to malaria diagnosis and treatment guidelines among healthcare workers in public and private sectors in Ogun State, Nigeria. A comparative cross-sectional study was carried out among 432 (216 public and 216 private) healthcare workers selected from nine Local Government Areas using a multistage sampling technique. A pre-tested interviewer administered questionnaire was used to collect information on availability and use of malaria Rapid Diagnostic Test (mRDT) and artemisinin combination therapy (ACT), for management of uncomplicated malaria. Adherence was defined as when choice of antimalarials for parasitological confirmed malaria cases was restricted to recommended antimalarial medicines. Association between adherence and independent variables were tested using Chi-square at 5 % level of significance. Malaria RDT was available in 81.9 % of the public health facilities and 19.4 % of the private health facilities (p = 0.001). Its use was higher among public healthcare workers (85.2 %) compared to 32.9 % in private facilities (p = 0.000). Presumptive diagnosis of malaria was higher among private healthcare workers (94.9 %) compared to 22.7 % public facilities (p = <0.0001). The main reason for non-usage of mRDT among private healthcare workers was its perceived unreliability of mRDT (40.9 %). Monotherapy including artesunate (58.3 % vs 12.5 %), amodiaquine (38.9 % vs 8.3 %) and chloroquine (26.4 % vs 4.2 %) were significantly more available in private than public health facilities, respectively. Adherence to guidelines was significantly higher among public healthcare workers (60.6 %) compared to those in private facilities (27.3 %). Availability of antimalarial medicine was the main factor that influenced treatment prescription in both healthcare settings (p = 0.27). However, drug promotion by manufactures (45.8 %) has a major influence on private healthcare workers' prescription practice. The findings of this study demonstrate significant difference between public and private healthcare workers on adherence to national malaria diagnosis and treatment guidelines. Interventions to improve private sector engagement in implementation of the guidelines, training and supply of recommended antimalarial medicines should be intensified.

[Malaria's seroepidemiology in a group of migrants in transit (Chiapas, 2008)].

PubMed

Betanzos-Reyes, Angel Francisco; González-Cerón, Lilia; Rodríguez, Mario Henry; Torres-Monzón, Jorge Aurelio

2012-10-01

To know the prevalence of malaria and the factors associated with the infection in migrants in the southern border of Mexico, during 2008. In 706 migrants, active malaria infection was investigated using a rapid diagnostic test and PCR and past infection using serology. A questionnaire was applied to investigate the conditions associated to infection. 85.6% originated from Central America, none presented an active infection, although 4.2% were seropositive, most of these came from the countries with the highest malaria incidence in the region. Seropositivity was associated with the number of previous malaria episodes (OR=1.44; IC95% 1.04-2.00), years living in their community of origin (OR=1.03; IC95% 1.00-1.07), and knowledge and self-medication with anti-malaria drugs (OR=3.38; IC95% 1.48-7.67). . The previous exposure of migrants and the difficulties for their detection indicate the need of new strategies for the epidemiological surveillance for these populations.

Malaria in the Australian Defence Force during and after participation in the International Force in East Timor (INTERFET).

PubMed

Kitchener, S J; Auliff, A M; Rieckmann, K H

Malaria in Australian Defence Force members has been far more common in East Timor than in other recent overseas deployments. By six months after all 5,500 members of the International Force in East Timor had returned to Australia, 267 malaria infections had been reported to the Army Malaria Institute. Only 64 of those affected had their first clinical episode during their 4-5 months in East Timor, and about two-thirds of these infections were caused by Plasmodium falciparum. The remaining 212 soldiers developed their first symptoms after returning to Australia, and all but two infections were caused by P. vivax. After treatment, 44 soldiers had relapses of their vivax infections; 11 had a second relapse and two had a third relapse. These findings raise several issues about prevention and management of malaria in the ADF.

A study on the epidemiological characteristics and infectious forecast model of malaria at Guangzhou Airport among Chinese returnees from Africa.

PubMed

Wu, Hui-Ming; Fang, Zhi-Qiang; Zhao, Dang; Chen, Yan-Ling; Liu, Chuan-Ge; Liang, Xi

2017-07-04

Cross-border malaria transmission in China is a major component of Chinese imported malaria cases. Such cases mostly are travellers returning from malaria endemic countries in Africa. By investigating malaria infectious status among Chinese worker in Africa, this study analysed the malaria risk factors, in order to establish infectious forecast model. Chinese returnees data from Africa were collected at Guangzhou Baiyun International Airport, Guangzhou, China between August 2015 and March 2016 and were included in the cross-sectional and retrospective survey. A total of 1492 respondents were included in the study with the majority consisting of junior middle school educated male. Most of them are manual and technical workers hired by companies, with average of 37.04 years of age. Overall malaria incidence rate of the population was 8.98% (134/1492), and there were no significant differences regarding age, gender, occupation, or team. Forecast model was developed on the basis of malaria risk factors including working country, local ecological environment type, work duration and intensity of mosquito bite prevention. The survey suggested that malaria incidence was high among Chinese travellers who had worked in Africa countries of heavy malaria burden. Further research on the frequency and severity of clinical episodes among Chinese travellers having worked in Africa is needed.

Severe and benign Plasmodium vivax malaria in Emberá (Amerindian) children and adolescents from an endemic municipality in Western Colombia.

PubMed

Medina-Morales, Diego A; Montoya-Franco, Estefanía; Sanchez-Aristizabal, Viviana D P; Machado-Alba, Jorge E; Rodríguez-Morales, Alfonso J

2016-01-01

Malaria in children is still an important public health problem in endemic areas of South-East Asia and Latin America. Certain forms of the disease, such as Plasmodium vivax severe malaria, are still neglected. This descriptive study assessed the frequency of severe and benign P. vivax infection in Emberá children (<14 years of age) from an endemic municipality in Colombia in 2013, using the WHO criteria. During 2013, 270 Emberá children presented 349 episodes of malaria. From them, 22 (8.1%) presented at least one of the criteria for severe malaria. Some patients with P. vivax presented with severe malaria (severe anemia, renal dysfunction, respiratory distress and seizure). Mixed malaria cases presented more complications than those with monoinfection (OR=5.535; 95%CI 1.81-16.9). In Colombia, few data are available about severe P. vivax malaria in children, especially in the Amerindian ethnic groups. Mixed infections were associated with increased risk of severe malaria. At the same time, detailed and prospective studies are needed to measure the real impact of severe vivax malaria, as was evidenced in this paper. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Participants’ perceptions and understanding of a malaria clinical trial in Bangladesh

PubMed Central

2014-01-01

Background Existing evidence suggests that there is often limited understanding among participants in clinical trials about the informed consent process, resulting in their providing consent without really understanding the purpose of the study, specific procedures, and their rights. The objective of the study was to determine the subjects’ understanding of research, perceptions of voluntariness and motivations for participation in a malaria clinical trial. Methods In this study semi-structured interviews of adult clinical trial participants with uncomplicated falciparum malaria were conducted in Ramu Upazila Health Complex, in Bangladesh. Results Of 16 participants, the vast majority (81%) were illiterate. All subjects had a ‘therapeutic misconception’ i.e. the trial was perceived to be conducted primarily for the benefit of individual patients when in fact the main objective was to provide information to inform public health policy. From the patients’ perspective, getting well from their illness was their major concern. Poor actual understanding of trial specific procedures was reported despite participants’ satisfaction with treatment and nursing care. Conclusion There is frequently a degree of overlap between research and provision of clinical care in malaria research studies. Patients may be motivated to participate to research without a good understanding of the principal objectives of the study despite a lengthy consent process. The findings suggest that use of a standard consent form following the current ICH-GCP guidelines does not result in achieving fully informed consent and the process should be revised, simplified and adapted to individual trial settings. PMID:24893933

The Case for Development of 11-Aza-artemisinins for Malaria.

PubMed

Harmse, Rozanne; Wong, Ho Ning; Smit, Frans; Haynes, Richard K; N'Da, David D

2015-01-01

The current treatment regimens for uncomplicated malaria comprise an artemisinin in combination with another drug (ACT). However, the recent emergence of resistance to ACTs in South East Asia dramatically emphasizes the need for new artemisinins. The current artemisinins have been in use since the late 1970s and have relatively poor thermal, chemical and metabolic stabilities - all are metabolized or hydrolyzed in vivo to dihydroartemisinin (DHA) that itself undergoes facile decomposition in vivo. The current artemisinins possess neurotoxicity as demonstrated in animal models, an issue that mandates increased vigilance in view of trends to use of protracted treatment regimens involving sequential administration of different ACTs against the resistant disease. As artemisinins induce the most rapid reduction in parasitaemia of any drug, common sense dictates that any new artemisinin derivative, selected on the bases of more robust chemical and thermal stability, metabolic stability with respect to the generation of DHA in vivo, and relatively benign neurotoxicity should be used in any new ACT whose components are rationally chosen in order to counter resistant malaria and inhibit transmission. 11-Azaartemisinin and its N-substituted derivatives attract because of overall ease of preparation from artemisinin. Some derivatives also possess notable thermal stabilities and although metabolic pathways of the derivatives are as yet unknown, none can provide DHA. The azaartemisinins synthesized over the past 20 years are critically discussed on the basis of their synthetic accessibility and biological activities with the view to assessing suitability to serve as new artemisinin derivatives for treatment of malaria.

Participants' perceptions and understanding of a malaria clinical trial in Bangladesh.

PubMed

Das, Debashish; Cheah, Phaik Yeong; Akter, Fateha; Paul, Dulal; Islam, Akhterul; Sayeed, Abdullah A; Samad, Rasheda; Rahman, Ridwanur; Hossain, Amir; Dondorp, Arjen; Day, Nicholas P; White, Nicholas J; Hasan, Mahtabuddin; Ghose, Aniruddha; Ashley, Elizabeth A; Faiz, Abul

2014-06-04

Existing evidence suggests that there is often limited understanding among participants in clinical trials about the informed consent process, resulting in their providing consent without really understanding the purpose of the study, specific procedures, and their rights. The objective of the study was to determine the subjects' understanding of research, perceptions of voluntariness and motivations for participation in a malaria clinical trial. In this study semi-structured interviews of adult clinical trial participants with uncomplicated falciparum malaria were conducted in Ramu Upazila Health Complex, in Bangladesh. Of 16 participants, the vast majority (81%) were illiterate. All subjects had a 'therapeutic misconception' i.e. the trial was perceived to be conducted primarily for the benefit of individual patients when in fact the main objective was to provide information to inform public health policy. From the patients' perspective, getting well from their illness was their major concern. Poor actual understanding of trial specific procedures was reported despite participants' satisfaction with treatment and nursing care. There is frequently a degree of overlap between research and provision of clinical care in malaria research studies. Patients may be motivated to participate to research without a good understanding of the principal objectives of the study despite a lengthy consent process. The findings suggest that use of a standard consent form following the current ICH-GCP guidelines does not result in achieving fully informed consent and the process should be revised, simplified and adapted to individual trial settings.

The Plasmodium berghei RC strain is highly diverged and harbors putatively novel drug resistance variants

PubMed Central

Kulawonganunchai, Supasak; Wilantho, Alisa; Koonyosying, Pongpisid; Uthaipibull, Chairat

2017-01-01

Background The current first line drugs for treating uncomplicated malaria are artemisinin (ART) combination therapies. However, Plasmodium falciparum parasites resistant to ART and partner drugs are spreading, which threatens malaria control efforts. Rodent malaria species are useful models for understanding antimalarial resistance, in particular genetic variants responsible for cross resistance to different compounds. Methods The Plasmodium berghei RC strain (PbRC) is described as resistant to different antimalarials, including chloroquine (CQ) and ART. In an attempt to identify the genetic basis for the antimalarial resistance trait in PbRC, its genome was sequenced and compared with five other previously sequenced P. berghei strains. Results We found that PbRC is eight-fold less sensitive to the ART derivative artesunate than the reference strain PbANKA. The genome of PbRC is markedly different from other strains, and 6,974 single nucleotide variants private to PbRC were identified. Among these PbRC private variants, non-synonymous changes were identified in genes known to modulate antimalarial sensitivity in rodent malaria species, including notably the ubiquitin carboxyl-terminal hydrolase 1 gene. However, no variants were found in some genes with strong evidence of association with ART resistance in P. falciparum such as K13 propeller protein. Discussion The variants identified in PbRC provide insight into P. berghei genome diversity and genetic factors that could modulate CQ and ART resistance in Plasmodium spp. PMID:29018598

Cognitive performance of children living in endemic areas for Plasmodium vivax.

PubMed

Brasil, Laélia M B F; Vieira, José L F; Araújo, Eliete C; Piani, Pedro P F; Dias, Rosa M; Ventura, Ana M R S; Cabral, Bianca C; Santa Brígida, Renée C R; de Andrade, Marcieni A

2017-09-12

The role of repeated episodes of malaria on the cognitive development of children is a relevant issue in endemic areas since it can have a long-lasting impact on individual lifespan. The aim of the current paper was to investigate whether the history of malaria can impair the verbal and performance skills of children living in an endemic area with low transmission of Plasmodium vivax malaria. A cross-sectional study was conducted with children living in an endemic area of P. vivax malaria in Brazilian Amazon basin. The history of episodes of malaria was used as criteria for inclusion of children in the groups. The cognitive performance was assessed by the Wechsler intelligence scale for children-III edition (WISC-III), which was applied to the participants of study by two trained psychologists. A total of 17 cases and 26 controls was included in the study. A significant low score of verbal quotient was found in the cases (p = 0.005), however, the performance IQ was similar in both groups (p = 0.304). The full-scale IQ was significantly lower in the cases when compared to the controls (p = 0.042). The factorials index showed significant difference only in the subtest of verbal comprehension with the lower values in the cases (p = 0.0382), compared to the controls. The perceptual organization (p = 0.363), freedom from distractability (p = 0.180) and processing speed (p = 0.132) were similar in both groups. Children with a history of vivax malaria has a significant impairment of verbal and full-scale quotients as well as a significant low index of verbal comprehension. These findings are likely due to the absenteeism caused by malaria and by the low parental education, which impairs an adequate response to the environmental stimulus.

Time To Move from Presumptive Malaria Treatment to Laboratory-Confirmed Diagnosis and Treatment in African Children with Fever

PubMed Central

D'Acremont, Valérie; Lengeler, Christian; Mshinda, Hassan; Mtasiwa, Deo; Tanner, Marcel; Genton, Blaise

2009-01-01

Background to the debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five. PMID:19127974

Narrative review of current context of malaria and management strategies in Uganda (Part I).

PubMed

Kassam, Rosemin; Collins, John B; Liow, Eric; Rasool, Nabeela

2015-12-01

In accordance with international targets, the Uganda National Malaria Control Strategic Plan established specific targets to be achieved by 2010. For children under five, this included increasing the number of children sleeping under mosquito nets and those receiving a first-line antimalarial to 85%, and decreasing case fatality to 2%. This narrative review offers contextual information relevant to malaria management in Uganda since the advent of artemisinin combination therapy (ACT) as first-line antimalarial treatment in 2004. A comprehensive search using key words and phrases was conducted using the web search engines Google and Google Scholar, as well as the databases of PubMed, ERIC, EMBASE, CINAHL, OvidSP (MEDLINE), PSYC Info, Springer Link, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews were searched. A total of 147 relevant international and Ugandan literature sources meeting the inclusion criteria were included. This review provides an insightful understanding on six topic areas: global and local priorities, malarial pathology, disease burden, malaria control, treatment guidelines for uncomplicated malaria, and role of the health system in accessing antimalarial medicines. Plasmodium falciparum remains the most common cause of malaria in Uganda, with children under five being most vulnerable due to their underdeveloped immunity. While international efforts to scale up malaria control measures have resulted in considerable decline in malaria incidence and mortality in several regions of sub-Saharan Africa, this benefit has yet to be substantiated for Uganda. At the local level, key initiatives have included implementation of a new antimalarial drug policy in 2004 and strengthening of government health systems and programs. Examples of such programs include removal of user fees, training of frontline health workers, providing free ACT from government systems and subsidized ACT from licensed private outlets, and introduction of the integrated community case management program to bring diagnostics and treatment for malaria, pneumonia and diarrhea closer to the community. However despite notable efforts, Uganda is far from achieving its 2010 targets. Several challenges in the delivery of care and treatment remain, with those most vulnerable and living in rural settings remaining at greatest risk from malaria morbidity and mortality. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

PubMed Central

2013-01-01

Background Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil. Methods The study was carried out in Paragominas, Pará State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-119) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-γ and IL-10 were measured by enzyme-linked immunosorbent assay. Results The prevalence of activated CD4+ was greater than CD8+ T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-119 and PSS1 antigen. A low proliferative response against PvMSP-119 and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-γ and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-119 stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient’s cells while low levels of IFN-γ and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-119 was evidenced, regardless class or IgG subclass.PvMSP-119-induced antibodies were predominantly on non-cytophilic subclasses. Conclusions The results presented here shows that PvMSP-119 was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-119 in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate. PMID:24041406

Plasmodium vivax malaria vaccines: why are we where we are?

PubMed

Reyes-Sandoval, Arturo; Bachmann, Martin F

2013-12-01

Malaria is one of the few diseases in which morbidity is still measured in hundreds of millions of cases every year. Plasmodium vivax and Plasmodium falciparum are responsible for nearly all the malaria cases in the world and despite difficulties in obtaining an exact number, estimates indicate an astonishing 349-552 million clinical cases of malaria due to P. falciparum in 2007 and between 132-391 million clinical episodes due to P. vivax in 2009. It is becoming evident that eradication of malaria will be an arduous task and P. vivax will be one of the most difficult species to eliminate and perhaps become the last standing malaria parasite. Indeed, in countries that succeed in decreasing the disease burden, nearly all the remaining malaria cases are caused by P. vivax. Such resilience is mainly due to the sophisticated mechanism that the parasite has evolved to remain dormant for months or years forming hypnozoites, a small structure in the liver that will be a major hurdle in the efforts toward malaria eradication. Furthermore, while clinical trials of vaccines against P. falciparum are making fast progress, a very different picture is seen with P. vivax, where only few candidates are currently active in clinical trials.

A cost-effectiveness analysis of artemether lumefantrine for treatment of uncomplicated malaria in Zambia

PubMed Central

Chanda, Pascalina; Masiye, Felix; Chitah, Bona M; Sipilanyambe, Naawa; Hawela, Moonga; Banda, Patrick; Okorosobo, Tuoyo

2007-01-01

Background Malaria remains a leading cause of morbidity, mortality and non-fatal disability in Zambia, especially among children, pregnant women and the poor. Data gathered by the National Malaria Control Centre has shown that recently observed widespread treatment failure of SP and chloroquine precipitated a surge in malaria-related morbidity and mortality. As a result, the Government has recently replaced chloroquine and SP with combination therapy as first-line treatment for malaria. Despite the acclaimed therapeutic advantages of ACTs over monotherapies with SP and CQ, the cost of ACTs is much greater, raising concerns about affordability in many poor countries such as Zambia. This study evaluates the cost-effectiveness analysis of artemether-lumefantrine, a version of ACTs adopted in Zambia in mid 2004. Methods Using data gathered from patients presenting at public health facilities with suspected malaria, the costs and effects of using ACTs versus SP as first-line treatment for malaria were estimated. The study was conducted in six district sites. Treatment success and reduction in demand for second line treatment constituted the main effectiveness outcomes. The study gathered data on the efficacy of, and compliance to, AL and SP treatment from a random sample of patients. Costs are based on estimated drug, labour, operational and capital inputs. Drug costs were based on dosages and unit prices provided by the Ministry of Health and the manufacturer (Norvatis). Findings The results suggest that AL produces successful treatment at less cost than SP, implying that AL is more cost-effective. While it is acknowledged that implementing national ACT program will require considerable resources, the study demonstrates that the health gains (treatment success) from every dollar spent are significantly greater if AL is used rather than SP. The incremental cost-effectiveness ratio is estimated to be US$4.10. When the costs of second line treatment are considered the ICER of AL becomes negative, indicating that there are greater resource savings associated with AL in terms of reduction of costs of complicated malaria treatment. Conclusion This study suggests the decision to adopt AL is justifiable on both economic and public health grounds. PMID:17313682

Preliminary Investigation of the Contribution of CYP2A6, CYP2B6, and UGT1A9 Polymorphisms on Artesunate-Mefloquine Treatment Response in Burmese Patients with Plasmodium falciparum Malaria

PubMed Central

Phompradit, Papichaya; Muhamad, Poonuch; Cheoymang, Anurak; Na-Bangchang, Kesara

2014-01-01

CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response. In one patient who had the CYP2A6*1A/*4C genotype (decreased enzyme activity), plasma concentration of artesunate at one hour appeared to be higher, and the concentration of dihydroartemisinin was lower than for those carrying other genotypes (415 versus 320 ng/mL). The proportion of patients with adequate clinical and parasitologic response who had the CYP2B6*9/*9 genotype (mutant genotype) was significantly lower compared with those with late parasitologic failure (14.0% versus 19.0%). Confirmation through a larger study in various malaria-endemic areas is required before a definite conclusion on the role of genetic polymorphisms of these drug-metabolizing enzymes on treatment response after artesunate-based combination therapy can be made. PMID:24891466

A cost-effectiveness analysis of provider interventions to improve health worker practice in providing treatment for uncomplicated malaria in Cameroon: a study protocol for a randomized controlled trial.

PubMed

Wiseman, Virginia; Mangham, Lindsay J; Cundill, Bonnie; Achonduh, Olivia A; Nji, Akindeh Mbuh; Njei, Abanda Ngu; Chandler, Clare; Mbacham, Wilfred F

2012-01-06

Governments and donors all over Africa are searching for sustainable, affordable and cost-effective ways to improve the quality of malaria case management. Widespread deficiencies have been reported in the prescribing and counselling practices of health care providers treating febrile patients in both public and private health facilities. Cameroon is no exception with low levels of adherence to national guidelines, the frequent selection of non-recommended antimalarials and the use of incorrect dosages. This study evaluates the effectiveness and cost-effectiveness of introducing two different provider training packages, alongside rapid diagnostic tests (RDTs), designed to equip providers with the knowledge and practical skills needed to effectively diagnose and treat febrile patients. The overall aim is to target antimalarial treatment better and to facilitate optimal use of malaria treatment guidelines. A 3-arm stratified, cluster randomized trial will be conducted to assess whether introducing RDTs with provider training (basic or enhanced) is more cost-effective than current practice without RDTs, and whether there is a difference in the cost effectiveness of the provider training interventions. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit public and mission health facilities. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider knowledge. Costs will be estimated from a societal and provider perspective using standard economic evaluation methodologies. ClinicalTrials.gov: NCT00981877.

Evidence for the contribution of the hemozoin synthesis pathway of the murine Plasmodium yoelii to the resistance to artemisinin-related drugs.

PubMed

Witkowski, Benoit; Lelièvre, Joel; Nicolau-Travers, Marie-Laure; Iriart, Xavier; Njomnang Soh, Patrice; Bousejra-Elgarah, Fatima; Meunier, Bernard; Berry, Antoine; Benoit-Vical, Françoise

2012-01-01

Plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. In response to the spreading of P. falciparum drug resistance, WHO recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called ACT) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. Currently, ACT are often the last treatments that can effectively and rapidly cure P. falciparum infections permitting to significantly decrease the mortality and the morbidity due to malaria. However, alarming signs of emerging resistance to artemisinin derivatives along the Thai-Cambodian border are of major concern. Through long-term in vivo pressures, we have been able to select a murine malaria model resistant to artemisinins. We demonstrated that the resistance of Plasmodium to artemisinin-based compounds depends on alterations of heme metabolism and on a loss of hemozoin formation linked to the down-expression of the recently identified Heme Detoxification Protein (HDP). These artemisinins resistant strains could be able to detoxify the free heme by an alternative catabolism pathway involving glutathione (GSH)-mediation. Finally, we confirmed that artemisinins act also like quinolines against Plasmodium via hemozoin production inhibition. The work proposed here described the mechanism of action of this class of molecules and the resistance to artemisinins of this model. These results should help both to reinforce the artemisinins activity and avoid emergence and spread of endoperoxides resistance by focusing in adequate drug partners design. Such considerations appear crucial in the current context of early artemisinin resistance in Asia.

[Economic evaluation of rapid diagnostic tests in malaria treatment].

PubMed

Faye, Adama; Ndiaye, Papa; Diagne-Camara, Maty; Badiane, Ousseynou; Wone, Issa; Diongue, Mayassine; Seck, Ibrahima; Dia, Anta Tal; Dia, Amadou Lamine

2010-01-01

This study aimed to evaluate the economic implications of rapid diagnostic tests (RDTs) on malaria management through the rational use of artemisinin-based combination therapy (ACT). The study was carried out in 2006 from November 10th to December 10th; it focused on patients who were seen and treated with ACT for suspicion of uncomplicated malaria in the health district of Ziguinchor, Senegal. The variables studied included age, sex, RDT results, and costs of care and RDT. The cost of care for malaria, estimated in CFA Francs, was evaluated both with and without the use of RDT. Among the 379 patients, 25,1% were aged 0-4 years, 12,7% of 5-14 years and 62,2% of at least 15 years; 51% were women. The result of the RDT was negative in 60% of cases. Without the use of diagnostic testing, the cost of care for all 379 cases was estimated at 299 957 CFA: patient contributions would cover 184 500 CFA and the State would cover the rest (115 457 CFA). With the use of RDTs, the overall cost of the RDT screening for 379 patients and the cost of treatment for the 150 positive cases amounted to 254 786 CFA, with patients bearing the cost of 205 550 CFA and the State subsidizing up to 49 236 CFA. RDT can help identify the positive cases of malaria, and avoid up to 60% of unnecessary treatments, corresponding to an estimated 27 297 cases at the district level and 584 630 cases nationally. The RDT also allow a more rational use of ACTs and a lower risk of emergence of Plasmodium resistance. The use of RDTs could result in savings of 45 171 CFA at the level of the district health centre and 111 240 136 CFA nationally.

Evidence for the Contribution of the Hemozoin Synthesis Pathway of the Murine Plasmodium yoelii to the Resistance to Artemisinin-Related Drugs

PubMed Central

Nicolau-Travers, Marie-Laure; Iriart, Xavier; Njomnang Soh, Patrice; Bousejra-ElGarah, Fatima; Meunier, Bernard; Berry, Antoine; Benoit-Vical, Françoise

2012-01-01

Plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. In response to the spreading of P. falciparum drug resistance, WHO recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called ACT) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. Currently, ACT are often the last treatments that can effectively and rapidly cure P. falciparum infections permitting to significantly decrease the mortality and the morbidity due to malaria. However, alarming signs of emerging resistance to artemisinin derivatives along the Thai-Cambodian border are of major concern. Through long-term in vivo pressures, we have been able to select a murine malaria model resistant to artemisinins. We demonstrated that the resistance of Plasmodium to artemisinin-based compounds depends on alterations of heme metabolism and on a loss of hemozoin formation linked to the down-expression of the recently identified Heme Detoxification Protein (HDP). These artemisinins resistant strains could be able to detoxify the free heme by an alternative catabolism pathway involving glutathione (GSH)-mediation. Finally, we confirmed that artemisinins act also like quinolines against Plasmodium via hemozoin production inhibition. The work proposed here described the mechanism of action of this class of molecules and the resistance to artemisinins of this model. These results should help both to reinforce the artemisinins activity and avoid emergence and spread of endoperoxides resistance by focusing in adequate drug partners design. Such considerations appear crucial in the current context of early artemisinin resistance in Asia. PMID:22403683

Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments.

PubMed

Sowunmi, Akintunde; Akano, Kazeem; Ntadom, Godwin; Ayede, Adejumoke I; Ibironke, Folasade O; Aderoyeje, Temitope; Adewoye, Elsie O; Fatunmbi, Bayo; Oguche, Stephen; Okafor, Henrietta U; Watila, Ismaila; Meremikwu, Martin; Agomo, Philip; Ogala, William; Agomo, Chimere; Folarin, Onikepe A; Gbotosho, Grace O; Happi, Christian T

2017-02-07

Artemisinin-based combination treatments (ACTs) are the first-line treatments of uncomplicated Plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children. Therapeutic efficacy of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine was evaluated in 437 anaemic and 909 non-anaemic malarious children following treatment during a seven-year period (2008-2014). Patterns of temporal changes in haematocrit were classified based on haematocrit values <30% and ≥30%. Kinetics of the disposition of the deficit in haematocrit from 30% following treatment were evaluated using a non-compartment model. PCR-corrected parasitological efficacy 28 days after start of treatment was significantly higher in artesunate-amodiaquine- compared to artemether-lumefantrine-treated children [97% (95%CI: 92.8-100) versus 96.4% (95%CI: 91.3-99.4), P = 0.02], but it was similar in non-anaemic and anaemic children. Fall in haematocrit/1 000 asexual parasites cleared from peripheral blood was significantly greater at lower compared to higher parasitaemias (P < 0.0001), and in non-anaemic compared to anaemic children (P = 0.007). In anaemic children at presentation, mean anaemia recovery time (AnRT) was 15.4 days (95%CI: 13.3-17.4) and it did not change over the years. Declines in haematocrit deficits from 30% were monoexponential with mean estimated half-time of 1.4 days (95%CI: 1.2-1.6). Anaemia half-time (t ½anaemia ) correlated positively with AnRT in the same patients (r = 0.69, P < 0.0001). Bland-Altman analysis of 10 multiples of t ½anaemia and AnRT showed narrow limit of agreement with insignificant bias (P = 0.07) suggesting both can be used interchangeably in the same patients. Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated P. falciparum infections in non-anaemic and anaemic Nigerian children in the last 7 years of adoption as first-line treatments. These ACTs may also conserve haematocrit at high parasitaemias and in anaemic children. Pan African Clinical Trial Registry PACTR201508001188143 , 3 July 2015; PACTR201510001189370 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015.

Does malaria epidemiology project Cameroon as 'Africa in miniature'?

PubMed

Mbenda, Huguette Gaelle Ngassa; Awasthi, Gauri; Singh, Poonam K; Gouado, Inocent; Das, Aparup

2014-09-01

Cameroon, a west-central African country with a ~ 20 million population, is commonly regarded as 'Africa in miniature' due to the extensive biological and cultural diversities of whole Africa being present in a single-country setting. This country is inhabited by ancestral human lineages in unique eco-climatic conditions and diverse topography. Over 90 percent Cameroonians are at risk of malaria infection, and ~ 41 percent have at least one episode of malaria each year. Historically, the rate of malaria infection in Cameroon has fluctuated over the years; the number of cases was about 2 million in 2010 and 2011. The Cameroonian malaria control programme faces an uphill task due to high prevalence of multidrug-resistant parasites and insecticide-resistant malaria vectors. Above all, continued human migration from the rural to urban areas as well as population exchange with adjoining countries, high rate of ecological instabilities caused by deforestation, poor housing, lack of proper sanitation and drainage system might have resulted in the recent increase in incidences of malaria and other vector-borne diseases in Cameroon. The available data on eco-environmental variability and intricate malaria epidemiology in Cameroon reflect the situation in the whole of Africa, and warrant the need for in-depth study by using modern surveillance tools for meaningful basic understanding of the malaria triangle (host-parasite-vector-environment).

The economic costs of malaria in four Kenyan districts: do household costs differ by disease endemicity?

PubMed

Chuma, Jane; Okungu, Vincent; Molyneux, Catherine

2010-06-02

Malaria inflicts significant costs on households and on the economy of malaria endemic countries. There is also evidence that the economic burden is higher among the poorest in a population, and that cost burdens differ significantly between wet and dry seasons. What is not clear is whether, and how, the economic burden of malaria differs by disease endemicity. The need to account for geographical and epidemiological differences in the estimation of the social and economic burden of malaria is well recognized, but there is limited data, if any, to support this argument. This study sought to contribute towards filling this gap by comparing malaria cost burdens in four Kenyan districts of different endemicity. A cross-sectional household survey was conducted during the peak malaria transmission season in the poorest areas in four Kenyan districts with differing malaria transmission patterns (n = 179 households in Bondo; 205 Gucha; 184 Kwale; 141 Makueni). There were significant differences in duration of fever, perception of fever severity and cost burdens. Fever episodes among adults and children over five years in Gucha and Makueni districts (highland endemic and low acute transmission districts respectively) lasted significantly longer than episodes reported in Bondo and Kwale districts (high perennial transmission and seasonal, intense transmission, respectively). Perceptions of illness severity also differed between districts: fevers reported among older children and adults in Gucha and Makueni districts were reported as severe compared to those reported in the other districts. Indirect and total costs differed significantly between districts but differences in direct costs were not significant. Total household costs were highest in Makueni (US$ 19.6 per month) and lowest in Bondo (US$ 9.2 per month). Cost burdens are the product of complex relationships between social, economic and epidemiological factors. The cost data presented in this study reflect transmission patterns in the four districts, suggesting that a relationship between costs burdens and the nature of transmission might exist, and that the same warrants more attention from researchers and policy makers.

Does treatment of intestinal helminth infections influence malaria? Background and methodology of a longitudinal study of clinical, parasitological and immunological parameters in Nangapanda, Flores, Indonesia (ImmunoSPIN Study)

PubMed Central

2010-01-01

Background Given that helminth infections are thought to have strong immunomodulatory activity, the question whether helminth infections might affect responses to malaria antigens needs to be addressed. Different cross-sectional studies using diverse methodologies have reported that helminth infections might either exacerbate or reduce the severity of malaria attacks. The same discrepancies have been reported for parasitemia. Methods/Design To determine the effect of geohelminth infections and their treatment on malaria infection and disease outcome, as well as on immunological parameters, the area of Nangapanda on Flores Island, Indonesia, where malaria and helminth parasites are co-endemic was selected for a longitudinal study. Here a Double-blind randomized trial will be performed, incorporating repeated treatment with albendazole (400 mg) or placebo at three monthly intervals. Household characteristic data, anthropometry, the presence of intestinal helminth and Plasmodium spp infections, and the incidence of malaria episodes are recorded. In vitro cultures of whole blood, stimulated with a number of antigens, mitogens and toll like receptor ligands provide relevant immunological parameters at baseline and following 1 and 2 years of treatment rounds. The primary outcome of the study is the prevalence of Plasmodium falciparum and P. vivax infection. The secondary outcome will be incidence and severity of malaria episodes detected via both passive and active follow-up. The tertiary outcome is the inflammatory cytokine profile in response to parasite antigens. The project also facilitates the transfer of state of the art methodologies and technologies, molecular diagnosis of parasitic diseases, immunology and epidemiology from Europe to Indonesia. Discussion The study will provide data on the effect of helminth infections on malaria. It will also give information on anthelminthic treatment efficacy and effectiveness and could help develop evidence-based policymaking. Trial registration This study was approved by The Ethical Committee of Faculty of Medicine, University of Indonesia, ref:194/PT02.FK/Etik/2006 and has been filed by ethics committee of the Leiden University Medical Center. Clinical trial number:ISRCTN83830814. The study is reported in accordance with the CONSORT guidelines for cluster-randomized studies. PMID:20338054

A cross-sectional analysis of traditional medicine use for malaria alongside free antimalarial drugs treatment amongst adults in high-risk malaria endemic provinces of Indonesia.

PubMed

Suswardany, Dwi Linna; Sibbritt, David W; Supardi, Sudibyo; Pardosi, Jerico F; Chang, Sungwon; Adams, Jon

2017-01-01

The level of traditional medicine use, particularly Jamu use, in Indonesia is substantial. Indonesians do not always seek timely treatment for malaria and may seek self-medication via traditional medicine. This paper reports findings from the first focused analyses of traditional medicine use for malaria in Indonesia and the first such analyses worldwide to draw upon a large sample of respondents across high-risk malaria endemic areas. A sub-study of the Indonesia Basic Health Research/Riskesdas Study 2010 focused on 12,226 adults aged 15 years and above residing in high-risk malaria-endemic provinces. Logistic regression was undertaken to determine the significant associations for traditional medicine use for malaria symptoms. Approximately one in five respondents use traditional medicine for malaria symptoms and the vast majority experiencing multiple episodes of malaria use traditional medicine alongside free antimalarial drug treatments. Respondents consuming traditional medicine for general health/common illness purposes every day (odds ratio: 3.75, 95% Confidence Interval: 2.93 4.79), those without a hospital in local vicinity (odds ratio: 1.31, 95% Confidence Interval: 1.10 1.57), and those living in poorer quality housing, were more likely to use traditional medicine for malaria symptoms. A substantial percentage of those with malaria symptoms utilize traditional medicine for treating their malaria symptoms. In order to promote safe and effective malaria treatment, all providing malaria care in Indonesia need to enquire with their patients about possible traditional medicine use.

A cross-sectional analysis of traditional medicine use for malaria alongside free antimalarial drugs treatment amongst adults in high-risk malaria endemic provinces of Indonesia

PubMed Central

Suswardany, Dwi Linna; Sibbritt, David W.; Supardi, Sudibyo; Pardosi, Jerico F.; Chang, Sungwon; Adams, Jon

2017-01-01

Background The level of traditional medicine use, particularly Jamu use, in Indonesia is substantial. Indonesians do not always seek timely treatment for malaria and may seek self-medication via traditional medicine. This paper reports findings from the first focused analyses of traditional medicine use for malaria in Indonesia and the first such analyses worldwide to draw upon a large sample of respondents across high-risk malaria endemic areas. Methods A sub-study of the Indonesia Basic Health Research/Riskesdas Study 2010 focused on 12,226 adults aged 15 years and above residing in high-risk malaria-endemic provinces. Logistic regression was undertaken to determine the significant associations for traditional medicine use for malaria symptoms. Findings Approximately one in five respondents use traditional medicine for malaria symptoms and the vast majority experiencing multiple episodes of malaria use traditional medicine alongside free antimalarial drug treatments. Respondents consuming traditional medicine for general health/common illness purposes every day (odds ratio: 3.75, 95% Confidence Interval: 2.93 4.79), those without a hospital in local vicinity (odds ratio: 1.31, 95% Confidence Interval: 1.10 1.57), and those living in poorer quality housing, were more likely to use traditional medicine for malaria symptoms. Conclusion A substantial percentage of those with malaria symptoms utilize traditional medicine for treating their malaria symptoms. In order to promote safe and effective malaria treatment, all providing malaria care in Indonesia need to enquire with their patients about possible traditional medicine use. PMID:28329019

Low birth weight and fetal anaemia as risk factors for infant morbidity in rural Malawi.

PubMed

Kalanda, Boniface; Verhoeff, Francine; le Cessie, Saskia; Brabin, John

2009-06-01

Low birth weight (LBW) and fetal anaemia (FA) are common in malaria endemic areas. To investigate the incidence of infectious morbidity in infants in rural Malawi in relation to birth weight and fetal anaemia, a cohort of babies was followed for a year on the basis of LBW (<2500) and FA (cord haemoglobin < 12.5 g/dl). A matched group of normal birth weight (NBW), non-anaemic (NFA) new-borns were enrolled as controls. Morbidity episodes were recorded at 4-weekly intervals and at each extra visit made to a health centre with any illness. Infants in the NBW NFA group experienced an average of 1.15 (95% C.I. 0.99, 1.31), 1.04 (0.89, 1.19), 0.92 (0.73, 1.11) episodes per year of malaria, respiratory infection and diarrhoea respectively. Corresponding values for the LBW FA group were 0.83 (0.5, 1.16), 0.82 (0.5, 1.16) and 0.76 (0.33, 1.19). FA was not associated with a higher incidence of morbidity, but was significantly associated with a shorter time to first illness episode (p = 0.014). LBW was not a significant risk factor for higher morbidity incidence. LBW and FA were not significant risk factors for incidence of illness episodes in infants.

Anti-malarial landscape in Myanmar: results from a nationally representative survey among community health workers and the private sector outlets in 2015/2016.

PubMed

Thein, Si Thu; Khin, Hnin Su Su; Thi, Aung

2017-04-25

In 2015/2016, an ACTwatch outlet survey was implemented to assess the anti-malarial and malaria testing landscape in Myanmar across four domains (Eastern, Central, Coastal, Western regions). Indicators provide an important benchmark to guide Myanmar's new National Strategic Plan to eliminate malaria by 2030. This was a cross-sectional survey, which employed stratified cluster-random sampling across four regions in Myanmar. A census of community health workers (CHWs) and private outlets with potential to distribute malaria testing and/or treatment was conducted. An audit was completed for all anti-malarials, malaria rapid diagnostic tests. A total of 28,664 outlets were approached and 4416 met the screening criteria. The anti-malarial market composition comprised CHWs (41.5%), general retailers (27.9%), itinerant drug vendors (11.8%), pharmacies (10.9%), and private for-profit facilities (7.9%). Availability of different anti-malarials and diagnostic testing among anti-malarial-stocking CHWs was as follows: artemisinin-based combination therapy (ACT) (81.3%), chloroquine (67.0%), confirmatory malaria test (77.7%). Less than half of the anti-malarial-stocking private sector had first-line treatment in stock: ACT (41.7%) chloroquine (41.8%), and malaria diagnostic testing was rare (15.4%). Oral artemisinin monotherapy (AMT) was available in 27.7% of private sector outlets (Western, 54.1%; Central, 31.4%; Eastern; 25.0%, Coastal; 15.4%). The private-sector anti-malarial market share comprised ACT (44.0%), chloroquine (26.6%), and oral AMT (19.6%). Among CHW the market share was ACT (71.6%), chloroquine (22.3%); oral AMT (3.8%). More than half of CHWs could correctly state the national first-line treatment for uncomplicated falciparum and vivax malaria (59.2 and 56.9%, respectively) compared to the private sector (15.8 and 13.2%, respectively). Indicators on support and engagement were as follows for CHWs: reportedly received training on malaria diagnosis (60.7%) or national malaria treatment guidelines (59.6%), received a supervisory or regulatory visit within 12 months (39.1%), kept records on number of patients tested or treated for malaria (77.3%). These indicators were less than 20% across the private sector. CHWs have a strong foundation for achieving malaria goals and their scale-up is merited, however gaps in malaria commodities and supplies must be addressed. Intensified private sector strategies are urgently needed and must be scaled up to improve access and coverage of first-line treatments and malaria diagnosis, and remove oral AMT from the market place. Future policies and interventions on malaria control and elimination in Myanmar should take these findings into consideration across all phases of implementation.

Are patent medicine vendors effective agents in malaria control? Using lot quality assurance sampling to assess quality of practice in Jigawa, Nigeria.

PubMed

Berendes, Sima; Adeyemi, Olusegun; Oladele, Edward Adekola; Oresanya, Olusola Bukola; Okoh, Festus; Valadez, Joseph J

2012-01-01

Patent medicine vendors (PMV) provide antimalarial treatment and care throughout Sub-Saharan Africa, and can play an important role in the fight against malaria. Their close-to-client infrastructure could enable lifesaving artemisinin-based combination therapy (ACT) to reach patients in time. However, systematic assessments of drug sellers' performance quality are crucial if their role is to be managed within the health system. Lot quality assurance sampling (LQAS) could be an efficient method to monitor and evaluate PMV practice, but has so far never been used for this purpose. In support of the Nigeria Malaria Booster Program we assessed PMV practices in three Senatorial Districts (SDs) of Jigawa, Nigeria. A two-stage LQAS assessed whether at least 80% of PMV stores in SDs used national treatment guidelines. Acceptable sampling errors were set in consultation with government officials (alpha and beta <0.10). The hypergeometric formula determined sample sizes and cut-off values for SDs. A structured assessment tool identified high and low performing SDs for quality of care indicators. Drug vendors performed poorly in all SDs of Jigawa for all indicators. For example, all SDs failed for stocking and selling first-line antimalarials. PMV sold no longer recommended antimalarials, such as Chloroquine, Sulfadoxine-Pyrimethamine and oral Artesunate monotherapy. Most PMV were ignorant of and lacked training about new treatment guidelines that had endorsed ACTs as first-line treatment for uncomplicated malaria. There is urgent need to regularly monitor and improve the availability and quality of malaria treatment provided by medicine sellers in Nigeria; the irrational use of antimalarials in the ACT era revealed in this study bears a high risk of economic loss, death and development of drug resistance. LQAS has been shown to be a suitable method for monitoring malaria-related indicators among PMV, and should be applied in Nigeria and elsewhere to improve service delivery.

Are Patent Medicine Vendors Effective Agents in Malaria Control? Using Lot Quality Assurance Sampling to Assess Quality of Practice in Jigawa, Nigeria

PubMed Central

Berendes, Sima; Adeyemi, Olusegun; Oladele, Edward Adekola; Oresanya, Olusola Bukola; Okoh, Festus; Valadez, Joseph J.

2012-01-01

Background Patent medicine vendors (PMV) provide antimalarial treatment and care throughout Sub-Saharan Africa, and can play an important role in the fight against malaria. Their close-to-client infrastructure could enable lifesaving artemisinin-based combination therapy (ACT) to reach patients in time. However, systematic assessments of drug sellers’ performance quality are crucial if their role is to be managed within the health system. Lot quality assurance sampling (LQAS) could be an efficient method to monitor and evaluate PMV practice, but has so far never been used for this purpose. Methods In support of the Nigeria Malaria Booster Program we assessed PMV practices in three Senatorial Districts (SDs) of Jigawa, Nigeria. A two-stage LQAS assessed whether at least 80% of PMV stores in SDs used national treatment guidelines. Acceptable sampling errors were set in consultation with government officials (alpha and beta <0.10). The hypergeometric formula determined sample sizes and cut-off values for SDs. A structured assessment tool identified high and low performing SDs for quality of care indicators. Findings Drug vendors performed poorly in all SDs of Jigawa for all indicators. For example, all SDs failed for stocking and selling first-line antimalarials. PMV sold no longer recommended antimalarials, such as Chloroquine, Sulfadoxine-Pyrimethamine and oral Artesunate monotherapy. Most PMV were ignorant of and lacked training about new treatment guidelines that had endorsed ACTs as first-line treatment for uncomplicated malaria. Conclusion There is urgent need to regularly monitor and improve the availability and quality of malaria treatment provided by medicine sellers in Nigeria; the irrational use of antimalarials in the ACT era revealed in this study bears a high risk of economic loss, death and development of drug resistance. LQAS has been shown to be a suitable method for monitoring malaria-related indicators among PMV, and should be applied in Nigeria and elsewhere to improve service delivery. PMID:22984555

Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects.

PubMed

McGready, Rose; Phyo, Aung Pyae; Rijken, Marcus J; Tarning, Joel; Lindegardh, Niklas; Hanpithakpon, Warunee; Than, Hla Hla; Hlaing, Nathar; Zin, Naw Thida; Singhasivanon, Pratap; White, Nicholas J; Nosten, François

2012-03-01

To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance. In a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4mgkg(-1) ) on the first day and oral ARS (4mgkg(-1) ) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4mgkg(-1) day(-1) ) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography-mass-spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum). I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n= 20) and in controls (n= 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ngml(-1) h)/(mgkg(-1) )] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P= 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P= 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P= 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P= 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P= 0.084). This study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

The effect of an anti-malarial subsidy programme on the quality of service provision of artemisinin-based combination therapy in Kenya: a cluster-randomized, controlled trial

PubMed Central

2013-01-01

Background Many patients with suspected malaria in sub-Saharan Africa seek treatment from private providers, but this sector suffers from sub-standard medicine dispensing practices. To improve the quality of care received for presumptive malaria from the highly accessed private retail sector in western Kenya, subsidized pre-packaged artemether-lumefantrine (AL) was provided to private retailers, together with a one day training for retail staff on malaria diagnosis and treatment, job aids and community engagement activities. Methods The intervention was assessed using a cluster-randomized, controlled design. Provider and mystery-shopper cross-sectional surveys were conducted at baseline and eight months post-intervention to assess provider practices. Data were analysed based on cluster-level summaries, comparing control and intervention arms. Results On average, 564 retail outlets were interviewed per year. At follow-up, 43% of respondents reported that at least one staff member had attended the training in the intervention arm. The intervention significantly increased the percentage of providers knowing the first line treatment for uncomplicated malaria by 24.2% points (confidence interval (CI): 14.8%, 33.6%; adjusted p=0.0001); the percentage of outlets stocking AL by 31.7% points (CI: 22.0%, 41.3%; adjusted p=0.0001); and the percentage of providers prescribing AL for presumptive malaria by 23.6% points (CI: 18.7%, 28.6%; adjusted p=0.0001). Generally outlets that received training and job aids performed better than those receiving one or none of these intervention components. Conclusion Overall, subsidizing ACT and retailer training can significantly increase the percentage of outlets stocking and selling AL for the presumptive treatment of malaria, but further research is needed on strategies to improve the provision of counselling advice to retail customers. PMID:23452547

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial.

PubMed

Koita, Ousmane A; Sangaré, Lansana; Miller, Haiyan D; Sissako, Aliou; Coulibaly, Moctar; Thompson, Trevor A; Fongoro, Saharé; Diarra, Youssouf; Ba, Mamadou; Maiga, Ababacar; Diallo, Boubakar; Mushatt, David M; Mather, Frances J; Shaffer, Jeffrey G; Anwar, Asif H; Krogstad, Donald J

2017-12-01

Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964. Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2-4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference -6·1%, 95% CI -14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI -5·6 to 23·8). The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended. US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Malaria Rapid Diagnostic Tests and Malaria Microscopy for Guiding Malaria Treatment of Uncomplicated Fevers in Nigeria and Prereferral Cases in 3 African Countries.

PubMed

Falade, Catherine O; Ajayi, IkeOluwapo O; Nsungwa-Sabiiti, Jesca; Siribié, Mohamadou; Diarra, Amidou; Sermé, Luc; Afonne, Chinenye; Yusuf, Oyindamola B; Gansane, Zakaria; Jegede, Ayodele S; Singlovic, Jan; Gomes, Melba

2016-12-15

 The World Health Organization recommends that malaria treatment be based on demonstration of the infecting Plasmodium parasite specie. Malaria rapid diagnostic tests (RDTs) are recommended at community points of care because they are accurate and rapid. We report on parasitological results in a malaria study in selected rural communities in 3 African countries.  In Nigeria, community health workers (CHWs) performed RDTs (SD-Bioline) and thick blood smears on all children suspected to have malaria. Malaria RDT-positive children able to swallow received artemisinin-based combination therapy (Coartem). In all countries, children unable to take oral drugs received prereferral rectal artesunate irrespective of RDT result and were referred to the nearest health facility. Thick blood smears and RDTs were usually taken at hospital admission. In Nigeria and Burkina Faso, RDT cassettes and blood smears were re-read by an experienced investigator at study end.  Trained CHWs enrolled 2148 children in Nigeria. Complete parasitological data of 1860 (86.6%) enrollees were analyzed. The mean age of enrollees was 30.4 ± 15.7 months. The prevalence of malaria parasitemia in the study population was 77.8% (1447/1860), 77.6% (1439/1855), and 54.1% (862/1593) by RDT performed by CHWs vs an expert clinical research assistant vs microscopy (gold standard), respectively. Geometric mean parasite density was 6946/µL (range, 40-436 450/µL). There were 49 cases of RDT false-negative results with a parasite density range of 40-54 059/µL. False-negative RDT results with high parasitemia could be due to non-falciparum infection or result from a prozone effect. Sensitivity and specificity of SD-Bioline RDT results as read by CHWs were 94.3% and 41.6%, respectively, while the negative and positive predictive values were 86.1% and 65.6%, respectively. The level of agreement in RDT reading by the CHWs and experienced research staff was 86.04% and κ statistic of 0.60. The malaria parasite positivity rate by RDT and microscopy among children with danger signs in the 3 countries was 67.9% and 41.8%, respectively.  RDTs are useful in guiding malaria management and were successfully used for diagnosis by trained CHWs. However, false-negative RDT results were identified and can undermine confidence in results and control efforts. © 2016 World Health Organization; licensee Oxford Journals.

Health systems readiness and management of febrile outpatients under low malaria transmission in Vanuatu.

PubMed

Zurovac, Dejan; Guintran, Jean-Olivier; Donald, Wesley; Naket, Esau; Malinga, Josephine; Taleo, George

2015-12-02

Vanuatu, an archipelago country in Western Pacific harbouring low Plasmodium falciparum and Plasmodium vivax malaria transmission, has been implementing a malaria case management policy, recommending parasitological testing of patients with fever and anti-malarial treatment for test-positive only patients. A health facility survey to evaluate the health systems readiness to implement the policy and the quality of outpatient management for patients with fever was undertaken. A cross-sectional, cluster sample survey, using a range of quality-of-care methods, included all health centres and hospitals in Vanuatu. The main outcome measures were coverage of health facilities and health workers with commodities and support interventions, adherence to test and treatment recommendations, and factors influencing malaria testing. The survey was undertaken in 2014 during the low malaria season and included 41 health facilities, 67 health workers and 226 outpatient consultations for patients with fever. All facilities had capacity for parasitological diagnosis, 95.1 % stocked artemether-lumefantrine and 63.6 % primaquine. The coverage of health workers with support interventions ranged from 50 to 70 %. Health workers' knowledge was high only regarding treatment policy for uncomplicated P. falciparum malaria (83.4 %). History taking and clinical examination practices were sub-optimal. Some 35.0 % (95 % CI 23.4-48.6) of patients with fever were tested for malaria, of which all results were negative and only one patient received anti-malarial treatment. Testing was significantly higher for patients age 5 years and older (OR = 2.33; 95 % CI 1.48-5.02), seen by less qualified health workers (OR = 2.73; 95 % CI 1.48-5.02), health workers who received malaria case management training (OR = 2.39; 95 % CI 1.28-4.47) and patients with increased temperature (OR = 2.56; 95 % CI 1.17-5.57), main complaint of fever (OR = 5.82; 95 % CI 1.26-26.87) and without runny nose (OR = 3.75; 95 % CI 1.36-10.34). Antibiotic use was very high (77.4 %) with sub-optimal dispensing and counselling practices. Health facility and health worker readiness to implement policy is higher for falciparum than vivax malaria. Clinical and malaria testing practices are sub-optimal, however adherence to test negative results is nearly universal. Use of antibiotics is irrational. Quantitative and qualitative improvements of ongoing interventions are needed to re-inforce clinical practices in this area characterized by difficult access, human resource shortages but aspiring towards malaria elimination.

Malaria Rapid Diagnostic Tests and Malaria Microscopy for Guiding Malaria Treatment of Uncomplicated Fevers in Nigeria and Prereferral Cases in 3 African Countries

PubMed Central

Falade, Catherine O.; Ajayi, IkeOluwapo O.; Nsungwa-Sabiiti, Jesca; Siribié, Mohamadou; Diarra, Amidou; Sermé, Luc; Afonne, Chinenye; Yusuf, Oyindamola B.; Gansane, Zakaria; Jegede, Ayodele S.; Singlovic, Jan; Gomes, Melba

2016-01-01

Background. The World Health Organization recommends that malaria treatment be based on demonstration of the infecting Plasmodium parasite specie. Malaria rapid diagnostic tests (RDTs) are recommended at community points of care because they are accurate and rapid. We report on parasitological results in a malaria study in selected rural communities in 3 African countries. Methods. In Nigeria, community health workers (CHWs) performed RDTs (SD-Bioline) and thick blood smears on all children suspected to have malaria. Malaria RDT-positive children able to swallow received artemisinin-based combination therapy (Coartem). In all countries, children unable to take oral drugs received prereferral rectal artesunate irrespective of RDT result and were referred to the nearest health facility. Thick blood smears and RDTs were usually taken at hospital admission. In Nigeria and Burkina Faso, RDT cassettes and blood smears were re-read by an experienced investigator at study end. Results. Trained CHWs enrolled 2148 children in Nigeria. Complete parasitological data of 1860 (86.6%) enrollees were analyzed. The mean age of enrollees was 30.4 ± 15.7 months. The prevalence of malaria parasitemia in the study population was 77.8% (1447/1860), 77.6% (1439/1855), and 54.1% (862/1593) by RDT performed by CHWs vs an expert clinical research assistant vs microscopy (gold standard), respectively. Geometric mean parasite density was 6946/µL (range, 40–436 450/µL). There were 49 cases of RDT false-negative results with a parasite density range of 40–54 059/µL. False-negative RDT results with high parasitemia could be due to non-falciparum infection or result from a prozone effect. Sensitivity and specificity of SD-Bioline RDT results as read by CHWs were 94.3% and 41.6%, respectively, while the negative and positive predictive values were 86.1% and 65.6%, respectively. The level of agreement in RDT reading by the CHWs and experienced research staff was 86.04% and κ statistic of 0.60. The malaria parasite positivity rate by RDT and microscopy among children with danger signs in the 3 countries was 67.9% and 41.8%, respectively. Conclusions. RDTs are useful in guiding malaria management and were successfully used for diagnosis by trained CHWs. However, false-negative RDT results were identified and can undermine confidence in results and control efforts. PMID:27941107

Malaria Early Warning: The MalarSat project

NASA Astrophysics Data System (ADS)

Roca, M.; Escorihuela, M. J.; Martínez, D.; Torrent, M.; Aponte, J.; Nunez, F.; Garcia, J.

2009-04-01

Malaria is one of the major public health challenges undermining development in the world. The aim of MalarSat Project is to provide a malaria risks infection maps at global scale using Earth Observation data to support and prevent epidemic episodes. The proposed service for creating malaria risk maps would be critically useful to improve the efficiency in insecticide programs, vaccine campaigns and the logistics epidemic treatment. Different teams have already carried out studies in order to exploit the use of Earth Observation (EO) data with epidemiology purposes. In the case of malaria risk maps, it has been shown that meteorological data is not sufficient to fulfill this objective. In particular being able to map the malaria mosquito habitat would increase the accuracy of risk maps. The malaria mosquitoes mainly reproduce in new water puddles of very reduced dimensions (about 1 meter wide). There is no instrument that could detect such small patches of water unless there are many of them spread in an area of several hundreds of meters. MalarSat aims at using the radar altimeter data from the EnviSat, RA-2, to try and build indicators of mosquitoes existence. This presentation will show the scientific objectives and principles of the MalarSat project.

Malaria-Related Anemia in Patients from Unstable Transmission Areas in Colombia

PubMed Central

Lopez-Perez, Mary; Álvarez, Álvaro; Gutierrez, Juan B.; Moreno, Alberto; Herrera, Sócrates; Arévalo-Herrera, Myriam

2015-01-01

Information about the prevalence of malarial anemia in areas of low-malaria transmission intensity, like Latin America, is scarce. To characterize the malaria-related anemia, we evaluated 929 malaria patients from three sites in Colombia during 2011–2013. Plasmodium vivax was found to be the most prevalent species in Tierralta (92%), whereas P. falciparum was predominant in Tumaco (84%) and Quibdó (70%). Although severe anemia (hemoglobin < 7 g/dL) was almost absent (0.3%), variable degrees of non-severe anemia were observed in 36.9% of patients. In Tierralta, hemoglobin levels were negatively associated with days of illness. Moreover, in Tierralta and Quibdó, the number of previous malaria episodes and hemoglobin levels were positively associated. Both Plasmodium species seem to have similar potential to induce malarial anemia with distinct cofactors at each endemic setting. The target age in these low-transmission settings seems shifting toward adolescents and young adults. In addition, previous malaria experience seems to induce protection against anemia development. Altogether, these data suggest that early diagnosis and prompt treatment are likely preventing more frequent and serious malaria-related anemia in Colombia. PMID:25510719

Severe thrombocytopaenia in patients with vivax malaria compared to falciparum malaria: a systematic review and meta-analysis.

PubMed

Naing, Cho; Whittaker, Maxine A

2018-02-09

Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria. A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (< 50 000/mm 3 ) to very severe thrombocytopaenia (< 20 000/mm 3 ) was observed in 10.1% of patients with P. vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P < 0.001 in all comparisons). A pooled analysis of two other studies showed a similar proportion of bleeding episodes with thrombocytopaenia in severe P. vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited. The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.

In vitro and in vivo antileishmanial activity of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans.

PubMed

Mesa, Luz Estella; Vasquez, Daniel; Lutgen, Pierre; Vélez, Iván Darío; Restrepo, Adriana María; Ortiz, Isabel; Robledo, Sara María

2017-01-01

Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases. Here, we aimed to determine the usefulness of A. annua gel capsules in CL. The antileishmanial activity and cytotoxicity of A. annua L. capsules was determined via in vitro and in vivo studies. Moreover, a preliminary evaluation of its therapeutic potential as antileishmanial treatment in humans was conducted in 2 patients with uncomplicated CL. Artemisia annua capsules showed moderate in vitro activity in amastigotes of Leishmania (Viannia) panamensis; no cytotoxicity in U-937 macrophages or genotoxicity in human lymphocytes was observed. Five of 6 (83.3%) hamsters treated with A. annua capsules (500mg/kg/day) for 30 days were cured, and the 2 examined patients were cured 45 days after initiation of treatment with 30g of A. annua capsules, without any adverse reactions. Both patients remained disease-free 26 and 24 months after treatment completion. Capsules of A. annua L. represent an effective treatment for uncomplicated CL, although further randomized controlled trials are needed to validate its efficacy and safety.

Pregnancy-associated malaria and malaria in infants: an old problem with present consequences.

PubMed

Moya-Alvarez, Violeta; Abellana, Rosa; Cot, Michel

2014-07-11

Albeit pregnancy-associated malaria (PAM) poses a potential risk for over 125 million women each year, an accurate review assessing the impact on malaria in infants has yet to be conducted. In addition to an effect on low birth weight (LBW) and prematurity, PAM determines foetal exposure to Plasmodium falciparum in utero and is correlated to congenital malaria and early development of clinical episodes during infancy. This interaction plausibly results from an ongoing immune tolerance process to antigens in utero, however, a complete explanation of this immune process remains a question for further research, as does the precise role of protective maternal antibodies. Preventive interventions against PAM modify foetal exposure to P. falciparum in utero, and have thus an effect on perinatal malaria outcomes. Effective intermittent preventive treatment in pregnancy (IPTp) diminishes placental malaria (PM) and its subsequent malaria-associated morbidity. However, emerging resistance to sulphadoxine-pyrimethamine (SP) is currently hindering the efficacy of IPTp regimes and the efficacy of alternative strategies, such as intermittent screening and treatment (IST), has not been accurately evaluated in different transmission settings. Due to the increased risk of clinical malaria for offspring of malaria infected mothers, PAM preventive interventions should ideally start during the preconceptual period. Innovative research examining the effect of PAM on the neurocognitive development of the infant, as well as examining the potential influence of HLA-G polymorphisms on malaria symptoms, is urged to contribute to a better understanding of PAM and infant health.

Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission.

PubMed

Lusingu, John P A; Vestergaard, Lasse S; Alifrangis, Michael; Mmbando, Bruno P; Theisen, Michael; Kitua, Andrew Y; Lemnge, Martha M; Theander, Thor G

2005-09-29

Several studies conducted in areas of medium or low malaria transmission intensity have found associations between malaria immunity and plasma antibody levels to glutamate rich protein (GLURP). This study was conducted to analyse if a similar relationship could be documented in an area of intense malaria transmission. A six month longitudinal study was conducted in an area of holoendemic malaria transmission in north-eastern Tanzania, where the incidence of febrile malaria decreased sharply by the age of three years, and anaemia constituted a significant part of the malaria disease burden. Plasma antibodies to glutamate rich protein (GLURP) were analysed and related with protection against malaria morbidity in models correcting for the effect of age. The risk of febrile malaria episodes was reduced significantly in children with measurable anti-GLURP IgG1 antibodies at enrollment [adjusted odds ratio: 0.39 (95% CI: 0.15, 0.99); P = 0.047]. Interestingly, there was an inverse relationship between the plasma anti-GLURP IgG1 and IgG3 levels and the levels of parasitaemia at enrollment. However, anti-GLURP IgG2 and IgG4 levels were not associated with reduction in parasite density. Similarly, antibody levels were not associated with haemoglobin levels or anaemia risk. Cytophilic IgG1 and IgG3 antibodies against R0-GLURP may contribute to the control of parasite multiplication and reduction in febrile malaria incidence in children living in an area of intense malaria transmission.

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

PubMed

Taylor, W Robert; Naw, Htee Khu; Maitland, Kathryn; Williams, Thomas N; Kapulu, Melissa; D'Alessandro, Umberto; Berkley, James A; Bejon, Philip; Okebe, Joseph; Achan, Jane; Amambua, Alfred Ngwa; Affara, Muna; Nwakanma, Davis; van Geertruyden, Jean-Pierre; Mavoko, Muhindo; Lutumba, Pascal; Matangila, Junior; Brasseur, Philipe; Piola, Patrice; Randremanana, Rindra; Lasry, Estrella; Fanello, Caterina; Onyamboko, Marie; Schramm, Birgit; Yah, Zolia; Jones, Joel; Fairhurst, Rick M; Diakite, Mahamadou; Malenga, Grace; Molyneux, Malcolm; Rwagacondo, Claude; Obonyo, Charles; Gadisa, Endalamaw; Aseffa, Abraham; Loolpapit, Mores; Henry, Marie-Claire; Dorsey, Grant; John, Chandy; Sirima, Sodiomon B; Barnes, Karen I; Kremsner, Peter; Day, Nicholas P; White, Nicholas J; Mukaka, Mavuto

2018-01-18

In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

Imported malaria to Northern Ireland: improving surveillance for better intervention

PubMed Central

Ong, GM; Smyth, B

2006-01-01

Malaria is a preventable disease, which is under notified in the UK. This study sought to evaluate the current surveillance arrangements in Northern Ireland (NI), describe the epidemiology of malaria and make appropriate recommendations. A case was defined as a resident or visitor to NI with laboratory confirmed malaria, diagnosed by the NI haematology laboratories and/or the Malaria Reference Laboratory (MRL) from 1998–2003. Laboratory data were compared with notifications and hospital admission data. One hundred and fourteen laboratory cases were identified compared with 63 notifications received by the regional surveillance centre. Six cases were associated with two episodes of malaria reflecting recurrence and or reinfection. P. falciparum was the most common infection with two fatalities reported; this was particularly associated with travel to West Africa. Most cases were associated with short visits to malarious areas. Thirty-three percent of all cases did not take prophylaxis and, of those that did, approximately half were taking a prophylactic regime appropriate to the region visited. This study highlights the need for improved surveillance of malaria in order to capture risk factors and other relevant information to inform public and professional education. This would facilitate increasing local awareness, enhancing prescription of and compliance with appropriate chemoprophylaxis and enabling early diagnosis and treatment of malaria. PMID:16755943

Precarity and Preparedness: Non-Adherence as Institutional Work in Diagnosing and Treating Malaria in Uganda.

PubMed

Umlauf, René

2017-07-01

Access to anti-malarial drugs is increasingly governed by novel regulation technologies like rapid diagnostic tests (RDTs). However, high rates of non-adherence particularly to negative RDT results have been reported, threatening the cost-effectiveness of the two interrelated goals of improving diagnosis and reducing the over-prescription of expensive anti-malarial drugs. Below I set out to reconstruct prior treatment forms like presumptive treatment of malaria by paying particular attention to their institutional groundings. I show how novel regulation technologies affect existing institutions of care and argue that the institutional work of presumptive treatment goes beyond the diagnosis and treatment of a currently observed fever episode. Instead, in contexts of precarity, through what I will call "practices of preparedness," presumptive treatment includes a variety of practices, performances, temporalities, and opportunities that allow individuals to prepare for future episodes of fever.

Dengue infection as a potential trigger of an imported Plasmodium ovale malaria relapse or a long incubation period in a non-endemic malaria region.

PubMed

Lupi, Otília; Ridolfi, Felipe; da Silva, Sidnei; Zanini, Graziela Maria; Lavigne, Aline; Nogueira, Rita Maria Ribeiro; da Cruz, Maria de Fátima Ferreira; Daniel-Ribeiro, Cláudio Tadeu; Brasil, Patrícia

2016-03-01

To report that dengue fever (DF) could have triggered Plasmodium ovale wallikeri malaria. A retrospective case report of P. ovale malaria and DF in a single patient in Rio de Janeiro, Brazil, who had lived in Angola, is presented. On the second week of illness, the patient was referred to our research service. As symptoms had persisted up to day 14, malaria was also considered, based on the patient's long-standing epidemiological history. On day 16 of illness, a thick blood smear was positive for P. ovale (3480 parasites/mm(3)), PCR for malaria was positive for P. ovale wallikeri, and the kinetics of dengue virus (DENV) antibodies suggested a recent primary dengue infection. Concurrent infections of DENV and malaria have rarely been reported; the actual impact of these sequential or simultaneous infections remains unknown. Therefore, DF must be considered as a potential co-morbidity for malaria, because of its influence on fluid electrolyte management. The case presented showed consistent temporal, clinical, and laboratory evidence that the relapse or the long incubation period of P. ovale malaria may have been triggered by a recent DF episode. To the authors' knowledge, this is the first report of DENV and P. ovale co-infection. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cost-Effectiveness of Long-Lasting Insecticide-Treated Hammocks in Preventing Malaria in South-Central Vietnam

PubMed Central

Morel, Chantal M.; Thang, Ngo Duc; Erhart, Annette; Xa, Nguyen Xuan; Peeters Grietens, Koen; Xuan Hung, Le; Thuan, Le Khan; Van Ky, Pham; Hung, Nguyen Manh; Coosemans, Marc; D'Alessandro, Umberto; Mills, Anne

2013-01-01

Background Despite much success in reducing the burden of malaria in Vietnam, pockets of malaria persist and eliminating them remains an important development goal. In central Vietnam, insecticide-treated hammocks have recently been introduced to help counter the disease in the highly forested, mountainous areas, where other measures have so far been unsuccessful. This study assesses the cost-effectiveness of using long-lasting insecticide-treated hammocks in this area. Methods and Findings This cost-effectiveness study was run alongside a randomized control trial testing the efficacy of the long-lasting insecticide-treated hammocks. Data were collected through an exit survey, a household survey, expenditure records and key informant interviews. The study estimates that under normal (non-trial) conditions the total net societal cost per malaria episode averted in using long-lasting insecticide-treated hammocks in this area was 126 USD. Cost per hammock, including insecticidal netting, sewing, transport, and distribution was found to be approximately 11.76 USD per hammock. Average savings per episode averted were estimated to be $14.60 USD for the health system and 14.37 USD for households (including both direct and indirect cost savings). The study estimates that the annual financial outlay required of government to implement this type of programme to be 3.40 USD per person covered per year. Conclusion The study finds that the use of a hammock intervention could represent good value for money to help prevent malaria in more remote areas, where traditional control measures such as insecticide-treated bednets and indoor residual spraying are insufficient or inappropriate to control malaria. However, the life span of the hammock–the number of years over which it effectively deters mosquitoes–has a significant impact on the cost-effectiveness of the intervention and study results should be interpreted in light of the evidence on effectiveness gathered in the years to come. PMID:23536790

Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum.

PubMed

Pradines, B; Fusai, T; Daries, W; Laloge, V; Rogier, C; Millet, P; Panconi, E; Kombila, M; Parzy, D

2001-08-01

The in vitro activities of ferrochloroquine, chloroquine, quinine, mefloquine, halofantrine, amodiaquine, primaquine, atovaquone and artesunate were evaluated against Plasmodium falciparum isolates from children with uncomplicated malaria from Libreville (Gabon), using an isotopic, micro, drug susceptibility test. The IC(50) values for ferrochloroquine were in the range 0.43-30.9 nM and the geometric mean IC(50) for the 103 isolates was 10.8 nM (95% CI 8.6-13.5 nM), while the geometric means for chloroquine, quinine, mefloquine, amodiaquine and primaquine were 370 nM, 341 nM, 8.3 nM, 18.1 nM and 7.6 microM, respectively. Ferrochloroquine was active against P. falciparum isolates, 95% of which showed in vitro resistance to chloroquine. Weak positive significant correlations were observed between the responses to ferrochloroquine and that to chloroquine, amodiaquine and quinine, but too low to suggest cross-resistance. There was no significant correlation between the response to ferrochloroquine and those to mefloquine, halofantrine, primaquine, atovaquone or artesunate. Ferrochloroquine may be an important alternative drug for the treatment of chloroquine-resistant malaria.

Creation of first malaria vaccine raises troubling questions about "intellectual racism". Interview by Kirsteen MacLeod.

PubMed Central

Patarroyo, M

1995-01-01

Some of the problems caused by malaria, which places a huge roadblock in front of economic progress in the Third World, may be solved by a new vaccine created by Dr. Manuel Patarroyo, a Columbian physician and researcher. "Imagine how things would be if Canadians had malaria," he says. "Episodes last 10 days, then there are 10 days of recovering. This leaves only 10 days each month in which to do some productive work. Then imagine killing the population of Toronto each year, and you can see the huge toll in terms of the number of yearly deaths globally from malaria." His discovery also raises the issue of "intellectual racism" because of criticism of Patarroyo's methods by Western scientists. Patarroyo, meanwhile, turned down a $60-million offer for his vaccine, and instead donated the patent to the World Health Organization. Images p1320-a PMID:7497394

Positioning, labelling, and medical information control of co-artemether tablets (CPG 56697): a fixed novel combination of artemether and benflumetol. Novartis Co-Artemether International Development Team.

PubMed

Skelton-Stroud, P; Mull, R

1998-01-01

Coartemether is a fixed 1:6 ratio of artemether and lumefantrine (benflumetol), a joint development between Novartis Pharma and the Academy of Military Medical Sciences (Beijing, China). It is well tolerated and has a high efficacy against uncomplicated and drug resistant falciparum malaria by oral administration. The preclinical profile of coartemether revealed no prohibitive toxicological, teratogenic or mutagenic findings. No evidence of neurotoxicity was seen in oral preclinical studies. It shows a negative response to the induction of resistance and prevents recrudescence. Clinically, coartemether shows a rapid onset of antiparasitic action, resolution of symptoms, no clinical neurotoxicity and excellent parasite clearance.

Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.

PubMed

Toure, Offianan Andre; Rulisa, Stephen; Anvikar, Anupkumar R; Rao, Ballamudi S; Mishra, Pitabas; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Valecha, Neena

2015-11-25

The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and safety results observed in children warrants further studies on FDC of arterolane maleate and PQP dispersible tablets. Clinical Trial Registry India: CTRI/2009/091/000531.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention.

PubMed

Kranz, Jennifer; Schmidt, Stefanie; Lebert, Cordula; Schneidewind, Laila; Mandraka, Falitsa; Kunze, Mirjam; Helbig, Sina; Vahlensieck, Winfried; Naber, Kurt; Schmiemann, Guido; Wagenlehner, Florian M

2018-01-01

We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010-2015. For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients. © 2018 S. Karger AG, Basel.

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania.

PubMed

Massaga, J J; Lusingu, J P; Makunde, R; Malebo, H M; Chile, M M; Akida, J A; Lemnge, M M; Rønn, A M; Theander, T G; Bygbjerg, I C; Kitua, A Y

2008-07-01

Amodiaquine (AQ), an effective antimalarial drug for uncomplicated malaria, has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety, tolerability, and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3% CQ treated-aparasitaemic, 23.8% of CQ treated-parasitaemic, 28.6% ofAQ-treated parasitaemic and 14.3% of aparasitaemic receiving AQ. Amodiaquine attained 100% parasitological clearance rate versus 70% in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects.

C-terminal polymorphism of Plasmodium falciparium merozoite surface protein-1 (MSP-1) from Tak Province, Thailand.

PubMed

Viputtigul, Kwanjai; Tungpukdee, Noppadon; Ruangareerate, Toon; Luplertlop, Natthanej; Wilairatana, Polrat; Gaywee, Jariyanart; Krudsood, Srivicha

2013-01-01

This study was undertaken to ascertain the extent of polymorphism in the C-terminal region of Plasmodium falciparum merozoite surface protein (MSP-1) from 119 malaria patients in Tak Province on the western border of Thailand, who were admitted to the Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. P. falciparum infection was confirmed by microscopic examination of peripheral blood smears. Clinical manifestations were categorized into 2 groups: uncomplicated (94 cases) and complicated/severe (25 cases). A 1,040 basepair fragment of P. falciparum MSP-1 gene was compared with MSP-1 of reference strains retrieved from GenBank. The consensus sequences of MSP-1 block 16 showed it belonged to MAD20 genotype, which is the major allele of falciparum malaria from the western border of Thailand. MSP-1 block 16 amino acid fragment could be separated into 2 groups: similar and dissimilar to reference sequence. Four variations in MSP-1 block 16 were -1494K, D1510G, D1556N, and K1696I. MSP-1 block 16 diversity is not significantly associated with clinical manifestation although MAD 20 genotype is the predominant genotype in this area. The genetic data of MSP1 gene of faciparum malaria isolated from western Thai border contribute to the existing genetic database of Thai P. falciparum strain.

Pharmacokinetics and pharmacodynamics of qinghaosu derivatives: how do they impact on the choice of drug and the dosage regimens?

PubMed

Kyle, D E; Teja-Isavadharm, P; Li, Q; Leo, K

1998-01-01

The critical decisions of which artemisinin derivative(s) to use and by which route(s) of administration for falciparum malaria are complex scientifically and politically. Despite the need for additional pharmacokinetic, pharmacodynamic and toxicokinetic data, these drugs are too important to delay concise, rational recommendations any longer. These types of decisions must be made now, implemented on a multinational level with WHO leadership, and revised as new findings emerge. For acute, uncomplicated disease, per os dosing of artesunate or artemether for three days is recommended, but only in combination with other antimalarial drugs like mefloquine. For severe falciparum malaria, intravenous administration is the preferred route, yet current formulations for intravenous dosing are not optimal and should be an area for future development emphasis. Clearly intramuscular administration of artemether has proven effective for severe disease, yet dosing regimens shouldn't be designed with ultimate parasitological cure as the aim and the problem of bioavailability of the sesame oil formulations must be examined further. Once the life-saving reduction in parasitemia and pathophysiological sequelae have been achieved, the patient can be given oral medication to affect radical cure. Much more data will be required to define the role of per rectum dosing for the treatment of severe malaria, yet this approach holds great promise as a life-saving intervention in rural areas where this disease has it most dramatic impact.

A Field Trial to Assess a Blood-Stage Malaria Vaccine

PubMed Central

Thera, Mahamadou A.; Doumbo, Ogobara K.; Coulibaly, Drissa; Laurens, Matthew B.; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Thompson, Darby; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.

2011-01-01

BACKGROUND Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. METHODS In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. RESULTS The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P = 0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P = 0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. CONCLUSIONS On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. PMID:21916638

Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania.

PubMed

Croke, Kevin; Ishengoma, Deus S; Francis, Filbert; Makani, Julie; Kamugisha, Mathias L; Lusingu, John; Lemnge, Martha; Larreguy, Horacio; Fink, Günther; Mmbando, Bruno P

2017-08-15

Sickle Cell Trait (SCT) has been shown to be protective against malaria. A growing literature suggests that malaria exposure can reduce educational attainment. This study assessed the relationship and interactions between malaria, SCT and educational attainment in north-eastern Tanzania. Seven hundred sixty seven children were selected from a list of individuals screened for SCT. Febrile illness and malaria incidence were monitored from January 2006 to December 2013 by community health workers. Education outcomes were extracted from the Korogwe Health and Demographic Surveillance system in 2015. The primary independent variables were malaria and SCT. The association between SCT and the number of fever and malaria episodes from 2006 to 2013 was analyzed. Main outcomes of interest were school enrolment and educational attainment in 2015. SCT was not associated with school enrolment (adjusted OR 1.42, 95% CI [0.593,3.412]) or highest grade attained (adjusted grade difference 0.0597, 95% CI [-0.567, 0.686]). SCT was associated with a 29% reduction in malaria incidence (adjusted IRR 0.71, 95% CI [0.526, 0.959]) but not with fever incidence (adjusted IRR 0.905, 95% CI [0.709-1.154]). In subgroup analysis of individuals with SCT, malaria exposure was associated with reduced school enrollment (adjusted OR 0.431, 95% CI [0.212, 0.877]). SCT appears to reduce incidence of malaria. Overall, children with SCT do not appear to attend more years of school; however children who get malaria despite SCT appear to have lower levels of enrolment in education than their peers.

Detection of Plasmodium knowlesi, Plasmodium falciparum and Plasmodium vivax using loop-mediated isothermal amplification (LAMP) in a co-endemic area in Malaysia.

PubMed

Piera, Kim A; Aziz, Ammar; William, Timothy; Bell, David; González, Iveth J; Barber, Bridget E; Anstey, Nicholas M; Grigg, Matthew J

2017-01-13

Plasmodium knowlesi is the most common cause of malaria in Malaysia. However, microscopic diagnosis is inaccurate and rapid diagnostic tests (RDTs) are insufficiently sensitive. PCR is sensitive and specific but not feasible at a district level. Loop-mediated isothermal amplification (LAMP) shows potential with only basic requirements. A commercially available LAMP assay, the Eiken Loopamp™ MALARIA Pan Detection kit, is sensitive for Plasmodium falciparum and Plasmodium vivax, but has not previously been evaluated for P. knowlesi. This study aims to determine the sensitivity of this LAMP assay for detecting P. knowlesi infection. Study participants included 73 uncomplicated malaria patients with PCR species confirmation: 50 P. knowlesi, 20 P. falciparum and 3 P. vivax. Nineteen malaria-negative, non-endemic area controls were also included. The sensitivity of the Eiken Loopamp™ MALARIA Pan Detection kit (Pan LAMP) for detecting each Plasmodium species was evaluated. Sensitivity and specificity of the Eiken Loopamp™ MALARIA Pf Detection kit (Pf LAMP) for P. falciparum were also determined. The limit of detection for each LAMP assay was evaluated, with results compared to PCR. All P. knowlesi patients were also tested by CareStart™ (Pf/VOM) and OptiMAL-IT™ (Pan/Pf) RDTs. The sensitivity of the Pan LAMP assay was 100% for P. knowlesi (95% CI 92.9-100), P. falciparum (95% CI 83.2-100), and P. vivax (95% CI 29.2-100). The Pf LAMP was 100% sensitive and specific for P. falciparum detection, with all P. knowlesi samples having a negative reaction. LAMP sensitivity was superior to both RDTs, with only 10 and 28% of P. knowlesi samples testing positive to CareStart™ and OptiMAL-IT™, respectively. Limit of detection using the Pan LAMP for both P. knowlesi and P. vivax was 2 parasites/μL, comparable to PCR. For P. falciparum both the Pan LAMP and Pf LAMP demonstrated a limit of detection of 20 parasites/μL. The Eiken Loopamp™ MALARIA Pan Detection kit is sensitive for detection of P. knowlesi in low parasitaemia clinical infections, as well as P. falciparum and P. vivax. However, a P. knowlesi-specific field assay in a simpler format would assist correct species identification and initiation of optimal treatment for all malaria patients.

Vaccines for preventing malaria (blood-stage).

PubMed

Graves, P; Gelband, H

2006-10-18

A malaria vaccine is needed because of the heavy burden of mortality and morbidity due to this disease. This review describes the results of trials of blood (asexual)-stage vaccines. Several are under development, but only one (MSP/RESA, also known as Combination B) has been tested in randomized controlled trials. To assess the effect of blood-stage malaria vaccines in preventing infection, disease, and death. In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. Randomized controlled trials comparing blood-stage vaccines (other than SPf66) against P. falciparum, P. vivax, P. malariae, or P. ovale with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving a challenge malaria infection. Both authors independently assessed trial quality and extracted data. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI). Five trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 microg of each antigen (39 to 45 microg total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to 0.57; 719 participants) while those with the other main subtype, FC27, were not (720 participants). The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.

An in-depth study of patent medicine sellers' perspectives on malaria in a rural Nigerian community

PubMed Central

Okeke, Theodora A; Uzochukwu, Benjamin SC; Okafor, Henrietta U

2006-01-01

Background Malaria remains a major cause of mortality among under five children in Nigeria. Most of the early treatments for fever and malaria occur through self-medication with antimalarial drugs bought from medicine sellers. These have led to increasing calls for interventions to improve treatment obtained in these outlets. However, information about the current practices of these medicine sellers is needed before such interventions. This study aims to determine the medicine sellers' perspectives on malaria and the determinants that underlie their dispensing patterns of antimalarial drugs. Methods The study was conducted in Ugwugo-Nike, a rural community in south-east Nigeria. It involved in-depth interviews with 13 patent medicine sellers. Results A majority of the medicine sellers were not trained health professionals and malaria is recognized as a major health problem by them. There is poor knowledge and poor dispensing behaviour in relation to childhood malaria episodes. Although referral of severe malaria is common, there are those who will not refer. Verbal advice is rarely given to the care-givers. Conclusion More action research and interventions to improve prescription and referral practices and giving verbal advice to care-givers is recommended. Ways to integrate the drug sellers in the health system are also recommended. PMID:17078875

An in-depth study of patent medicine sellers' perspectives on malaria in a rural Nigerian community.

PubMed

Okeke, Theodora A; Uzochukwu, Benjamin S C; Okafor, Henrietta U

2006-11-01

Malaria remains a major cause of mortality among under five children in Nigeria. Most of the early treatments for fever and malaria occur through self-medication with antimalarial drugs bought from medicine sellers. These have led to increasing calls for interventions to improve treatment obtained in these outlets. However, information about the current practices of these medicine sellers is needed before such interventions. This study aims to determine the medicine sellers' perspectives on malaria and the determinants that underlie their dispensing patterns of antimalarial drugs. The study was conducted in Ugwugo-Nike, a rural community in south-east Nigeria. It involved in-depth interviews with 13 patent medicine sellers. A majority of the medicine sellers were not trained health professionals and malaria is recognized as a major health problem by them. There is poor knowledge and poor dispensing behaviour in relation to childhood malaria episodes. Although referral of severe malaria is common, there are those who will not refer. Verbal advice is rarely given to the care-givers. More action research and interventions to improve prescription and referral practices and giving verbal advice to care-givers is recommended. Ways to integrate the drug sellers in the health system are also recommended.

An Analysis of the Spatial Distribution of Plasmodium sporozoites and Effects of Climatic Correlates on Malaria Infection in Anyigba Town, Nigeria

PubMed Central

Ifatimehin, O. O.; Falola, O. O.; Odogbo, E. V.

2014-01-01

The infectivity of sporozoites on both mosquitoes and human is the major cause of malaria infection on its host, Man. Malaria infection had continued to blossom despite measures to curb it. Clinically diagnosed malaria data for 3 years, capture of mosquitoes for laboratory analysis to determining the infectivity of sporozoites, responses from the population on the number of episode of malaria in the last 60 days were all collected and generated, and also subjected to various analysis using methods accepted tools and methods. A fifteen weeks climatic data was also collected. It was discovered that malaria incidence of 467.2853/1000 persons is very high. This high rate is possible as out of every 10 mosquitoes in Anyigba, 4 are infected by sporozoites and can possibly transmit these sporozoites during blood feeding on the population. This is affirmed by the prevalence of malaria by 54.75% among Anyigba’s population. At p>001 (0.829), climatic variables and sporozoites rate showed a strong affinity with the prevalence of malaria. The risk map showed that the university community and the surrounding students’ lodges are areas of very high risk. Therefore, the populace is strongly advised to employed practicable measures such as regular environmental sanitation and the use of Insecticidal Treated Nets (ITN) in order to drastically address this epidemic. PMID:24373271

An analysis of the spatial distribution of Plasmodium sporozoites and effects of climatic correlates on malaria infection in Anyigba town, Nigeria.

PubMed

Ifatimehin, Olarewaju Oluseyi; Falola, O O; Odogbo, E V

2013-10-27

The infectivity of sporozoites on both mosquitoes and human is the major cause of malaria infection on its host, Man. Malaria infection had continued to blossom despite measures to curb it. Clinically diagnosed malaria data for 3 years, capture of mosquitoes for laboratory analysis to determining the infectivity of sporozoites, responses from the population on the number of episode of malaria in the last 60 days were all collected and generated, and also subjected to various analysis using methods accepted tools and methods. A fifteen weeks climatic data was also collected. It was discovered that malaria incidence of 467.2853/1000 persons is very high. This high rate is possible as out of every 10 mosquitoes in Anyigba, 4 are infected by sporozoites and can possibly transmit these sporozoites during blood feeding on the population. This is affirmed by the prevalence of malaria by 54.75% among Anyigba's population. At p>001 (0.829), climatic variables and sporozoites rate showed a strong affinity with the prevalence of malaria. The risk map showed that the university community and the surrounding students' lodges are areas of very high risk. Therefore, the populace is strongly advised to employed practicable measures such as regular environmental sanitation and the use of Insecticidal Treated Nets (ITN) in order to drastically address this epidemic.

Malaria hotspots defined by clinical malaria, asymptomatic carriage, PCR and vector numbers in a low transmission area on the Kenyan Coast.

PubMed

Kangoye, David Tiga; Noor, Abdisalan; Midega, Janet; Mwongeli, Joyce; Mkabili, Dora; Mogeni, Polycarp; Kerubo, Christine; Akoo, Pauline; Mwangangi, Joseph; Drakeley, Chris; Marsh, Kevin; Bejon, Philip; Njuguna, Patricia

2016-04-14

Targeted malaria control interventions are expected to be cost-effective. Clinical, parasitological and serological markers of malaria transmission have been used to detect malaria transmission hotspots, but few studies have examined the relationship between the different potential markers in low transmission areas. The present study reports on the relationships between clinical, parasitological, serological and entomological markers of malaria transmission in an area of low transmission intensity in Coastal Kenya. Longitudinal data collected from 831 children aged 5-17 months, cross-sectional survey data from 800 older children and adults, and entomological survey data collected in Ganze on the Kenyan Coast were used in the present study. The spatial scan statistic test used to detect malaria transmission hotspots was based on incidence of clinical malaria episodes, prevalence of asymptomatic asexual parasites carriage detected by microscopy and polymerase chain reaction (PCR), seroprevalence of antibodies to two Plasmodium falciparum merozoite antigens (AMA1 and MSP1-19) and densities of Anopheles mosquitoes in CDC light-trap catches. There was considerable overlapping of hotspots by these different markers, but only weak to moderate correlation between parasitological and serological markers. PCR prevalence and seroprevalence of antibodies to AMA1 or MSP1-19 appeared to be more sensitive markers of hotspots at very low transmission intensity. These findings may support the choice of either serology or PCR as markers in the detection of malaria transmission hotspots for targeted interventions.

Malaria in paradise: characterization of imported cases in Gran Canaria Island (1993-2006).

PubMed

Espinosa-Vega, Elizabeth; Martín-Sánchez, Antonio Manuel; Elcuaz-Romano, Rosa; Hernández-Febles, Melisa; Molina-Cabrillana, Jesús; Pérez-Arellano, Jose Luis

2011-01-01

Spain obtained the official certificate of malaria eradication in 1964. However, imported malaria cases have been increasing during the last few decades in this country. This study aims to describe the clinical and epidemiological features of patients diagnosed with malaria on Gran Canaria Island. A retrospective study was conducted based on case review of all patients diagnosed with malaria microbiologically confirmed from 1993 to 2006, at the three referral teaching hospitals on Gran Canaria Island. One hundred eighty-four episodes in 181 patients were diagnosed, 170 of them were analyzed. Most of them (82%) were travelers. Nearly 15% (14.7%) declared having had some chemoprophylaxis, but only half of them completed the treatment. Twenty cases (10.9%) were diagnosed who had just arrived as immigrants, mainly children. Malaria was acquired in Africa by 94.7% of the cases and Plasmodium falciparum was responsible for the majority of the cases (84.1%). Clinical and epidemiological differences were observed among different groups of patients formed by their origin and travel purposes. At least one indicator of severe malaria was established in 22.9% of the cases. However, global mortality was 3.8%. Malaria in Gran Canaria Island is imported from endemic areas, mainly from African countries, observed mostly among young adult males, but clinical and epidemiological features may change among different groups of patients. The number of immigrants diagnosed with malaria is increasing in this area nowadays. © 2011 International Society of Travel Medicine.

Gametocyte Clearance Kinetics Determined by Quantitative Magnetic Fractionation in Melanesian Children with Uncomplicated Malaria Treated with Artemisinin Combination Therapy.

PubMed

Karl, Stephan; Laman, Moses; Moore, Brioni R; Benjamin, John; Koleala, Tamarah; Ibam, Clemencia; Kasian, Bernadine; Siba, Peter M; Waltmann, Andreea; Mueller, Ivo; Woodward, Robert C; St Pierre, Timothy G; Davis, Timothy M E

2015-08-01

Quantitative magnetic fractionation and a published mathematical model were used to characterize between-treatment differences in gametocyte density and prevalence in 70 Papua New Guinean children with uncomplicated Plasmodium falciparum and/or Plasmodium vivax malaria randomized to one of two artemisinin combination therapies (artemether-lumefantrine or artemisinin-naphthoquine) in an intervention trial. There was an initial rise in peripheral P. falciparum gametocyte density with both treatments, but it was more pronounced in the artemisinin-naphthoquine group. Model-derived estimates of the median pretreatment sequestered gametocyte population were 21/μl for artemether-lumefantrine and 61/μl for artemisinin-naphthoquine (P < 0.001). The median time for P. falciparum gametocyte density to fall to <2.5/μl (below which transmission becomes unlikely) was 16 days in the artemether-lumefantrine group and 20 days in artemisinin-naphthoquine group (P < 0.001). Gametocyte prevalence modeling suggested that artemisinin-naphthoquine-treated children became gametocytemic faster (median, 2.2 days) than artemether-lumefantrine-treated children (median, 5.3 days; P < 0.001) and had a longer median P. falciparum gametocyte carriage time per individual (20 versus 13 days; P < 0.001). Clearance of P. vivax gametocytes was rapid (within 3 days) in both groups; however, consistent with the reappearance of asexual forms in the main trial, nearly 40% of children in the artemether-lumefantrine group developed P. vivax gametocytemia between days 28 and 42 compared with 3% of children in the artemisinin-naphthoquine group. These data suggest that artemisinin is less active than artemether against sequestered gametocytes. Greater initial gametocyte release after artemisinin-naphthoquine increases the period of potential P. falciparum transmission by 4 days relative to artemether-lumefantrine, but the longer elimination half-life of naphthoquine than of lumefantrine suppresses P. vivax recurrence and consequent gametocytemia. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effect of coadministered fat on the tolerability, safety, and pharmacokinetic properties of dihydroartemisinin-piperaquine in Papua New Guinean children with uncomplicated malaria.

PubMed

Moore, B R; Benjamin, J M; Salman, S; Griffin, S; Ginny, E; Page-Sharp, M; Robinson, L J; Siba, P; Batty, K T; Mueller, I; Davis, T M E

2014-10-01

Coadministration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve bioavailability and antimalarial efficacy, but it might also increase toxicity. There have been no studies of these potential effects in the pediatric age group. The tolerability, safety, efficacy, and pharmacokinetics of DHA-PQ administered with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged 5 to 10 years diagnosed with uncomplicated falciparum malaria. Three daily 2.5:11.5-mg-base/kg doses were given with water (n = 14, group A) or milk (n = 16, group B), with regular clinical/laboratory assessment and blood sampling over 42 days. Plasma PQ was assayed by high-performance liquid chromatography with UV detection, and DHA was assayed using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models for PQ and DHA were developed using a population-based approach. DHA-PQ was generally well tolerated, and initial fever and parasite clearance were prompt. There were no differences in the areas under the concentration-time curve (AUC0-∞) for PQ (median, 41,906 versus 36,752 μg · h/liter in groups A and B, respectively; P = 0.24) or DHA (4,047 versus 4,190 μg · h/liter; P = 0.67). There were also no significant between-group differences in prolongation of the corrected electrocardiographic QT interval (QTc) initially during follow-up, but the QTc tended to be higher in group B children at 24 h (mean ± standard deviation [SD], 15 ± 10 versus 6 ± 15 ms(0.5) in group A, P = 0.067) and 168 h (10 ± 18 versus 1 ± 23 ms(0.5), P = 0.24) when plasma PQ concentrations were relatively low. A small amount of fat does not change the bioavailability of DHA-PQ in children, but a delayed persistent effect on ventricular repolarization cannot be excluded. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia

PubMed Central

2014-01-01

Background Mutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed. Methods After obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected. Results Pfdhfr and pfdhps genotypes from 24 P. falciparum-infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the pfdhfr/pfdhps combined haplotypes of ANRNI/SGTGA (n = 6), ANRNL/SGTGA (n = 4), and ANRNI/SGEAA(588F) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment. Conclusion Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F. PMID:25187019

Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia.

PubMed

Basuki, Sukmawati; Fitriah; Riyanto, Sugeng; Budiono; Dachlan, Yoes P; Uemura, Haruki

2014-04-04

Mutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed. After obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected. Pfdhfr and pfdhps genotypes from 24 P. falciparum-infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the pfdhfr/pfdhps combined haplotypes of ANRNI/SGTGA (n = 6), ANRNL/SGTGA (n = 4), and ANRNI/SGEAA(588F) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment. Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamine-amodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.

PubMed Central

Basco, Leonardo K.; Same-Ekobo, Albert; Ngane, Vincent Foumane; Ndounga, Mathieu; Metoh, Theresia; Ringwald, Pascal; Soula, Georges

2002-01-01

OBJECTIVE: To evaluate the therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine, and the sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon. METHODS: In a randomized study we evaluated the effectiveness and tolerance of (i) sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs. FINDINGS: Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects. CONCLUSION: SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited. PMID:12163917

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests

PubMed Central

2012-01-01

Background The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. Methods A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 h and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a non-febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. Results A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p = 0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p < 0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) Conclusion Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc.) may be needed to improve ACT targeting during low transmission seasons. PMID:22747655

Utility of nested polymerase chain reaction over the microscopy and immuno-chromatographic test in the detection of Plasmodium species and their clinical spectrum.

PubMed

Ranjan, P; Ghoshal, U

2016-09-01

Though demonstration of Plasmodium parasite in peripheral blood on microscopy remains gold standard, it may miss some patients resulting in delay in instituting life-saving therapy. Studies on polymerase chain reaction (PCR), a highly sensitive and specific technique that also discriminates among different species of malaria parasite, are scanty. Hence, we aimed to evaluate the role of PCR in diagnosis and species identification of Plasmodium. Of 2186 febrile patients with clinical suspicion of malaria screened between July 2013 to February 2015, 561 patients fulfilled inclusion criteria. Microscopy, rapid diagnostic test (RDT) and PCR were performed to identify the parasite. Plasmodium was detected in 64/561 (11.40 %), 92/561 (16.40 %) and 78/561 (13.90 %) cases using microscopy, RDT and PCR, respectively. Of 78 positive cases by PCR, 47 (60.25 %) were confirmed as Plasmodium falciparum (P. falciparum), 28 (35.89 %) were Plasmodium vivax (P. vivax) and 3 (3.84 %) had mixed infections. Sensitivity and specificity of microscopy and RDT were 82.10 %, 100 % and 98.70 %, 96.90 %, respectively (p = 0.139). Of total 93 patients, 67 (72.04 %) were classified as complicated and 26 (27.96 %) were as uncomplicated. Creatinine (p = <0.001), conjugated bilirubin (p = 0.003) and total bilirubin (p = <0.001) level was elevated in complicated malaria along with renal (65 %) and liver dysfunction (25 %). In the present study, P. falciparum was responsible for 40/67 (59.70 %) cases of complicated malaria; P. vivax was also found in 17/67 (25.37 %) complicated cases using PCR. The findings highlight the alarming number of complicated vivax malaria in addition to falciparum. Moreover, PCR proved to be highly sensitive and specific test for detecting Plasmodium species.

Malaria burden and anti-malarial drug efficacy in Owando, northern Congo.

PubMed

Singana, Brice P; Bogreau, Hervé; Matondo, Brunelle D; Dossou-Yovo, Louis R; Casimiro, Prisca N; Mbouka, Rigobert; Ha Nguyen, Kim Yen; Pradines, Bruno; Basco, Leonardo K; Ndounga, Mathieu

2016-01-08

In the Republic of Congo, previous epidemiological studies have only been conducted in the south of the country where it is most accessible. Nationally representative data on the efficacy of new anti-malarial tools are lacking in the country. As an initial step to close the gap, clinical efficacy of two artemisinin-based combinations, artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL), was assessed in Owando, a city in equatorial flooded forest in northern Republic of Congo. Under 12 years old febrile children attending public health facilities were screened for malaria parasites using lactate dehydrogenase (LDH)-based rapid diagnostic test (RDT) for malaria and microscopic examination of thick blood films. Patients with at least 1,000 asexual Plasmodium falciparum parasites/µl of blood were clinically examined, included after informed consent, and followed up for 28 days, according to the 2009 World Health Organization protocol. Patients were randomly assigned to co-formulated ASAQ (Coarsucam(®)) or AL (Coartem(®)) treatment groups. Plasmodium falciparum recrudescent isolates were compared to pre-treatment isolates by polymerase chain reaction (PCR) using msp1, msp2, and glurp genes to distinguish between re-infection and recrudescence. Between November 2012 and February 2013, 857 under 12 years old febrile children were screened, of whom 198 (23.1%) had positive RDT and 167 (19.5%) positive thick films. ASAQ and AL efficacies were 92.7 and 94.2% before PCR correction, respectively. After genotyping, the overall efficacy was 100% for ASAQ and 98.0% for AL. The data reported here represent partially the burden of malaria in 0-11 years old febrile children examined in public health centres of Owando city and serve as reference for further studies. Both artemisinin-based combinations were highly efficacious in patients under 12 years old with acute uncomplicated malaria. ASAQ was associated with more adverse events, which may reduce compliance in unsupervised treatment. ACTRN12612000940875.

Malaria rapid diagnostic tests in endemic settings.

PubMed

Maltha, J; Gillet, P; Jacobs, J

2013-05-01

Malaria rapid diagnostic tests (RDTs) are instrument-free tests that provide results within 20 min and can be used by community health workers. RDTs detect antigens produced by the Plasmodium parasite such as Plasmodium falciparum histidine-rich protein-2 (PfHPR2) and Plasmodium lactate dehydrogenase (pLDH). The accuracy of RDTs for the diagnosis of uncomplicated P. falciparum infection is equal or superior to routine microscopy (but inferior to expert microscopy). Sensitivity for Plasmodium vivax is 75-100%; for Plasmodium ovale and Plasmodium malariae, diagnostic performance is poor. Design limitations of RDTs include poor sensitivity at low parasite densities, susceptibility to the prozone effect (PfHRP2-detecting RDTs), false-negative results due to PfHRP2 deficiency in the case of pfhrp2 gene deletions (PfHRP2-detecting RDTs), cross-reactions between Plasmodium antigens and detection antibodies, false-positive results by other infections and susceptibility to heat and humidity. End-user's errors relate to safety, procedure (delayed reading, incorrect sample and buffer volumes) and interpretation (not recognizing invalid test results, disregarding faint test lines). Withholding antimalarial treatment in the case of negative RDT results tends to be infrequent and tendencies towards over-prescription of antibiotics have been noted. Numerous shortcomings in RDT kits' labelling, instructions for use (correctness and readability) and contents have been observed. The World Health Organization and partners actively address quality assurance of RDTs by comparative testing of RDTs, inspections of manufacturing sites, lot testing and training tools but no formal external quality assessment programme of end-user performance exists. Elimination of malaria requires RDTs with lower detection limits, for which nucleic acid amplification tests are under development. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Emergence of FY*Anull in a Plasmodium vivax-endemic region of Papua New Guinea

PubMed Central

Zimmerman, Peter A.; Woolley, Ian; Masinde, Godfred L.; Miller, Stephanie M.; McNamara, David T.; Hazlett, Fred; Mgone, Charles S.; Alpers, Michael P.; Genton, Blaise; Boatin, B. A.; Kazura, James W.

1999-01-01

In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is α+-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that α+-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that α+-thalassemia may facilitate so-called “benign” Plasmodium vivax infection to act later in life as a “natural vaccine” against severe Plasmodium falciparum malaria. Here, in a P. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of α+-thalassemia ≥0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a−b−]) on the FY*A allele. In this study population there were 23 heterozygous and no homozygous individuals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous (FY*A/FY*Anull) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.163) compared with FY*A/FY*Anull (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47–8.91). Emergence of FY*Anull in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise α+-thalassemia/P. vivax-mediated protection against severe P. falciparum malaria. PMID:10570183

Effects of sevuparin on rosette formation and cytoadherence of Plasmodium falciparum infected erythrocytes

PubMed Central

Saiwaew, Somporn; Sritabal, Juntima; Piaraksa, Nattaporn; Keayarsa, Srisuda; Ruengweerayut, Ronnatrai; Utaisin, Chirapong; Sila, Patima; Niramis, Rangsan; Udomsangpetch, Rachanee; Charunwatthana, Prakaykaew; Pongponratn, Emsri; Pukrittayakamee, Sasithon; Leitgeb, Anna M.; Wahlgren, Mats; Lee, Sue J.; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.; Chotivanich, Kesinee

2017-01-01

In severe falciparum malaria cytoadherence of parasitised red blood cells (PRBCs) to vascular endothelium (causing sequestration) and to uninfected red cells (causing rosette formation) contribute to microcirculatory flow obstruction in vital organs. Heparin can reverse the underlying ligand-receptor interactions, but may increase the bleeding risks. As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Sevuparin has been evaluated recently in patients with uncomplicated falciparum malaria, and is currently investigated in a clinical trial for sickle cell disease. The effects of sevuparin on rosette formation and cytoadherence of Plasmodium falciparum isolates from Thailand were investigated. Trophozoite stages of P. falciparum-infected RBCs (Pf-iRBCs) were cultured from 49 patients with malaria. Pf-iRBCs were treated with sevuparin at 37°C and assessed in rosetting and in cytoadhesion assays with human dermal microvascular endothelial cells (HDMECs) under static and flow conditions. The proportion of Pf-iRBCs forming rosettes ranged from 6.5% to 26.0% (median = 12.2%). Rosetting was dose dependently disrupted by sevuparin (50% disruption by 250 μg/mL). Overall 57% of P. falciparum isolates bound to HDMECs under static conditions; median (interquartile range) Pf-iRBC binding was 8.5 (3.0–38.0) Pf-iRBCs/1000 HDMECs. Sevuparin in concentrations ≥ 100 μg/mL inhibited cytoadherence. Sevuparin disrupts P. falciparum rosette formation in a dose dependent manner and inhibits cytoadherence to endothelial cells. The data support assessment of sevuparin as an adjunctive treatment to the standard therapy in severe falciparum malaria. PMID:28249043

Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection.

PubMed

Portugal, Silvia; Tran, Tuan M; Ongoiba, Aissata; Bathily, Aboudramane; Li, Shanping; Doumbo, Safiatou; Skinner, Jeff; Doumtabe, Didier; Kone, Younoussou; Sangala, Jules; Jain, Aarti; Davies, D Huw; Hung, Christopher; Liang, Li; Ricklefs, Stacy; Homann, Manijeh Vafa; Felgner, Philip L; Porcella, Stephen F; Färnert, Anna; Doumbo, Ogobara K; Kayentao, Kassoum; Greenwood, Brian M; Traore, Boubacar; Crompton, Peter D

2017-03-01

Chronic asymptomatic Plasmodium falciparum infections are common in endemic areas and are thought to contribute to the maintenance of malaria immunity. Whether treatment of these infections increases the subsequent risk of clinical episodes of malaria is unclear. In a 3-year study in Mali, asymptomatic individuals with or without P. falciparum infection at the end of the 6-month dry season were identified by polymerase chain reaction (PCR), and clinical malaria risk was compared during the ensuing 6-month malaria transmission season. At the end of the second dry season, 3 groups of asymptomatic children were identified: (1) children infected with P. falciparum as detected by rapid diagnostic testing (RDT) who were treated with antimalarials (n = 104), (2) RDT-negative children whose untreated P. falciparum infections were detected retrospectively by PCR (n = 55), and (3) uninfected children (RDT/PCR negative) (n = 434). Clinical malaria risk during 2 subsequent malaria seasons was compared. Plasmodium falciparum-specific antibody kinetics during the dry season were compared in children who did or did not harbor asymptomatic P. falciparum infections. Chronic asymptomatic P. falciparum infection predicted decreased clinical malaria risk during the subsequent malaria season(s); treatment of these infections did not alter this reduced risk. Plasmodium falciparum-specific antibodies declined similarly in children who did or did not harbor chronic asymptomatic P. falciparum infection during the dry season. These findings challenge the notion that chronic asymptomatic P. falciparum infection maintains malaria immunity and suggest that mass drug administration during the dry season should not increase the subsequent risk of clinical malaria. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Plasmodium falciparum msp1 and msp2 genetic diversity and allele frequencies in parasites isolated from symptomatic malaria patients in Bobo-Dioulasso, Burkina Faso.

PubMed

Somé, Anyirékun Fabrice; Bazié, Thomas; Zongo, Issaka; Yerbanga, R Serge; Nikiéma, Frédéric; Neya, Cathérine; Taho, Liz Karen; Ouédraogo, Jean-Bosco

2018-05-30

In Burkina Faso, malaria remains the overall leading cause of morbidity and mortality accounting for 35.12% of consultations, 40.83% of hospitalizations and 37.5% of deaths. Genotyping of malaria parasite populations remains an important tool to determine the types and number of parasite clones in an infection. The present study aimed to evaluate the merozoite surface protein 1 (msp1) and merozoite surface protein 2 (msp2) genetic diversity and allele frequencies in Bobo-Dioulasso, Burkina Faso. Dried blood spots (DBS) were collected at baseline from patients with uncomplicated malaria in urban health centers in Bobo-Dioulasso. Parasite DNA was extracted using chelex-100 and species were identified using nested PCR. Plamodium falciparum msp1 and msp2 genes were amplified by nested polymerase chain reaction (PCR) and PCR products were analyzed by electrophoresis on a 2.5% agarose gel. Alleles were categorized according to their molecular weight. A total of 228 blood samples were analyzed out of which 227 (99.9%) were confirmed as P. falciparum-positive and one sample classified as mixed infection for P. malaria and P. falciparum. In msp1, the K1 allelic family was predominant with 77.4% (162/209) followed respectively by the MAD20 allelic family with 41.3% and R033 allelic family with 36%. In msp2, the 3D7 allelic family was the most frequently detected with 93.1 % compared to FC27 with 41.3%. Twenty-one different alleles were observed in msp1 with 9 alleles for K1, 8 alleles for MAD20 and 4 alleles for R033. In msp2, 25 individual alleles were detected with 10 alleles for FC27 and 15 alleles for 3D7. The mean multiplicity of falciparum infection was 1.95 with respectively 1.8 (1.76-1.83) and 2.1 (2.03-2.16) for msp1 and msp2 (P = 0.01). Our study showed high genetic diversity and allelic frequencies of msp1 and msp2 in Plasmodium falciparum isolates from symptomatic malaria patients in Bobo-Dioulasso.

[Imported malaria in adults. Clinical, epidemiological and analytical features].

PubMed

Ramírez-Olivencia, G; Herrero, M D; Subirats, M; de Juanes, J R; Peña, J M; Puente, S

2012-01-01

Up to now, the epidemiological and clinical features of imported malaria in Spain have been described in small series from general hospitals. Almost all diagnosis had been made based on symptomatic patients. The aim of this study has been to determine the epidemiological, clinical and laboratorial characteristics of imported malaria in a Reference Unit for Tropical Diseases. We performed a cross-sectional, observational and retrospective study. The series consisted of patients diagnosed of malaria who had been attended at the Hospital Carlos III from January 1, 2002 to December 31, 2007. We identified 484 episodes of malaria, of which 398 cases were included in the analysis. Almost 50% of the patients were natives of endemic areas, while the rest were native-travelers or travelers. Most cases (88-98% according to the group) had not taken malaria chemoprophylaxis correctly when indicated. At the time of diagnosis, 30.4% of patients were asymptomatic and 28.1% of asymptomatic patients had anemia, 19.8% thrombocytopenia, 14% leukopenia, 5% hypocholesterolemia, 5% renal failure and 4.1% hypoglycemia. Low parasitemia was present in 97.5% of asymptomatic individuals compared to 80.5% of the symptomatic patients (P<0.001). Absence of chemoprophylaxis (or poor compliance) is the main reason for malaria in individuals traveling to endemic areas. Malaria must be ruled out in individuals coming from tropical countries with compatible symptoms, and it also should be suspected in certain groups of asymptomatic individuals with abnormal laboratorial parameters. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Trend analysis of imported malaria in London; observational study 2000 to 2014.

PubMed

Rees, Eleanor; Saavedra-Campos, Maria; Usdin, Martine; Anderson, Charlotte; Freedman, Joanne; de Burgh, Jane; Kirkbride, Hilary; Chiodini, Peter; Smith, Valerie; Blaze, Marie; Whitty, Christopher J M; Balasegaram, Sooria

We describe trends of malaria in London (2000-2014) in order to identify preventive opportunities and we estimated the cost of malaria admissions (2009/2010-2014/2015). We identified all cases of malaria, resident in London, reported to the reference laboratory and obtained hospital admissions from Hospital Episode Statistics. The rate of malaria decreased (19.4[2001]-9.1[2014] per 100,000). Males were over-represented (62%). Cases in older age groups increased overtime. The rate was highest amongst people of Black African ethnicity followed by Indian, Pakistani, Bangladeshi ethnicities combined (103.3 and 5.5 per 100,000, respectively). The primary reason for travel was visiting friends and relatives (VFR) in their country of origin (69%), mostly sub-Saharan Africa (92%). The proportion of cases in VFRs increased (32%[2000]-50%[2014]) and those taking chemoprophylaxis decreased (36%[2000]-14%[2014]). The overall case fatality rate was 0.3%. We estimated the average healthcare cost of malaria admissions to be just over £1 million per year. Our study highlighted that people of Black African ethnicity, travelling to sub-Saharan Africa to visit friends and relatives in their country of origin remain the most affected with also a decline in chemoprophylaxis use. Malaria awareness should focus on this group in order to have the biggest impact but may require new approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of primary health care on malaria morbidity - defining access by disease burden

PubMed Central

O’Meara, W.P.; Noor, A.; Gatakaa, H.; Tsofa, B.; McKenzie, F. E.; Marsh, K.

2009-01-01

Objectives The convergence of malaria endemicity and poor health care infrastructure has resulted in persistently high rates of malaria morbidity and mortality in many parts of sub-Saharan Africa. Primary care facilities are increasingly becoming the focal point for distribution of intervention strategies, but physical access to these facilities may limit the extent to which communities can be reached. Here we investigate the impact of travel time to primary care on the incidence of hospitalized malaria episodes in a rural district in Kenya. Methods The incidence of hospitalized malaria in a population under continuous demographic surveillance was recorded over three years. The time to travel to the nearest primary health care facility was calculated for every child between birth and five years of age and trends in incidence of hospitalized malaria as a function of travel time were evaluated. Results and conclusions We show that the incidence of hospitalized malaria more than doubled as travel time to the nearest primary care facility increased from ten minutes up to two hours. Good access to primary health facilities may reduce the burden of disease by as much as 66%. Our results highlight both the potential of the primary health care system in reaching those most at risk and reducing the disease burden, and that insufficient access is an important risk factor, one that may be inequitably distributed to the poorest households. PMID:19121148

The evil circle of poverty: a qualitative study of malaria and disability

PubMed Central

2012-01-01

Background This article discusses the link between disability and malaria in a poor rural setting. Global malaria programmes and rehabilitation programmes are organized as vertical and separate programmes, and as such they focus on prevention, cure and control, and disability respectively. When looking at specific conditions and illnesses, the impairing long-term consequences of illness incidents during childhood are not questioned. Methods The study design was ethnographic with an open, exploratory approach. Data were collected in Mangochi District in Malawi through qualitative in-depth interviews and participant observation. Results Despite a local-based health service system, people living in poor rural areas are confronted with a multitude of barriers when accessing malaria prevention and treatment. Lack of skilled health personnel and equipment add to the general burden of poverty: insufficient knowledge about health care, problems connected to accessing the health facility in time, insufficient initiatives to prevent malaria attacks, and a general lack of attention to the long term disabling effects of a malaria attack. Conclusions This study points to the importance of building malaria programmes, research and statistics that take into consideration the consequences of permanent impairment after a malaria attack, as well as the context of poverty in which they often occur. In order to do so, one needs to develop methods for detecting people whose disabilities are a direct result of not having received health services after a malaria episode. This may be done through qualitative approaches in local communities and should also be supplemented by suitable surveys in order to estimate the problem on a larger scale. PMID:22236358

The evil circle of poverty: a qualitative study of malaria and disability.

PubMed

Ingstad, Benedicte; Munthali, Alister C; Braathen, Stine H; Grut, Lisbet

2012-01-11

This article discusses the link between disability and malaria in a poor rural setting. Global malaria programmes and rehabilitation programmes are organized as vertical and separate programmes, and as such they focus on prevention, cure and control, and disability respectively. When looking at specific conditions and illnesses, the impairing long-term consequences of illness incidents during childhood are not questioned. The study design was ethnographic with an open, exploratory approach. Data were collected in Mangochi District in Malawi through qualitative in-depth interviews and participant observation. Despite a local-based health service system, people living in poor rural areas are confronted with a multitude of barriers when accessing malaria prevention and treatment. Lack of skilled health personnel and equipment add to the general burden of poverty: insufficient knowledge about health care, problems connected to accessing the health facility in time, insufficient initiatives to prevent malaria attacks, and a general lack of attention to the long term disabling effects of a malaria attack. This study points to the importance of building malaria programmes, research and statistics that take into consideration the consequences of permanent impairment after a malaria attack, as well as the context of poverty in which they often occur. In order to do so, one needs to develop methods for detecting people whose disabilities are a direct result of not having received health services after a malaria episode. This may be done through qualitative approaches in local communities and should also be supplemented by suitable surveys in order to estimate the problem on a larger scale. © 2012 Ingstad et al; licensee BioMed Central Ltd.

Assessment of individual and household malaria risk factors among women in a South African village.

PubMed

Mutegeki, Ezra; Chimbari, Moses John; Mukaratirwa, Samson

2017-11-01

There is need to understand how various malaria risk factors interact at the individual, household and community levels, as well as wider contexts, in order to guide the design and implementation of effective and more comprehensive control strategies. Using a cross-sectional approach, this study investigated various malaria risk factors among residents of Mgedula Village, a malaria-endemic community located in Jozini Local Municipality, UMkhanyakude District, South Africa from May to August 2014. Data from 121 randomly sampled women were collected using close-ended questionnaires. The women were aged between 18 and 40 years; and had been residents in the study area for five years or more. A multivariable logistic regression model was used to measure the association between a history of malaria infection in the previous 12 months and various potential risk factors. The results showed that practicing animal husbandry (OR 20), residing in household structures that had not been sprayed (OR 16.7) and cross-border movement (OR 14.3) were greatly associated with malaria infection. Other factors that were significantly associated with this infection included illiteracy (OR 9.1), having a largely populated household (OR 6.1) and low income (OR 1.65). Individuals with a history of malaria infection were less likely to lack basic malaria-related knowledge (OR 0.58), to have negative attitude towards malaria (OR 0.29) and also to have poor malaria practices (OR 0.3). There was no association between a malaria episode and residing at a long distance from the health facility. Indoor residual spraying indicated a notable reduction of malaria risk at the community level. However, other socio-economic, geographical and socio-demographic factors interacted at different levels to increase this risk among different individuals and households. To achieve malaria elimination by the year 2018, these aspects should be considered when developing and implementing elimination strategies at the individual, household and community levels, among high-risk populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Cost-effectiveness of malaria diagnosis using rapid diagnostic tests compared to microscopy or clinical symptoms alone in Afghanistan.

PubMed

Hansen, Kristian S; Grieve, Eleanor; Mikhail, Amy; Mayan, Ismail; Mohammed, Nader; Anwar, Mohammed; Baktash, Sayed H; Drake, Thomas L; Whitty, Christopher J M; Rowland, Mark W; Leslie, Toby J

2015-05-28

Improving access to parasitological diagnosis of malaria is a central strategy for control and elimination of the disease. Malaria rapid diagnostic tests (RDTs) are relatively easy to perform and could be used in primary level clinics to increase coverage of diagnostics and improve treatment of malaria. A cost-effectiveness analysis was undertaken of RDT-based diagnosis in public health sector facilities in Afghanistan comparing the societal and health sector costs of RDTs versus microscopy and RDTs versus clinical diagnosis in low and moderate transmission areas. The effect measure was 'appropriate treatment for malaria' defined using a reference diagnosis. Effects were obtained from a recent trial of RDTs in 22 public health centres with cost data collected directly from health centres and from patients enrolled in the trial. Decision models were used to compare the cost of RDT diagnosis versus the current diagnostic method in use at the clinic per appropriately treated case (incremental cost-effectiveness ratio, ICER). RDT diagnosis of Plasmodium vivax and Plasmodium falciparum malaria in patients with uncomplicated febrile illness had higher effectiveness and lower cost compared to microscopy and was cost-effective across the moderate and low transmission settings. RDTs remained cost-effective when microscopy was used for other clinical purposes. In the low transmission setting, RDTs were much more effective than clinical diagnosis (65.2% (212/325) vs 12.5% (40/321)) but at an additional cost (ICER) of US$4.5 per appropriately treated patient including a health sector cost (ICER) of US$2.5 and household cost of US$2.0. Sensitivity analysis, which varied drug costs, indicated that RDTs would remain cost-effective if artemisinin combination therapy was used for treating both P. vivax and P. falciparum. Cost-effectiveness of microscopy relative to RDT is further reduced if the former is used exclusively for malaria diagnosis. In the health service setting of Afghanistan, RDTs are a cost-effective intervention compared to microscopy. RDTs remain cost-effective across a range of drug costs and if microscopy is used for a range of diagnostic services. RDTs have significant advantages over clinical diagnosis with minor increases in the cost of service provision. The trial was registered at ClinicalTrials.gov under identifier NCT00935688.

Delayed haemolysis secondary to treatment of severe malaria with intravenous artesunate: Report on the experience of a referral centre for tropical infections in Spain.

PubMed

Aldámiz-Echevarría Lois, Teresa; López-Polín, Ana; Norman, Francesca F; Monge-Maillo, Begoña; López-Vélez, Rogelio; Perez-Molina, Jose A

Post-artesunate delayed haemolysis is described as hemolytic anemia presenting days after malaria treatment in hyperparasitemic patients. Physiopathological mechanisms and clinical manifestations have not been thoroughly characterised. We conducted a retrospective study of hospitalised malaria patients who received artemisinin derivatives from January 1, 2010 to December 31, 2015. 21 patients were included in the study: 11 travellers, 8 travellers visiting friends and relatives and 2 immigrants. Median age was 35.5 years (IQR: 25.7-44.8) and 11 were men. Eight patients received oral and 13 received intravenous (IV) artemisinin-based drugs. Follow-up after the malaria episode was available for 15 patients (12 with IV treatment). Four patients presented with delayed haemolysis 9-14 days after artesunate treatment; all had been admitted with severe malaria, were treated IV and had hyperparasitaemia (17%-33%). Other than hyperparasitaemia, no other factors were associated with artesunate haemolysis. Patients' outcomes were favourable and the only additional therapeutic measure needed was a blood transfusion. Delayed haemolysis is a frequent complication in hyperparasitemic malaria treated with IV artesunate. Follow-up is mandatory for at least 2 weeks after treatment initiation. This condition is potentially severe but does not appear to be life threatening. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Imported malaria and HIV infection in Madrid. Clinical and epidemiological features].

PubMed

Ramírez-Olivencia, G; Herrero, M D; Subirats, M; de Juanes, J R; Peña, J M; Puente, S

2012-01-01

Few data are available in Spain data on human immunodeficiency virus (HIV) patients coinfected with malaria. This study has aimed to determine the epidemiological and clinical characteristics of imported malaria in patients coinfected with HIV. A case-series retrospective study was performed using the patient's medical records. The study population consisted on patients diagnosed with malaria attended in our center from january 1, 2002 to december 31, 2007. A total of 484 episodes of malaria, 398 of which were included in this study, were identified. Co-infection with HIV was described in 32 cases. All of them occurred in individuals presumably with some degree of semi-immunity. In the coinfected group, there were 13 cases (40.6%) asymptomatic, whereas this event occurred in 99 cases of patients not coinfected (37.2%) (P=0.707). The greater presence of anemia in co-infected patients (62.5% vs 32.3% in non-coinfected [P=0.001]) stands out. In present study, the clinical presentation forms were similar, regardless of the presence or absence of HIV infection. Although the study population does not reflect all possible scenarios of malaria and HIV coinfection, our results indicate the reality of patients attended in the Autonomous Community of Madrid. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria.

PubMed

Gogtay, Nithya; Kannan, Sridharan; Thatte, Urmila M; Olliaro, Piero L; Sinclair, David

2013-10-25

Plasmodium vivax is an important cause of malaria in many parts of Asia and South America, and parasite resistance to the standard treatment (chloroquine) is now high in some parts of Oceania. This review aims to assess the current treatment options in the light of increasing chloroquine resistance. To compare artemisinin-based combination therapies (ACTs) with alternative antimalarial regimens for treating acute uncomplicated P. vivax malaria. We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and the metaRegister of Controlled Trials (mRCT) up to 28 March 2013 using "vivax" and "arte* OR dihydroarte*" as search terms. Randomized controlled trials comparing ACTs versus standard therapy, or comparing alternative ACTs, in adults and children with uncomplicated P. vivax malaria. Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We used recurrent parasitaemia prior to day 28 as a proxy for effective treatment of the blood stage parasite, and compared drug treatments using risk ratios (RR) and 95% confidence intervals (CIs). We used trials following patients for longer than 28 days to assess the duration of the post-treatment prophylactic effect of ACTs. We assessed the quality of the evidence using the GRADE approach. We included 14 trials, that enrolled 2592 participants, and were all conducted in Asia and Oceania between 2002 and 2011. ACTs versus chloroquine: ACTs clear parasites from the peripheral blood quicker than chloroquine monotherapy (parasitaemia after 24 hours of treatment: RR 0.42, 95% CI 0.36 to 0.50, four trials, 1652 participants, high quality evidence).In settings where chloroquine remains effective, ACTs are as effective as chloroquine at preventing recurrent parasitaemias before day 28 (RR 0.58, 95% CI 0.18 to 1.90, five trials, 1622 participants, high quality evidence). In four of these trials, recurrent parasitaemias before day 28 were very low following treatment with both chloroquine and ACTs. The fifth trial, from Thailand in 2011, found increased recurrent parasitaemias following treatment with chloroquine (9%), while they remained low following ACT (2%) (RR 0.25, 95% CI 0.09 to 0.66, one trial, 437 participants).ACT combinations with long half-lives probably also provide a longer prophylactic effect after treatment, with significantly fewer recurrent parasitaemias between day 28 and day 42 or day 63 (RR 0.57, 95% CI 0.40 to 0.82, three trials, 1066 participants, moderate quality evidence). One trial, from Cambodia, Thailand, India and Indonesia, gave additional primaquine to both treatment groups to reduce the risk of spontaneous relapses. Recurrent parasitaemias after day 28 were lower than seen in the trials that did not give primaquine, but the ACT still appeared to have an advantage (RR 0.27, 95% CI 0.08 to 0.94, one trial, 376 participants, low quality evidence). ACTs versus alternative ACTs: In high transmission settings, dihydroartemisinin-piperaquine is probably superior to artemether-lumefantrine, artesunate plus sulphadoxine-pyrimethamine and artesunate plus amodiaquine at preventing recurrent parasitaemias before day 28 (RR 0.20, 95% CI 0.08 to 0.49, three trials, 334 participants, moderate quality evidence).Dihydroartemisinin-piperaquine may also have an improved post-treatment prophylactic effect lasting for up to six weeks, and this effect may be present even when primaquine is also given to achieve radical cure (RR 0.21, 95% CI 0.10 to 0.46, two trials, 179 participants, low quality evidence).The data available from low transmission settings is too limited to reliably assess the relative effectiveness of ACTs. ACTs appear at least equivalent to chloroquine at effectively treating the blood stage of P. vivax infection. Even in areas where chloroquine remains effective, this finding may allow for simplified protocols for treating all forms of malaria with ACTs. In areas where chloroquine no longer cures the infection, ACTs offer an effective alternative.Dihydroartemisinin-piperaquine is the most studied ACT. It may provide a longer period of post-treatment prophylaxis than artemether-lumefantrine or artesunate plus amodiaquine. This effect may be clinically important in high transmission settings whether primaquine is also given or not.

The need for preventive and curative services for malaria when the military is deployed in endemic overseas territories: a case study and lessons learned.

PubMed

Fernando, Sumadhya Deepika; Booso, Rahuman; Dharmawardena, Priyani; Harintheran, Arunagirinathan; Raviraj, Kugapiriyan; Rodrigo, Chaturaka; Danansuriya, Manjula; Wickremasinghe, Rajitha

2017-01-01

Sri Lanka has been free from indigenous malaria since November 2012 and received the WHO certificate for malaria-free status in September 2016. Due to increased global travel, imported malaria cases continue to be reported in the country. Military personnel returning home from international peace-keeping missions in malaria endemic countries represent a key risk group in terms of imported malaria. The present study intended to characterize the potential causes of a malaria outbreak among the Sri Lankan security forces personnel deployed in the Central African Republic (CAR). Data were collected from a cross-sectional survey distributed among Sri Lankan Air Force personnel who had returned from United Nations peace-keeping missions in the CAR region. A pre-tested questionnaire was used for the data collection, and focus group discussions were also conducted. One hundred twenty male Air Force personnel were interviewed (out of a group of 122 officers and airmen). All participants were deployed in the CAR for 14 months and were aware of the existence of chemoprophylaxis against malaria. The majority of the subjects (92.5%, 111/120) also knew that prophylaxis should be started prior to departure. However, the regular use of chemoprophylaxis was reported by only 61.7% (74/120) of the sample. Overall, 30.8% of the participants (37/120) had 44 symptomatic episodes of malaria during deployment, and one person succumbed to severe malaria. All cases were associated with noncompliance with chemoprophylaxis. Better coordination with overseas healthcare services and the establishment of directly observed chemoprophylaxis may help to avoid similar outbreaks in the future.

High Antibody Responses against Plasmodium falciparum in Immigrants after Extended Periods of Interrupted Exposure to Malaria

PubMed Central

Jiménez, Alfons; Nhabomba, Augusto; Casas-Vila, Núria; Puyol, Laura; Campo, Joseph J.; Manaca, Maria Nelia; Aguilar, Ruth; Pinazo, María-Jesús; Almirall, Mercè; Soler, Cristina; Muñoz, José; Bardají, Azucena; Angov, Evelina; Dutta, Sheetij; Chitnis, Chetan E.; Alonso, Pedro L.; Gascón, Joaquim; Dobaño, Carlota

2013-01-01

Background Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. Methods A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or without malaria (n=37), naïve adults (travelers) with a first clinical malaria episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-142 (3D7 and FVO strains), EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry. Results Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026), but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-142 (P≤0.015), similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001), both with malaria. Conclusions Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its effect on protection, with important implications for future vaccine design and public health control measures. PMID:23967347

Molecular epidemiology of malaria in Cameroon. XXX. sequence analysis of Plasmodium falciparum ATPase 6, dihydrofolate reductase, and dihydropteroate synthase resistance markers in clinical isolates from children treated with an artesunate-sulfadoxine-pyrimethamine combination.

PubMed

Menemedengue, Virginie; Sahnouni, Khalifa; Basco, Leonardo; Tahar, Rachida

2011-07-01

Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are reliable molecular markers for antifolate resistance. The P. falciparum ATPase 6 (pfatp6) gene has been proposed to be a potential marker for artemisinin resistance. In our previous clinical study, we showed that artesunate-sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in Yaoundé, Cameroon. In the present study, dhfr, dhps, and pfatp6 mutations in P. falciparum isolates obtained from children treated with artesunate-sulfadoxine-pyrimethamine were determined. All 61 isolates had wild-type Pfatp6 263, 623, and 769 alleles, and 11 (18%) had a single E431K substitution. Three additional mutations, E643Q, E432K, and E641Q, were detected. The results did not indicate any warning signal of serious concern (i.e., no parasites were seen with quintuple dhfr-dhps, DHFR Ile164Leu, or pfatp6 mutations), as confirmed by the high clinical efficacy of artesunate-sulfadoxine-pyrimethamine. Further studies are required to identify a molecular marker that reliably predicts artemisinin resistance.

Molecular Epidemiology of Malaria in Cameroon. XXX. Sequence Analysis of Plasmodium falciparum ATPase 6, Dihydrofolate Reductase, and Dihydropteroate Synthase Resistance Markers in Clinical Isolates from Children Treated with an Artesunate-Sulfadoxine-Pyrimethamine Combination

PubMed Central

Menemedengue, Virginie; Sahnouni, Khalifa; Basco, Leonardo; Tahar, Rachida

2011-01-01

Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are reliable molecular markers for antifolate resistance. The P. falciparum ATPase 6 (pfatp6) gene has been proposed to be a potential marker for artemisinin resistance. In our previous clinical study, we showed that artesunate-sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in Yaoundé, Cameroon. In the present study, dhfr, dhps, and pfatp6 mutations in P. falciparum isolates obtained from children treated with artesunate-sulfadoxine-pyrimethamine were determined. All 61 isolates had wild-type Pfatp6 263, 623, and 769 alleles, and 11 (18%) had a single E431K substitution. Three additional mutations, E643Q, E432K, and E641Q, were detected. The results did not indicate any warning signal of serious concern (i.e., no parasites were seen with quintuple dhfr-dhps, DHFR Ile164Leu, or pfatp6 mutations), as confirmed by the high clinical efficacy of artesunate-sulfadoxine-pyrimethamine. Further studies are required to identify a molecular marker that reliably predicts artemisinin resistance. PMID:21734119

Diverticular disease: guidelines of the german society for gastroenterology, digestive and metabolic diseases and the german society for general and visceral surgery.

PubMed

Kruis, Wolfgang; Germer, Christoph-Thomas; Leifeld, Ludger

2014-01-01

Diverticular disease is one of the most common disorders of the gastrointestinal tract. 28-45% of the population develop colonic diverticula, while about 25% suffer symptoms and about 5% complications. To create formal guidelines for diagnosis and management. Six working groups with 44 participants analyzed key questions in subject areas assigned to them. Following a systematic literature search, 451 publications were included. Consensus was obtained by agreement within the working groups, two Delphi processes and a guideline conference. Targeted management of diverticular disease requires a classificatory diagnosis. A new classification was created. In addition to the clinical examination, intestinal ultrasound or computed tomography is the determining factor. Interval colonoscopy is recommended to exclude comorbidities. A low-fiber diet, obesity, lack of exercise, smoking and immunosuppression have an adverse impact on diverticulosis. This can lead to diverticulitis. Antibiotics are no longer recommended in uncomplicated diverticulitis if no risk factors such as immunosuppression are present. If close monitoring is ensured, uncomplicated diverticulitis can be treated on an outpatient basis. Complicated diverticulitis should be treated in hospital, involving broad-spectrum antibiotic therapy, where necessary abscess drainage, and surgery, if possible laparoscopically. In the case of chronic relapsing diverticulitis, the risk of perforation decreases with each episode, so that surgery is no longer recommended after the second episode but only following individual assessment. New findings on diverticular disease call into question the overuse of antibiotics and excessive indications for surgery. Targeted treatment requires a precise diagnosis and intensive interdisciplinary cooperation. © 2014 S. Karger AG, Basel.

The effect of dams and seasons on malaria incidence and anopheles abundance in Ethiopia

PubMed Central

2013-01-01

Background Reservoirs created by damming rivers are often believed to increase malaria incidence risk and/or stretch the period of malaria transmission. In this paper, we report the effects of a mega hydropower dam on P. falciparum malaria incidence in Ethiopia. Methods A longitudinal cohort study was conducted over a period of 2 years to determine Plasmodium falciparum malaria incidence among children less than 10 years of age living near a mega hydropower dam in Ethiopia. A total of 2080 children from 16 villages located at different distances from a hydropower dam were followed up from 2008 to 2010 using active detection of cases based on weekly house to house visits. Of this cohort of children, 951 (48.09%) were females and 1059 (51.91%) were males, with a median age of 5 years. Malaria vectors were simultaneously surveyed in all the 16 study villages. Frailty models were used to explore associations between time-to-malaria and potential risk factors, whereas, mixed-effects Poisson regression models were used to assess the effect of different covariates on anopheline abundance. Results Overall, 548 (26.86%) children experienced at least one clinical malaria episode during the follow up period with mean incidence rate of 14.26 cases/1000 child-months at risk (95% CI: 12.16 - 16.36). P. falciparum malaria incidence showed no statistically significant association with distance from the dam reservoir (p = 0.32). However, P. falciparum incidence varied significantly between seasons (p < 0.01). The malaria vector, Anopheles arabiensis, was however more abundant in villages nearer to the dam reservoir. Conclusions P. falciparum malaria incidence dynamics were more influenced by seasonal drivers than by the dam reservoir itself. The findings could have implications in timing optimal malaria control interventions and in developing an early warning system in Ethiopia. PMID:23566411

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

PubMed Central

Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

2018-01-01

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

Efficacy and safety of a combination of azithromycin and chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in two multi-country randomised clinical trials in African adults.

PubMed

Sagara, Issaka; Oduro, Abraham R; Mulenga, Modest; Dieng, Yemou; Ogutu, Bernhards; Tiono, Alfred B; Mugyenyi, Peter; Sie, Ali; Wasunna, Monique; Kain, Kevin C; Djimdé, Abdoulaye A; Sarkar, Shirsendu; Chandra, Richa; Robbins, Jeffery; Dunne, Michael W

2014-11-25

Given increasing rates of resistance to existing therapy, new options for treatment and prophylaxis of malaria are needed. Two randomised, comparative, non-inferiority studies were conducted in Africa, one double-blinded and one open-label. Adults with fever, a positive peripheral blood smear, and a positive rapid diagnostic test for Plasmodium falciparum were randomised in both studies to either azithromycin (AZ) 1,000 mg plus chloroquine (CQ) 600-mg base (AZCQ 1,000 mg) once daily for three days or mefloquine hydrochloride (MQ) 1,250 mg (split dose). In the first study, an additional regimen of AZ 500 mg plus CQ 600-mg base (AZCQ 500 mg) once daily for three days was included. All study participants were hospitalised until three consecutive daily blood smears were negative for asexual P. falciparum parasitaemia. Study participants were evaluated weekly for 42 days, with Day 28 polymerase chain reaction (PCR)-corrected parasitological clearance rate as primary endpoint. A total of 467 subjects were randomised in the two studies. At 28 days' follow-up, PCR-corrected parasitological clearance rates in the per protocol population in the first study were 101/103 (98%) with AZCQ 1,000 mg compared with 102/103 (99%) with MQ (95% confidence interval [CI]: -5.2, 3.3). The AZCQ 500-mg regimen was stopped during an interim study review (six [86%] clearance of seven evaluable; two lost to follow-up). In the second study, clearance rates were similar: AZCQ 1,000 mg 107/107 (100%) vs MQ 111/112 (99%; 95% CI: -1.8, 3.6). Among the participating countries, in vitro CQ resistance based on pfcrt mutation frequency in the baseline isolates across both studies ranged from 20.8% (Zambia) to 96.1% (Uganda). Serious adverse events (AEs; all causality) were observed more frequently with MQ compared with AZCQ (four vs one, respectively), though discontinuations for AEs were similar (four vs three, respectively). Common AEs in the AZ-containing arms included pruritus, vomiting, dizziness, and headache. Among adults with symptomatic uncomplicated falciparum malaria in Africa, the combination of AZ 1,000 mg and CQ 600-mg base once daily for three days resulted in Day 28 PCR-corrected parasitological clearance rates of ≥98% and was non-inferior to treatment with MQ. AZCQ was well tolerated. ClinicalTrials.gov identifiers NCT00082576 and NCT00367653.

Malaria increased the risk of stunting and wasting among young children in Ethiopia: Results of a cohort study.

PubMed

Gari, Taye; Loha, Eskindir; Deressa, Wakgari; Solomon, Tarekegn; Lindtjørn, Bernt

2018-01-01

Given the high prevalence of malnutrition in a malaria-endemic setting, improving nutritional status could serve as a tool to prevent malaria. However, the relationship between the two conditions remains unclear. Therefore, this study assessed the association between under-nutrition and malaria among a cohort of children aged 6 to 59 months old. Two cohorts of children were followed for 89 weeks in a rural Rift Valley area of Ethiopia. In the first approach (malaria-malnutrition), a cohort of 2,330 non-stunted and 4,204 non-wasted children were included to assess under-nutrition (outcome) based on their previous malaria status (exposure). In the second approach (malnutrition-malaria), a cohort of 4,468 children were followed-up to measure malaria (outcome), taking under-nutrition as an exposure. A weekly home visit was carried out to identify malaria cases. Four anthropometry surveys were conducted, and generalized estimating equation (GEE) method was used to measure the association between undernutrition and malaria. The prevalence of stunting was 44.9% in December 2014, 51.5% in August 2015, 50.7% in December 2015 and 48.1% in August 2016. We observed 103 cases with 118 episodes of malaria, 684 new stunting and 239 new wasting cases. The incidence rate per 10,000 weeks of observation was 3.8 for malaria, 50.4 for stunting and 8.2 for wasting. Children with malaria infection, [Adjusted Odds Ratio (AOR) = 1.9; 95% Confidence Interval (CI), 1.2-2.9)] and younger age (AOR = 1.3; 95% CI, 1.1-1.5) were more likely to be stunted. Furthermore, children with malaria infection (AOR = 8.5; 95% CI, 5.0-14.5) and young age group (AOR = 1.6; 95% CI, 1.2-2.1) were more likely to be wasted. However, stunting and wasting were not risk factors of subsequent malaria illness. Malaria infection was a risk factor for stunting and wasting, but stunting or wasting was not associated with subsequent malaria illness. As our study shows that malaria is a risk factor for stunting and wasting, a close follow-up of the nutritional status of such children may be needed. PACT R2014 11000 882128 (8 September 2014).

Malaria increased the risk of stunting and wasting among young children in Ethiopia: Results of a cohort study

PubMed Central

Loha, Eskindir; Deressa, Wakgari; Solomon, Tarekegn; Lindtjørn, Bernt

2018-01-01

Introduction Given the high prevalence of malnutrition in a malaria-endemic setting, improving nutritional status could serve as a tool to prevent malaria. However, the relationship between the two conditions remains unclear. Therefore, this study assessed the association between under-nutrition and malaria among a cohort of children aged 6 to 59 months old. Methods Two cohorts of children were followed for 89 weeks in a rural Rift Valley area of Ethiopia. In the first approach (malaria-malnutrition), a cohort of 2,330 non-stunted and 4,204 non-wasted children were included to assess under-nutrition (outcome) based on their previous malaria status (exposure). In the second approach (malnutrition–malaria), a cohort of 4,468 children were followed-up to measure malaria (outcome), taking under-nutrition as an exposure. A weekly home visit was carried out to identify malaria cases. Four anthropometry surveys were conducted, and generalized estimating equation (GEE) method was used to measure the association between undernutrition and malaria. Results The prevalence of stunting was 44.9% in December 2014, 51.5% in August 2015, 50.7% in December 2015 and 48.1% in August 2016. We observed 103 cases with 118 episodes of malaria, 684 new stunting and 239 new wasting cases. The incidence rate per 10,000 weeks of observation was 3.8 for malaria, 50.4 for stunting and 8.2 for wasting. Children with malaria infection, [Adjusted Odds Ratio (AOR) = 1.9; 95% Confidence Interval (CI), 1.2–2.9)] and younger age (AOR = 1.3; 95% CI, 1.1–1.5) were more likely to be stunted. Furthermore, children with malaria infection (AOR = 8.5; 95% CI, 5.0–14.5) and young age group (AOR = 1.6; 95% CI, 1.2–2.1) were more likely to be wasted. However, stunting and wasting were not risk factors of subsequent malaria illness. Conclusions Malaria infection was a risk factor for stunting and wasting, but stunting or wasting was not associated with subsequent malaria illness. As our study shows that malaria is a risk factor for stunting and wasting, a close follow-up of the nutritional status of such children may be needed. Trial registration PACT R2014 11000 882128 (8 September 2014). PMID:29324840

Clinical malaria case definition and malaria attributable fraction in the highlands of western Kenya.

PubMed

Afrane, Yaw A; Zhou, Guofa; Githeko, Andrew K; Yan, Guiyun

2014-10-15

In African highland areas where endemicity of malaria varies greatly according to altitude and topography, parasitaemia accompanied by fever may not be sufficient to define an episode of clinical malaria in endemic areas. To evaluate the effectiveness of malaria interventions, age-specific case definitions of clinical malaria needs to be determined. Cases of clinical malaria through active case surveillance were quantified in a highland area in Kenya and defined clinical malaria for different age groups. A cohort of over 1,800 participants from all age groups was selected randomly from over 350 houses in 10 villages stratified by topography and followed for two-and-a-half years. Participants were visited every two weeks and screened for clinical malaria, defined as an individual with malaria-related symptoms (fever [axillary temperature≥37.5°C], chills, severe malaise, headache or vomiting) at the time of examination or 1-2 days prior to the examination in the presence of a Plasmodium falciparum positive blood smear. Individuals in the same cohort were screened for asymptomatic malaria infection during the low and high malaria transmission seasons. Parasite densities and temperature were used to define clinical malaria by age in the population. The proportion of fevers attributable to malaria was calculated using logistic regression models. Incidence of clinical malaria was highest in valley bottom population (5.0% cases per 1,000 population per year) compared to mid-hill (2.2% cases per 1,000 population per year) and up-hill (1.1% cases per 1,000 population per year) populations. The optimum cut-off parasite densities through the determination of the sensitivity and specificity showed that in children less than five years of age, 500 parasites per μl of blood could be used to define the malaria attributable fever cases for this age group. In children between the ages of 5-14, a parasite density of 1,000 parasites per μl of blood could be used to define the malaria attributable fever cases. For individuals older than 14 years, the cut-off parasite density was 3,000 parasites per μl of blood. Clinical malaria case definitions are affected by age and endemicity, which needs to be taken into consideration during evaluation of interventions.

Chemoprophylaxis and the epidemiological characteristics of re-emergent P. vivax malaria in the Republic of Korea.

PubMed Central

Kim, Changsoo; Shin, Dong Chun; Yong, Tai Soon; Oh, Dae Kyu; Kim, Rock Kwon; Park, Keeho; Suh, I. L.

2006-01-01

OBJECTIVE: In the Republic of Korea (ROK), soldiers stationed where there is a risk of contracting malaria have received antimalarial chemoprophylaxis since 1997. However, chemoprophylaxis may facilitate the development of drug resistance, and late primary attacks in individuals who have received chemoprophylaxis are becoming more frequent. We investigated the association between chemoprophylaxis and the epidemiological characteristics and effectiveness of treatment for re-emergent Plasmodium vivax malaria, using a nationwide malaria database. METHODS: Among soldiers at risk of malaria between 1999 and 2001, we reviewed all P. vivax malaria cases (1158) that occurred before 31 December 2003. Early and late primary attacks were defined as cases occurring 2 months after the last day of exposure to risk of malaria, respectively. FINDINGS: Of these cases, 634 (72.0%) had received chemoprophylaxis, and 324 (28.0%) had not. Cases occurred mostly in summer, with a peak in July-August. Stratification by chemoprophylaxis history revealed different times to onset. Early primary attacks were more prevalent in the group not receiving chemoprophylaxis, while in the group receiving chemoprophylaxis most cases were late primary attacks. Of the latter, 312 out of 461 (67.7%) did not take primaquine regularly. After treatment of the first attack, 14 (1.2%) of 1158 were re-treated; all re-treated cases were cured using the same doses and regimen used for the first treatment. CONCLUSION: In ROK, the increase in late primary episodes of re-emergent P. vivax malaria is associated with the use of antimalarial chemoprophylaxis. PMID:17128363

Vaccines against malaria-still a long way to go.

PubMed

Matuschewski, Kai

2017-08-01

Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure. In malaria-endemic countries, continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity. Herein, three principal concepts in evidence-based malaria vaccine development are compared. Feasible leads are typically stand-alone subunit vaccine approaches that block Plasmodium parasite life cycle progression or parasite/host interactions, and they constitute the majority of candidates in preclinical research and early clinical testing. Integrated approaches incorporate malaria antigen(s) into licensed or emerging pediatric vaccine formulations. This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01. Experimental whole parasite vaccine approaches have been repeatedly shown to elicit sterile and lasting protection against identical parasite strains, but mass production, proof of broad protection against different parasite strains, and routes of vaccine delivery remain significant translational road blocks. Global access to an effective and affordable malaria vaccine will critically depend on innovative translational research that builds on a better molecular understanding of Plasmodium biology and host immunity. © 2017 Federation of European Biochemical Societies.

Stakeholders' opinions and questions regarding the anticipated malaria vaccine in Tanzania.

PubMed

Mtenga, Sally; Kimweri, Angela; Romore, Idda; Ali, Ali; Exavery, Amon; Sicuri, Elisa; Tanner, Marcel; Abdulla, Salim; Lusingu, John; Kafuruki, Shubi

2016-04-05

Within the context of combined interventions, malaria vaccine may provide additional value in malaria prevention. Stakeholders' perspectives are thus critical for informed recommendation of the vaccine in Tanzania. This paper presents the views of stakeholders with regards to malaria vaccine in 12 Tanzanian districts. Quantitative and qualitative methods were employed. A structured questionnaire was administered to 2123 mothers of under five children. Forty-six in-depth interviews and 12 focus group discussions were conducted with teachers, religious leaders, community health workers, health care professionals, and scientists. Quantitative data analysis involved frequency distributions and cross tabulations using Chi square test to determine the association between malaria vaccine acceptability and independent variables. Qualitative data were analysed thematically. Overall, 84.2% of the mothers had perfect acceptance of malaria vaccine. Acceptance varied significantly according to religion, occupation, tribe and region (p < 0.001). Ninety two percent reported that they will accept the malaria vaccine despite the need to continue using insecticide-treated nets (ITNs), while 88.4% reported that they will accept malaria vaccine even if their children get malaria less often than non-vaccinated children. Qualitative results revealed that the positive opinions towards malaria vaccine were due to a need for additional malaria prevention strategies and expectations that the vaccine will reduce visits to the health facility, deaths, malaria episodes and treatment-related expenses. Vaccine related questions included its side effects, efficacy, protective duration, composition, interaction with other medications, provision schedule, availability to the pregnant women, mode of administration (oral or injection?) and whether a child born of HIV virus or with a chronic illness will be eligible for the vaccine? Stakeholders had high acceptance and positive opinions towards the combined use of the anticipated malaria vaccine and ITNs, and that their acceptance remains high even when the vaccine may not provide full protection, this is a crucial finding for malaria vaccine policy decisions in Tanzania. An inclusive communication strategy should be designed to address the stakeholders' questions through a process that should engage and be implemented by communities and health care professionals. Social cultural aspects associated with vaccine acceptance should be integrated in the communication strategy.

Epidemiology of malaria in an area of seasonal transmission in Niger and implications for the design of a seasonal malaria chemoprevention strategy.

PubMed

Guillebaud, Julia; Mahamadou, Aboubacar; Zamanka, Halima; Katzelma, Mariama; Arzika, Ibrahim; Ibrahim, Maman L; Eltahir, Elfatih Ab; Labbo, Rabiou; Druilhe, Pierre; Duchemin, Jean-Bernard; Fandeur, Thierry

2013-10-30

Few data are available about malaria epidemiological situation in Niger. However, implementation of new strategies such as vaccination or seasonal treatment of a target population requires the knowledge of baseline epidemiological features of malaria. A population-based study was conducted to provide better characterization of malaria seasonal variations and population groups the most at risk in this particular area. From July 2007 to December 2009, presumptive cases of malaria among a study population living in a typical Sahelian village of Niger were recorded, and confirmed by microscopic examination. In parallel, asymptomatic carriers were actively detected at the end of each dry season in 2007, 2008 and 2009. Among the 965 presumptive malaria cases recorded, 29% were confirmed by microscopic examination. The incidence of malaria was found to decrease significantly with age (p < 0.01). The mean annual incidence was 0.254. The results show that the risk of malaria was higher in children under ten years (p < 0.0001). The number of malaria episodes generally followed the temporal pattern of changes in precipitation levels, with a peak of transmission in August and September. One-thousand and ninety subjects were submitted to an active detection of asymptomatic carriage of whom 16% tested positive; asymptomatic carriage decreased with increasing age. A higher prevalence of gametocyte carriage among asymptomatic population was recorded in children aged two to ten years, though it did not reach significance. In Southern Niger, malaria transmission mostly occurs from July to October. Children aged two to ten years are the most at risk of malaria, and may also represent the main reservoir for gametocytes. Strategies such as intermittent preventive treatment in children (IPTc) could be of interest in this area, where malaria transmission is highly seasonal. Based on these preliminary data, a pilot study could be implemented in Zindarou using IPTc targeting children aged two to ten years, during the three months of malaria transmission, together with an accurate monitoring of drug resistance.

Quality and safety of integrated community case management of malaria using rapid diagnostic tests and pneumonia by community health workers

PubMed Central

Hamer, Davidson H; Brooks, Erin Twohig; Semrau, Katherine; Pilingana, Portipher; MacLeod, William B; Siazeele, Kazungu; Sabin, Lora L; Thea, Donald M; Yeboah-Antwi, Kojo

2012-01-01

Objectives To assess the quality and safety of having community health workers (CHWs) in rural Zambia use rapid diagnostic tests (RDTs) and provide integrated management of malaria and pneumonia. Design/methods In the context of a cluster-randomized controlled trial of two models for community-based management of malaria and/or non-severe pneumonia in children under 5 years old, CHWs in the intervention arm were trained to use RDTs, follow a simple algorithm for classification and treat malaria with artemether–lumefantrine (AL) and pneumonia with amoxicillin. CHW records were reviewed to assess the ability of the CHWs to appropriately classify and treat malaria and pneumonia, and account for supplies. Patients were also followed up to assess treatment safety. Results During the 12-month study, the CHWs evaluated 1017 children with fever and/or fast/difficult breathing and performed 975 RDTs. Malaria and/or pneumonia were appropriately classified 94–100% of the time. Treatment based on disease classification was correct in 94–100% of episodes. Supply management was excellent with over 98% of RDTs, amoxicillin, and AL properly accounted for. The use of RDTs, amoxicillin, and AL was associated with few minor adverse events. Most febrile children (90%) with negative RDT results recovered after being treated with an antipyretic alone. Conclusions Volunteer CHWs in rural Zambia are capable of providing integrated management of malaria and pneumonia to children safely and at high quality. PMID:22595272

Imported malaria in children in Madrid, Spain, 2007-2013.

PubMed

Sánchez, Beatriz Soto; Tato, L M Prieto; Martín, S Guillén; Pérez, E; Grasa, C; Valderrama, S; Augusto, I de; Sierra, M; Ros, M García; Aguado, I; Hortelano, M García López

The majority of malaria cases diagnosed in Europe in the last few years have occurred in people living in non-endemic areas travelling back to their home country to visit friends and relatives (VFRs). Children account for 15-20% of imported malaria, with known higher risk of severe disease. A retrospective multicentre study was conducted in 24 hospitals in Madrid (Spain) including patients under 16 years diagnosed with malaria (2007-2013). A total of 149 episodes in 147 children were reported. Plasmodium falciparum was the species most commonly isolated. Twenty-five patients developed severe malaria and there was one death related to malaria. VFR accounted for 45.8% of our children. Only 17 VFRs had received prophylaxis, and 4 of them taken appropriately. They presented more frequently with fever (98% vs. 69%), a longer time with fever (55 vs. 26%), delay in diagnosis of more than three days (62 vs. 37%), and more thrombocytopenia (65 vs. 33%) than non-VFRs, and with significant differences (p<0.05). VFRs represent a large proportion of imported malaria cases in our study. They seldom took adequate prophylaxis, and delayed the visit to the physician, increasing the length of fever and subsequent delaying in diagnosis. Appropriate preventive measures, such as education and pre-travel advices should be taken in this population. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Quality and safety of integrated community case management of malaria using rapid diagnostic tests and pneumonia by community health workers.

PubMed

Hamer, Davidson H; Brooks, Erin Twohig; Semrau, Katherine; Pilingana, Portipher; MacLeod, William B; Siazeele, Kazungu; Sabin, Lora L; Thea, Donald M; Yeboah-Antwi, Kojo

2012-03-01

To assess the quality and safety of having community health workers (CHWs) in rural Zambia use rapid diagnostic tests (RDTs) and provide integrated management of malaria and pneumonia. In the context of a cluster-randomized controlled trial of two models for community-based management of malaria and/or non-severe pneumonia in children under 5 years old, CHWs in the intervention arm were trained to use RDTs, follow a simple algorithm for classification and treat malaria with artemether-lumefantrine (AL) and pneumonia with amoxicillin. CHW records were reviewed to assess the ability of the CHWs to appropriately classify and treat malaria and pneumonia, and account for supplies. Patients were also followed up to assess treatment safety. During the 12-month study, the CHWs evaluated 1017 children with fever and/or fast/difficult breathing and performed 975 RDTs. Malaria and/or pneumonia were appropriately classified 94-100% of the time. Treatment based on disease classification was correct in 94-100% of episodes. Supply management was excellent with over 98% of RDTs, amoxicillin, and AL properly accounted for. The use of RDTs, amoxicillin, and AL was associated with few minor adverse events. Most febrile children (90%) with negative RDT results recovered after being treated with an antipyretic alone. Volunteer CHWs in rural Zambia are capable of providing integrated management of malaria and pneumonia to children safely and at high quality.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

PubMed Central

2012-01-01

Background Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). Interpretation The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected. PMID:22545573

[Antibacterial therapy for acute cystitis in the age of growing pathogen resistance].

PubMed

Siniakova, L A

2014-01-01

Acute cystitis refers to uncomplicated lower urinary tract infections, with the recurrence rates after the first cystitis episode being 50%. The basic treatment for the above diseases is antibacterial therapy, whose efficiency depends entirely on the right choice of a drug during initial empiric therapy. The paper gives the European Association of Urology guidelines and Russian guidelines, which are based on the results of both international (ARESC) and Russian (DARMIS) studies of urinary tract infection pathogens and their susceptibility to antibacterial drugs. Phosphomycin trometamol and furasidine potassium are the drugs of choice to treat acute cystitis in Russia now.

Prevalence of malaria and anaemia among HIV infected pregnant women receiving co-trimoxazole prophylaxis in Tanzania: a cross sectional study in Kinondoni Municipality.

PubMed

Manyanga, Vicent P; Minzi, Omary; Ngasala, Billy

2014-04-24

HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy. This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin <11 g/dl). Data were collected on the adherence to co-trimoxazole prophylaxis and other risk factors for malaria infection and anaemia. Pearson chi-square test, Fischer's exact test and multivariate logistic regression were used in the statistical analysis. This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95% CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95% CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy. The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women.

Prevalence of malaria and anaemia among HIV infected pregnant women receiving co-trimoxazole prophylaxis in Tanzania: a cross sectional study in Kinondoni Municipality

PubMed Central

2014-01-01

Background HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy. Methods This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin <11 g/dl). Data were collected on the adherence to co-trimoxazole prophylaxis and other risk factors for malaria infection and anaemia. Pearson chi-square test, Fischer’s exact test and multivariate logistic regression were used in the statistical analysis. Results This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95% CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95% CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy. Conclusion The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women. PMID:24761799

Abandoning Presumptive Antimalarial Treatment for Febrile Children Aged Less Than Five Years—A Case of Running Before We Can Walk?

PubMed Central

English, Mike; Reyburn, Hugh; Goodman, Catherine; Snow, Robert W

2009-01-01

Background to the debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five. PMID:19127977

The malaria testing and treatment landscape in mainland Tanzania, 2016.

PubMed

Michael, Daniel; Mkunde, Sigsbert Patila

2017-04-24

Understanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and price of anti-malarials and malaria diagnosis in 2016. A nationally-representative malaria outlet survey was conducted between 18th May and 2nd July, 2016. A census of public and private outlets with potential to distribute malaria testing and/or treatment was conducted among a representative sample of administrative units. An audit was completed for all anti-malarials, malaria rapid (RDT) diagnostic tests and microscopy. A total of 5867 outlets were included in the nationally representative survey, across both public and private sectors. In the public sector, availability of malaria testing was 92.3% and quality-assured (QA) ACT was 89.1% among all screened outlets. Sulfadoxine-pyrimethamine (SP) was stocked by 51.8% of the public sector and injectable artesunate was found in 71.4% of all screened public health facilities. Among anti-malarial private-sector stockists, availability of testing was 15.7, and 65.1% had QA ACT available. The public sector accounted for 83.4% of the total market share for malaria diagnostics. The private sector accounted for 63.9% of the total anti-malarial market, and anti-malarials were most commonly distributed through accredited drug dispensing outlets (ADDOs) (39.0%), duka la dawa baridi (DLDBs) (13.3%) and pharmacies (6.7%). QA ACT comprised 33.1% of the national market share (12.2% public sector and 20.9% private sector). SP accounted for 53.3% of the total market for anti-malarials across both private and public sectors (31.3 and 22.0% of the total market, respectively). The median price per adult equivalent treatment dose (AETD) of QA ACT in the private sector was $1.40, almost 1.5 times more expensive than the median price per AETD of SP ($1.05). In the private sector, 79.3% of providers perceived ACT to be the most effective treatment for uncomplicated malaria for adults and 88.4% perceived this for children. While public sector preparedness for appropriate malaria testing and case management is showing encouraging signs, QA ACT availability and market share in the private sector continues to be sub-optimal for most outlet types. Furthermore, it is concerning that SP continues to predominate in the anti-malarial market. The reasons for this remain unclear, but are likely to be in part related to price, availability and provider knowledge or preferences. Continued efforts to implement government policy around malaria diagnosis and case management should be encouraged.

[Effects of an educational and participatory community intervention on malaria control in Buenaventura, Colombia].

PubMed

Alvarado, Beatriz Eugenia; Alzate, Alberto; Mateus, Julio Cesar; Carvajal, Rocío

2006-09-01

A four-component, non randomized, primary-care based intervention for malaria control was implemented in Buenaventura, Colombia. To evaluate the effect of the applied intervention on knowledge about malaria, attention of febrile events and frequency of malaria occurrence in three communities of Buenaventura. A post-intervention evaluation with a non-equivalent control group was performed. Two non-intervened groups (those residing more and less than six months, respectively, in the area) and one intervened group were identified. We interviewed 661 women household heads. Contact was defined as having been exposed to at least one of the four intervention components. Fourteen percent of the respondents had contact with the intervention. The attention of a febrile episode was better in those who had contact with the intervention than in the nonintervened ones who had resided in the area for more than six months. Those without contact and with less than six months stay in the area reported lower use of bed-nets (OR:0.46; 95% CI:0.23-0.93) and less fumigation practices (OR:0.38; 95% CI:0.19-0.75). The analysis of the malaria case trend showed a reduction in the proportion of cases contributed by the intervened communities, from 25% to 17%, six years after the intervention. An educational strategy is effective to enhance knowledge and modify the practices of the urban population of Buenaventura with respect to malaria.

Evaluating the impact of two training interventions to improve diagnosis and case-management of malaria and pneumonia in Uganda.

PubMed

Ssebuliba, D M; Ouifki, R; Pretorius, C; Burnett, S M; Mbonye, M K; Naikoba, S; Willis, K; Weaver, M R

2017-01-01

We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2·4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16·0% across all age groups. IMID decreases pneumonia prevalence by more than 3·0% across all age groups while IMID + OSS decreases it by more than 1·0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7·8% by IMID across all age groups and IMID + OSS decreases this number by 30·5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0·52% at baseline, and IMID and IMID + OSS reduce it by 6·6% and 23·6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14-91% in reduction of disease cases.

Implementation of G6PD testing and primaquine for P. vivax radical cure: Operational perspectives from Thailand and Cambodia.

PubMed

Kitchakarn, Suravadee; Lek, Dysoley; Thol, Sea; Hok, Chantheasy; Saejeng, Aungkana; Huy, Rekol; Chinanonwait, Nipon; Thimasarn, Krongthong; Wongsrichanalai, Chansuda

2017-09-01

Following progressive success in reducing the burden of malaria over the past two decades, countries of the Asia Pacific are now aiming for elimination of malaria by 2030. Plasmodium falciparum and Plasmodium vivax are the two main malaria species that are endemic in the region. P. vivax is generally perceived to be less severe but will be harder to eliminate, owing partly to its dormant liver stage (known as a hypnozoite) that can cause multiple relapses following an initial clinical episode caused by a mosquito-borne infection. Primaquine is the only anti-hypnozoite drug against P. vivax relapse currently available, with tafenoquine in the pipeline. However, both drugs may cause severe haemolysis in individuals with deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD), a hereditary defect. The overall incidence of malaria has significantly declined in both Thailand and Cambodia over the last 15 years. However, P. vivax has replaced P. falciparum as the dominant species in large parts of both countries. This paper presents the experience of the national malaria control programmes of the two countries, in their efforts to implement safe primaquine therapy for the radical cure, i.e. relapse prevention, of P. vivax malaria by introducing a rapid, point-of-care test to screen for G6PD deficiency.

Contribution of dengue fever to the burden of acute febrile illnesses in Papua New Guinea: an age-specific prospective study.

PubMed

Senn, Nicolas; Luang-Suarkia, Dagwin; Manong, Doris; Siba, Peter Max; McBride, William John Hannan

2011-07-01

Malaria is a major contributor to the burden of febrile illnesses in Papua New Guinea (PNG). Dengue fever (DF) is likely to contribute; however, its epidemiology in PNG is poorly understood. We performed a prospective age-stratified study in outpatient clinics investigating the prevalence of DF; 578 patients were enrolled, and 317 patients with a negative rapid diagnostic test (RDT) for malaria were tested for dengue. Malaria was confirmed in 52% (301/578, 95% confidence interval [CI] = 48-56%), DF was diagnosed in 8% (46/578, 95% CI = 6-10%), and 40% (95% CI = 36-44%) had neither diagnosis. Among the 317 malaria RDT-negative patients, 14% (45/317, 95% CI = 10-18%) had DF. The seroprevalence of dengue immunoglobulin G (IgG) was 83% (204/247, 95% CI = 78-87%), and no dengue hemorrhagic fever was seen. This study provides good evidence for the first time that DF is common in PNG and is responsible for 8% of fever episodes. The common occurrence of DF in a population with presumed previous exposure to dengue is an important observation.

Leukoerythroblastosis in a Young Child with Severe Malaria and Superimposed Gram Negative Infection.

PubMed

Varo, Rosauro; Sitoe, Antonio; Cossa, Anelsio; Ordi, Jaume; Rozman, Maria; Bassat, Quique

2017-12-18

Leukoerythroblastosis, a non-specific and often short-lasting response of the bone marrow to different diseases such as malignancies or infections, is characterized by the presence in the peripheral blood of immature red and white cells. We present a case of leukoerythoblastosis occurring in a 24 months old Mozambican girl, in the context of a severe malaria episode and an associated urinary tract infection. Peripheral blood smear was used for diagnosis of malaria and leukoerythroblastosis. Enterobacter cloacae isolation and antibiotic susceptibility testing were performed by conventional microbiology. Peripheral blood smear was positive for Plasmodium falciparum and showed a leukoerythroblastosis with red cell anisopoikilocytosis and left shifted neutrophils. Urine culture confirmed the presence of a multi-resistant E. cloacae. Treatment of underlying conditions resolved the leukoerythroblastic reaction. Leukoerythroblastosis may be related to different infectious diseases and may also appear in the context of severe malaria. Bacterial superinfection needs to be investigated. © The Author(s) [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Environmental determinant of malaria cases among travellers.

PubMed

Texier, Gaëtan; Machault, Vanessa; Barragti, Meili; Boutin, Jean-Paul; Rogier, Christophe

2013-03-04

Approximately 125 million travellers visit malaria-endemic countries annually and about 10,000 cases of malaria are reported after returning home. Due to the fact that malaria is insect vector transmitted, the environment is a key determinant of the spread of infection. Geo-climatic factors (such as temperature, moisture, water quality) determine the presence of Anopheles breeding sites, vector densities, adult mosquito survival rate, longevity and vector capacity. Several studies have shown the association between environmental factors and malaria incidence in autochthonous population. The association between the incidence of clinical malaria cases among non-immune travellers and environmental factors is yet to be evaluated. The objective of the present study was to identify, at a country scale (Ivory Coast), the environmental factors that are associated with clinical malaria among non-immune travellers, opening the way for a remote sensing-based counselling for malaria risk prevention among travellers. The study sample consisted in 87 cohorts, including 4,531 French soldiers who travelled to Ivory Coast, during approximately four months, between September 2002 and December 2006. Their daily locations were recorded during the entire trip. The association between the incidence of clinical malaria and other factors (including individual, collective and environmental factors evaluated by remote sensing methods) was analysed in a random effect mixed Poisson regression model to take into account the sampling design. One hundred and forty clinical malaria cases were recorded during 572,363 person-days of survey, corresponding to an incidence density of 7.4 clinical malaria episodes per 1,000 person-months under survey. The risk of clinical malaria was significantly associated with the cumulative time spent in areas with NDVI > 0.35 (RR = 2,42), a mean temperature higher than 27°C (RR = 2,4), a longer period of dryness during the preceding month (RR = 0,275) and the cumulative time spent in urban areas (RR = 0,52). The present results suggest that remotely-sensed environmental data could be used as good predictors of the risk of clinical malaria among vulnerable individuals travelling through African endemic areas.

Mefloquine for preventing malaria in pregnant women

PubMed Central

González, Raquel; Pons-Duran, Clara; Piqueras, Mireia; Aponte, John J; ter Kuile, Feiko O; Menéndez, Clara

2018-01-01

Background The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine. Objectives To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate: the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials. Selection criteria Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen. Data collection and analysis Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting. Main results Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria. Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo. Study participants included women of all gravidities and of all ages (four trials) or = 18 years (two trials). Gestational age at recruitment was = 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes. When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I2 statistic = 0%; high-certainty evidence). IPTp-mefloquine increased drug-related vomiting (RR 4.76, 95% CI 4.13 to 5.49; 6272 participants, 2 studies; high-certainty evidence) and dizziness (RR 4.21, 95% CI 3.36 to 5.27; participants = 6272, 2 studies; high-certainty evidence). When compared with cotrimoxazole, IPTp-mefloquine plus cotrimoxazole probably results in a 48% reduction in maternal peripheral parasitaemia at delivery (RR 0.52, 95% CI 0.30 to 0.93; 989 participants, 2 studies; moderate-certainty evidence) and a 72% reduction in placental malaria (RR 0.28, 95% CI 0.14 to 0.57; 977 participants, 2 studies; high-certainty evidence) but has little or no effect on the incidence of clinical malaria episodes during pregnancy (IRR 0.76, 95% CI 0.33 to 1.76, 1 study; high-certainty evidence) and probably no effect on maternal anaemia at delivery (RR 0.94, 95% CI 0.73 to 1.20; 1197 participants, 2 studies; moderate-certainty evidence), low birth weight rates (RR 1.20, 95% CI 0.89 to 1.60; 1220 participants, 2 studies; moderate-certainty evidence), and rates of spontaneous abortion and stillbirth (RR 1.12, 95% CI 0.42 to 2.98; 1347 participants, 2 studies; very low-certainty evidence). Mefloquine was associated with higher risks of drug-related vomiting (RR 7.95, 95% CI 4.79 to 13.18; 1055 participants, one study; high-certainty evidence) and dizziness (RR 3.94, 95% CI 2.85 to 5.46; 1055 participants, 1 study; high-certainty evidence). Authors' conclusions Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women. Mefloquine for preventing malaria in pregnant women What is the aim of this review? The aim of this Cochrane Review was to find out whether the antimalarial drug mefloquine is efficacious and safe for prevention of malaria in pregnant women living in stable transmission areas. We found six relevant studies to help us answer this question. Key messages The antimalarial drug mefloquine is efficacious for malaria prevention in pregnant women. The drug has been found to be safe in terms of adverse pregnancy outcomes, such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations. However, it is worse tolerated than other antimalarial drugs. What was studied in the review? Pregnant women are vulnerable to malaria infection, especially if they are living with HIV. The consequences of malaria during pregnancy can be severe and include poor health outcomes for both women and their children. For this reason, in malaria-endemic areas of stable transmission, women are recommended to prevent malaria infection by sleeping under mosquito bed-nets and by taking effective drugs (such as sulphadoxine-pyrimethamine or cotrimoxazole in case of HIV infection) as chemoprevention against malaria throughout pregnancy. This Cochrane Review looked at the effects of mefloquine for prevention of malaria in both HIV-uninfected and HIV-infected pregnant women. What are the main results of the review? We found five relevant studies conducted in sub-Saharan Africa and one in Thailand between 1987 and 2013. These studies compared mefloquine with placebo or other antimalarial drugs currently recommended for prevention of malaria in pregnant women. The review shows the following: Compared with sulfadoxine-pyrimethamine, mefloquine chemoprevention in HIV-uninfected women: reduces risks of maternal peripheral parasitaemia (presence of malaria parasites in the blood of women) and anaemia at delivery;makes no difference in the prevalence of adverse maternal outcomes (such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations) and in the incidence of clinical malaria episodes during pregnancy; andincreases risks of drug-related adverse events including vomiting, fatigue/weakness, and dizziness. Compared with cotrimoxale prophylaxis alone, mefloquine chemoprevention plus cotrimoxazole in HIV-infected women:reduces the risk of maternal peripheral parasitaemia at delivery and the risk of placental malaria;makes no difference in the prevalence of adverse pregnancy outcomes (such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations) and in the incidence of clinical malaria episodes during pregnancy; andincreases the risk of drug-related adverse events such as vomiting and dizziness. Overall, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women. How up-to-date is this review? The review authors searched for studies up to 31 January 2018. PMID:29561063

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Ouest and Sud-Est departments of Haiti.

PubMed

von Fricken, Michael E; Weppelmann, Thomas A; Eaton, Will T; Alam, Meer T; Carter, Tamar E; Schick, Laura; Masse, Roseline; Romain, Jean R; Okech, Bernard A

2014-07-01

Malaria remains a significant public health issue in Haiti, with chloroquine (CQ) used almost exclusively for the treatment of uncomplicated infections. Recently, single dose primaquine (PQ) was added to the Haitian national malaria treatment policy, despite a lack of information on the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency within the population. G6PD deficient individuals who take PQ are at risk of developing drug induced hemolysis (DIH). In this first study to examine G6PD deficiency rates in Haiti, 22.8% (range 14.9%-24.7%) of participants were found to be G6PD deficient (class I, II, or III) with 2.0% (16/800) of participants having severe deficiency (class I and II). Differences in deficiency were observed by gender, with males having a much higher prevalence of severe deficiency (4.3% vs. 0.4%) compared to females. Male participants were 1.6 times more likely to be classified as deficient and 10.6 times more likely to be classified as severely deficient compared to females, as expected. Finally, 10.6% (85/800) of the participants were considered to be at risk for DIH. Males also had much higher rates than females (19.3% vs. 4.6%) with 4.9 times greater likelihood (p value 0.000) of having an activity level that could lead to DIH. These findings provide useful information to policymakers and clinicians who are responsible for the implementation of PQ to control and manage malaria in Haiti. Copyright © 2014 Elsevier B.V. All rights reserved.

Plasma metabolomics reveals membrane lipids, aspartate/asparagine and nucleotide metabolism pathway differences associated with chloroquine resistance in Plasmodium vivax malaria

PubMed Central

Salinas, Jorge L.; Monteiro, Wuelton M.; Val, Fernando; Cordy, Regina J.; Liu, Ken; Melo, Gisely C.; Siqueira, Andre M.; Magalhaes, Belisa; Galinski, Mary R.; Lacerda, Marcus V. G.; Jones, Dean P.

2017-01-01

Background Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance. Methods An untargeted high-resolution metabolomics analysis was performed on plasma samples collected in a malaria clinic in Manaus, Brazil. Male and female patients with Plasmodium vivax were included (n = 46); samples were collected before CQ treatment and followed for 28 days to determine PvCR, defined as the recurrence of parasitemia with detectable plasma concentrations of CQ ≥100 ng/dL. Differentially expressed metabolic features between CQ-Resistant (CQ-R) and CQ-Sensitive (CQ-S) patients were identified using partial least squares discriminant analysis and linear regression after adjusting for covariates and multiple testing correction. Pathway enrichment analysis was performed using Mummichog. Results Linear regression and PLS-DA methods yielded 69 discriminatory features between CQ-R and CQ-S groups, with 10-fold cross-validation classification accuracy of 89.6% using a SVM classifier. Pathway enrichment analysis showed significant enrichment (p<0.05) of glycerophospholipid metabolism, glycosphingolipid metabolism, aspartate and asparagine metabolism, purine and pyrimidine metabolism, and xenobiotics metabolism. Glycerophosphocholines levels were significantly lower in the CQ-R group as compared to CQ-S patients and also to independent control samples. Conclusions The results show differences in lipid, amino acids, and nucleotide metabolism pathways in the plasma of CQ-R versus CQ-S patients prior to antimalarial treatment. Metabolomics phenotyping of P. vivax samples from patients with well-defined clinical CQ-resistance is promising for the development of new tools to understand the biological process and to identify potential biomarkers of PvCR. PMID:28813452

Quality of care in integrated community case management services in Bugoye, Uganda: a retrospective observational study.

PubMed

Miller, James S; English, Lacey; Matte, Michael; Mbusa, Rapheal; Ntaro, Moses; Bwambale, Shem; Kenney, Jessica; Siedner, Mark J; Reyes, Raquel; Lee, Patrick T; Mulogo, Edgar; Stone, Geren S

2018-02-27

Village health workers (VHWs) in five villages in Bugoye subcounty (Kasese District, Uganda) provide integrated community case management (iCCM) services, in which VHWs evaluate and treat malaria, pneumonia, and diarrhoea in children under 5 years of age. VHWs use a "Sick Child Job Aid" that guides them through the evaluation and treatment of these illnesses. A retrospective observational study was conducted to measure the quality of iCCM care provided by 23 VHWs in 5 villages in Bugoye subcounty over a 2-year period. Patient characteristics and clinical services were summarized using existing aggregate programme data. Lot quality assurance sampling of individual patient records was used to estimate adherence to the iCCM algorithm, VHW-level quality (based on adherence to the iCCM protocol), and change over time in quality of care (using generalized estimating equations regression modelling). For each of 23 VHWs, 25 patient visits were randomly selected from a 2-year period after iCCM care initiation. In these visits, 97% (150) of patients with diarrhoea were treated with oral rehydration and zinc, 95% (216) of patients with pneumonia were treated with amoxicillin, and 94% (240) of patients with malaria were treated with artemisinin-based combination therapy or rectal artesunate. However, only 44% (44) of patients with a negative rapid test for malaria were appropriately referred to a health facility. Overall, 75% (434) of patients received all the correct evaluation and management steps. Only 9 (39%) of the 23 VHWs met the pre-determined LQAS threshold for high-quality care over the 2-year observation period. Quality of care increased significantly in the first 6 months after initiation of iCCM services (p = 0.003), and then plateaued during months 7-24. Quality of care was high for uncomplicated malaria, pneumonia and diarrhoea. Overall quality of care was lower, in part because VHWs often did not follow the guidelines to refer patients with fever who tested negative for malaria. Quality of care appears to improve in the initial months after iCCM implementation, as VHWs gain initial experience in iCCM care.

High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria.

PubMed

Adukpo, Selorme; Kusi, Kwadwo A; Ofori, Michael F; Tetteh, John K A; Amoako-Sakyi, Daniel; Goka, Bamenla Q; Adjei, George O; Edoh, Dominic A; Akanmori, Bartholomew D; Gyan, Ben A; Dodoo, Daniel

2013-01-01

Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM. Paediatric malaria patients, 0.5 to 13 years were recruited and grouped into CM and uncomplicated malaria (UM) patients, based on well defined criteria. Standardized ELISA protocol was used to measure soluble ICAM-1 (sICAM-1) levels from acute plasma samples. Levels of IgG to CD36- or ICAM-1-binding VSA were measured by flow cytometry during acute and convalescent states. Wilcoxon sign rank-test analysis to compare groups revealed association between sICAM-1 levels and CM (p<0.0037). Median levels of antibodies to CD36-binding VSA were comparable in the two groups at the time of admission and 7 days after treatment was initiated (p>0.05). Median levels of antibodies to CD36-binding VSAs were also comparable between acute and convalescent samples within any patient group. Median levels of antibodies to ICAM-1-binding VSAs were however significantly lower at admission time than during recovery in both groups. High levels of sICAM-1 were associated with CM, and the sICAM-1 levels may reflect expression levels of the membrane bound form. Anti-VSA antibody levels to ICAM-binding parasites was more strongly associated with both UM and CM than antibodies to CD36 binding parasites. Thus, increasing host sICAM-1 levels were associated with CM whilst antibodies to parasite expressing non-ICAM-1-binding VSAs were not.

The feasibility, patterns of use and acceptability of using mobile phone text-messaging to improve treatment adherence and post-treatment review of children with uncomplicated malaria in western Kenya.

PubMed

Otieno, Gabriel; Githinji, Sophie; Jones, Caroline; Snow, Robert W; Talisuna, Ambrose; Zurovac, Dejan

2014-02-03

Trials evaluating the impact of mobile phone text-messaging to support management of acute diseases, such as malaria, are urgently needed in Africa. There has been however a concern about the feasibility of interventions that rely on access to mobile phones among caregivers in rural areas. To assess the feasibility and inform development of an intervention to improve adherence to malaria medications and post-treatment review, mobile phone network, access, ownership and use among caregivers in western Kenya was assessed. A cross-sectional survey based on outpatient exit interviews was undertaken among caregivers of children with malaria at four trial facilities. The main outcomes were proportions of caregivers that have mobile signal at home; have access to mobile phones; are able to read; and use text-messaging. Willingness to receive text-message reminders was also explored. Descriptive analyses were performed. Of 400 interviewed caregivers, the majority were female (93.5%), mothers of the sick children (87.8%) and able to read (97.3%). Only 1.7% of caregivers were without any education. Nearly all (99.8%) reported access to a mobile signal at home. 93.0% (site range: 89-98%) had access to a mobile phone within their household while 73.8% (site range: 66-78%) possessed a personal phone. Among caregivers with mobile phone access, 93.6% (site range: 85-99%) used the phone to receive text-messages. Despite only 19% having electricity at home nearly all (99.7%) caregivers reported that they would be able to have permanent phone access to receive text-messages in the next 28 days. Willingness to receive text-message reminders was nearly universal (99.7%) with 41.7% of caregivers preferring texts in English, 32.3% in Kiswahili and 26.1% in Dholuo. Despite concerns that the feasibility of text-messaging interventions targeting caregivers may be compromised in rural high malaria risk areas in Kenya, very favourable conditions were found with respect to mobile network, access and ownership of phones, use of text-messaging and minimum literacy levels required for successful intervention delivery. Moreover, there was a high willingness of caregivers to receive text-message reminders. Impact evaluations of carefully tailored text-messaging interventions targeting caregivers of children with malaria are timely and justified.

Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

PubMed Central

2012-01-01

Background Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect vector mosquitoes. However, this has never been verified at a population level in a setting with intense transmission, where chronically infectious asymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected. Methods From 2001 to 2004, malaria vector densities were monitored using light traps in three Tanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates. Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxine-pyrimethamine (SP) monotherapy was used for treatment of uncomplicated malaria in the contiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, the standard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003. The effects of this change in case management on malaria parasite infection in the vectors were analysed. Results Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites per person per year at both sites over the whole period. The introduction of AS + SP in Rufiji was associated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p < 0.001), but had no consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). The estimated infectiousness of the human population in Rufiji was very low prior to the change in drug policy. Emergence rates and parous rates of the vectors varied substantially throughout the study period, which affected estimates of infectiousness. The latter consequently cannot be explained by the change in drug policy. Conclusions In high perennial transmission settings, only a small proportion of infections in humans are symptomatic or treated, so case management with ACT may have little impact on overall infectiousness of the human population. Variations in infection levels in vectors largely depend on the age distribution of the mosquito population. Benefits of ACT in suppressing transmission are more likely to be evident where transmission is already low or effective vector control is widely implemented. PMID:22513162

Timing of urinary catheter removal after uncomplicated total abdominal hysterectomy: a prospective randomized trial.

PubMed

Ahmed, Magdy R; Sayed Ahmed, Waleed A; Atwa, Khaled A; Metwally, Lobna

2014-05-01

To assess whether immediate (0h), intermediate (after 6h) or delayed (after 24h) removal of an indwelling urinary catheter after uncomplicated abdominal hysterectomy can affect the rate of re-catheterization due to urinary retention, rate of urinary tract infection, ambulation time and length of hospital stay. Prospective randomized controlled trial conducted at Suez Canal University Hospital, Egypt. Two hundred and twenty-one women underwent total abdominal hysterectomy for benign gynecological diseases and were randomly allocated into three groups. Women in group A (73 patients) had their urinary catheter removed immediately after surgery. Group B (81 patients) had the catheter removed 6h post-operatively while in group C (67 patients) the catheter was removed after 24h. The main outcome measures were the frequency of urinary retention, urinary tract infections, ambulation time and length of hospital stay. There was a significantly higher number of urinary retention episodes requiring re-catheterization in the immediate removal group compared to the intermediate and delayed removal groups (16.4% versus 2.5% and 0% respectively). Delayed urinary catheter removal was associated with a higher incidence of urinary tract infections (15%), delayed ambulation time (10.3h) and longer hospital stay (5.6 days) compared to the early (1.4%, 4.1h and 3.2 days respectively) and intermediate (3.7%, 6.8h and 3.4 days respectively) removal groups. Removal of the urinary catheter 6h postoperatively appears to be more advantageous than early or late removal in cases of uncomplicated total abdominal hysterectomy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Conquering the intolerable burden of malaria: what's new, what's needed: a summary.

PubMed

Breman, Joel G; Alilio, Martin S; Mills, Anne

2004-08-01

Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden. Almost 3% of disability adjusted life years are due to malaria mortality globally, 10% in Africa. New information is presented in this supplement on malaria-related perinatal mortality, occurrence of human immunodeficiency virus in pregnancy, undernutrition, and neurologic, cognitive, and developmental sequelae. The entomologic determinants of transmission and uses of modeling for program planning and disease prediction and prevention are discussed. New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. This social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4-5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unlikely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseline data and reliable monitoring of key outcome indicators are needed to measure whether the ambitious goals for the control of malaria and other diseases has occurred. Such systems are being used for evidence-based decision making in Tanzania and several other countries. Baseline cluster sampling surveys in several countries across Africa indicate that only 53% of the children with febrile illness in malarious areas are being treated; chloroquine (CQ) is used 84% of the time, even where the drug may be ineffective. Insecticide-treated bed nets were used only 2% of the time by children less than five years of age. Progress in malaria vaccine research has been substantial over the past five years; 35 candidate malaria vaccines are in development, many of which are in clinical trials. Development of new vaccines and drugs has been the result of increased investments and formation of public-private partnerships. Before malaria vaccine becomes deployed, consideration must be given to disease burden, cost-effectiveness, financing, delivery systems, and approval by regulatory agencies. Key to evaluation of vaccine effectiveness will be collection and prompt analysis of epidemiologic information. Training of persons in every aspect of malaria research and control is essential for programs to succeed. The Multilateral Initiative on Malaria (MIM) is actively promoting research capacity strengthening and has established networks of institutions and scientists throughout the African continent, most of whom are now linked by modern information-sharing networks. Evidence over the past century is that successful control malaria programs have been linked to strong research activities. To ensure effective coordination and cooperation between the growing number of research and control coalitions forming in support of malaria activities, an umbrella group is needed. With continued support for scientists and control workers globally, particularly in low-income malarious countries, the long-deferred dream of malaria elimination can become a reality. Copyright 2004 The American Society of Tropical Medicine and Hygiene

The High Value Healthcare Collaborative: Observational Analyses of Care Episodes for Hip and Knee Arthroplasty Surgery.

PubMed

Weeks, William B; Schoellkopf, William J; Sorensen, Lyle S; Masica, Andrew L; Nesse, Robert E; Weinstein, James N

2017-03-01

Broader use of value-based reimbursement models will require providers to transparently demonstrate health care value. We sought to determine and report cost and quality data for episodes of hip and knee arthroplasty surgery among 13 members of the High Value Healthcare Collaborative (HVHC), a consortium of health care systems interested in improving health care value. We conducted a retrospective, cross-sectional observational cohort study of 30-day episodes of care for hip and knee arthroplasty in fee-for-service Medicare beneficiaries aged 65 or older who had hip or knee osteoarthritis and used 1 of 13 HVHC member systems for uncomplicated primary hip arthroplasty (N = 8853) or knee arthroplasty (N = 16,434), respectively, in 2012 or 2013. At the system level, we calculated: per-capita utilization rates; postoperative complication rates; standardized total, acute, and postacute care Medicare expenditures for 30-day episodes of care; and the modeled impact of reducing episode expenditures or per-capita utilization rates. Adjusted per-capita utilization rates varied across HVHC systems and postacute care reimbursements varied more than 3-fold for both types of arthroplasty in both years. Regression analysis confirmed that total episode and postacute care reimbursements significantly differed across HVHC members after considering patient demographic differences. Potential Medicare cost savings were greatest for knee arthroplasty surgery and when lower total reimbursement targets were achieved. The substantial variation that we found offers opportunities for learning and collaboration to collectively improve outcomes, reduce costs, and enhance value. Ceteris paribus, reducing per-episode reimbursements would achieve greater Medicare cost savings than reducing per-capita rates. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-treatment of malaria in a rural area of western Kenya.

PubMed Central

Ruebush, T. K.; Kern, M. K.; Campbell, C. C.; Oloo, A. J.

1995-01-01

Reported are the results of a study of residents' knowledge about malaria and antimalarial drugs and of their treatment-seeking behaviour in a rural area of western Kenya. The study subjects were generally well-informed about the symptoms of the disease. Malaria was perceived as a relatively mild illness, much less severe than acquired immunodeficiency syndrome (AIDS), measles, difficulty in breathing, and diarrhoea. Self-treatment was extremely common: of 138 episodes of febrile illness, 60% were treated at home with herbal remedies or medicines purchased at local shops, and only 18% received treatment at a health centre or hospital; no treatment was sought by the remainder. Commercially available chloroquine preparations were perceived as more effective than either antipyretics or herbal remedies for the treatment of malaria, and injections were regarded as more effective than oral medications. 4-Amino-quinolines were used to treat 58% of febrile illnesses but in only 12% of the cases was a curative dose of > or = 25 mg/kg body weight employed. Even attendance at a health centre did not ensure adequate treatment because of the common practice of sharing medication among family members. Greatly increased attention should be paid to the role of home treatment of malaria when policies are being developed for the management of febrile illnesses in sub-Saharan Africa. PMID:7743595

Clinical tolerability of artesunate-amodiaquine versus comparator treatments for uncomplicated falciparum malaria: an individual-patient analysis of eight randomized controlled trials in sub-Saharan Africa.

PubMed

Zwang, Julien; Dorsey, Grant; Djimdé, Abdoulaye; Karema, Corine; Mårtensson, Andreas; Ndiaye, Jean-Louis; Sirima, Sodiomon B; Olliaro, Piero

2012-08-02

The widespread use of artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria makes it important to gather and analyse information on its tolerability. An individual-patient tolerability analysis was conducted using data from eight randomized controlled clinical trials conducted at 17 sites in nine sub-Saharan countries comparing ASAQ to other anti-malarial treatments. All patients who received at least one dose of the study drug were included in the analysis. Differences in adverse event (AE) and treatment emergent adverse event (TEAE) were analysed by Day 28. Of the 6,179 patients enrolled (74% <5 years of age), 50% (n = 3,113) received ASAQ, 20% (n = 1,217) another ACT, and 30% (n = 1,849) a non-ACT (combination or single-agent) treatment. Overall, 8,542 AEs were recorded. The proportion of patients experiencing at least one gastro-intestinal AE on ASAQ was 43% (and higher than that with artemether-lumefantrine and dihydroartemisinin-piperaquine at two sites), and was 23% for any other AEs (not different from other treatments). Specifically, the risk of diarrhoea, vomiting, cough and weakness was lower with artemether-lumefantrine; artemether-lumefantrine and dihydroartemisinin-piperaquine carried a higher risk of pruritus, chloroquine-SP had a higher risk of nausea. Parasitological recurrence increased the risk of occurrence of any AE. No other difference was detected. Comparing AE to TEAE in patients who had pre-treatment occurrence and grades of intensity recorded, AEs were significantly more related to the pre-treatment prevalence of the symptom (p = 0.001, Fisher test); AEs overestimated TEAEs by a factor ranging from none to five-fold. The overall incidence of serious AEs (SAEs) with ASAQ was nine per 1,000 (29/3,113) and mortality was one per 1,000 (three deaths, none drug-related); both were similar to other treatments. ASAQ was comparatively well-tolerated. Safety information is important, and must be collected and analysed in a standardized way. TEAEs are a more objective measure of treatment-induced toxicity.