Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C.

PubMed

Poreba, Marcin; Mihelic, Marko; Krai, Priscilla; Rajkovic, Jelena; Krezel, Artur; Pawelczak, Malgorzata; Klemba, Michael; Turk, Dusan; Turk, Boris; Latajka, Rafal; Drag, Marcin

2014-04-01

Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad range of unnatural amino acids. Our approach identified very efficiently hydrolyzed substrates containing unnatural amino acids, which resulted in the design of significantly better substrates than those previously known. Additionally, in this study significant differences in terms of the structures of optimal substrates for human and malarial orthologs are important from the therapeutic point of view. These data can be also used for the design of specific inhibitors or activity-based probes.

[Malaria diagnosis and treatment: analysis of a cohort of hospitalised patients at a tertiary level hospital (1998-2010)].

PubMed

Iborra, María Asunción; García, Elisa; Carrilero, Bartolomé; Segovia, Manuel

2013-03-01

The increasing frequency of malaria infection in our area is due to the rise in international travel and immigration from endemic malaria areas. The aim of this study is to describe the chemoprophylaxis taken and treatment given as well as the clinical, epidemiological and microbiological characteristics for those patients admitted to our hospital with malaria. A retrospective study of patients with malaria admitted to the Hospital Virgen de la Arrixaca, between January 1998 and December 2010, was carried out. During this period, fifty one cases of malaria were diagnosed. 78.3% of them were immigrants of whom 65% resided in Spain and had travelled to their country of origin for a short stay. Seventy four per cent acquired the infection in central and west Africa, and Plasmodium falciparum was responsible for the majority of the cases (88%). Only four patients had taken antimalarial chemoprophylaxis but none correctly. The most frequently treatment used was a combination of quinine and doxycicline (64.7%). Inappropriate anti-malarial treatment occurred in 9 patients (17.6%). At least one indicator of severe malaria was established in 23.5% of the cases; however, the clinical outcome was successful in every case and no patient died. Imported malaria is observed mostly among immigrants who travel to their countries of origin for a short stay and do not take anti-malarial prophylaxis, increasing the risk of acquiring malaria. Inappropriate malarial treatment is relatively frequent in the case management of imported malaria.

Imported malaria in children: a comparative study between recent immigrants and immigrant travelers (VFRs).

PubMed

Arnáez, Juan; Roa, Miguel A; Albert, Leticia; Cogollos, Rosario; Rubio, Jose M; Villares, Rebeca; Alarabe, Abdulkareem; Cervera, Aurea; López-Vélez, Rogelio

2010-01-01

In Europe, imported malarial cases occur in returning travelers and immigrants mostly from African countries. There have been an increasing number of cases in the past years in Spain. An analysis of all cases of malaria who attended at the Hospital of Mostoles in the Southwest of Madrid from 1995 to 2007 was performed. Clinical, epidemiological, laboratory, and parasitological findings were analyzed and compared between immigrants coming from endemic countries (recent immigrants) and children who traveled to endemic areas to visit friends and relatives (VFRs). Sixty cases of imported malaria were detected. Most of the cases (59 of 60) were acquired in sub-Saharan Africa. The most common species was Plasmodium falciparum (43 of 60). Microscopic examination was positive in 95%, and the polymerase chain reaction (PCR) for Plasmodium achieved additional diagnosis in seven cases. Fourteen cases were VFRs; none of them used appropriate malaria chemoprophylaxis. Fever and thrombocytopenia were significantly more common among VFRs. They also had significantly higher parasite density. Twelve cases were asymptomatic at the time of diagnosis; all of them were recent immigrants. VFRs account for a significant number of childhood malarial cases. These patients had not taken malaria chemoprophylaxis and malarial cases were more severe. VFR children are a high-risk group, and pretravel advice should underline the risk for malaria. Recent immigrants can be asymptomatic and parasitemias are lower. Therefore, a high index of suspicion is necessary, and PCR for Plasmodium should be performed in case of negative thick smears.

Epidemiologic maps of Washington DC, 1878-1909.

PubMed Central

Vecchioli, D

1996-01-01

IN ORDER TO demonstrate the dire effects that contagious epidemic diseases were having on the population of Washington DC, Public Health Officers of the District of Columbia used epidemiological maps in their annual reports to city commissioners from 1878 until 1909. These maps charted information graphically that was included as statistical tables elsewhere in the reports. Their evolution occurred during a period when the Health Officers themselves were coming to grips with the causes of diseases that included diphtheria, scarlet fever, typhoid and malarial fevers, smallpox, consumption (tuberculosis), and diarrheal diseases. The maps may have encouraged laws that were passed during this period which required Washington DC physicians to report cases and deaths from these diseases. Images p315-a p315-b p315-c Figure 2. PMID:8711096

[Optimized application of nested PCR method for detection of malaria].

PubMed

Yao-Guang, Z; Li, J; Zhen-Yu, W; Li, C

2017-04-28

Objective To optimize the application of the nested PCR method for the detection of malaria according to the working practice, so as to improve the efficiency of malaria detection. Methods Premixing solution of PCR, internal primers for further amplification and new designed primers that aimed at two Plasmodium ovale subspecies were employed to optimize the reaction system, reaction condition and specific primers of P . ovale on basis of routine nested PCR. Then the specificity and the sensitivity of the optimized method were analyzed. The positive blood samples and examination samples of malaria were detected by the routine nested PCR and the optimized method simultaneously, and the detection results were compared and analyzed. Results The optimized method showed good specificity, and its sensitivity could reach the pg to fg level. The two methods were used to detect the same positive malarial blood samples simultaneously, the results indicated that the PCR products of the two methods had no significant difference, but the non-specific amplification reduced obviously and the detection rates of P . ovale subspecies improved, as well as the total specificity also increased through the use of the optimized method. The actual detection results of 111 cases of malarial blood samples showed that the sensitivity and specificity of the routine nested PCR were 94.57% and 86.96%, respectively, and those of the optimized method were both 93.48%, and there was no statistically significant difference between the two methods in the sensitivity ( P > 0.05), but there was a statistically significant difference between the two methods in the specificity ( P < 0.05). Conclusion The optimized PCR can improve the specificity without reducing the sensitivity on the basis of the routine nested PCR, it also can save the cost and increase the efficiency of malaria detection as less experiment links.

Access to artemisinin-based combination therapies and other anti-malarial drugs in Kinshasa.

PubMed

Nkoli Mandoko, P; Sinou, V; Moke Mbongi, D; Ngoyi Mumba, D; Kahunu Mesia, G; Losimba Likwela, J; Bi Shamamba Karhemere, S; Muepu Tshilolo, L; Tamfum Muyembe, J-J; Parzy, D

2018-06-01

Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa. We performed a cross-sectional survey of 404 pharmacies. Anti-malarial drugs were stocked in all surveyed pharmacies. Non-artemisinin-based anti-malarial therapies such as quinine or sulfadoxine-pyrimethamine, were the most frequently stocked drugs (93.8% of pharmacies). Artemisinin-based combination therapies were stocked in 88% of pharmacies. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies), but less than 3% were quality-assured products. Other non-officially recommended artemisinin-based therapies including oral monotherapies were widely available. Artemisinin-based combination therapies were widely available in the private pharmacies of Kinshasa. However, the private sector does not guarantee the use of nationally recommended anti-malarial drugs nor does it give priority to quality-assured anti-malarial drugs. These practices contribute to the risk of emergence and spread of resistance to anti-malarial drugs and to increasing treatment costs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Curcumin-loaded hydrogel nanoparticles: application in anti-malarial therapy and toxicological evaluation.

PubMed

Dandekar, Prajakta P; Jain, Ratnesh; Patil, Sushant; Dhumal, Rohit; Tiwari, Dinesh; Sharma, Shobhona; Vanage, Geeta; Patravale, Vandana

2010-12-01

The present investigation involved preparation of hydrogel nanoparticles using a combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The objective was to exploit the size and hydrophilic nature of the formulated nanocarriers to enhance absorption and prolong the rapid clearance of curcumin due to possible evasion of the reticulo-endothelial system. Reproducible nanoparticles of size around 100 nm, a fairly narrow distribution and encapsulation efficiency of 72%, were produced by the solvent emulsion-evaporation technique. This optimized system was further subjected to freeze-drying. The freeze-dried product was readily reconstituted with distilled water. The reconstituted product exhibited a size and distribution similar to that before freeze-drying, drug content of greater than 99% and presence of amorphous drug when analyzed by differential scanning calorimetry (DSC) which may result in possible improved absorption of curcumin. In vivo anti-malarial studies revealed significant superior action of nanoparticles over curcumin control suggesting the possibility of the formulation being employed as an adjunct anti-malarial therapy along with the standard therapy. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A battery of genotoxicity studies was conducted to evaluate the nongenotoxic potential of the developed formulation thus indicating the possibility of the formulation being employed for prolonged duration. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Crystal Structure of Arginase from Plasmodium falciparum and Implications for l-Arginine Depletion in Malarial Infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dowling, Daniel P.; Ilies, Monica; Olszewski, Kellen L.

The 2.15 {angstrom} resolution crystal structure of arginase from Plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) (K{sub d} = 11 {micro}M). This is the first crystal structure of a parasitic arginase. Various protein constructs were explored to identify an optimally active enzyme form for inhibition and structural studies and to probe the structure and function of two polypeptide insertions unique to malarial arginase: a 74-residue low-complexity region contained in loop L2 and an 11-residue segment contained in loop L8. Structural studies indicate that the low-complexity region ismore » largely disordered and is oriented away from the trimer interface; its deletion does not significantly compromise enzyme activity. The loop L8 insertion is located at the trimer interface and makes several intra- and intermolecular interactions important for enzyme function. In addition, we also demonstrate that arg- Plasmodium berghei sporozoites show significantly decreased liver infectivity in vivo. Therefore, inhibition of malarial arginase may serve as a possible candidate for antimalarial therapy against liver-stage infection, and ABH may serve as a lead for the development of inhibitors.« less

Male fertility following occupational exposure to dichlorodiphenyltrichloroethane (DDT).

PubMed

Campagna, Marcello; Satta, Giannina; Fadda, Domenica; Pili, Sergio; Cocco, Pierluigi

2015-04-01

The inconsistent epidemiological results of the endocrine disrupting effects of DDT fuel a harsh debate on its global ban. We tested the hypothesis that occupational exposure to dichloro-diphenyl-trichloroethane (DDT) causes impairment in male fertility in a cohort of DDT exposed workers, in Sardinia, Italy. We accessed official records on date of marriage and date of birth of the first child to estimate time to pregnancy (TTP) in the spouses of 1223 workers employed in a 1946-1950 anti-malarial campaign. The TTP calculation was censored at the 13th month after date of marriage. We used a modified Cox's proportional hazard model to calculate the fecundability ratio (FR) by job, by cumulative exposure to DDT, and by time window in relation to the anti-malarial operations, adjusting by paternal age at marriage. Among the spouses of DDT applicators, fecundability did not vary during DDT use (FR=1.22, 95% CI 0.84-1.77) nor in the following decade (FR=1.01, 95% CI 0.67-1.50) with reference to the prior years. A significant increase occurred among the unexposed and the less exposed sub-cohorts, which generated a non-significantly reduced FR among the DDT applicator sub-cohort with reference to the unexposed following exposure. We did not find evidence of an impairment in male fertility following heavy occupational exposure to DDT. However, although fecundability was highest among the spouses of the DDT applicators in the years prior to the anti-malarial campaign, we cannot exclude that DDT exposure prevented an increase parallel to that observed among the unexposed and the less exposed sub-cohorts. Copyright © 2015. Published by Elsevier Ltd.

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.

Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

PubMed Central

2011-01-01

Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT). The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors. Conclusions While data on the anti-malarial market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of diagnostic testing and treatment with full-course first-line anti-malarials. PMID:22039922

Malarial hepatopathy: Clinical profile and association with other malarial complications.

PubMed

Jain, Anshika; Kaushik, Reshma; Kaushik, Rajeev Mohan

2016-07-01

This prospective study assessed the incidence, clinical profile and outcome of malarial hepatopathy and its association with other complications in patients with malaria, proved by peripheral blood smear examination and rapid malaria test. Hyperbilirubinemia (Serum bilirubin >3mg/dL) with >3-fold rise in serum aminotransferases in absence of a different explanation for such derangement was considered as malarial hepatopathy. Of 134 (falciparum-81, vivax-48 and mixed falciparum and vivax-5) malaria cases, hyperbilirubinemia occurred in 41.04%. Serum aspartate aminotransferase (AST) was raised >3-fold in 17.16% and serum alanine aminotransferase (ALT) in 4.47% cases. Malarial hepatopathy was observed in 4.47% (falciparum-5 and vivax malaria-1) cases, but had insignificant association with the type of malaria (p=0.532). Serum bilirubin, AST and ALT levels were higher while age was lower in both overall (p<0.05 each) and falciparum malaria cases with hepatopathy than without hepatopathy (p<0.05 each). Malarial hepatopathy was associated with a higher incidence of cerebral malaria, shock, acute respiratory distress syndrome (ARDS) and acute kidney injury in both overall (p<0.05 each) and falciparum malaria (p<0.05 each) and hyponatremia and disseminated intravascular coagulation only in overall malaria (p<0.05). Malarial hepatopathy had significant association with duration of hospitalization, parasite clearance time, fever clearance time and jaundice clearance time in overall (p<0.05 each) and falciparum (p<0.05 each) but not vivax malaria cases (p>0.05 each). Mortality occurred in 1 (20%) case of falciparum-induced hepatopathy with an overall mortality of 16.66%. ARDS (p=0.003) and shock (p=0.026) were independently associated with malarial hepatopathy overall while only ARDS with falciparum-induced hepatopathy (p=0.006). Thus, hepatocellular dysfunction is common in malaria but that qualifying as malarial hepatopathy is not common. Malarial hepatopathy is likely to occur in presence of other malarial complications. It is an epiphenomenon in severe malaria and indicative of severe disease. Establishing a particular association with malaria or mortality would require a larger case-control study of severe malaria. Copyright © 2016 Elsevier B.V. All rights reserved.

Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts.

PubMed

Nonaka, Motohiro; Murata, Yuho; Takano, Ryo; Han, Yongmei; Bin Kabir, Md Hazzaz; Kato, Kentaro

2018-06-25

Malaria is a major infectious disease in the world. In 2015, approximately 212 million people were infected and 429,000 people were killed by this disease. Plasmodium falciparum, which causes falciparum malaria, is becoming resistant to artemisinin (ART) in Southeast Asia; therefore, new anti-malarial drugs are urgently needed. Some excellent anti-malarial drugs, such as quinine or ART, were originally obtained from natural plants. Hence, the authors screened a natural product library comprising traditional Chinese medicines (TCMs) to identify compounds/extracts with anti-malarial effects. The authors performed three assays: a malaria growth inhibition assay (GIA), a cytotoxicity assay, and a malaria stage-specific GIA. The malaria GIA revealed the anti-malarial ability and half-maximal inhibitory concentrations (IC 50 ) of the natural products, whereas the malaria stage-specific GIA revealed the point in the malaria life cycle where the products exerted their anti-malarial effects. The toxicity of the products to the host cells was evaluated with the cytotoxicity assay. Four natural compounds (berberine chloride, coptisine chloride, palmatine chloride, and dehydrocorydaline nitrate) showed strong anti-malarial effects (IC 50  < 50 nM), and low cytotoxicity (cell viability > 90%) using P. falciparum 3D7 strain. Two natural extracts (Phellodendri cortex and Coptidis rhizoma) also showed strong antiplasmodial effects (IC 50  < 1 µg/ml), and low cytotoxicity (cell viability > 80%). These natural products also demonstrated anti-malarial capability during the trophozoite and schizont stages of the malaria life cycle. The authors identified four compounds (berberine chloride, coptisine chloride, palmatine chloride, and dehydrocorydaline nitrate) and two extracts (Phellodendri cortex and Coptidis rhizoma) with anti-malarial activity, neither of which had previously been described. The IC 50 values of the compounds were comparable to that of chloroquine and better than that of pyrimethamine. These compounds and extracts derived from TCMs thus show promise as potential future anti-malarial drugs.

The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence.

PubMed

Karunamoorthi, Kaliyaperumal

2014-06-02

The counterfeiting of anti-malarials represents a form of attack on global public health in which fake and substandard anti-malarials serve as de facto weapons of mass destruction, particularly in resource-constrained endemic settings, where malaria causes nearly 660,000 preventable deaths and threatens millions of lives annually. It has been estimated that fake anti-malarials contribute to nearly 450,000 preventable deaths every year. This crime against humanity is often underestimated or ignored. This study attempts to describe and characterize the direct and indirect effects of counterfeit anti-malarials on public health, clinical care and socio-economic conditions. A search was performed using key databases, WHO documents, and English language search engines. Of 262 potential articles that were identified using a fixed set of criteria, a convenience sample of 105 appropriate articles was selected for this review. Artemisinin-based combination therapy (ACT) is an important tool in the fight against malaria, but a sizable number of patients are unable to afford to this first-line treatment. Consequently, patients tend to procure cheaper anti-malarials, which may be fake or substandard. Forensic palynology reveals that counterfeits originate in Asia. Fragile drug regulations, ineffective law-enforcement agencies and corruption further burden ailing healthcare facilities. Substandard/fake anti-malarials can cause (a) economic sabotage; (b) therapeutic failure; (c) increased risk of the emergence and spread of resistant strains of Plasmodium falciparum and Plasmodium vivax; (d) an undermining of trust/confidence in healthcare stakeholders/systems; and, (e) serious side effects or death. Combating counterfeit anti-malarials is a complex task due to limited resources and poor techniques for the detection and identification of fake anti-malarials. This situation calls for sustainable, global, scientific research and policy change. Further, responsible stakeholders in combination with the synthesis and supply of next generation malaria control tools, such as low-cost anti-malarials, must promote the development of a counterfeit-free and malaria-free future.

The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence

PubMed Central

2014-01-01

Background The counterfeiting of anti-malarials represents a form of attack on global public health in which fake and substandard anti-malarials serve as de facto weapons of mass destruction, particularly in resource-constrained endemic settings, where malaria causes nearly 660,000 preventable deaths and threatens millions of lives annually. It has been estimated that fake anti-malarials contribute to nearly 450,000 preventable deaths every year. This crime against humanity is often underestimated or ignored. This study attempts to describe and characterize the direct and indirect effects of counterfeit anti-malarials on public health, clinical care and socio-economic conditions. Methods A search was performed using key databases, WHO documents, and English language search engines. Of 262 potential articles that were identified using a fixed set of criteria, a convenience sample of 105 appropriate articles was selected for this review. Results Artemisinin-based combination therapy (ACT) is an important tool in the fight against malaria, but a sizable number of patients are unable to afford to this first-line treatment. Consequently, patients tend to procure cheaper anti-malarials, which may be fake or substandard. Forensic palynology reveals that counterfeits originate in Asia. Fragile drug regulations, ineffective law-enforcement agencies and corruption further burden ailing healthcare facilities. Substandard/fake anti-malarials can cause (a) economic sabotage; (b) therapeutic failure; (c) increased risk of the emergence and spread of resistant strains of Plasmodium falciparum and Plasmodium vivax; (d) an undermining of trust/confidence in healthcare stakeholders/systems; and, (e) serious side effects or death. Conclusion Combating counterfeit anti-malarials is a complex task due to limited resources and poor techniques for the detection and identification of fake anti-malarials. This situation calls for sustainable, global, scientific research and policy change. Further, responsible stakeholders in combination with the synthesis and supply of next generation malaria control tools, such as low-cost anti-malarials, must promote the development of a counterfeit-free and malaria-free future. PMID:24888370

Malaria Related Perceptions, Care Seeking after Onset of Fever and Anti-Malarial Drug Use in Malaria Endemic Settings of Southwest Ethiopia

PubMed Central

Birhanu, Zewdie; Abebe, Lakew; Sudhakar, Morankar; Dissanayake, Gunawardena; Yihdego, Yemane Ye-ebiyo; Alemayehu, Guda; Yewhalaw, Delenasaw

2016-01-01

Background Prompt care seeking and appropriate use of anti-malarial drugs are critical components of malaria prevention and control. This study assessed malaria related perceptions, care seeking behavior and anti-malarial drug use in malaria endemic settings of Ethiopia. Methods Data were generated from a community based cross-sectional study conducted among 798 households during January 2014 as part of a larger household behavioral study in three malaria endemic districts of Jimma Zone, Southwest Ethiopia. Both quantitative and qualitative data were collected and analyzed using SPSS 17.0 and STATA 12.0. Results In this study, only 76.1% of the respondents associated malaria to mosquito bite, and incorrect beliefs and perceptions were noted. Despite moderate level of knowledge (estimated mean = 62.2, Std Err = 0.7, 95% CI: 60.6–63.8%), quite high favorable attitude (overall estimated mean = 91.5, Std Err = 0.6, 95% CI: 90.1–92.9%) were recorded towards malaria preventive measures. The mean attitude score for prompt care seeking, appropriate use of anti-malarial drugs, LLIN use and Indoor Residual Spray acceptance was 98.5 (Std Err = 0.4, 95% CI:97.5–99.4), 92.7 (Std Err = 0.6 95% CI:91.5–93.9), 88.8 (Std Err = 0.5, 95% CI:85.5–92.1) and 86.5 (Std Err = 1.2, 95% CI: 83.9–89.1), respectively. The prevalence of fever was 2.9% (116/4107) and of the study participants with fever, 71.9% (95% CI: 65.5–78.3%) sought care and all of them consulted formal health care system. However, only 17 (19.8%) sought care within 24 hours after onset of fever. The frequency of care seeking was higher (77.8%, n = 21/27) and more prompt (28.6%, 6/21) for children under five as compared to old age groups despite it was not statistically significant (p > 0.05). However, higher median time of seeking first care was observed among Muslims and people who did not attend school (p < 0.05). Of those who used anti-malarial drugs, 9.1% indicated that they used it inappropriately through saving and/or sharing. Irregular availability of anti-malarial drugs; irregular presence of frontline health workers and misconceptions were mentioned to contribute to delayed care seeking and irrational use of anti-malarial drugs. Conclusions Although care seeking behavior for febrile illness was quite high in this community, the habit of prompt care seeking was very limited. Thus, malaria prevention and control programs need to take into account local misconceptions and wrong perceptions, and health system factors to achieve optimal health seeking behavior in such malaria endemic settings. PMID:27517717

[New concepts in hyperactive malarial splenomegaly].

PubMed

Moraes, M F; Soares, M; Arroz, M J; Do Rosário, V E; Da Graça, J Pimenta; Abecasis, P

2003-01-01

Hyperreactive malarial splenomegaly is thought to represent an immunological dysfunction due to recurrent episodes of malaria. The authors present a case of hyperreactive malarial splenomegaly in a patient from São Tomé e Príncipe and discuss aspects of its differential diagnosis and treatment. A revision is made of recent concepts related to its pathogenesis and relationship with lymphoproliferative disorders. Malarial DNA was found in the absence of parasite forms in the peripheral blood. This may indicate that latent infection plays a role in its pathogenesis.

Molecular characterization, biological forms and sporozoite rate of Anopheles stephensi in southern Iran

PubMed Central

Chavshin, Ali Reza; Oshaghi, Mohammad Ali; Vatandoost, Hasan; Hanafi-Bojd, Ahmad Ali; Raeisi, Ahmad; Nikpoor, Fatemeh

2014-01-01

Objective To identify the biological forms, sporozoite rate and molecular characterization of the Anopheles stephensi (An. stephensi) in Hormozgan and Sistan-Baluchistan provinces, the most important malarious areas in Iran. Methods Wild live An. stephensi samples were collected from different malarious areas in southern Iran. The biological forms were identified based on number of egg-ridges. Molecular characterization of biological forms was verified by analysis of the mitochondrial cytochrome oxidase subunit I and II (mtDNA-COI/COII). The Plasmodium infection was examined in the wild female specimens by species-specific nested–PCR method. Results Results showed that all three biological forms including mysorensis, intermediate and type are present in the study areas. Molecular investigations revealed no genetic variation between mtDNA COI/COII sequences of the biological forms and no Plasmodium parasites was detected in the collected mosquito samples. Conclusions Presence of three biological forms with identical sequences showed that the known biological forms belong to a single taxon and the various vectorial capacities reported for these forms are more likely corresponded to other epidemiological factors than to the morphotype of the populations. Lack of malaria parasite infection in An. stephensi, the most important vector of malaria, may be partly due to the success and achievement of ongoing active malaria control program in the region. PMID:24144130

Appropriateness of malaria diagnosis and treatment for fever episodes according to patient history and anti-malarial blood measurement: a cross-sectional survey from Tanzania.

PubMed

Gallay, Joanna; Mosha, Dominic; Lutahakana, Erick; Mazuguni, Festo; Zuakulu, Martin; Decosterd, Laurent Arthur; Genton, Blaise; Pothin, Emilie

2018-05-21

Monitoring the impact of case management strategies at large scale is essential to evaluate the public health benefit they confer. The use of methodologies relying on objective and standardized endpoints, such as drug levels in the blood, should be encouraged. Population drug use, diagnosis and treatment appropriateness in case of fever according to patient history and anti-malarials blood concentration was evaluated. A cross-sectional survey took place between May and August 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples were collected by dried blood spots through household surveys for further anti-malarial measurements. Appropriate testing when individuals attended care was defined as a patient with history of fever being tested for malaria and appropriate treatment as (i) having anti-malarial in the blood if the test result was positive (ii) having anti-malarial in the blood if the person was not tested, and (iii) no anti-malarial in the blood when the test result was negative. Amongst 6391 participants included in the anti-malarial analysis, 20.8% (1330/6391) had anti-malarial drug detected in the blood. Only 28.0% (372/1330) of the individuals with anti-malarials in their blood reported the use of anti-malarials within the previous month. Amongst all participants, 16.0% (1021/6391) reported having had a fever in the previous 2 weeks and 37.5% of them (383/1021) had detectable levels of anti-malarials in the blood. Of the individuals who sought care in health facilities, 69.4% (172/248) were tested and 52.0% (129/248) appropriately treated. When other providers were sought, 6% (23/382) of the persons were appropriately tested and 44.2% (169/382) appropriately treated. Overall, the proportion of individuals treated was larger than that being tested [47.3% (298/630) treated, 31.0% (195/630) tested]. This study showed high prevalence of circulating anti-malarial drug in the sampled population. Efforts should be made to increase rapid diagnostic tests use at all levels of health care and improve compliance to test result in order to target febrile patients that are sick with malaria and reduce drug pressure. Objective drug measurements collected at community level represent a reliable tool to evaluate overall impact of case management strategies on population drug pressure.

MALARIAL RETINOPATHY: A NEWLY ESTABLISHED DIAGNOSTIC SIGN IN SEVERE MALARIA

PubMed Central

BEARE, NICHOLAS A. V.; TAYLOR, TERRIE E.; HARDING, SIMON P.; LEWALLEN, SUSAN; MOLYNEUX, MALCOLM E.

2008-01-01

Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria. PMID:17123967

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

Malaria diagnosis and treatment under the strategy of the integrated management of childhood illness (IMCI): relevance of laboratory support from the rapid immunochromatographic tests of ICT Malaria P.f/P.v and OptiMal.

PubMed

Tarimo, D S; Minjas, J N; Bygbjerg, I C

2001-07-01

The algorithm developed for the integrated management of childhood illness (IMCI) provides guidelines for the treatment of paediatric malaria. In areas where malaria is endemic, for example, the IMCI strategy may indicate that children who present with fever, a recent history of fever and/or pallor should receive antimalarial chemotherapy. In many holo-endemic areas, it is unclear whether laboratory tests to confirm that such signs are the result of malaria would be very relevant or useful. Children from a holo-endemic region of Tanzania were therefore checked for malarial parasites by microscopy and by using two rapid immunochromatographic tests (RIT) for the diagnosis of malaria (ICT Malaria P.f/P.v and OptiMal. At the time they were tested, each of these children had been targeted for antimalarial treatment (following the IMCI strategy) because of fever and/or pallor. Only 70% of the 395 children classified to receive antimalarial drugs by the IMCI algorithm had malarial parasitaemias (68.4% had Plasmodium falciparum trophozoites, 1.3% only P. falciparum gametocytes, 0.3% P. ovale and 0.3% P. malariae). As indicators of P. falciparum trophozoites in the peripheral blood, fever had a sensitivity of 93.0% and a specificity of 15.5% whereas pallor had a sensitivity of 72.2% and a specificity of 50.8%. The RIT both had very high corresponding sensitivities (of 100.0% for the ICT and 94.0% for OptiMal) but the specificity of the ICT (74.0%) was significantly lower than that for OptiMal (100.0%). Fever and pallor were significantly associated with the P. falciparum asexual parasitaemias that equalled or exceeded the threshold intensity (2000/microl) that has the optimum sensitivity and specificity for the definition of a malarial episode. Diagnostic likelihood ratios (DLR) showed that a positive result in the OptiMal test (DLR = infinity) was a better indication of malaria than a positive result in the ICT (DLR = 3.85). In fact, OptiMal had diagnostic reliability (0.93) which approached that of an ideal test and, since it only detects live parasites, OptiMal is superior to the ICT in monitoring therapeutic responses. Although the RIT may seem attractive for use in primary health facilities because relatively inexperienced staff can perform them, the high cost of these tests is prohibitive. In holo-endemic areas, use of RIT or microscopical examination of bloodsmears may only be relevant when malaria needs to be excluded as a cause of illness (e.g. prior to treatment with toxic or expensive drugs, or during malaria epidemics). Wherever the effective drugs for the first-line treatment of malaria are cheap (e.g. chloroquine and Fansidar), treatment based on clinical diagnosis alone should prove cost-saving in health facilities without microscopy.

A case of hyper-reactive malarial splenomegaly. The role of rapid antigen-detecting and PCR-based tests.

PubMed

Mothe, B; Lopez-Contreras, J; Torres, O H; Muñoz, C; Domingo, P; Gurgui, M

2008-03-01

Hyper-reactive malarial splenomegaly (HMS) - originally referred to as tropical splenomegaly syndrome - is characterized by a massive splenomegaly, high titres of anti-malarial antibodies and polyclonal IgM hypergammaglobulinemia. It is believed to be a consequence of an aberrant immunological response to prolonged exposure to malarial parasites. Although it is a frequent disease in the tropics, it is infrequent in western countries and is only seen in long-term residents from endemic areas. We describe the case of a 67-year-old Spanish man, a missionary in Cameroon for 30 years, who presented with a clinical history that fulfilled the diagnosis of HMS. We discuss the role and importance of PCR-based techniques in demonstrating lowgrade malarial parasitemia and the usefulness of new rapid antigen-detecting dipstick tests.

Access to artemisinin-combination therapy (ACT) and other anti-malarials: national policy and markets in Sierra Leone.

PubMed

Amuasi, John H; Diap, Graciela; Nguah, Samuel Blay; Karikari, Patrick; Boakye, Isaac; Jambai, Amara; Lahai, Wani Kumba; Louie, Karly S; Kiechel, Jean-Rene

2012-01-01

Malaria remains the leading burden of disease in post-conflict Sierra Leone. To overcome the challenge of anti-malarial drug resistance and improve effective treatment, Sierra Leone adopted artemisinin-combination therapy artesunate-amodiaquine (AS+AQ) as first-line treatment for uncomplicated P. falciparum malaria. Other national policy anti-malarials include artemether-lumefantrine (AL) as an alternative to AS+AQ, quinine and artemether for treatment of complicated malaria; and sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp). This study was conducted to evaluate access to national policy recommended anti-malarials. A cross-sectional survey of 127 medicine outlets (public, private and NGO) was conducted in urban and rural areas. The availability on the day of the survey, median prices, and affordability policy and available non-policy anti-malarials were calculated. Anti-malarials were stocked in 79% of all outlets surveyed. AS+AQ was widely available in public medicine outlets; AL was only available in the private and NGO sectors. Quinine was available in nearly two-thirds of public and NGO outlets and over one-third of private outlets. SP was widely available in all outlets. Non-policy anti-malarials were predominantly available in the private outlets. AS+AQ in the public sector was widely offered for free. Among the anti-malarials sold at a cost, the same median price of a course of AS+AQ (US$1.56), quinine tablets (US$0.63), were found in both the public and private sectors. Quinine injection had a median cost of US$0.31 in the public sector and US$0.47 in the private sector, while SP had a median cost of US$0.31 in the public sector compared to US$ 0.63 in the private sector. Non-policy anti-malarials were more affordable than first-line AS+AQ in all sectors. A course of AS+AQ was affordable at nearly two days' worth of wages in both the public and private sectors.

Systematic review on traditional medicinal plants used for the treatment of malaria in Ethiopia: trends and perspectives.

PubMed

Alebie, Getachew; Urga, Befikadu; Worku, Amha

2017-08-01

Ethiopia is endowed with abundant medicinal plant resources and traditional medicinal practices. However, available research evidence on indigenous anti-malarial plants is highly fragmented in the country. The present systematic review attempted to explore, synthesize and compile ethno-medicinal research evidence on anti-malarial medicinal plants in Ethiopia. A systematic web search analysis and review was conducted on research literature pertaining to medicinal plants used for traditional malaria treatment in Ethiopia. Data were collected from a total of 82 Ethiopian studies meeting specific inclusion criteria including published research articles and unpublished thesis reports. SPSS Version 16 was used to summarize relevant ethno-botanical/medicinal information using descriptive statistics, frequency, percentage, tables, and bar graphs. A total of 200 different plant species (from 71 families) used for traditional malaria treatment were identified in different parts of Ethiopia. Distribution and usage pattern of anti-malarial plants showed substantial variability across different geographic settings. A higher diversity of anti-malarial plants was reported from western and southwestern parts of the country. Analysis of ethno-medicinal recipes indicated that mainly fresh leaves were used for preparation of remedies. Decoction, concoction and eating/chewing were found to be the most frequently employed herbal remedy preparation methods. Notably, anti-malarial herbal remedies were administered by oral route. Information on potential side effects of anti-malarial herbal preparations was patchy. However, some anti-malarial plants were reported to have potentially serious side effects using different local antidotes and some specific contra-indications. The study highlighted a rich diversity of indigenous anti-malarial medicinal plants with equally divergent herbal remedy preparation and use pattern in Ethiopia. Baseline information gaps were observed in key geographic settings. Likewise, herbal remedy toxicity risks and countermeasures generally entailed more exhaustive investigation. Experimental research and advanced chemical analysis are also required to validate the therapeutic potential of anti-malarial compounds from promising plant species.

Lead Optimization of Anti-Malarial Propafenone Analogs

PubMed Central

Lowes, David; Pradhan, Anupam; Iyer, Lalitha V.; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W. Armand; Sigal, Martina; Clark, Julie A.; Wilson, Emily; Tang, Liang; Connelly, Michele C.; DeRisi, Joseph L.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin

2015-01-01

Previously reported studies identified analogs of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are non-toxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges. PMID:22708838

Metabolic engineering of E.coli for the production of a precursor to artemisinin, an anti-malarial drug [Chapter 25 in Manual of Industrial Microbiology and Biotechnology, 3rd edition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petzold, Christopher; Keasling, Jay

This document is Chapter 25 in the Manual of Industrial Microbiology and Biotechnology, 3rd edition. Topics covered include: Incorporation of Amorpha-4,11-Diene Biosynthetic Pathway into E. coli; Amorpha-4,11-Diene Pathway Optimization; "-Omics" Analyses for Increased Amorpha-4,11-Diene Production; Biosynthetic Oxidation of Amorpha-4,11-Diene.

The impact of rapid malaria diagnostic tests upon anti-malarial sales in community pharmacies in Gwagwalada, Nigeria

PubMed Central

2013-01-01

Background Rapid diagnostics tests for malaria (RDT) have become established as a practical solution to the challenges of parasitological confirmation of malaria before treatment in the public sector. However, little is known of their impact in private health sector facilities, such as pharmacies and drug shops. This study aimed to assess the incidence of malaria among unwell patients seeking anti-malarial treatment in two community pharmacies in Nigeria and measure the impact RDTs have on anti-malarial sales. Methods This was a comparison study of two pharmacies located in the suburbs of Gwagwalada, in the Federal Capital Territory of Nigeria, between May and July 2012. In the intervention arm, patients seeking to purchase anti-malarials had an RDT performed before treatment while the control pharmacy continued normal routine practice. Results A total of 1,226 participants were enrolled into the study. The incidence of malaria in the intervention arm (n = 619) was 13.6% and adolescent participants had a statistically significant higher incidence (26.0%) compared to adults (11.9%) (P = 0.001). A history of fever in the last 48 hours was associated with a statistically significant higher incidence of malaria (28.3%) (P < 0.001). Having a RDT test reduced the chance of purchasing an anti-malarial by 42% (95% CI: 38%-46%) compared to not having a test. 51.6% (276) of the study participants with a RDT negative result still purchased anti-malarials, especially if anti-malarials had been recommended by a health professional (58.9%) compared to self-referral (44.2%) (P = 0.001). Patients with RDT negative results were also more likely to purchase an anti-malarial if there was a reported malaria positive laboratory test prior to presentation (66.2%; P = 0.007), a history of fever in the last 48 hours (60.5%; P = 0.027), and primary school education or less (69.4%; P = 0.009). After adjusting for age group and gender differences, having at least a secondary school education reduced the chance of buying an anti-malarial (OR 0.504 (95% CI: 0.256-0.993)) compared to having primary education or lower. Conclusion The study highlights the enormous potential for improving appropriate prescription of anti-malarials in pharmacies and preventing unnecessary use of artemisinin combination therapy (ACT). PMID:24172163

The impact of rapid malaria diagnostic tests upon anti-malarial sales in community pharmacies in Gwagwalada, Nigeria.

PubMed

Ikwuobe, John O; Faragher, Brian E; Alawode, Gafar; Lalloo, David G

2013-10-30

Rapid diagnostics tests for malaria (RDT) have become established as a practical solution to the challenges of parasitological confirmation of malaria before treatment in the public sector. However, little is known of their impact in private health sector facilities, such as pharmacies and drug shops. This study aimed to assess the incidence of malaria among unwell patients seeking anti-malarial treatment in two community pharmacies in Nigeria and measure the impact RDTs have on anti-malarial sales. This was a comparison study of two pharmacies located in the suburbs of Gwagwalada, in the Federal Capital Territory of Nigeria, between May and July 2012. In the intervention arm, patients seeking to purchase anti-malarials had an RDT performed before treatment while the control pharmacy continued normal routine practice. A total of 1,226 participants were enrolled into the study. The incidence of malaria in the intervention arm (n = 619) was 13.6% and adolescent participants had a statistically significant higher incidence (26.0%) compared to adults (11.9%) (P = 0.001). A history of fever in the last 48 hours was associated with a statistically significant higher incidence of malaria (28.3%) (P < 0.001). Having a RDT test reduced the chance of purchasing an anti-malarial by 42% (95% CI: 38%-46%) compared to not having a test. 51.6% (276) of the study participants with a RDT negative result still purchased anti-malarials, especially if anti-malarials had been recommended by a health professional (58.9%) compared to self-referral (44.2%) (P = 0.001). Patients with RDT negative results were also more likely to purchase an anti-malarial if there was a reported malaria positive laboratory test prior to presentation (66.2%; P = 0.007), a history of fever in the last 48 hours (60.5%; P = 0.027), and primary school education or less (69.4%; P = 0.009). After adjusting for age group and gender differences, having at least a secondary school education reduced the chance of buying an anti-malarial (OR 0.504 (95% CI: 0.256-0.993)) compared to having primary education or lower. The study highlights the enormous potential for improving appropriate prescription of anti-malarials in pharmacies and preventing unnecessary use of artemisinin combination therapy (ACT).

Maternal anaemia as an indicator for monitoring malaria control in pregnancy in sub-Saharan Africa.

PubMed

Savage, E J; Msyamboza, K; Gies, S; D'Alessandro, U; Brabin, B J

2007-10-01

Malarial anaemia is a major problem in many developing countries and often occurs more frequently in first pregnancies, as primigravidae are more susceptible to Plasmodium falciparum malaria and are at excess risk of malarial anaemia. To analyse the excess risk of anaemia in primigravidae as a potential indicator of malaria control and exposure in pregnant women living in sub-Saharan Africa. The sensitivity, specificity and predictive values for anaemia in first compared with later pregnancies are calculated for 27 studies from malarious and 7 studies from nonmalarious areas. Surveys of pregnancy anaemia reported for highly malarious and nonmalarious areas. In malarious areas, the weighted odds ratio for excess anaemia (haemoglobin [Hb] <11 g/dl) in primigravidae compared with multigravidae for all studies was 1.34 (95% CI 1.14-1.58). At an Hb cutoff below 8 g/dl, the weighted odds ratio was 1.79 (95% CI 1.52-2.10). In nonmalarious areas, there was no increased risk of anaemia in primigravidae with Hb below 11 g/dl (OR 0.80; 95% CI 0.63-1.90) or below 8 g/dl (OR 0.82, 95% CI 0.51-1.28). In view of the consistency of results across highly malarious areas compared with nonmalarious areas, maternal anaemia has the potential to be used for surveillance of malaria control in pregnancy. Based on the analysis, an anaemia nomogram is developed for use as a surveillance indicator in malarious areas in sub-Saharan Africa.

A qualitative assessment of the challenges of WHO prequalification for anti-malarial drugs in China.

PubMed

Huang, Yangmu; Pan, Ke; Peng, Danlu; Stergachis, Andy

2018-04-03

While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers. In-depth interviews were conducted in China between November 2014 and December 2016. A total of 26 key informants from central government agencies, pharmaceutical companies, universities, and research institutes were interviewed, all of which had current or previous experience overseeing or implementing anti-malarial research and development in China. Chinese anti-malarial drugs that lack WHO PQ are mainly exported for use in the African private market. High upfront costs with unpredictable benefits, as well as limited information and limited technical support on WHO PQ, were reported as the main barriers to obtain WHO PQ for anti-malarial drugs by respondents from Chinese pharmaceutical companies. Potential incentives identified by respondents included tax relief, human resource training and consultation, as well as other incentives related to drug approval, such as China's Fast Track Channel. Government support, as well as innovative incentives and collaboration mechanisms are needed for further adoption of WHO PQ for anti-malarial drugs in China.

A Novel ENU-Mutation in Ankyrin-1 Disrupts Malaria Parasite Maturation in Red Blood Cells of Mice

PubMed Central

Greth, Andreas; Lampkin, Shelley; Mayura-Guru, Preethi; Rodda, Fleur; Drysdale, Karen; Roberts-Thomson, Meredith; McMorran, Brendan J.; Foote, Simon J.; Burgio, Gaétan

2012-01-01

The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC) disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU) mutagenesis screen and have identified a novel dominant (haploinsufficient) mutation in the Ank-1 gene (Ank1MRI23420) of mice displaying hereditary spherocytosis (HS). Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt). A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6–8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05). We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites. PMID:22723917

Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach.

PubMed

Srinivasan, Venkataramanujam; Ahmad, Asma H; Mohamed, Mahaneem; Zakaria, Rahimah

2012-05-01

Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.

Determinants of price setting decisions on anti-malarial drugs at retail shops in Cambodia.

PubMed

Patouillard, Edith; Hanson, Kara; Kleinschmidt, Immo; Palafox, Benjamin; Tougher, Sarah; Pok, Sochea; O'Connell, Kate; Goodman, Catherine

2015-05-30

In many low-income countries, the private commercial sector plays an important role in the provision of malaria treatment. However, the quality of care it provides is often poor, with artemisinin combination therapy (ACT) generally being too costly for consumers. Decreasing ACT prices is critical for improving private sector treatment outcomes and reducing the spread of artemisinin resistance. Yet limited evidence exists on the factors influencing retailers' pricing decisions. This study investigates the determinants of price mark-ups on anti-malarial drugs in retail outlets in Cambodia. Taking an economics perspective, the study tests the hypothesis that the structure of the anti-malarial market determines the way providers set their prices. Providers facing weak competition are hypothesized to apply high mark-ups and set prices above the competitive level. To analyse the relationship between market competition and provider pricing, the study used cross-sectional data from retail outlets selling anti-malarial drugs, including outlet characteristics data (e.g. outlet type, anti-malarial sales volumes), range of anti-malarial drugs stocked (e.g. dosage form, brand status) and purchase and selling prices. Market concentration, a measure of the level of market competition, was estimated using sales volume data. Market accessibility was defined based on travel time to the closest main commercial area. Percent mark-ups were calculated using price data. The relationship between mark-ups and market concentration was explored using regression analysis. The anti-malarial market was on average highly concentrated, suggesting weak competition. Higher concentration was positively associated with higher mark-ups in moderately accessible markets only, with no significant relationship or a negative relationship in other markets. Other determinants of pricing included anti-malarial brand status and generic type, with higher mark-ups on cheaper products. The results indicate that provider pricing as well as other key elements of anti-malarial supply and demand may have played an important role in the limited access to appropriate malaria treatment in Cambodia. The potential for an ACT price subsidy at manufacturer level combined with effective communications directed at consumers and supportive private sector regulation should be explored to improve access to quality malaria treatment in Cambodia.

Tools for surveillance of anti-malarial drug resistance: an assessment of the current landscape.

PubMed

Nsanzabana, Christian; Djalle, Djibrine; Guérin, Philippe J; Ménard, Didier; González, Iveth J

2018-02-08

To limit the spread and impact of anti-malarial drug resistance and react accordingly, surveillance systems able to detect and track in real-time its emergence and spread need to be strengthened or in some places established. Currently, surveillance of anti-malarial drug resistance is done by any of three approaches: (1) in vivo studies to assess the efficacy of drugs in patients; (2) in vitro/ex vivo studies to evaluate parasite susceptibility to the drugs; and/or (3) molecular assays to detect validated gene mutations and/or gene copy number changes that are associated with drug resistance. These methods are complementary, as they evaluate different aspects of resistance; however, standardization of methods, especially for in vitro/ex vivo and molecular techniques, is lacking. The World Health Organization has developed a standard protocol for evaluating the efficacy of anti-malarial drugs, which is used by National Malaria Control Programmes to conduct their therapeutic efficacy studies. Regional networks, such as the East African Network for Monitoring Antimalarial Treatment and the Amazon Network for the Surveillance of Antimalarial Drug Resistance, have been set up to strengthen regional capacities for monitoring anti-malarial drug resistance. The Worldwide Antimalarial Resistance Network has been established to collate and provide global spatial and temporal trends information on the efficacy of anti-malarial drugs and resistance. While exchange of information across endemic countries is essential for monitoring anti-malarial resistance, sustainable funding for the surveillance and networking activities remains challenging. The technology landscape for molecular assays is progressing quite rapidly, and easy-to-use and affordable new techniques are becoming available. They also offer the advantage of high throughput analysis from a simple blood spots obtained from a finger prick. New technologies combined with the strengthening of national reference laboratories in malaria-endemic countries through standardized protocols and training plus the availability of a proficiency testing programme, would contribute to the improvement and sustainability of anti-malarial resistance surveillance networks worldwide.

Optimization of a New Cell-Based Fluorescence Assay for U.S. Army Global Malaria Surveillance Efforts in Support of the Warfighter

DTIC Science & Technology

2006-11-01

humans. Of these, Plasmodium falciparum is the most deadly. P . vivax, although it rarely causes death, is a constant annoyance and the leading...liver hepatocytes. Both P . vivax and P . falciparum have developed resistance to numerous antimalarial drugs, which has undermined the available...assay in our own laboratory. P . falciparum strains D6 and W2 were treated with a panel of known anti-malarial drugs and their respective IC50s were

The ACTwatch project: methods to describe anti-malarial markets in seven countries.

PubMed

Shewchuk, Tanya; O'Connell, Kathryn A; Goodman, Catherine; Hanson, Kara; Chapman, Steven; Chavasse, Desmond

2011-10-31

Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision-making. ACTwatch is a unique multi-country research project that threads together anti-malarial supply and consumer behaviour to provide an evidence base to policy makers that can help determine where interventions may positively impact access to and use of quality-assured ACT and RDTs. Because of its ability to detect change over time, it is well suited to monitor the effects of policy or intervention developments in a country.

The ACTwatch project: methods to describe anti-malarial markets in seven countries

PubMed Central

2011-01-01

Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision-making. Conclusions ACTwatch is a unique multi-country research project that threads together anti-malarial supply and consumer behaviour to provide an evidence base to policy makers that can help determine where interventions may positively impact access to and use of quality-assured ACT and RDTs. Because of its ability to detect change over time, it is well suited to monitor the effects of policy or intervention developments in a country. PMID:22039780

Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi.

PubMed

Amuasi, John H; Diap, Graciela; Blay-Nguah, Samuel; Boakye, Isaac; Karikari, Patrick E; Dismas, Baza; Karenzo, Jeanne; Nsabiyumva, Lievin; Louie, Karly S; Kiechel, Jean-René

2011-02-10

Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ) as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO) retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO), a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO) medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment) of AS-AQ, quinine and other anti-malarials were calculated. Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9%) compared to public (4.2%) and NGO (0%) outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu) for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu). Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu), private and NGO sectors (both US$1.61 or 2,000 FBu). Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors, whereas, it was equivalent to 1.5 days worth of wages in the private sector. AS-AQ was widely available and affordable in the public and NGO markets of hard-to-reach post-conflict communities in Burundi. However greater accessibility and affordability of policy recommended anti-malarials in the private market sector is needed to improve country-wide policy uptake.

Early hyperreactive malarial splenomegaly and risk factors for evolution into the full-blown syndrome: a single-centre, retrospective, longitudinal study.

PubMed

Bisoffi, Zeno; Leoni, Stefania; Buonfrate, Dora; Lodesani, Claudia; Eseme, Franklin Esoka; Monteiro, Geraldo Badona; Marocco, Stefania; Guerriero, Massimo

2015-12-02

The hyperreactive malarial splenomegaly (HMS) represents a chronic, potentially fatal complication of malaria. Case definition includes: gross splenomegaly, high level of anti-malarial antibody and IgM, response to long-term anti-malarial prophylaxis. In this study, a large series of patients not fully meeting the case definition was tentatively classified as early hyperreactive malarial splenomegaly (e-HMS). The main research questions was: does "e-HMS" tend to evolve to the full-blown syndrome? And if so, what are the main factors influencing this evolution? Retrospective, longitudinal study. The patient database was searched to retrieve all potentially eligible patients. e-HMS was defined by splenomegaly of any size (with or without raised IgM), high anti-malarial antibody titre and exclusion of other causes of splenomegaly. The clinical outcome at following visits was analysed in relation to re-exposure to malaria, and to treatment (only part of the patients with e-HMS were treated with a single anti-malarial treatment and advised to follow an effective anti-malarial prophylaxis, if re-exposed). The association of the outcome with the main independent variables was first assessed with univariate analysis. A stepwise logistic regression model was then performed to study the association of the outcome with the main independent variables. One hundred and twenty-six subjects with e-HMS were retrieved. Eighty-one had at least one follow-up visit. Of 46 re-exposed to malaria for a variable period, 21 (46 %) had progressed, including 10/46 (22 %) evolving to full-blown HMS, while of 29 patients not re-exposed, 24 (93 %) had improved or cured and five (7 %) progressed (p < 0.001). At logistic regression re-exposure was confirmed as a major risk factor of progression (OR 9.458, CI 1.767-50.616) while treatment at initial visit was protective (OR 0.187, CI 0.054-0.650). e-HMS should be regarded as a clinical condition predisposing to HMS. Although the case definition may include false positives, e-HMS should be treated just as the full-blown syndrome. A single anti-malarial treatment is probably adequate, followed by effective prophylaxis for patients exposed again to malaria transmission.

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa.

PubMed

Kayano, Ana Carolina A V; Lopes, Stefanie C P; Bueno, Fernanda G; Cabral, Elaine C; Souza-Neiras, Wanessa C; Yamauchi, Lucy M; Foglio, Mary A; Eberlin, Marcos N; Mello, João Carlos P; Costa, Fabio T M

2011-05-02

To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

PubMed Central

2011-01-01

Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4. PMID:21535894

Benzoxazine derivatives of phytophenols show anti-plasmodial activity via sodium homeostasis disruption.

PubMed

Sharma, Vijeta; Amarnath, Nagarjuna; Shukla, Swapnil; Ayana, R; Kumar, Naveen; Yadav, Nisha; Kannan, Deepika; Sehrawat, Seema; Pati, Soumya; Lochab, Bimlesh; Singh, Shailja

2018-05-15

Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na + levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490 nM from 17.54 µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds

PubMed Central

2014-01-01

Background Tafenoquine (TQ) is an 8-aminoquinoline (8AQ) that has been tested in several Phase II and Phase III clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. NPC-1161B is a promising 8AQ in late preclinical development. It has recently been reported that the 8AQ drug primaquine requires metabolic activation by CYP 2D6 for efficacy in humans and in mice, highlighting the importance of pharmacogenomics in the target population when administering primaquine. A logical follow-up study was to determine whether CYP 2D activation is required for other compounds in the 8AQ structural class. Methods In the present study, the anti-malarial activities of NPC-1161B and TQ were assessed against luciferase expressing Plasmodium berghei in CYP 2D knock-out mice in comparison with normal C57BL/6 mice (WT) and with humanized/CYP 2D6 knock-in mice by monitoring luminescence with an in vivo imaging system. These experiments were designed to determine the direct effects of CYP 2D metabolic activation on the anti-malarial efficacy of NPC-1161B and TQ. Results NPC-1161B and TQ exhibited no anti-malarial activity in CYP 2D knock-out mice when dosed at their ED100 values (1 mg/kg and 3 mg/kg, respectively) established in WT mice. TQ anti-malarial activity was partially restored in humanized/CYP 2D6 knock-in mice when tested at two times its ED100. Conclusions The results reported here strongly suggest that metabolism of NPC-1161B and TQ by the CYP 2D enzyme class is essential for their anti-malarial activity. Furthermore, these results may provide a possible explanation for therapeutic failures for patients who do not respond to 8AQ treatment for relapsing malaria. Because CYP 2D6 is highly polymorphic, variable expression of this enzyme in humans represents a significant pharmacogenomic liability for 8AQs which require CYP 2D metabolic activation for efficacy, particularly for large-scale prophylaxis and eradication campaigns. PMID:24386891

Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds.

PubMed

Marcsisin, Sean R; Sousa, Jason C; Reichard, Gregory A; Caridha, Diana; Zeng, Qiang; Roncal, Norma; McNulty, Ronan; Careagabarja, Julio; Sciotti, Richard J; Bennett, Jason W; Zottig, Victor E; Deye, Gregory; Li, Qigui; Read, Lisa; Hickman, Mark; Dhammika Nanayakkara, N P; Walker, Larry A; Smith, Bryan; Melendez, Victor; Pybus, Brandon S

2014-01-03

Tafenoquine (TQ) is an 8-aminoquinoline (8AQ) that has been tested in several Phase II and Phase III clinical studies and is currently in late stage development as an anti-malarial prophylactic agent. NPC-1161B is a promising 8AQ in late preclinical development. It has recently been reported that the 8AQ drug primaquine requires metabolic activation by CYP 2D6 for efficacy in humans and in mice, highlighting the importance of pharmacogenomics in the target population when administering primaquine. A logical follow-up study was to determine whether CYP 2D activation is required for other compounds in the 8AQ structural class. In the present study, the anti-malarial activities of NPC-1161B and TQ were assessed against luciferase expressing Plasmodium berghei in CYP 2D knock-out mice in comparison with normal C57BL/6 mice (WT) and with humanized/CYP 2D6 knock-in mice by monitoring luminescence with an in vivo imaging system. These experiments were designed to determine the direct effects of CYP 2D metabolic activation on the anti-malarial efficacy of NPC-1161B and TQ. NPC-1161B and TQ exhibited no anti-malarial activity in CYP 2D knock-out mice when dosed at their ED100 values (1 mg/kg and 3 mg/kg, respectively) established in WT mice. TQ anti-malarial activity was partially restored in humanized/CYP 2D6 knock-in mice when tested at two times its ED100. The results reported here strongly suggest that metabolism of NPC-1161B and TQ by the CYP 2D enzyme class is essential for their anti-malarial activity. Furthermore, these results may provide a possible explanation for therapeutic failures for patients who do not respond to 8AQ treatment for relapsing malaria. Because CYP 2D6 is highly polymorphic, variable expression of this enzyme in humans represents a significant pharmacogenomic liability for 8AQs which require CYP 2D metabolic activation for efficacy, particularly for large-scale prophylaxis and eradication campaigns.

Prevalence and risk factors of Plasmodium falciparum infections in pregnant women of Luanda, Angola.

PubMed

Valente, Bianor; Campos, Paulo A; do Rosário, Virgílio E; Varandas, Luis; Silveira, Henrique

2011-10-01

Pregnant women are at increased risk of malaria, but in Angola, epidemiologic data from this group is almost inexistent. We conducted a cross-sectional study to determine the prevalence and risk factors of Plasmodium falciparum infections in 567 pregnant Angolan women living in Luanda province. One in five women had P. falciparum at delivery, diagnosed by PCR assay. Age, residence and history of malaria during pregnancy were significantly associated with P. falciparum infection, but gravidity and use of anti-malarial drugs were not. Placental infections were significantly more common in women ≤18 years old and in primigravidae, but we could not correlate placental infections with poor pregnancy outcomes. These findings are relevant to malaria control policies in Luanda, Angola. © 2011 Blackwell Publishing Ltd.

Malaria ecology and climate change

NASA Astrophysics Data System (ADS)

McCord, G. C.

2016-05-01

Understanding the costs that climate change will exact on society is crucial to devising an appropriate policy response. One of the channels through while climate change will affect human society is through vector-borne diseases whose epidemiology is conditioned by ambient ecology. This paper introduces the literature on malaria, its cost on society, and the consequences of climate change to the physics community in hopes of inspiring synergistic research in the area of climate change and health. It then demonstrates the use of one ecological indicator of malaria suitability to provide an order-of-magnitude assessment of how climate change might affect the malaria burden. The average of Global Circulation Model end-of-century predictions implies a 47% average increase in the basic reproduction number of the disease in today's malarious areas, significantly complicating malaria elimination efforts.

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

PubMed Central

2011-01-01

Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed. Results Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. Conclusions Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems. PMID:22152094

Screening of Anti-Malarial Activity of Different Extracts Obtained from Three Species of Scrophularia Growing in Iran

PubMed Central

Heshmati Afshar, Fariba; Delazar, Abbas; Asnaashari, Solmaz; Vaez, Haleh; Zolali, Elmira; Asgharian, Parina

2018-01-01

Scrophularia genus belonging to the family of Scrophulariaceae, is a medicinal plant widely distributed in Iran. In the present study, the anti-malarial activity of different extracts of three Iranian endemic species of Scrophularia including S. frigida, S. subaphylla and S. atropatana, was screened by an in-vitro preliminary assay. The plant materials were extracted successively with n-hexane, dichloromethane (DCM), and methanol (MeOH) at room temperature by soxhlet extractor. In order to assess anti-malarial activity of obtained extracts, cell free β-hematin formation assay was applied. Amongst the extracts, DCM extract of S. frigida exhibited remarkable anti-malarial activity with IC50 value of 0.67 ± 0.11 mg/mL. In contrast, MeOH and n-hexane extracts of all plants illustrated insignificant or moderate activity in this assay. Furthermore, preliminary phytochemical analysis along with TLC and GC-MS analysis of potent extract (DCM extract of S. frigida) were performed for more clarification. These methods revealed that the notable anti-malarial activity might be due to the presence of active constituents like methoxylated flavonoids, methylated coumarins, and diterpenoids. From the nine extracts of different species of Scrophularia, DCM extract of S. frigida showed potent inhibitory activity on β-hematin formation assay. Hence, it seems that it is noteworthy to concentrate on purifying the active chemical constituents of DCM extract and determining the pure anti-malarial components. PMID:29881424

Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

PubMed Central

2010-01-01

Background Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart. Methods The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects. Results Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC50 values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine. Conclusions In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity. PMID:21067575

New molecular settings to support in vivo anti-malarial assays.

PubMed

Bahamontes-Rosa, Noemí; Alejandre, Ane Rodriguez; Gomez, Vanesa; Viera, Sara; Gomez-Lorenzo, María G; Sanz-Alonso, Laura María; Mendoza-Losana, Alfonso

2016-03-08

Quantitative real-time PCR (qPCR) is now commonly used as a method to confirm diagnosis of malaria and to differentiate recrudescence from re-infection, especially in clinical trials and in reference laboratories where precise quantification is critical. Although anti-malarial drug discovery is based on in vivo murine efficacy models, use of molecular analysis has been limited. The aim of this study was to develop qPCR as a valid methodology to support pre-clinical anti-malarial models by using filter papers to maintain material for qPCR and to compare this with traditional methods. FTA technology (Whatman) is a rapid and safe method for extracting nucleic acids from blood. Peripheral blood samples from mice infected with Plasmodium berghei, P. yoelii, or P. falciparum were kept as frozen samples or as spots on FTA cards. The extracted genetic material from both types of samples was assessed for quantification by qPCR using sets of specific primers specifically designed for Plasmodium 18S rRNA, LDH, and CytB genes. The optimal conditions for nucleic acid extraction from FTA cards and qPCR amplification were set up, and were confirmed to be suitable for parasite quantification using DNA as template after storage at room temperature for as long as 26 months in the case of P. berghei samples and 52 months for P. falciparum and P. yoelii. The quality of DNA extracted from the FTA cards for gene sequencing and microsatellite amplification was also assessed. This is the first study to report the suitability of FTA cards and qPCR assay to quantify parasite load in samples from in vivo efficacy models to support the drug discovery process.

The educative impact of health care treatment on malarial prevention behavior for the poor in Guinea, West Africa

PubMed Central

McFadden, Daniel L.; Sunkara, Vasu

2004-01-01

We analyze the malarial health behavior of rural populations by using data from the 1999 Demographic and Health Survey for Guinea, West Africa. We find that prior formal health care treatment is associated with heightened malaria prevention behaviors for the poorest uneducated populations in this rural cohort. Individuals from this subgroup that report no history of malarial infection and exclude themselves from health care treatment further appear to be misdiagnosing the disease at a substantial level. We conjecture that the use of formal health care options provides informational exposure to the clinical aspects of malarial pathogenesis. For individuals steeped in the most severe poverty, this exposure appears to have a particularly robust educative effect. The health behavioral dynamics we observe here have putative extensions for regional health policy as well with other infectious diseases, such as HIV/AIDS. PMID:15277676

The Usefulness of Rapid Diagnostic Tests in the New Context of Low Malaria Transmission in Zanzibar

PubMed Central

Shakely, Delér; Msellem, Mwinyi I.; Morris, Ulrika; Omar, Rahila; Weiping, Xu; Petzold, Max; Greenhouse, Bryan; Baltzell, Kimberly A.; Ali, Abdullah S.; Björkman, Anders; Mårtensson, Andreas

2013-01-01

Background We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar. Methods and Findings We enrolled 3890 patients aged ≥2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5–14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0–83.9%) and 99.9% (95% CI 99.7–100%), and against blood smear microscopy 78.6% (95% CI 70.8–85.1%) and 99.7% (95% CI 99.6–99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children <5 years as compared with other age groups. Conclusions The sensitivity of HRP-2 based RDT in the hands of health care workers compared with both PCR and microscopy for P. falciparum case detection was relatively low, whereas adherence to test results with anti-malarial treatment was excellent. Moreover, the results provide evidence that RDT can be reliably integrated in IMCI as a tool for improved childhood fever management. However, the relatively low RDT sensitivity highlights the need for improved quality control of RDT use in primary health care facilities, but also for more sensitive point-of-care malaria diagnostic tools in the new epidemiological context of low malaria transmission in Zanzibar. Trial registration ClinicalTrials.gov NCT01002066 PMID:24023791

Multiple e-pharmacophore modelling pooled with high-throughput virtual screening, docking and molecular dynamics simulations to discover potential inhibitors of Plasmodium falciparum lactate dehydrogenase (PfLDH).

PubMed

Saxena, Shalini; Durgam, Laxman; Guruprasad, Lalitha

2018-05-14

Development of new antimalarial drugs continues to be of huge importance because of the resistance of malarial parasite towards currently used drugs. Due to the reliance of parasite on glycolysis for energy generation, glycolytic enzymes have played important role as potential targets for the development of new drugs. Plasmodium falciparum lactate dehydrogenase (PfLDH) is a key enzyme for energy generation of malarial parasites and is considered to be a potential antimalarial target. Presently, there are nearly 15 crystal structures bound with inhibitors and substrate that are available in the protein data bank (PDB). In the present work, we attempted to consider multiple crystal structures with bound inhibitors showing affinity in the range of 1.4 × 10 2 -1.3 × 10 6  nM efficacy and optimized the pharmacophore based on the energy involved in binding termed as e-pharmacophore mapping. A high throughput virtual screening (HTVS) combined with molecular docking, ADME predictions and molecular dynamics simulation led to the identification of 20 potential compounds which could be further developed as novel inhibitors for PfLDH.

Why do health workers give anti-malarials to patients with negative rapid test results? A qualitative study at rural health facilities in western Uganda.

PubMed

Altaras, Robin; Nuwa, Anthony; Agaba, Bosco; Streat, Elizabeth; Tibenderana, James K; Strachan, Clare E

2016-01-11

The large-scale introduction of malaria rapid diagnostic tests (RDTs) promises to improve management of fever patients and the rational use of valuable anti-malarials. However, evidence on the impact of RDT introduction on the overprescription of anti-malarials has been mixed. This study explored determinants of provider decision-making to prescribe anti-malarials following a negative RDT result. A qualitative study was conducted in a rural district in mid-western Uganda in 2011, ten months after RDT introduction. Prescriptions for all patients with negative RDT results were first audited from outpatient registers for a two month period at all facilities using RDTs (n = 30). Facilities were then ranked according to overall prescribing performance, defined as the proportion of patients with a negative RDT result prescribed any anti-malarial. Positive and negative deviant facilities were sampled for qualitative investigation; positive deviants (n = 5) were defined ex post facto as <0.75% and negative deviants (n = 7) as >5%. All prescribing clinicians were targeted for qualitative observation and in-depth interview; 55 fever cases were observed and 22 providers interviewed. Thematic analysis followed the 'framework' approach. 8344 RDT-negative patients were recorded at the 30 facilities (prescription audit); 339 (4.06%) were prescribed an anti-malarial. Of the 55 observed patients, 38 tested negative; one of these was prescribed an anti-malarial. Treatment decision-making was influenced by providers' clinical beliefs, capacity constraints, and perception of patient demands. Although providers generally trusted the accuracy of RDTs, anti-malarial prescription was driven by perceptions of treatment failure or undetectable malaria in patients who had already taken artemisinin-based combination therapy prior to facility arrival. Patient assessment and other diagnostic practices were minimal and providers demonstrated limited ability to identify alternative causes of fever. Provider perceptions of patient expectations sometimes appeared to influence treatment decisions. The study found high provider adherence to RDT results, but that providers believed in certain clinical exceptions and felt they lacked alternative options. Guidance on how the RDT works and testing following partial treatment, better methods for assisting providers in diagnostic decision-making, and a context-appropriate provider behaviour change intervention package are needed.

Epidemiology and pathology of avian malaria in penguins undergoing rehabilitation in Brazil.

PubMed

Vanstreels, Ralph Eric Thijl; da Silva-Filho, Rodolfo Pinho; Kolesnikovas, Cristiane Kiyomi Miyaji; Bhering, Renata Cristina Campos; Ruoppolo, Valeria; Epiphanio, Sabrina; Amaku, Marcos; Ferreira Junior, Francisco Carlos; Braga, Érika Martins; Catão-Dias, José Luiz

2015-03-13

Seabird rehabilitation is a valuable strategy to mitigate the impacts of oil pollution and other anthropogenic factors, and can significantly contribute to the conservation of penguins. However, infectious diseases such as avian malaria (Plasmodium spp.) can hamper the success of rehabilitation efforts. We combined morphological and molecular diagnostic methods to investigate the epidemiology and pathology of Plasmodium in Magellanic penguins (Spheniscus magellanicus) at rehabilitation centers along 2500 km of the coastline of Brazil. True prevalence of malarial parasites was estimated between 6.6% and 13.5%. We identified five species, three of which had not been described infecting penguins (P. cathemerium, P. nucleophilum, P. unalis); an additional five distinct Plasmodium lineages were also distinguished, and albeit unidentified these clearly correspond to species that also have not yet been reported in penguins. Our results indicate that the diversity of plasmodia that may infect these birds is greater than previously recognised. Considering the well-defined seasonality observed in this study, it is clear that rehabilitation centers could benefit by narrowing their preventative efforts on penguins maintained or admitted during the Austral spring-summer, particularly by preventing mosquitoes from coming into contact with penguins.

Hyperreactive malarial splenomegaly in Venezuela.

PubMed

Torres, J; Noya, O; Mondolfi, A; Peceño, C; Botto, C

1988-07-01

A cross-sectional seroepidemiological survey seeking hyperreactive malarial splenomegaly was carried out in isolated Yanomami hamlets in Amazonas Territory in Venezuela. All 110 inhabitants greater than 1 year of age were evaluated clinically and 98 were studied immunologically. The spleen index for individuals greater than 10 years of age was 44%. Only 3 patients had Plasmodium spp. on thick blood smears. All had serological evidence of infection with Plasmodium falciparum and P. vivax. Twenty-three patients were considered to show hyperreactive malarial splenomegaly. Clinical manifestations of the syndrome did not differ from those described in other parts of the world.

Synthesis and exploration of novel curcumin analogues as anti-malarial agents.

PubMed

Mishra, Satyendra; Karmodiya, Krishanpal; Surolia, Namita; Surolia, Avadhesha

2008-03-15

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC(50) of approximately 3.25 microM (MIC=13.2 microM) and IC(50) 4.21 microM (MIC=14.4 microM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC(50) of 0.48, 0.87, 0.92 microM and CQ-R P. falciparum at IC(50) of 0.45 microM, 0.89, 0.75 microM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.

Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study.

PubMed

Talisuna, Ambrose O; Daumerie, Penny Grewal; Balyeku, Andrew; Egan, Timothy; Piot, Bram; Coghlan, Renia; Lugand, Maud; Bwire, Godfrey; Rwakimari, John Bosco; Ndyomugyenyi, Richard; Kato, Fred; Byangire, Maria; Kagwa, Paul; Sebisubi, Fred; Nahamya, David; Bonabana, Angela; Mpanga-Mukasa, Susan; Buyungo, Peter; Lukwago, Julius; Batte, Allan; Nakanwagi, Grace; Tibenderana, James; Nayer, Kinny; Reddy, Kishore; Dokwal, Nilesh; Rugumambaju, Sylvester; Kidde, Saul; Banerji, Jaya; Jagoe, George

2012-10-29

Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Four intervention districts were purposefully selected to receive branded subsidized medicines - "ACT with a leaf", while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention's impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, "ACT with a leaf" accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p<0.0001) at evaluation. Children less than five years of age had "ACT with a leaf" purchased for them more often than those aged above five years. There was no evidence of price gouging. These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda.

Stated preferences for anti-malarial drug characteristics in Zomba, a malaria endemic area of Malawi

PubMed Central

2014-01-01

Background The evidence on determinants of individuals’ choices for anti-malarial drug treatments is scarce. This study sought to measure the strength of preference for adult antimalarial drug treatment attributes of heads of urban, rural and peri-urban households in a resource-limited malaria-endemic area of sub-Saharan Africa. Methods Discrete choice experiments were conducted with 508 heads of household interviewed face-to-face for a household population survey of health-seeking behavior in Zomba District, Malawi. The interviews were held in Chichewa and the choice experiment questions were presented with cartoon aids. The anti-malarial drug attributes included in the stated preference experiment were: speed of fever resolution, side effects (pruritus) risk, protection (duration of prophylactic effect), price, duration of treatment course and recommendation by a health professional. Sixteen treatment profiles from a fractional factorial design by orthogonal array were paired into choice scenarios, and scenarios were randomly assigned to participants so that each participant was presented with a series of eight pairwise choice scenarios. Respondents had the option to state indifference between the two profiles or decline to choose. Data were analysed in a mixed logit model, with normally distributed coefficients for all six attributes. Results The sex ratio was balanced in urban areas, whereas 63% of participants in rural areas were male. The proportion of individuals with no education was considerably higher in the rural group (25%) than in the urban (5%) and peri-urban (6%) groups. All attributes investigated had the expected influence, and traded-off in most respondents’ choices. There were heterogeneous effects of price, pruritus risk, treatment recommendation by a professional, and duration of prophylaxis across respondents, only partly explained by their differences in education, household per capita expenditure, sex and age. Individuals´ demand elasticity (simulated median, inter-quartile range) was highest (most responsive) to speed of symptom resolution (0.88, 0.80-0.89) and pruritus risk (0.25, 0.08-0.62). Conclusions Most adult antimalarial users are willing to use treatments without recommendation from health professional, and may be influenced by price. Future studies should investigate the magnitude of differences in price and treatment attribute sensitivity between adult anti-malarial drug users in rural, peri-urban and urban areas in order to determine optimal price subsidies. PMID:25005466

Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study

PubMed Central

2012-01-01

Background Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p<0.0001) at evaluation. Children less than five years of age had “ACT with a leaf” purchased for them more often than those aged above five years. There was no evidence of price gouging. Conclusions These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda. PMID:23107021

Hemozoin (Malarial Pigment) Directly Promotes Apoptosis of Erythroid Precursors

PubMed Central

Lamikanra, Abigail A.; Theron, Michel; Kooij, Taco W. A.; Roberts, David J.

2009-01-01

Severe malarial anemia is the most common syndrome of severe malaria in endemic areas. The pathophysiology of chronic malaria is characterised by a striking degree of abnormal development of erythroid precursors (dyserythropoiesis) and an inadequate erythropoietic response in spite of elevated levels of erythropoietin. The cause of dyserythropoiesis is unclear although it has been suggested that bone-marrow macrophages release cytokines, chemokines or lipo-peroxides after exposure to hemozoin, a crystalloid form of undigested heme moieties from malarial infected erythrocytes, and so inhibit erythropoiesis. However, we have previously shown that hemozoin may directly inhibit erythroid development in vitro and the levels of hemozoin in plasma from patients with malarial anemia and hemozoin within the bone marrow was associated with reduced reticulocyte response. We hypothesized that macrophages may reduce, not enhance, the inhibitory effect of hemozoin on erythropoiesis. In an in vitro model of erythropoiesis, we now show that inhibition of erythroid cell development by hemozoin isolated from P. falciparum is characterised by delayed expression of the erythroid markers and increased apoptosis of progenitor cells. Crucially, macrophages appear to protect erythroid cells from hemozoin, consistent with a direct contribution of hemozoin to the depression of reticulocyte output from the bone marrow in children with malarial anemia. Moreover, hemozoin isolated from P. falciparum in vitro inhibits erythroid development independently of inflammatory mediators by inducing apoptotic pathways that not only involve activation of caspase 8 and cleavage of caspase 3 but also loss of mitochondrial potential. Taken together these data are consistent with a direct effect of hemozoin in inducing apoptosis in developing erythroid cells in malarial anemia. Accumulation of hemozoin in the bone marrow could therefore result in inadequate reticulocytosis in children that have adequate levels of circulating erythropoietin. PMID:20041181

Social and cultural complexities of anti-malarial drug circulation: an ethnographic investigation in three rural remote communes of Cambodia.

PubMed

Res, Phasy

2017-10-25

Anti-malarial medicine has a central role in malaria case management in Cambodia. It is, therefore, essential to study how anti-malarial drugs are distributed and consumed. This study aims to understand the socio-cultural complexity of anti-malarial drugs provision and usage practices. Semi-structured interviews and observation were conducted in Cambodia at the communal, provincial, and national levels from January 2014 to January 2015. Health ministers, non-governmental officers, anti-malarial medicines distributors, village malaria volunteers and malaria patients were interviewed. The findings show that artemisinin-based combination therapy (ACT) flows into unregulated outlets, and was sold without any diagnostic tests. Affordable Medicines Facility for malaria scheme (AMFm) cannot drive ineffective anti-malarial medicines out of the market because ACT is still more expensive due to price absortion by private and public providers. Malaria patients might not consume ACT because of patients' notions of 'Korp', and pharmaceutical and parasitic familiarity. The findings reflect that neither public nor private institutions have the capacity and resources to control the flow of ACT from going into the unlicensed sector. They do not have the ability to ensure that ACT is consumed after a positive rapid diagnostic test. With a weak regulation system and ailing public health infrastructure, pharmaceutical-neoliberal mechanism like AMFm is not an effective means to eradicate any forms of malaria. Therefore, horizontal programmes, such as public health infrastructure improvement, and population participation must be implemented. Ethnical responsibilities of medical practitioners must be enforced and be included into the national curriculum. The awareness of drug resistance must be implemented at all levels.

Detection of falciparum malarial forms in naturally infected anophelines in Cameroon using a fluorescent anti-25-kD monoclonal antibody.

PubMed

Robert, V; Le Goff, G; Essong, J; Tchuinkam, T; Faas, B; Verhave, J P

1995-04-01

Anopheles gambiae s.s. and An. funestus were sampled in houses located in a Plasmodium falciparum-holoendemic site in southern Cameroon. The midguts of female mosquitoes in half-gravid or gravid stages of blood digestion were incubated with a fluorescent monoclonal antibody directed against the P. falciparum zygote/ookinete surface protein Pfs25 and examined using a fluorescent light microscope. Malarial forms were detected in 11.6% of the half-gravid mosquitoes and in 0.0% of the gravid ones (P = 0.012). No difference in infections or the occurrence of malarial forms between An. gambiae and An. funestus was observed. Overall, 127 malarial forms were counted and distributed among round forms, retorts, and ookinetes in 77.2%, 9.5%, and 13.4%, respectively. Round forms include macrogametes, activating microgametocytes, and zygotes. The mean number of malarial forms per infected midgut was 2.16 and the maximum number observed was 13. In four anophelines, round forms, retorts, and ookinetes were simultaneously observed. Sporozoite rates were 5.7% for An. gambiae and 3.8% for An. funestus. In the human population, the gametocyte index for P. falciparum was 38% with a mean density of 1.11 gametocytes per microliter of blood. Differences concerning malarial forms in mosquito midguts were observed between houses (range percentage = 4.7--21.3%; mean range of forms per positive anopheline = 1.1--3.1). In each house, relationships existed between infected vectors and the gametocyte reservoir of their inhabitants. The role in transmission of people with very low gametocytemia, approximately one per microliter, as a reservoir of falciparum malaria in highly endemic areas, is emphasized.

CRIMALDDI: a co-ordinated, rational, and integrated effort to set logical priorities in anti-malarial drug discovery initiatives

PubMed Central

2010-01-01

Despite increasing efforts and support for anti-malarial drug R&D, globally anti-malarial drug discovery and development remains largely uncoordinated and fragmented. The current window of opportunity for large scale funding of R&D into malaria is likely to narrow in the coming decade due to a contraction in available resources caused by the current economic difficulties and new priorities (e.g. climate change). It is, therefore, essential that stakeholders are given well-articulated action plans and priorities to guide judgments on where resources can be best targeted. The CRIMALDDI Consortium (a European Union funded initiative) has been set up to develop, through a process of stakeholder and expert consultations, such priorities and recommendations to address them. It is hoped that the recommendations will help to guide the priorities of the European anti-malarial research as well as the wider global discovery agenda in the coming decade. PMID:20626844

Lizards infected with malaria: physiological and behavioral consequences.

PubMed

Schall, J J

1982-09-10

In northern California, western fence lizards, Sceloporus occidentalis, are frequently parasitized by Plasmodium mexicanum, which causes malaria. Animals with this naturally occurring malarial infection are anemic: immature erythrocytes in peripheral blood become abundant (1 to 30 percent), and blood hemoglobin concentration decreases 25 percent. Maximal oxygen consumption decreases 15 percent and aerobic scope drops 29 percent in infected lizards; both correlate with blood hemoglobin concentration. Running stamina, but not burst running speed, is reduced in malarious lizards. There is a hierarchical relation between infection with malaria and effects on hematology, physiological function, and behavioral capacity. The results suggest that malarial infection may have significant effects on the ecology of lizard hosts.

Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.

PubMed

Monatrakul, Preeyaporn; Mungthin, Mathirut; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Wilairatana, Polrat; White, Nicholas J; Chotivanich, Kesinee

2010-11-16

The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake. Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4). 'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent in vitro anti-malarial drug susceptibility of P. falciparum. The IC90 was much less affected than the IC50 measurement.

In vitro activity of anti-malarial ozonides against an artemisinin-resistant isolate.

PubMed

Baumgärtner, Fabian; Jourdan, Joëlle; Scheurer, Christian; Blasco, Benjamin; Campo, Brice; Mäser, Pascal; Wittlin, Sergio

2017-01-25

Recently published data suggest that artemisinin derivatives and synthetic peroxides, such as the ozonides OZ277 and OZ439, have a similar mode of action. Here the cross-resistance of OZ277 and OZ439 and four additional next-generation ozonides was probed against the artemisinin-resistant clinical isolate Plasmodium falciparum Cam3.I, which carries the K13-propeller mutation R539T (Cam3.I R539T ). The previously described in vitro ring-stage survival assay (RSA 0-3h ) was employed and a simplified variation of the original protocol was developed. At the pharmacologically relevant concentration of 700 nM, all six ozonides were highly effective against the dihydroartemisinin-resistant P. falciparum Cam3.I R539T parasites, showing a per cent survival ranging from <0.01 to 1.83%. A simplified version of the original RSA 0-3h method was developed and gave similar results, thus providing a practical drug discovery tool for further optimization of next-generation anti-malarial peroxides. The absence of in vitro cross-resistance against the artemisinin-resistant clinical isolate Cam3.I R539T suggests that ozonides could be effective against artemisinin-resistant P. falciparum. How this will translate to the human situation in clinical settings remains to be investigated.

Molecular surveillance of Plasmodium falciparum drug resistance in the Republic of Congo: four and nine years after the introduction of artemisinin-based combination therapy.

PubMed

Koukouikila-Koussounda, Felix; Jeyaraj, Sankarganesh; Nguetse, Christian N; Nkonganyi, Charles Nchotebah; Kokou, Kossiwa Clarisse; Etoka-Beka, Mandingha K; Ntoumi, Francine; Velavan, Thirumalaisamy P

2017-04-19

Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. Blood samples of 431 febrile children aged 1-10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All samples were screened for malaria parasites using nested PCR. Direct sequencing was used to determine the frequency distribution of genetic variants in the anti-malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6, Pfk13) in malaria-positive isolates. One-hundred and nineteen (N = 70 from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A relative decrease in the proportion of chloroquine-resistant haplotype (CVIET) from 100% in 2005, 1 year before the introduction and implementation of ACT in 2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug transporter gene, a considerable reduction in the frequency of the mutations N86Y (from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015). Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced to null in 2015. None of the parasites harboured the Pfk13 mutations associated with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new Pfk13 variants are reported among the investigated isolates. The implementation of ACT has led to the decline in prevalence of chloroquine-resistant parasites in the Republic of Congo. However, the constant prevalence of the PfMDR1 Y184F mutation, associated with lumefantrine susceptibility, indicate a selective drug pressure still exists. Taken together, this study could serve as the basis for epidemiological studies monitoring the distribution of molecular markers of artemisinin resistance in the Republic of Congo.

Population- and individual-specific regulatory variation in Sardinia.

PubMed

Pala, Mauro; Zappala, Zachary; Marongiu, Mara; Li, Xin; Davis, Joe R; Cusano, Roberto; Crobu, Francesca; Kukurba, Kimberly R; Gloudemans, Michael J; Reinier, Frederic; Berutti, Riccardo; Piras, Maria G; Mulas, Antonella; Zoledziewska, Magdalena; Marongiu, Michele; Sorokin, Elena P; Hess, Gaelen T; Smith, Kevin S; Busonero, Fabio; Maschio, Andrea; Steri, Maristella; Sidore, Carlo; Sanna, Serena; Fiorillo, Edoardo; Bassik, Michael C; Sawcer, Stephen J; Battle, Alexis; Novembre, John; Jones, Chris; Angius, Andrea; Abecasis, Gonçalo R; Schlessinger, David; Cucca, Francesco; Montgomery, Stephen B

2017-05-01

Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.

Redefining cerebral malaria by including malaria retinopathy.

PubMed

Beare, Nicholas A V; Lewallen, Susan; Taylor, Terrie E; Molyneux, Malcolm E

2011-03-01

Accurate diagnosis of cerebral malaria (CM) is important for patient management, epidemiological and end point surveillance, and enrolling patients with CM in studies of pathogenesis or therapeutic trials. In malaria-endemic areas, where asymptomatic Plasmodium falciparum parasitemia is common, a positive blood film in a comatose individual does not prove that the coma is due to malaria. A retinopathy consisting of two unique features - patchy retinal whitening and focal changes of vessel color - is highly specific for encephalopathy of malarial etiology. White-centered retinal hemorrhages are a common but less specific feature. Either indirect or direct ophthalmoscopy can be used to identify the changes, and both procedures can be learned and practiced by nonspecialist clinicians. In view of its important contributions to both clinical care and research, examination of the retina should become a routine component of the assessment of a comatose child or adult when CM is a possible diagnosis.

Redefining cerebral malaria by including malaria retinopathy

PubMed Central

Beare, Nicholas AV; Lewallen, Susan; Taylor, Terrie E; Molyneux, Malcolm E

2011-01-01

Accurate diagnosis of cerebral malaria (CM) is important for patient management, epidemiological and end point surveillance, and enrolling patients with CM in studies of pathogenesis or therapeutic trials. In malaria-endemic areas, where asymptomatic Plasmodium falciparum parasitemia is common, a positive blood film in a comatose individual does not prove that the coma is due to malaria. A retinopathy consisting of two unique features – patchy retinal whitening and focal changes of vessel color – is highly specific for encephalopathy of malarial etiology. White-centered retinal hemorrhages are a common but less specific feature. Either indirect or direct ophthalmoscopy can be used to identify the changes, and both procedures can be learned and practiced by nonspecialist clinicians. In view of its important contributions to both clinical care and research, examination of the retina should become a routine component of the assessment of a comatose child or adult when CM is a possible diagnosis. PMID:21449844

Use of RDTs to improve malaria diagnosis and fever case management at primary health care facilities in Uganda.

PubMed

Kyabayinze, Daniel J; Asiimwe, Caroline; Nakanjako, Damalie; Nabakooza, Jane; Counihan, Helen; Tibenderana, James K

2010-07-12

Early and accurate diagnosis of malaria followed by prompt treatment reduces the risk of severe disease in malaria endemic regions. Presumptive treatment of malaria is widely practised where microscopy or rapid diagnostic tests (RDTs) are not readily available. With the introduction of artemisinin-based combination therapy (ACT) for treatment of malaria in many low-resource settings, there is need to target treatment to patients with parasitologically confirmed malaria in order to improve quality of care, reduce over consumption of anti-malarials, reduce drug pressure and in turn delay development and spread of drug resistance. This study evaluated the effect of malaria RDTs on health workers' anti-malarial drug (AMD) prescriptions among outpatients at low level health care facilities (LLHCF) within different malaria epidemiological settings in Uganda. All health workers (HWs) in 21 selected intervention (where RDTs were deployed) LLHF were invited for training on the use RDTs. All HWs were trained to use RDTs for parasitological diagnosis of all suspected malaria cases irrespective of age. Five LLHCFs with clinical diagnosis (CD only) were included for comparison. Subsequently AMD prescriptions were compared using both a 'pre-post' and 'intervention-control' analysis designs. In-depth interviews of the HWs were conducted to explore any factors that influence AMD prescription practices. A total of 166,131 out-patient attendances (OPD) were evaluated at 21 intervention LLHCFs. Overall use of RDTs resulted in a 38% point reduction in AMD prescriptions. There was a two-fold reduction (RR 0.62, 95% CI 0.55-0.70) in AMD prescription with the greatest reduction in the hypo-endemic setting (RR 0.46 95% CI 0.51-0.53) but no significant change in the urban setting (RR1.01, p-value=0.820). Over 90% of all eligible OPD patients were offered a test. An average of 30% (range 25%-35%) of the RDT-negative fever patients received AMD prescriptions. When the test result was negative, children under five years of age were two to three times more likely (OR 2.6 p-value<0.001) to receive anti-malarial prescriptions relative to older age group. Of the 63 HWs interviewed 92% believed that a positive RDT result confirmed malaria, while only 49% believed that a negative RDT result excluded malaria infection. Use of RDTs resulted in a 2-fold reduction in anti-malarial drug prescription at LLHCFs. The study demonstrated that RDT use is feasible at LLHCFs, and can lead to better targetting of malaria treatment. Nationwide deployment of RDTs in a systematic manner should be prioritised in order to improve fever case management. The process should include plans to educate HWs about the utility of RDTs in order to maximize acceptance and uptake of the diagnostic tools and thereby leading to the benefits of parasitological diagnosis of malaria.

Genetic determinants of anti-malarial acquired immunity in a large multi-centre study.

PubMed

Shelton, Jennifer M G; Corran, Patrick; Risley, Paul; Silva, Nilupa; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Craik, Rachel; Cornelius, Victoria; Hensmann, Meike; Molloy, Sile; Sepulveda, Nuno; Clark, Taane G; Band, Gavin; Clarke, Geraldine M; Spencer, Christopher C A; Kerasidou, Angeliki; Campino, Susana; Auburn, Sarah; Tall, Adama; Ly, Alioune Badara; Mercereau-Puijalon, Odile; Sakuntabhai, Anavaj; Djimdé, Abdoulaye; Maiga, Boubacar; Touré, Ousmane; Doumbo, Ogobara K; Dolo, Amagana; Troye-Blomberg, Marita; Mangano, Valentina D; Verra, Frederica; Modiano, David; Bougouma, Edith; Sirima, Sodiomon B; Ibrahim, Muntaser; Hussain, Ayman; Eid, Nahid; Elzein, Abier; Mohammed, Hiba; Elhassan, Ahmed; Elhassan, Ibrahim; Williams, Thomas N; Ndila, Carolyne; Macharia, Alexander; Marsh, Kevin; Manjurano, Alphaxard; Reyburn, Hugh; Lemnge, Martha; Ishengoma, Deus; Carter, Richard; Karunaweera, Nadira; Fernando, Deepika; Dewasurendra, Rajika; Drakeley, Christopher J; Riley, Eleanor M; Kwiatkowski, Dominic P; Rockett, Kirk A

2015-08-28

Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

The D113N mutation in the RING E3 ubiquitin protein ligase gene is not associated with ex vivo susceptibility to common anti-malarial drugs in African Plasmodium falciparum isolates.

PubMed

Gendrot, Mathieu; Foguim, Francis Tsombeng; Robert, Marie Gladys; Amalvict, Rémy; Mosnier, Joel; Benoit, Nicolas; Madamet, Marylin; Pradines, Bruno

2018-03-12

Plasmodium falciparum resistance to artemisinin-based combination therapy has emerged and spread in Southeast Asia. In areas where artemisinin resistance is emerging, the efficacy of combination is now based on partner drugs. In this context, the identification of novel markers of resistance is essential to monitor the emergence and spread of resistance to these partner drugs. The ubiquitylation pathway could be a possible target for anti-malarial compounds and might be involved in resistance. Polymorphisms in the E3 ubiquitin-protein ligase (PF3D7_0627300) gene could be associated with decreased in vitro susceptibility to anti-malarial drugs. Plasmodium falciparum isolates were collected from patients hospitalized in France with imported malaria from a malaria-endemic country from January 2015 to December 2016 and, more particularly, from African French-speaking countries. In total, 215 isolates were successfully sequenced for the E3 ubiquitin-protein ligase gene and assessed for ex vivo susceptibility to anti-malarial drugs. The D113N mutation in the RING E3 ubiquitin-protein ligase gene was present in 147 out of the 215 samples (68.4%). The IC 50 values for the ten anti-malarial drugs were not significantly different between the wild-type and mutant parasites (p values between 0.225 and 0.933). There was no significant difference in terms of the percentage of parasites with decreased susceptibility between the D113 wild-type and the 133N mutated P. falciparum strains (p values between 0.541 and 1). The present data confirmed the absence of the association between polymorphisms in the RING E3 ubiquitin-protein ligase gene and the ex vivo susceptibility to common anti-malarial drugs in African P. falciparum isolates.

Anti-malarial activity and HS-SPME-GC-MS chemical profiling of Plinia cerrocampanensis leaf essential oil

PubMed Central

2014-01-01

Background Plinia cerrocampanensis is an endemic plant of Panama. The leaf essential oil of this plant has shown antibacterial activity. However, anti-malarial activity and chemical profiling by HS-SPME-GC-MS of this essential oil have not been reported before. Methods Anti-malarial activity of the essential oil (EO) was evaluated in vitro against chloroquine-sensitive HB3 and chloroquine-resistant W2 strains of Plasmodium falciparum. Synergistic effect of chloroquine and the EO on parasite growth was evaluated by calculating the combination index. A methodology involving headspace solid phase microextraction and gas chromatography-mass spectrometry (HS-SPME-GC-MS) was developed to investigate the composition of Plinia cerrocampanensis EO. Results Plinia cerrocampanensis EO showed a high anti-malarial activity and a synergistic interaction with chloroquine. The Plinia cerrocampanensis EO inhibited P. falciparum growth in vitro at an IC50 of 7.3 μg/mL. Chloroquine together with the EO decreased the IC50 of chloroquine from 0.1 μg/mL to 0.05 μg/mL, and of the EO from 7.3 μg/mL to 1.1 μg/mL. The measured combination index was 0.58, which clearly indicates that the EO acts synergistically with chloroquine. Since the EO maintained its inhibitory activity on the chloroquine-sensitive strain of the parasite, it could be acting by a different mechanism of action than chloroquine. The best HS-SPME-GC-MS analytical conditions were obtained when the temperature of extraction was 49°C, incubation time 14 min, and the time of extraction 10 min. This method allowed for the identification of 53 volatile constituents in the EO, including new compounds not reported earlier. Conclusions The anti-malarial activity exhibited by the Plinia cerrocampanensis EO may lend support for its possible use as an alternative for anti-malarial therapy. PMID:24410874

Comparison of MDCK-MDR1 and Caco-2 cell based permeability assays for anti-malarial drug screening and drug investigations.

PubMed

Jin, Xiannu; Luong, Thu-Lan; Reese, Necole; Gaona, Heather; Collazo-Velez, Vanessa; Vuong, Chau; Potter, Brittney; Sousa, Jason C; Olmeda, Raul; Li, Qigui; Xie, Lisa; Zhang, Jing; Zhang, Ping; Reichard, Greg; Melendez, Victor; Marcsisin, Sean R; Pybus, Brandon S

2014-01-01

Malaria is a major health concern and affects over 300million people a year. Accordingly, there is an urgent need for new efficacious anti-malarial drugs. A major challenge in developing new anti-malarial drugs is to design active molecules that have preferable drug-like characteristics. These "drug-like" characteristics include physiochemical properties that affect drug absorption, distribution, metabolism, and excretion (ADME). Compounds with poor ADME profiles will likely fail in vivo due to poor pharmacokinetics and/or other drug delivery related issues. There have been numerous assays developed in order to pre-screen compounds that would likely fail in further development due to poor absorption properties including PAMPA, Caco-2, and MDCK permeability assays. The use of cell-based permeability assays such as Caco-2 and MDCK serve as surrogate indicators of drug absorption and transport, with the two approaches often used interchangeably. We sought to evaluate both approaches in support of anti-malarial drug development. Accordingly, a comparison of both assays was conducted utilizing apparent permeability coefficient (Papp) values determined from liquid chromatography/tandem mass spectrometry (LC-MS) analyses. Both Caco-2 and MDCK permeability assays produced similar Papp results for potential anti-malarial compounds with low and medium permeability. Differences were observed for compounds with high permeability and compounds that were P-gp substrates. Additionally, the utility of MDCK-MDR1 permeability measurements was demonstrated in probing the role of P-glycoprotein transport in Primaquine-Chloroquine drug-drug interactions in comparison with in vivo pharmacokinetic changes. This study provides an in-depth comparison of the Caco-2 and MDCK-MDR1 cell based permeability assays and illustrates the utility of cell-based permeability assays in anti-malarial drug screening/development in regard to understanding transporter mediated changes in drug absorption/distribution. Published by Elsevier Inc.

The malaria testing and treatment landscape in the southern Lao People's Democratic Republic (PDR).

PubMed

Phanalasy, Saysana

2017-04-25

In the context of national and regional goals to eliminate malaria by 2030, the Center for Malaria Parasitology and Entomology in the Lao PDR is implementing strategies to ensure all malaria cases are detected and appropriately treated with first-line artemisinin combination therapy, artemether-lumefantrine (AL). Timely and relevant evidence to inform policies and strategies is needed to ensure the most effective and efficient use of resources, and to accelerate progress towards elimination goals. A 2015 outlet survey conducted in five provinces of the southern Lao PDR was the first of its kind to study the total market for malaria treatments and diagnostics. The sub-national outlet survey was designed to describe the market and to assess public and private sector readiness and performance for malaria case management. Additionally, key indicators were estimated among private outlets within districts with and without a Public Private Mix (PPM) programme. Over half of anti-malarial stockists were public sector (65.1%). In the private sector, pharmacies most commonly stocked anti-malarials, although anti-malarials were also found in private health facilities, drug stores, general retailers, and itinerant drug vendors. Nearly all anti-malarial stocking public health facilities had AL (99.5%) and 90.8% had confirmatory testing. Fewer than half of anti-malarial stocking private outlets stocked AL (40.8%) and malaria testing (43.5%). Chloroquine has not been a first-line treatment for Plasmodium falciparum malaria since 2005 and Plasmodium vivax since 2011 yet private sector availability was 77.6% and chloroquine accounted for 62.2% of the total anti-malarial market share. AL and confirmatory testing availability were higher in private outlets in PPM (68.1, 72.6%) versus non-PPM districts (2.5, 12.1%). Chloroquine was available in 63.6% of PPM and 96.7% of non-PPM-district outlets, and was the most commonly distributed anti-malarial among private outlets in both PPM (61.7%) and non-PPM districts (99.1%). Public sector outlets in the southern Lao PDR are typically equipped to test and appropriately treat malaria. There is need to address widespread private sector availability and distribution of chloroquine. The PPM programme has improved private provider readiness to manage malaria according to national guidelines. However, supporting interventions to address provider and consumer behaviours are needed to further drive uptake.

In vitro and in vivo anti-malarial activity of plants from the Brazilian Amazon.

PubMed

Lima, Renata B S; Rocha e Silva, Luiz F; Melo, Marcia R S; Costa, Jaqueline S; Picanço, Neila S; Lima, Emerson S; Vasconcellos, Marne C; Boleti, Ana Paula A; Santos, Jakeline M P; Amorim, Rodrigo C N; Chaves, Francisco C M; Coutinho, Julia P; Tadei, Wanderli P; Krettli, Antoniana U; Pohlit, Adrian M

2015-12-18

The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice. High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71% suppression of P. berghei parasitaemia versus untreated controls). Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present.

The malaria testing and treatment market in Kinshasa, Democratic Republic of the Congo, 2013.

PubMed

Mpanya, Godéfroid; Tshefu, Antoinette; Likwela, Joris Losimba

2017-02-28

The Democratic Republic of Congo (DRC) is one of the two most leading contributors to the global burden of disease due to malaria. This paper describes the malaria testing and treatment market in the nation's capital province of Kinshasa, including availability of malaria testing and treatment and relative anti-malarial market share for the public and private sector. A malaria medicine outlet survey was conducted in Kinshasa province in 2013. Stratified multi-staged sampling was used to select areas for the survey. Within sampled areas, all outlets with the potential to sell or distribute anti-malarials in the public and private sector were screened for eligibility. Among outlets with anti-malarials or malaria rapid diagnostic tests (RDT) in stock, a full audit of all available products was conducted. Information collected included product information (e.g. active ingredients, brand name), amount reportedly distributed to patients in the past week, and retail price. In total, 3364 outlets were screened for inclusion across Kinshasa and 1118 outlets were eligible for the study. Among all screened outlets in the private sector only about one in ten (12.1%) were stocking quality-assured Artemisinin-based Combination Therapy (ACT) medicines. Among all screened public sector facilities, 24.5% had both confirmatory testing and quality-assured ACT available, and 20.2% had sulfadoxine-pyrimethamine (SP) available for intermittent preventive therapy during pregnancy (IPTp). The private sector distributed the majority of anti-malarials in Kinshasa (96.7%), typically through drug stores (89.1% of the total anti-malarial market). Non-artemisinin therapies were the most commonly distributed anti-malarial (50.1% of the total market), followed by non quality-assured ACT medicines (38.5%). The median price of an adult quality-assured ACT was $6.59, and more expensive than non quality-assured ACT ($3.71) and SP ($0.44). Confirmatory testing was largely not available in the private sector (1.1%). While the vast majority of anti-malarial medicines distributed to patients in Kinshasa province are sold within the private sector, availability of malaria testing and appropriate treatment for malaria is alarmingly low. There is a critical need to improve access to confirmatory testing and quality-assured ACT in the private sector. Widespread availability and distribution of non quality-assured ACT and non-artemisinin therapies must be addressed to ensure effective malaria case management.

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.

Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries.

PubMed

O'Connell, Kathryn A; Gatakaa, Hellen; Poyer, Stephen; Njogu, Julius; Evance, Illah; Munroe, Erik; Solomon, Tsione; Goodman, Catherine; Hanson, Kara; Zinsou, Cyprien; Akulayi, Louis; Raharinjatovo, Jacky; Arogundade, Ekundayo; Buyungo, Peter; Mpasela, Felton; Adjibabi, Chérifatou Bello; Agbango, Jean Angbalu; Ramarosandratana, Benjamin Fanomezana; Coker, Babajide; Rubahika, Denis; Hamainza, Busiku; Chapman, Steven; Shewchuk, Tanya; Chavasse, Desmond

2011-10-31

Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector. These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries

PubMed Central

2011-01-01

Background Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector. Conclusions These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria. PMID:22039838

Studies on the effects of sida acuta and vetiveria zizanioides against the malarial vector, anopheles stephensi and malarial parasite, plasmodium berghei

USDA-ARS?s Scientific Manuscript database

Methanolic extracts of Sida acuta and Vetiveria zizanioides leaves and root were studied for toxicity to Anopheles stephensi mosquitoes and to the malaria parasite Plasmodium berghei in mice. The extracts reduced parasitemia levels in mice by 17-69%, depending on extract concentration. Median le...

A clinical trial of malaria prophylaxis using a single dose of chloroquine at different intervals in an endemic malarious area.

PubMed

Karunakaran, C S

1980-10-01

A controlled trial of chloroquine prophylaxis was carried out to find whether this drug could be administered at intervals longer than the conventional ones recommended, in endemic malarious areas. Statistically significant results obtained show that chloroquine at suitable doses could be used successfully at intervals of 3 months. The possibility of chloroquine and acquired immunity acting together synergistically is discussed. The author is of the opinion that with this dose regime, the community would still be able to build up substantial immunity, so that in the event of the drug being discontinued, the community would not be faced with the problem of overwhelming malarial infections. The various advantages in using this regime are also considered.

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.

The epidemiology of malaria in the Papua New Guinea highlands: 5. Aseki, Menyamya and Wau-Bulolo, Morobe Province.

PubMed

Mueller, Ivo; Sie, Albert; Ousari, Moses; Iga, Jonah; Yala, Simon; Ivivi, Rex; Reeder, John C

2007-01-01

Although not strictly a highlands province, Morobe encompasses large highlands areas, the most important being Aseki, Menyamya and Wau-Bulolo. A series of rapid malaria surveys conducted in both the wet and dry seasons found malaria to be clearly endemic in areas below 1400 m in Menyamya and Wau-Bulolo, with overall prevalence rates in the wet season (25.5%, range: 9.1%-39.2%) greatly exceeding those in the dry season (8.3%, range: 2.4%-22.8%; p < 0.001). In the wet season surveys Plasmodium falciparum was the clearly predominant species, accounting for 63% of all infections. P. vivax increased in frequency in the dry season (from 27% to 46%, p < 0.001), while P. falciparum and P. malariae decreased. In line with past surveys a low prevalence of malaria was found in the Aseki area. Malaria was found to be the main source of febrile illness in the wet season with at least 60% of measured or reported fever associated with parasitaemia. Other causes of febrile illness dominated in the dry. In villages with parasite prevalence rates < 20% mean haemoglobin levels and prevalence of severe anaemia were strongly correlated with overall parasite prevalence. In addition concurrent malarial infections were associated with a strong reduction of individual haemoglobin levels (-1.2 g/dl) and there was increased risk of moderate-to-severe anaemia with concurrent malaria. Malarial infections are thus the most significant cause of febrile illness and anaemia in the highlands fringe populations in Morobe. As a consequence all villages below 1500-1600 m in Morobe Province should be included in malaria control activities.

Primaquine revisited six decades after its discovery.

PubMed

Vale, Nuno; Moreira, Rui; Gomes, Paula

2009-03-01

Primaquine was firstly synthesized in 1946 in the USA, and is the most representative member of the anti-malarial 8-aminoquinolines. Six decades have passed and primaquine is still the only transmission-blocking anti-malarial clinically available, displaying a marked activity against gametocytes of all species of human malaria, including multi-resistant Plasmodium falciparum strains. Primaquine is also effective against all exoerythrocytic forms of the parasite and is used in conjunction with other anti-malarials for the treatment of vivax and ovale malaria. However, primaquine is often associated with serious adverse effects, in consequence of its toxic metabolites. 5-Hydroxyprimaquine or 6-methoxy-8-aminoquinoline has been considered to be directly responsible for complications such as hemolytic anemia. Primaquine toxicity is aggravated in people deficient of 6-glucose phosphate dehydrogenase or glutathione synthetase. Adverse effects are further amplified by the fact that primaquine must be repeatedly administered at high doses, due to its limited oral bioavailability. Over the last two decades, Medicinal Chemists have battled against primaquine's disadvantages, while keeping or even improving its unequalled performance as an anti-malarial. The present text revisits primaquine and its properties on the occasion of its 60th anniversary and aims to give a general overview of what has been the path towards the development of effective and safe primaquine-based anti-malarials. Presently, aablaquine and tafenoquine the two most promising primaquine analogues are already in the final stages of clinical trials against Plasmodium vivax and P. falciparum. Both compounds are a new hope against malaria and other primaquine-sensitive illnesses, such as Pneumocystis Pneumonia or the Chagas disease.

Developing a novel risk prediction model for severe malarial anemia.

PubMed

Brickley, E B; Kabyemela, E; Kurtis, J D; Fried, M; Wood, A M; Duffy, P E

2017-01-01

As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002-2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a Plasmodium falciparum infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1β provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70-0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54-0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood.

Evidence on anti-malarial and diagnostic markets in Cambodia to guide malaria elimination strategies and policies.

PubMed

Phok, Sochea; Lek, Dysoley

2017-04-25

Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities. From August 17th to October 1st, 2015, a cross sectional, nationally-representative malaria outlet survey was conducted in Cambodia. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was conducted among 180 communes. An audit was completed for all anti-malarials, malaria rapid diagnostic tests (RDT) and microscopy. A total of 26,664 outlets were screened, and 1303 outlets were eligible and interviewed. Among all screened outlets in the public sector, 75.9% of public health facilities and 67.7% of community health workers stocked both malaria diagnostic testing and a first-line artemisinin-based combination therapy (ACT). Among anti-malarial-stocking private sector outlets, 64.7% had malaria blood testing available, and 70.9% were stocking a first-line ACT. Market share data illustrate that most of the anti-malarials were sold or distributed through the private sector (58.4%), including itinerant drug vendors (23.4%). First-line ACT accounted for the majority of the market share across the public and private sectors (90.3%). Among private sector outlets stocking any anti-malarial, the proportion of outlets with a first-line ACT or RDT was higher among outlets that had reportedly received one or more forms of 'support' (e.g. reportedly received training in the previous year on malaria diagnosis [RDT and/or microscopy] and/or the national treatment guidelines for malaria) compared to outlets that did not report receiving any support (ACT: 82.1 and 60.6%, respectively; RDT: 78.2 and 64.0%, respectively). The results point to high availability and distribution of first-line ACT and widespread availability of malaria diagnosis, especially in the public sector. This suggests that there is a strong foundation for achieving elimination goals in Cambodia. However, key gaps in terms of availability of malaria commodities for case management must be addressed, particularly in the private sector where most people seek treatment. Continued engagement with the private sector will be important to ensure accelerated progress towards malaria elimination.

The Development and Evaluation of a Teleprocessed Computer-Assisted Instruction Course in the Recognition of Malarial Parasites. Final Report; May 1, 1967 - June 30, 1968.

ERIC Educational Resources Information Center

Mitzel, Harold E.

A computer-assisted instruction course in the recognition of malarial parasites was developed and evaluated. The course includes stage discrimination, species discrimination, and case histories. Segments developed use COURSEWRITER as an author language and are presented via a display terminal that permits two-way communication with an IBM computer…

SMS for Life: a pilot project to improve anti-malarial drug supply management in rural Tanzania using standard technology

PubMed Central

2010-01-01

Background Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. Methods A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL) and quinine injectable. Results Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93%) was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable) fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. Conclusions The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has the potential to alleviate restricted availability of anti-malarial drugs or other medicines in rural or under-resourced areas. PMID:20979633

SMS for Life: a pilot project to improve anti-malarial drug supply management in rural Tanzania using standard technology.

PubMed

Barrington, Jim; Wereko-Brobby, Olympia; Ward, Peter; Mwafongo, Winfred; Kungulwe, Seif

2010-10-27

Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL) and quinine injectable. Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93%) was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable) fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has the potential to alleviate restricted availability of anti-malarial drugs or other medicines in rural or under-resourced areas.

Comparative analysis of two methods for measuring sales volumes during malaria medicine outlet surveys.

PubMed

Patouillard, Edith; Kleinschmidt, Immo; Hanson, Kara; Pok, Sochea; Palafox, Benjamin; Tougher, Sarah; O'Connell, Kate; Goodman, Catherine

2013-09-05

There is increased interest in using commercial providers for improving access to quality malaria treatment. Understanding their current role is an essential first step, notably in terms of the volume of diagnostics and anti-malarials they sell. Sales volume data can be used to measure the importance of different provider and product types, frequency of parasitological diagnosis and impact of interventions. Several methods for measuring sales volumes are available, yet all have methodological challenges and evidence is lacking on the comparability of different methods. Using sales volume data on anti-malarials and rapid diagnostic tests (RDTs) for malaria collected through provider recall (RC) and retail audits (RA), this study measures the degree of agreement between the two methods at wholesale and retail commercial providers in Cambodia following the Bland-Altman approach. Relative strengths and weaknesses of the methods were also investigated through qualitative research with fieldworkers. A total of 67 wholesalers and 107 retailers were sampled. Wholesale sales volumes were estimated through both methods for 62 anti-malarials and 23 RDTs and retail volumes for 113 anti-malarials and 33 RDTs. At wholesale outlets, RA estimates for anti-malarial sales were on average higher than RC estimates (mean difference of four adult equivalent treatment doses (95% CI 0.6-7.2)), equivalent to 30% of mean sales volumes. For RDTs at wholesalers, the between-method mean difference was not statistically significant (one test, 95% CI -6.0-4.0). At retail outlets, between-method differences for both anti-malarials and RDTs increased with larger volumes being measured, so mean differences were not a meaningful measure of agreement between the methods. Qualitative research revealed that in Cambodia where sales volumes are small, RC had key advantages: providers were perceived to remember more easily their sales volumes and find RC less invasive; fieldworkers found it more convenient; and it was cheaper to implement than RA. Both RA and RC had implementation challenges and were prone to data collection errors. Choice of empirical methods is likely to have important implications for data quality depending on the study context.

Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica.

PubMed

Dua, Virendra K; Verma, Gaurav; Singh, Bikram; Rajan, Aswathy; Bagai, Upma; Agarwal, Dau Dayal; Gupta, N C; Kumar, Sandeep; Rastogi, Ayushi

2013-06-10

In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya. In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits. Compound conessine showed in vitro anti-plasmodial activity with its IC₅₀ value 1.9 μg/ml and 1.3 μg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC₅₀= 14 μg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed. The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992–2004)

PubMed Central

Munier, Aline; Diallo, Aldiouma; Cot, Michel; Ndiaye, Ousmane; Arduin, Pascal; Chippaux, Jean-Philippe

2009-01-01

Background In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006. The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region. Methods The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992–2004. Results Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change. Conclusion The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines. PMID:19397797

Comparative analysis of two methods for measuring sales volumes during malaria medicine outlet surveys

PubMed Central

2013-01-01

Background There is increased interest in using commercial providers for improving access to quality malaria treatment. Understanding their current role is an essential first step, notably in terms of the volume of diagnostics and anti-malarials they sell. Sales volume data can be used to measure the importance of different provider and product types, frequency of parasitological diagnosis and impact of interventions. Several methods for measuring sales volumes are available, yet all have methodological challenges and evidence is lacking on the comparability of different methods. Methods Using sales volume data on anti-malarials and rapid diagnostic tests (RDTs) for malaria collected through provider recall (RC) and retail audits (RA), this study measures the degree of agreement between the two methods at wholesale and retail commercial providers in Cambodia following the Bland-Altman approach. Relative strengths and weaknesses of the methods were also investigated through qualitative research with fieldworkers. Results A total of 67 wholesalers and 107 retailers were sampled. Wholesale sales volumes were estimated through both methods for 62 anti-malarials and 23 RDTs and retail volumes for 113 anti-malarials and 33 RDTs. At wholesale outlets, RA estimates for anti-malarial sales were on average higher than RC estimates (mean difference of four adult equivalent treatment doses (95% CI 0.6-7.2)), equivalent to 30% of mean sales volumes. For RDTs at wholesalers, the between-method mean difference was not statistically significant (one test, 95% CI −6.0-4.0). At retail outlets, between-method differences for both anti-malarials and RDTs increased with larger volumes being measured, so mean differences were not a meaningful measure of agreement between the methods. Qualitative research revealed that in Cambodia where sales volumes are small, RC had key advantages: providers were perceived to remember more easily their sales volumes and find RC less invasive; fieldworkers found it more convenient; and it was cheaper to implement than RA. Discussion/conclusions Both RA and RC had implementation challenges and were prone to data collection errors. Choice of empirical methods is likely to have important implications for data quality depending on the study context. PMID:24010526

MEASURING ECONOMIC GROWTH FROM OUTER SPACE.

PubMed

Henderson, J Vernon; Storeygard, Adam; Weil, David N

2012-04-01

GDP growth is often measured poorly for countries and rarely measured at all for cities or subnational regions. We propose a readily available proxy: satellite data on lights at night. We develop a statistical framework that uses lights growth to augment existing income growth measures, under the assumption that measurement error in using observed light as an indicator of income is uncorrelated with measurement error in national income accounts. For countries with good national income accounts data, information on growth of lights is of marginal value in estimating the true growth rate of income, while for countries with the worst national income accounts, the optimal estimate of true income growth is a composite with roughly equal weights. Among poor-data countries, our new estimate of average annual growth differs by as much as 3 percentage points from official data. Lights data also allow for measurement of income growth in sub- and supranational regions. As an application, we examine growth in Sub Saharan African regions over the last 17 years. We find that real incomes in non-coastal areas have grown faster by 1/3 of an annual percentage point than coastal areas; non-malarial areas have grown faster than malarial ones by 1/3 to 2/3 annual percent points; and primate city regions have grown no faster than hinterland areas. Such applications point toward a research program in which "empirical growth" need no longer be synonymous with "national income accounts."

Structural Plasticity of Malaria Dihydroorotate Dehydrogenase Allows Selective Binding of Diverse Chemical Scaffolds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Xiaoyi; Gujjar, Ramesh; El Mazouni, Farah

Malaria remains a major global health burden and current drug therapies are compromised by resistance. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) was validated as a new drug target through the identification of potent and selective triazolopyrimidine-based DHODH inhibitors with anti-malarial activity in vivo. Here we report x-ray structure determination of PfDHODH bound to three inhibitors from this series, representing the first of the enzyme bound to malaria specific inhibitors. We demonstrate that conformational flexibility results in an unexpected binding mode identifying a new hydrophobic pocket on the enzyme. Importantly this plasticity allows PfDHODH to bind inhibitors from different chemical classes andmore » to accommodate inhibitor modifications during lead optimization, increasing the value of PfDHODH as a drug target. A second discovery, based on small molecule crystallography, is that the triazolopyrimidines populate a resonance form that promotes charge separation. These intrinsic dipoles allow formation of energetically favorable H-bond interactions with the enzyme. The importance of delocalization to binding affinity was supported by site-directed mutagenesis and the demonstration that triazolopyrimidine analogs that lack this intrinsic dipole are inactive. Finally, the PfDHODH-triazolopyrimidine bound structures provide considerable new insight into species-selective inhibitor binding in this enzyme family. Together, these studies will directly impact efforts to exploit PfDHODH for the development of anti-malarial chemotherapy.« less

Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.

PubMed

Srimuang, Krongkan; Miotto, Olivo; Lim, Pharath; Fairhurst, Rick M; Kwiatkowski, Dominic P; Woodrow, Charles J; Imwong, Mallika

2016-11-08

Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials. The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011-2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods. Pfmdr1 amplification, a marker of mefloquine and lumefantrine resistance, was highly prevalent at Mae Sot on the Thailand-Myanmar border (59.8% of isolates) and common (more than 10%) at sites in central Myanmar, eastern Thailand and western Cambodia; however, its prevalence was lower than previously documented in Pailin, western Cambodia. The pfmdr1 Y184F mutation was common, particularly in and around Cambodia, and the F1226Y mutation was found in about half of samples in Mae Sot. The functional significance of these two mutations remains unclear. Other previously documented pfmdr1 mutations were absent or very rare in the region. The pfcrt mutation K76T associated with chloroquine resistance was found in 98.2% of isolates. The CVIET haplotype made up 95% or more of isolates in western SEA while the CVIDT haplotype was common (30-40% of isolates) in north and northeastern Cambodia, southern Laos, and southern Vietnam. These findings generate cause for concern regarding the mid-term efficacy of artemether-lumefantrine in Myanmar, while the absence of resistance-conferring pfmdr1 mutations and SVMNT pfcrt haplotypes suggests that amodiaquine could be an efficacious component of anti-malarial regimens in SEA.

Artemisinin Directly Targets Malarial Mitochondria through Its Specific Mitochondrial Activation

PubMed Central

Wang, Juan; Huang, Liying; Li, Jian; Fan, Qiangwang; Long, Yicheng; Li, Ying; Zhou, Bing

2010-01-01

The biological mode of action of artemisinin, a potent antimalarial, has long been controversial. Previously we established a yeast model addressing its mechanism of action and found mitochondria the key in executing artemisinin's action. Here we present data showing that artemisinin directly acts on mitochondria and it inhibits malaria in a similar way as yeast. Specifically, artemisinin and its homologues exhibit correlated activities against malaria and yeast, with the peroxide bridge playing a key role for their inhibitory action in both organisms. In addition, we showed that artemisinins are distributed to malarial mitochondria and directly impair their functions when isolated mitochondria were tested. In efforts to explore how the action specificity of artemisinin is achieved, we found strikingly rapid and dramatic reactive oxygen species (ROS) production is induced with artemisinin in isolated yeast and malarial but not mammalian mitochondria, and ROS scavengers can ameliorate the effects of artemisinin. Deoxyartemisinin, which lacks an endoperoxide bridge, has no effect on membrane potential or ROS production in malarial mitochondria. OZ209, a distantly related antimalarial endoperoxide, also causes ROS production and depolarization in isolated malarial mitochondria. Finally, interference of mitochondrial electron transport chain (ETC) can alter the sensitivity of the parasite towards artemisinin. Addition of iron chelator desferrioxamine drastically reduces ETC activity as well as mitigates artemisinin-induced ROS production. Taken together, our results indicate that mitochondrion is an important direct target, if not the sole one, in the antimalarial action of artemisinins. We suggest that fundamental differences among mitochondria from different species delineate the action specificity of this class of drugs, and differing from many other drugs, the action specificity of artemisinins originates from their activation mechanism. PMID:20221395

Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity

PubMed Central

Matar, Caline G.; Anthony, Neil R.; O’Flaherty, Brigid M.; Jacobs, Nathan T.; Priyamvada, Lalita; Engwerda, Christian R.; Speck, Samuel H.; Lamb, Tracey J.

2015-01-01

Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission. PMID:25996913

ACP1 and human adaptability: association with past malarial morbidity in the Sardinian population.

PubMed

Bottini, E; Palmarino, R; Lucarelli, P; Lista, F; Bottini, N

2001-01-01

Acid Phosphatase locus 1 (ACP1) is a polymorphic enzyme controlled by a locus on chromosome 2 with three common codominant alleles: *A, *B, and *C. ACP1 shows two major isoforms, F and S. The ratio of their concentration differs markedly among genotypes. Two functions have been proposed for the enzyme: flavin-mononucleotide phosphatase and tyrosine phosphatase activity. An association between ACP1 polymorphism and past malarial morbidity in Sardinia and the Po Valley has been described. Genetic polymorphisms could contribute to natural resistance or susceptibility to the disease. On the other hand, malaria pressure may select for genes that increase susceptibility to common diseases of modern civilization. Thus, the association between ACP1 and malaria in Sardinia in the light of recent understanding of the function of ACP1 and the molecular basis of malaria pathophysiology, especially aspects of the structure of band 3 protein (B3P) and the role of cytokines have been revisited. There is a significant negative correlation between ACP1 S isoform concentration, directly related to the ACP1*C allele, and past malarial morbidity in Sardinia. Populations subjected in the past to a heavy malarial burden show, at present, a lower concentration of the S isoform compared to a nearby malaria-free population, suggesting that genotypes with high S isoform concentration have been subjected to negative selection in a malarial environment. Correlation analysis and analysis of the joint G-6-PD/ACP1 distribution suggest that the relationship between past endemic malaria and the S isoform has not been mediated by glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, thus pointing to a direct effect of malaria on ACP1. Copyright 2001 Wiley-Liss, Inc.

Availability and quality of anti-malarials among private sector outlets in Myanmar in 2012: results from a large, community-based, cross-sectional survey before a large-scale intervention.

PubMed

Khin, Hnin Su Su; Chen, Ingrid; White, Chris; Sudhinaraset, May; McFarland, Willi; Littrell, Megan; Montagu, Dominic; Aung, Tin

2015-07-14

Global malaria control efforts are threatened by the spread and emergence of artemisinin-resistant Plasmodium falciparum parasites. In 2012, the widespread sale of partial courses of artemisinin-based monotherapy was suspected to take place in the highly accessed, weakly regulated private sector in Myanmar, posing potentially major threats to drug resistance. This study investigated the presence of artemisinin-based monotherapies in the Myanmar private sector, particularly as partial courses of therapy, to inform the targeting of future interventions to stop artemisinin resistance. A large cross-sectional survey comprised of a screening questionnaire was conducted across 26 townships in Myanmar between March and May, 2012. For outlets that stocked anti-malarials at the time of survey, a stock audit was conducted, and for outlets that stocked anti-malarials within 3 months of the survey, a provider survey was conducted. A total of 3,658 outlets were screened, 83% were retailers (pharmacies, itinerant drug vendors and general retailers) and 17% were healthcare providers (private facilities and health workers). Of the 3,658 outlets screened, 1,359 outlets (32%) stocked at least one anti-malarial at the time of study. Oral artemisinin-based monotherapy comprised of 33% of self-reported anti-malarials dispensing volumes found. The vast majority of artemisinin-based monotherapy was sold by retailers, where 63% confirmed that they sold partial courses of therapy by cutting blister packets. Very few retailers (5%) had malaria rapid diagnostic tests available, and quality-assured artemisinin-based combination therapy was virtually nonexistent among retailers. Informal private pharmacies, itinerant drug vendors and general retailers should be targeted for interventions to improve malaria treatment practices in Myanmar, particularly those that threaten the emergence and spread of artemisinin resistance.

On the birefringence of healthy and malaria-infected red blood cells

NASA Astrophysics Data System (ADS)

Dharmadhikari, Aditya K.; Basu, Himanish; Dharmadhikari, Jayashree A.; Sharma, Shobhona; Mathur, Deepak

2013-12-01

The birefringence of a red blood cell (RBC) is quantitatively monitored as it becomes infected by a malarial parasite. Large changes occur in the cell's refractive index at different stages of malarial infection. The observed rotation of an optically trapped, malaria-infected RBC is not a simple function of shape distortion: the malarial parasite is found to itself exercise a profound influence on the rotational dynamics by inducing stage-specific birefringence. Our measurements shed new light on the competition between shape- and form-birefringence in RBCs. We demonstrate the possibility of using birefringence to establish very early stages of infected parasites and of assessing various factors that contribute to birefringence in normal and infected cells. Our results have implications for the development and use of noninvasive techniques of quantifying changes in cell properties induced by malaria disease pathology.

Investigating the activity of quinine analogues versus chloroquine resistant Plasmodium falciparum.

PubMed

Dinio, Theresa; Gorka, Alexander P; McGinniss, Andrew; Roepe, Paul D; Morgan, Jeremy B

2012-05-15

Plasmodium falciparum, the deadliest malarial parasite species, has developed resistance against nearly all man-made antimalarial drugs within the past century. However, quinine (QN), the first antimalarial drug, remains efficacious worldwide. Some chloroquine resistant (CQR) P. falciparum strains or isolates show mild cross resistance to QN, but many do not. Further optimization of QN may provide a well-tolerated therapy with improved activity versus CQR malaria. Thus, using the Heck reaction, we have pursued a structure-activity relationship study, including vinyl group modifications of QN. Certain derivatives show good antiplasmodial activity in QN-resistant and QN-sensitive strains, with lower IC(50) values relative to QN. Copyright © 2012 Elsevier Ltd. All rights reserved.

Malaria in South America: a drug discovery perspective.

PubMed

Cruz, Luiza R; Spangenberg, Thomas; Lacerda, Marcus V G; Wells, Timothy N C

2013-05-24

The challenge of controlling and eventually eradicating malaria means that new tools are urgently needed. South America's role in this fight spans both ends of the research and development spectrum: both as a continent capable of discovering and developing new medicines, and also as a continent with significant numbers of malaria patients. This article reviews the contribution of groups in the South American continent to the research and development of new medicines over the last decade. Therefore, the current situation of research targeting malaria control and eradication is discussed, including endemicity, geographical distribution, treatment, drug-resistance and diagnosis. This sets the scene for a review of efforts within South America to discover and optimize compounds with anti-malarial activity.

Private sector role, readiness and performance for malaria case management in Uganda, 2015.

PubMed

Kaula, Henry; Buyungo, Peter; Opigo, Jimmy

2017-05-25

Several interventions have been put in place to promote access to quality malaria case management services in Uganda's private sector, where most people seek treatment. This paper describes evidence using a mixed-method approach to examine the role, readiness and performance of private providers at a national level in Uganda. These data will be useful to inform strategies and policies for improving malaria case management in the private sector. The ACTwatch national anti-malarial outlet survey was conducted concurrently with a fever case management study. The ACTwatch nationally representative anti-malarial outlet survey was conducted in Uganda between May 18th 2015 and July 2nd 2015. A representative sample of sub-counties was selected in 14 urban and 13 rural clusters with probability proportional to size and a census approach was used to identify outlets. Outlets eligible for the survey met at least one of three criteria: (1) one or more anti-malarials were in stock on the day of the survey; (2) one or more anti-malarials were in stock in the 3 months preceding the survey; and/or (3) malaria blood testing (microscopy or RDT) was available. The fever case management study included observations of provider-patient interactions and patient exit interviews. Data were collected between May 20th and August 3rd, 2015. The fever case management study was implemented in the private sector. Potential outlets were identified during the main outlet survey and included in this sub-sample if they had both artemisinin-based combination therapy (ACT) [artemether-lumefantrine (AL)], in stock on the day of survey as well as diagnostic testing available. A total of 9438 outlets were screened for eligibility in the ACTwatch outlet survey and 4328 outlets were found to be stocking anti-malarials and were interviewed. A total of 9330 patients were screened for the fever case management study and 1273 had a complete patient observation and exit interview. Results from the outlet survey illustrate that the majority of anti-malarials were distributed through the private sector (54.3%), with 31.4% of all anti-malarials distributed through drug stores and 14.4% through private for-profit health facilities. Availability of different anti-malarials and diagnostic testing in the private sector was: ACT (80.7%), quality-assured (QA) ACT (72.0%), sulfadoxine-pyrimethamine (SP) (47.1%), quinine (73.2%) and any malaria blood testing (32.9%). Adult QAACT ($1.62) was three times more expensive than SP ($0.48). The results from the fever case management study found 44.4% of respondents received a malaria test, and among those who tested positive for malaria, 60.0% received an ACT, 48.5% received QAACT; 14.4% a non-artemisinin therapy; 14.9% artemether injection, and 42.5% received an antibiotic. The private sector plays an important role in malaria case management in Uganda. While several private sector initiatives have improved availability of QAACT, there are gaps in malaria diagnosis and distribution of non-artemisinin monotherapies persists. Further private sector strategies, including those focusing on drug stores, are needed to increase coverage of parasitological testing and removal of non-artemisinin therapies from the marketplace.

Chloroquine induced pruritus--questionnaire based epidemiological study.

PubMed

George, Adekunle O

2004-01-01

Chloroquine (CQ) is a very useful drug with a broad spectrum of uses (as anti malarial, anti amoebiasis and for connective tissue diseases). A major side effect preventing or limiting its utilization in blacks is chloroquine induced pruritus (CP). A descriptive cross sectional questionnaire based epidemiological study of medical and nursing students, medical doctors and other workers with historic CP in a Nigerian tertiary (teaching) hospital was carried out to determine factors and features related to the development of CP. From the study the intensity of CP was not reduced by taking less CQ. About 92% of the subjects had close relations who suffered from CP. 84.5% of responders itched for 1-3 days. The longest duration for CP was 7 days. The sites of itching in descending order were generalized (49.2%) hands (46%), legs and feet (46%), perineum/genitalia (28.5%). Relieving factor/drug was identified in 66.6% of responders. Itching with oral CQ occurred in 100%. Intramuscular injection of CQ caused 49% of itching. 19% had pre-chloroquine itch. 28.5% had CP with other antimalarials notably Amodiaquine (23.8%). 50.7% took other antimalarials when down with malaria. There is a need for the identification of a cheap and readily available antidote for CP to enable CQ remain useful/relevant in Nigeria and in the West African sub-region.

The Epidemiology of Imported Malaria in Taiwan between 2002–2013: The Importance of Sensitive Surveillance and Implications for Pre-Travel Medical Advice

PubMed Central

Chen, Shou-Chien; Chang, Hsiao-Ling; Chen, Kow-Tong

2014-01-01

The purpose of this study was to assess the epidemiology of imported malaria in Taiwan between 2002 and 2013. We analyzed the national data recorded by the Taiwan Centers for Disease Control (Taiwan CDC). Malaria cases were diagnosed by blood films, polymerase chain reaction, or rapid diagnostic tests. The risk of re-establishment of malarial transmission in Taiwan was assessed. A total of 229 malaria cases were included in our analysis. All of the cases were imported. One hundred and ninety-two cases (84%) were diagnosed within 13 days of the start of symptoms/signs; 43% of these cases were acquired in Africa and 44% were acquired in Asia. Plasmodium falciparum was responsible for the majority (56%) of these cases. Travel to an endemic area was associated with the acquisition of malaria. The malaria importation rate was 2.36 per 1,000,000 travelers (range 1.20–5.74). The reproductive number under control (Rc) was 0. No endemic transmission of malaria in Taiwan was identified. This study suggests that a vigilant surveillance system, vector-control efforts, case management, and an educational approach focused on travelers and immigrants who visit malaria endemic countries are needed to prevent outbreaks and sustain the elimination of malaria in Taiwan. PMID:24871257

Evaluation of a malarial antibody assay for use in the screening of blood and tissue products for clinical use.

PubMed

Kitchen, A D; Lowe, P H J; Lalloo, K; Chiodini, P L

2004-10-01

A new recombinant Plasmodium antigen enzyme immunoassay (EIA) for the detection of malarial antibodies was evaluated for the screening of 'malaria-risk' blood and tissue donations. A total of 13,269 donor and patient samples were tested by both the EIA and the standard diagnostic antibody immunofluorescence test (IFAT). A total of 114/138 (82.6%) samples from patients with P. falciparum and 11/13 (84.6%) samples from patients with P. vivax tested positive. A total of 714/13,053 (5.47%) samples from donors identified as 'malaria risk', owing to residency or travel, were reactive in the EIA. The assay is more sensitive than a previously implemented malarial antibody EIA (73% in acute P. falciparum and 56% in acute P. vivax infections). The sensitivity of this new EIA is comparable to that of the IFAT, and the specificity is sufficient to screen 'malaria-risk' donors.

Automated Detection of Leakage in Fluorescein Angiography Images with Application to Malarial Retinopathy

PubMed Central

Zhao, Yitian; J. C. MacCormick, Ian; G. Parry, David; Leach, Sophie; A. V. Beare, Nicholas; P. Harding, Simon; Zheng, Yalin

2015-01-01

The detection and assessment of leakage in retinal fluorescein angiogram images is important for the management of a wide range of retinal diseases. We have developed a framework that can automatically detect three types of leakage (large focal, punctate focal, and vessel segment leakage) and validated it on images from patients with malarial retinopathy. This framework comprises three steps: vessel segmentation, saliency feature generation and leakage detection. We tested the effectiveness of this framework by applying it to images from 20 patients with large focal leak, 10 patients with punctate focal leak, and 5,846 vessel segments from 10 patients with vessel leakage. The sensitivity in detecting large focal, punctate focal and vessel segment leakage are 95%, 82% and 81%, respectively, when compared to manual annotation by expert human observers. Our framework has the potential to become a powerful new tool for studying malarial retinopathy, and other conditions involving retinal leakage. PMID:26030010

Automated detection of leakage in fluorescein angiography images with application to malarial retinopathy.

PubMed

Zhao, Yitian; MacCormick, Ian J C; Parry, David G; Leach, Sophie; Beare, Nicholas A V; Harding, Simon P; Zheng, Yalin

2015-06-01

The detection and assessment of leakage in retinal fluorescein angiogram images is important for the management of a wide range of retinal diseases. We have developed a framework that can automatically detect three types of leakage (large focal, punctate focal, and vessel segment leakage) and validated it on images from patients with malarial retinopathy. This framework comprises three steps: vessel segmentation, saliency feature generation and leakage detection. We tested the effectiveness of this framework by applying it to images from 20 patients with large focal leak, 10 patients with punctate focal leak, and 5,846 vessel segments from 10 patients with vessel leakage. The sensitivity in detecting large focal, punctate focal and vessel segment leakage are 95%, 82% and 81%, respectively, when compared to manual annotation by expert human observers. Our framework has the potential to become a powerful new tool for studying malarial retinopathy, and other conditions involving retinal leakage.

Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite.

PubMed

Das, Pronay; Babbar, Palak; Malhotra, Nipun; Sharma, Manmohan; Jachak, Gorakhnath R; Gonnade, Rajesh G; Shanmugam, Dhanasekaran; Harlos, Karl; Yogavel, Manickam; Sharma, Amit; Reddy, D Srinivasa

2018-05-21

The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral centre anti-malarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme- and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency where changes at C3 are sensed by rotameric flipping of Glutamate332. Given that scores of anti-malarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of anti-microbial drug development.

The potential of anti-malarial compounds derived from African medicinal plants, part II: a pharmacological evaluation of non-alkaloids and non-terpenoids

PubMed Central

2014-01-01

Malaria is currently a public health concern in many countries in the world due to various factors which are not yet under check. Drug discovery projects targeting malaria often resort to natural sources in the search for lead compounds. A survey of the literature has led to a summary of the major findings regarding plant-derived compounds from African flora, which have shown anti-malarial/antiplasmodial activities, tested by in vitro and in vivo assays. Considerations have been given to compounds with activities ranging from “very active” to “weakly active”, leading to >500 chemical structures, mainly alkaloids, terpenoids, flavonoids, coumarins, phenolics, polyacetylenes, xanthones, quinones, steroids and lignans. However, only the compounds that showed anti-malarial activity, from “very active” to “moderately active”, are discussed in this review. PMID:24602358

Malarial retinopathy in northern Nigerian children.

PubMed

Mohammed, I; Ibrahim, U Y; Mukhtar, M; Farouq, Z; Obiagwu, P N; Yashua, A H

2010-01-01

This is a prospective study involving two centres. Children younger than 16 years old who had severe malaria underwent funduscopy. In one centre, direct ophthalmoscopy was performed by both an ophthalmologist and a non-ophthalmologist physician. At the other, two ophthalmologists performed a funduscopy on each patient using different methods (one using direct and the other indirect ophthalmoscopy). The objective was to determine the frequency of retinopathy and evaluate the effectiveness of direct ophthalmoscopy in detecting retinopathy in constantly dilated eyes. Of 62 children seen at both centres, 37% were found to have malarial retinopathy. Macula whitening was the most common finding. There was substantial agreement between the ophthalmologists using either the direct or indirect ophthalmoscopy techniques (Kappa value 0.604). However, at the centre using only direct ophthalmoscopy, there was poor agreement between the ophthalmologist and the non-ophthalmologist (kappa value -0.244). Direct ophthalmoscopy seemed to be effective in detecting malarial retinopathy, but only when performed by experienced personnel.

The efficiency of sporozoite transmission in the human malarias, Plasmodium falciparum and P. vivax*

PubMed Central

Burkot, T. R.; Graves, P. M.; Cattan, J. A.; Wirtz, R. A.; Gibson, F. D.

1987-01-01

Reported are malaria sporozoite and inoculation rates over a 1-year period in eight epidemiologically defined villages of different endemicity in Madang Province, Papua New Guinea. In the study, more than 41 000 wild-caught mosquitos were analysed for Plasmodium falciparum and P. vivax sporozoites by ELISA. In a given village the entomological inoculation rates correlated strongly with the prevalences of both these malarial parasites in children. However, the prevalence of P. falciparum infections in children was much higher than that of P. vivax, despite similar inoculation rates for the two species. These data suggest that in Papua New Guinea P. falciparum is more efficiently transmitted than P. vivax from mosquito to man. The increased efficiency of transmission of P. falciparum may be due to the heavier sporozoite densities in wild-caught mosquitos naturally infected with P. falciparum sporozoites that were tenfold greater than the sporozoite densities in mosquitos infected with P. vivax. PMID:3311441

Current Mathematical Models for Analyzing Anti-Malarial Antibody Data with an Eye to Malaria Elimination and Eradication

PubMed Central

Sepúlveda, Nuno; Stresman, Gillian; White, Michael T.; Drakeley, Chris J.

2015-01-01

The last decade has witnessed a steady reduction of the malaria burden worldwide. With various countries targeting disease elimination in the near future, the popular parasite infection or entomological inoculation rates are becoming less and less informative of the underlying malaria burden due to a reduced number of infected individuals or mosquitoes at the time of sampling. To overcome such problem, alternative measures based on antibodies against specific malaria antigens have gained recent interest in malaria epidemiology due to the possibility of estimating past disease exposure in absence of infected individuals. This paper aims then to review current mathematical models and corresponding statistical approaches used in antibody data analysis. The application of these models is illustrated with three data sets from Equatorial Guinea, Brazilian Amazonia region, and western Kenyan highlands. A brief discussion is also carried out on the future challenges of using these models in the context of malaria elimination. PMID:26770994

Malaria eradication in Mexico: Some historico-parasitological views oncold war, deadly fevers by Marcos Cueto, Ph.D

PubMed Central

Malagón, Filiberto

2008-01-01

This review of Professor Marcos Cueto's Cold War Deadly Fevers: Malaria Eradication in Mexico, 1955–1975 discusses some of the historical, sociological, political and parasitological topics included in Dr. Cueto's superbly well-informed volume. The reviewer, a parasitologist, follows the trail illuminated by Dr. Cueto through the foundations of the malaria eradication campaign; the release in Mexico of the first postage stamp in the world dedicated to malaria control; epidemiological facts on malarial morbidity and mortality in Mexico when the campaign began; the emergence of problem areas that impeded eradication; considerations on mosquitoes and malaria transmission in Mexico; the role of business and society in malaria eradication; the results of the campaign; the relationship between malaria and poverty; and the parasitological lessons to be learned from the history of malaria eradication campaigns. Dr. Cueto's excellent and well-informed exploration of malaria – not merely as a disease but as a social, economic and human problem – makes this book required reading.

Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study

PubMed Central

Taiwe, Germain Sotoing

2016-01-01

Background. Malaria remains a major killer of children in Sub-Saharan Africa, while anaemia is a public health problem with significant morbidity and mortality. Examining the factors associated with moderate to severe anaemia (MdSA) and malarial anaemia as well as the haematological characteristics is essential. Methodology. Children (1–14 years) at presentation at the Regional Hospital Annex-Buea were examined clinically and blood samples were collected for malaria parasite detection and full blood count evaluation. Results. Plasmodium falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of the 216 children, respectively. Anaemia prevalence was significantly higher in malaria parasite positive children and those with fever than their respective counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was significantly higher in children whose household head had no formal education, resided in the lowland, or was febrile, while MdSMA was significantly higher in febrile children only. Children with MdSMA had significantly lower mean white blood cell, lymphocyte, and platelet counts while the mean granulocyte count was significantly higher. Conclusion. Being febrile was the only predictor of both MdSA and MdSMA. More haematological insult occurred in children with MdSMA compared to MdSA. PMID:27895939

New developments in anti-malarial target candidate and product profiles.

PubMed

Burrows, Jeremy N; Duparc, Stephan; Gutteridge, Winston E; Hooft van Huijsduijnen, Rob; Kaszubska, Wiweka; Macintyre, Fiona; Mazzuri, Sébastien; Möhrle, Jörg J; Wells, Timothy N C

2017-01-13

A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

The potential of anti-malarial compounds derived from African medicinal plants, part I: a pharmacological evaluation of alkaloids and terpenoids

PubMed Central

2013-01-01

Traditional medicine caters for about 80% of the health care needs of many rural populations around the world, especially in developing countries. In addition, plant-derived compounds have played key roles in drug discovery. Malaria is currently a public health concern in many countries in the world due to factors such as chemotherapy faced by resistance, poor hygienic conditions, poorly managed vector control programmes and no approved vaccines. In this review, an attempt has been made to assess the value of African medicinal plants for drug discovery by discussing the anti-malarial virtue of the derived phytochemicals that have been tested by in vitro and in vivo assays. This survey was focused on pure compounds derived from African flora which have exhibited anti-malarial properties with activities ranging from “very active” to “weakly active”. However, only the compounds which showed anti-malarial activities from “very active” to “moderately active” are discussed in this review. The activity of 278 compounds, mainly alkaloids, terpenoids, flavonoids, coumarines, phenolics, polyacetylenes, xanthones, quinones, steroids, and lignans have been discussed. The first part of this review series covers the activity of 171 compounds belonging to the alkaloid and terpenoid classes. Data available in the literature indicated that African flora hold an enormous potential for the development of phytomedicines for malaria. PMID:24330395

Glucose-6-phosphate dehydrogenase deficiency in an endemic area for malaria in Manaus: a cross-sectional survey in the Brazilian Amazon.

PubMed

Santana, Marli Stela; de Lacerda, Marcus Vinícius Guimarães; Barbosa, Maria das Graças Vale; Alecrim, Wilson Duarte; Alecrim, Maria das Graças Costa

2009-01-01

There is a paucity of information regarding glucose-6-phosphate dehydrogenase (G6PD) deficiency in endemic areas for malaria in Latin America. This study determined the prevalence of the G6PD deficiency in 200 male non-consanguineous individuals residing in the Ismail Aziz Community, on the outskirts of Manaus (Brazilian Amazon). Six individuals (3%) were deficient using the qualitative Brewer's test. Gel electrophoresis showed that five of these patients were G6PD A(-). The deficiency was not associated with the ethnic origin (P = 0.571). In a multivariate logistic regression analysis, G6PD deficiency protected against three or more episodes of malaria (P = 0.049), independently of the age, and was associated with a history of jaundice (P = 0.020) and need of blood transfusion (P = 0.045) during previous treatment for malarial infection, independently of the age and the previous malarial exposure. The frequency of G6PD deficiency was similar to other studies performed in Brazil and the finding of a predominant G6PD A(-) variant will help the clinical management of patients with drug-induced haemolysis. The history of jaundice and blood transfusion during previous malarial infection may trigger the screening of patients for G6PD deficiency. The apparent protection against multiple malarial infections in an area primarily endemic for Plasmodium vivax needs further investigation.

The association between price, competition, and demand factors on private sector anti-malarial stocking and sales in western Kenya: considerations for the AMFm subsidy.

PubMed

O'Meara, Wendy Prudhomme; Obala, Andrew; Thirumurthy, Harsha; Khwa-Otsyula, Barasa

2013-06-05

Households in sub-Saharan Africa are highly reliant on the retail sector for obtaining treatment for malaria fevers and other illnesses. As donors and governments seek to promote the use of artemisinin combination therapy in malaria-endemic areas through subsidized anti-malarials offered in the retail sector, understanding the stocking and pricing decisions of retail outlets is vital. A survey of all medicine retailers serving Bungoma East District in western Kenya was conducted three months after the launch of the AMFm subsidy in Kenya. The survey obtained information on each anti-malarial in stock: brand name, price, sales volume, outlet characteristics and GPS co-ordinates. These data were matched to household-level data from the Webuye Health and Demographic Surveillance System, from which population density and fever prevalence near each shop were determined. Regression analysis was used to identify the factors associated with retailers' likelihood of stocking subsidized artemether lumefantrine (AL) and the association between price and sales for AL, quinine and sulphadoxine-pyrimethamine (SP). Ninety-seven retail outlets in the study area were surveyed; 11% of outlets stocked subsidized AL. Size of the outlet and having a pharmacist on staff were associated with greater likelihood of stocking subsidized AL. In the multivariable model, total volume of anti-malarial sales was associated with greater likelihood of stocking subsidized AL and competition was important; likelihood of stocking subsidized AL was considerably higher if the nearest neighbour stocked subsidized AL. Price was a significant predictor of sales volume for all three types of anti-malarials but the relationship varied, with the largest price sensitivity found for SP drugs. The results suggest that helping small outlets overcome the constraints to stocking subsidized AL should be a priority. Competition between retailers and prices can play an important role in greater adoption of AL.

Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

PubMed Central

Mishra, Kirti; Dash, Aditya P; Swain, Bijay K; Dey, Nrisingha

2009-01-01

Background Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. Results The 50% inhibitory concentration (IC50) of AP (7.2 μg/ml) was found better than HC (10.8 μg/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. Conclusion Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs. PMID:19216765

Substandard anti-malarial drugs in Burkina Faso

PubMed Central

Tipke, Maike; Diallo, Salou; Coulibaly, Boubacar; Störzinger, Dominic; Hoppe-Tichy, Torsten; Sie, Ali; Müller, Olaf

2008-01-01

Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers) and illicit (market and street vendors, shops) sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50%) chloroquine, 10/77 (13%) pyrimethamine-sulphadoxine, 9/77 (12%) quinine, 6/77 (8%) amodiaquine, 9/77 (12%) artesunate, and 4/77 (5%) artemether-lumefantrine. 32/77 (42%) drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6%) and 27/30 (90.0%) samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the now wider available and substantially more costly artemisinin-based combination therapies. PMID:18505584

The association between price, competition, and demand factors on private sector anti-malarial stocking and sales in western Kenya: considerations for the AMFm subsidy

PubMed Central

2013-01-01

Background Households in sub-Saharan Africa are highly reliant on the retail sector for obtaining treatment for malaria fevers and other illnesses. As donors and governments seek to promote the use of artemisinin combination therapy in malaria-endemic areas through subsidized anti-malarials offered in the retail sector, understanding the stocking and pricing decisions of retail outlets is vital. Methods A survey of all medicine retailers serving Bungoma East District in western Kenya was conducted three months after the launch of the AMFm subsidy in Kenya. The survey obtained information on each anti-malarial in stock: brand name, price, sales volume, outlet characteristics and GPS co-ordinates. These data were matched to household-level data from the Webuye Health and Demographic Surveillance System, from which population density and fever prevalence near each shop were determined. Regression analysis was used to identify the factors associated with retailers’ likelihood of stocking subsidized artemether lumefantrine (AL) and the association between price and sales for AL, quinine and sulphadoxine-pyrimethamine (SP). Results Ninety-seven retail outlets in the study area were surveyed; 11% of outlets stocked subsidized AL. Size of the outlet and having a pharmacist on staff were associated with greater likelihood of stocking subsidized AL. In the multivariable model, total volume of anti-malarial sales was associated with greater likelihood of stocking subsidized AL and competition was important; likelihood of stocking subsidized AL was considerably higher if the nearest neighbour stocked subsidized AL. Price was a significant predictor of sales volume for all three types of anti-malarials but the relationship varied, with the largest price sensitivity found for SP drugs. Conclusion The results suggest that helping small outlets overcome the constraints to stocking subsidized AL should be a priority. Competition between retailers and prices can play an important role in greater adoption of AL. PMID:23738604

MEASURING ECONOMIC GROWTH FROM OUTER SPACE

PubMed Central

Henderson, J. Vernon; Storeygard, Adam; Weil, David N.

2013-01-01

GDP growth is often measured poorly for countries and rarely measured at all for cities or subnational regions. We propose a readily available proxy: satellite data on lights at night. We develop a statistical framework that uses lights growth to augment existing income growth measures, under the assumption that measurement error in using observed light as an indicator of income is uncorrelated with measurement error in national income accounts. For countries with good national income accounts data, information on growth of lights is of marginal value in estimating the true growth rate of income, while for countries with the worst national income accounts, the optimal estimate of true income growth is a composite with roughly equal weights. Among poor-data countries, our new estimate of average annual growth differs by as much as 3 percentage points from official data. Lights data also allow for measurement of income growth in sub- and supranational regions. As an application, we examine growth in Sub Saharan African regions over the last 17 years. We find that real incomes in non-coastal areas have grown faster by 1/3 of an annual percentage point than coastal areas; non-malarial areas have grown faster than malarial ones by 1/3 to 2/3 annual percent points; and primate city regions have grown no faster than hinterland areas. Such applications point toward a research program in which “empirical growth” need no longer be synonymous with “national income accounts.” PMID:25067841

Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

PubMed

Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

2016-08-21

The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Private sector opportunities and threats to achieving malaria elimination in the Greater Mekong Subregion: results from malaria outlet surveys in Cambodia, the Lao PDR, Myanmar, and Thailand.

PubMed

Phok, Sochea; Phanalasy, Saysana; Thein, Si Thu; Likhitsup, Asawin

2017-05-02

The aim of this paper is to review multi-country evidence of private sector adherence to national regulations, guidelines, and quality-assurance standards for malaria case management and to document current coverage of private sector engagement and support through ACTwatch outlet surveys implemented in 2015 and 2016. Over 76,168 outlets were screened, and approximately 6500 interviews were conducted (Cambodia, N = 1303; the Lao People's Democratic Republic (PDR), N = 724; Myanmar, N = 4395; and Thailand, N = 74). There was diversity in the types of private sector outlets providing malaria treatment across countries, and the extent to which they were authorized to test and treat for malaria differed. Among outlets stocking at least one anti-malarial, public sector availability of the first-line treatment for uncomplicated Plasmodium falciparum or Plasmodium vivax malaria was >75%. In the anti-malarial stocking private sector, first-line treatment availability was variable (Cambodia, 70.9%; the Lao PDR, 40.8%; Myanmar P. falciparum = 42.7%, P. vivax = 19.6%; Thailand P. falciparum = 19.6%, P. vivax = 73.3%), as was availability of second-line treatment (the Lao PDR, 74.9%; Thailand, 39.1%; Myanmar, 19.8%; and Cambodia, 0.7%). Treatment not in the National Treatment Guidelines (NTGs) was most common in Myanmar (35.8%) and Cambodia (34.0%), and was typically stocked by the informal sector. The majority of anti-malarials distributed in Cambodia and Myanmar were first-line P. falciparum or P. vivax treatments (90.3% and 77.1%, respectively), however, 8.8% of the market share in Cambodia was treatment not in the NTGs (namely chloroquine) and 17.6% in Myanmar (namely oral artemisinin monotherapy). In the Lao PDR, approximately 9 in 10 anti-malarials distributed in the private sector were second-line treatments-typically locally manufactured chloroquine. In Cambodia, 90% of anti-malarials were distributed through outlets that had confirmatory testing available. Over half of all anti-malarial distribution was by outlets that did not have confirmatory testing available in the Lao PDR (54%) and Myanmar (59%). Availability of quality-assured rapid diagnostic tests (RDT) amongst the RDT-stocking public sector ranged from 99.3% in the Lao PDR to 80.1% in Cambodia. In Cambodia, the Lao PDR, and Myanmar, less than 50% of the private sector reportedly received engagement (access to subsidized commodities, supervision, training or caseload reporting), which was most common among private health facilities and pharmacies. Findings from this multi-country study suggest that Cambodia, the Lao PDR, Myanmar, and Thailand are generally in alignment with national regulations, treatment guidelines, and quality-assurance standards. However, important gaps persist in the private sector which pose a threat to national malaria control and elimination goals. Several options are discussed to help align the private sector anti-malarial market with national elimination strategies.

Urban malaria treatment behaviour in the context of low levels of malaria transmission in Lagos, Nigeria.

PubMed

Brieger, W R; Sesay, H R; Adesina, H; Mosanya, M E; Ogunlade, P B; Ayodele, J O; Orisasona, S A

2001-01-01

Urban malaria in West Africa is not well documented. While rapid urbanisation may create environmental conditions that favour mosquito breeding, urban pollution may inhibit the growth of Anopheles species. In 1996, the Basic Support for Institutionalizing Child Survival (BASICS) Project of the U.S. Agency for International Development (USAID) started building urban community health coalitions in Lagos, Nigeria, to empower communities to provide prompt treatment and appropriate prevention for major causes of childhood morbidity and mortality, including malaria, diarrhoeal disease, acute respiratory infections and vaccine preventable diseases. Intervention against malaria was predicated on national policies that assumed Nigeria was holo-endemic for malaria and that prompt treatment of febrile illness with anti-malarial drugs was an appropriate action. At the suggestion and with the assistance of another USAID programme, the Environmental Health Project (EHP), BASICS embarked on a rapid assessment of the epidemiological, entomological and sociological situation of malaria transmission and case management in three Lagos communities. During April and May 1998, blood film investigation of 916 children between the ages of 6 months and 5 years yielded a parasite prevalence rate of 0.9%. Night knockdown collections of mosquitoes in rooms yielded only C. quinquefasciatus and A. aegypti. The same results were obtained for night landing collections on human bait. Very low densities of A. gambiae larvae were found in breeding sites in Lagos Island (0.7) and Ajegunle (0.3). In contrast, community members, during focus group discussion identified malaria, in it various culturally defined forms, as a major health problem. Among the children examined clinically, 186 (20.3%) reported an illness, which they called "malaria" in the previous two weeks, and 180 had sought treatment for this illness. Data obtained from 303 shops in the area documented that a minimum of US dollars 4,000 was spent on purchases of anti-malarial drugs in the previous week. The implications of these findings for both professional and community education are discussed.

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.

Mast cells and histamine alter intestinal permeability during malaria parasite infection.

PubMed

Potts, Rashaun A; Tiffany, Caitlin M; Pakpour, Nazzy; Lokken, Kristen L; Tiffany, Connor R; Cheung, Kong; Tsolis, Renée M; Luckhart, Shirley

2016-03-01

Co-infections with malaria and non-typhoidal Salmonella serotypes (NTS) can present as life-threatening bacteremia, in contrast to self-resolving NTS diarrhea in healthy individuals. In previous work with our mouse model of malaria/NTS co-infection, we showed increased gut mastocytosis and increased ileal and plasma histamine levels that were temporally associated with increased gut permeability and bacterial translocation. Here, we report that gut mastocytosis and elevated plasma histamine are also associated with malaria in an animal model of falciparum malaria, suggesting a broader host distribution of this biology. In support of mast cell function in this phenotype, malaria/NTS co-infection in mast cell-deficient mice was associated with a reduction in gut permeability and bacteremia. Further, antihistamine treatment reduced bacterial translocation and gut permeability in mice with malaria, suggesting a contribution of mast cell-derived histamine to GI pathology and enhanced risk of bacteremia during malaria/NTS co-infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

Susceptibility of human Plasmodium knowlesi infections to anti-malarials

PubMed Central

2013-01-01

Background Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed. Methods Here the ex vivo sensitivity of human P. knowlesi isolates in Malaysian Borneo were studied, using a WHO schizont maturation assay modified to accommodate the quotidian life cycle of this parasite. The in vitro sensitivities of P. knowlesi H strain adapted from a primate infection to in vitro culture (by measuring the production of Plasmodium lactate dehydrogenase) were also examined together with some assays using Plasmodium falciparum and Plasmodium vivax. Results Plasmodium knowlesi is uniformly highly sensitive to artemisinins, variably and moderately sensitive to chloroquine, and less sensitive to mefloquine. Conclusions Taken together with reports of clinical failures when P. knowlesi is treated with mefloquine, the data suggest that caution is required if using mefloquine in prevention or treatment of P. knowlesi infections, until further studies are undertaken. PMID:24245918

New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum.

PubMed

Lobo, Lis; Cabral, Lília I L; Sena, Maria Inês; Guerreiro, Bruno; Rodrigues, António Sebastião; de Andrade-Neto, Valter Ferreira; Cristiano, Maria L S; Nogueira, Fatima

2018-04-03

The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs. A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model. Ring survival and mature stage survival assays were performed against artemisinin-resistant and artemisinin-sensitive P. falciparum strains. Cytotoxicity was evaluated against mammalian cell lines V79 and HepG2, using the MTT assay. The synthesis and anti-malarial activity of 21 new endoperoxide-derived compounds is reported, where the peroxide pharmacophore is part of a trioxolane (ozonide) or a tetraoxane moiety, flanked by adamantane and a substituted cyclohexyl ring. Eight compounds exhibited sub-micromolar anti-malarial activity (IC 50 0.3-71.1 nM), no cross-resistance with artemisinin or quinolone derivatives and negligible cytotoxicity towards mammalian cells. From these, six produced ring stage survival < 1% against the resistant strain IPC5202 and three of them totally suppressed Plasmodium berghei parasitaemia in mice after oral administration. The investigated, trioxolane-tetrazole conjugates LC131 and LC136 emerged as potential anti-malarial candidates; they show negligible toxicity towards mammalian cells, ability to kill intra-erythrocytic asexual stages of artemisinin-resistant P. falciparum and capacity to totally suppress P. berghei parasitaemia in mice.

Some ecological attributes of malarial vector Anopheles superpictus Grassi in endemic foci in southeastern Iran

PubMed Central

Nejati, Jalil; Vatandoost, Hasan; Oshghi, Mohammad Ali; Salehi, Masud; Mozafari, Ehssan; Moosa-Kazemi, Seyed Hasan

2013-01-01

Objective To determine the bionomics and susceptibility status of the malarial vector Anopheles superpictus (An. superpictus) to different insecticides in the Sistan-Baluchestan province which has the highest malarial prevalence in Iran. Methods Different sampling methods, in addition to scoring abdominal conditions, were used to define the seasonal activity and endo/exophilic behavior of this species. In addition, the standard WHO susceptibility tests were applied on adult field strains. Results Most adult mosquitoes were collected from outdoor shelters. The peak of seasonal activity of An. superpictus occurred at the end of autumn. Most larvae were collected from natural and permanent breeding places with full sunlight and no vegetation. Blood feeding activities occurred around midnight. Compared with the abdominal conditions of adult mosquitoes collected indoors, the abdominal conditions of adult mosquitoes collected outdoors were gravid and semigravid. This species was suspected to be resistant to DDT, but was susceptible to other insecticides. Conclusions An. superpictus was present in almost all outdoor shelters, and the ratios of gravid, semigravid/unfed, and freshly fed confirmed that this species had a higher tendency to rest outdoors than indoors. This behavior can protect An. superpictus from indoor residual spraying in this malarious area. To the best of our knowledge, this is the first report on the susceptibility status of An. superpictus in Southeastern Iran. We do not suggest the use of DDT for indoor residual spraying in southeast Iran. PMID:24093794

BDA-410: a novel synthetic calpain inhibitor active against blood stage malaria.

PubMed

Li, Xuerong; Chen, Huiqing; Jeong, Jong-Jin; Chishti, Athar H

2007-09-01

Falcipains, the papain-family cysteine proteases of the Plasmodium falciparum, are potential drug targets for malaria parasite. Pharmacological inhibition of falcipains can block the hydrolysis of hemoglobin, parasite development, and egress, suggesting that falcipains play a key role at the blood stage of parasite life cycle. In the present study, we evaluated the anti-malarial effects of BDA-410, a novel cysteine protease inhibitor as a potential anti-malarial drug. Recombinant falcipain (MBP-FP-2B) and P. falciparum trophozoite extract containing native falcipains were used for enzyme inhibition studies in vitro. The effect of BDA-410 on the malaria parasite development in vitro as well as its anti-malarial activity in vivo was evaluated using the Plasmodium chabaudi infection rodent model. The 50% inhibitory concentrations of BDA-410 were determined to be 628 and 534nM for recombinant falcipain-2B and parasite extract, respectively. BDA-410 inhibited the malaria parasite growth in vitro with an IC(50) value of 173nM causing irreversible damage to the intracellular parasite. In vivo, the BDA-410 delayed the progression of malaria infection significantly using a mouse model of malaria pathogenesis. The characterization of BDA-410 as a potent inhibitor of P. falciparum cysteine proteases, and the demonstration of its efficacy in blocking parasite growth both in vitro and in vivo assays identifies BDA-410 is an important lead compound for the development of novel anti-malarial drugs.

Serological responses and immunity to superinfection with avian malaria in experimentally-infected Hawaii Amakihi

USGS Publications Warehouse

Atkinson, Carter T.; Dusek, Robert J.; Lease, Julie K.

2001-01-01

Six of seven Hawaii Amakihi (Hemignathus virens) with chronic malarial infections had no increases in peripheral parasitemia, declines in food consumption, or loss of body weight when rechallenged with the homologous isolate of Plasmodium relictum 61 to 62 days after initial infection. Five uninfected control amakihi exposed at the same time to infective mosquito bites developed acute infections with high parasitemias. Reductions in food consumption and loss of body weight occurred in all control birds and three of these individuals eventually died. When surviving birds were rechallenged >2 yr later with either the same parasite isolate or an isolate of P. relictum collected on the island of Kauai, all individuals were immune to superinfection. Chronically infected birds developed antibodies to a common suite of malarial antigens ranging in size from 22 to 170 kDa that were detectable as early as 8 days post infection on immunoblots of SDS-polyacrylamide gels. Antibodies to this suite of malarial antigens persisted as long as 1,248 days after initial infection and were consistently detectable at times when parasites were not easily found by microscopy on Giemsa-stained blood smears. The immunoblotting method that is described here appears to be an effective technique for identifying birds with chronic, low-intensity malarial infections when circulating parasites are not easily detectable by microscopy. Hawaiian honeycreepers that are capable of recovering from acute infections develop concomitant immunity to superinfection, making them functionally immune in areas where malaria transmission has become endemic.

Potential Antagonist of Folic Acid Metabolism as Malarial Drugs,

DTIC Science & Technology

1982-09-01

which sen.irited from the hydrocloric acid was filtered and then washed with water (25 ml). The reaction gave 2.3 g of the product which melted be...neutralized with cold dilute hydrocloric acid and evaporated to dryness. The residue was then extracted with methylene chloride filtered, and again...FhGh6/15hEE 1281 12.5 ~I1.50 IIA 132ii MJCRc)tll I’RE SOLU i UN ltIS CHiARI AD FINAL REPORT POTENTIAL ANTAGONIST OF FOLIC ACID METABOLISM AS MALARIAL

Characterization and storage of malaria antigens: Localization and chemical characterization of Plasmodium knowlesi schizont antigens

PubMed Central

Deans, J. A.; Cohen, S.

1979-01-01

The identification of malarial antigens that induce protective immunity could provide a rational basis for developing an effective antimalarial vaccine as well as specific serodiagnostic tests indicative of clinical immune status. Since protective immunity is probably induced by stage-dependent rather than stage-independent antigens, the antigenic composition of different stages of Plasmodium knowlesi has been compared, and a limited chemical characterization undertaken. This information should provide some insight into the types of preparative procedure appropriate for the purification of functionally important malarial antigens. PMID:120777

Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children.

PubMed

Abanyie, Francisca A; McCracken, Courtney; Kirwan, Patrick; Molloy, Síle F; Asaolu, Samuel O; Holland, Celia V; Gutman, Julie; Lamb, Tracey J

2013-01-02

Co-infection with malaria and intestinal parasites such as Ascaris lumbricoides is common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection. Ascaris is known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whether Ascaris co-infection can minimize the severity of malarial anaemia. Data from a randomized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged (6-59 months) children conducted in 2006-2007 were analysed to examine the effect of malaria and Ascaris co-infection on anaemia severity. Children were enrolled and tested for malaria, helminths and anaemia at baseline, four, and eight months. Six hundred and ninety subjects were analysed in this study. Generalized linear mixed models were used to assess the relationship between infection status and Ascaris and Plasmodium parasite intensity on severity of anaemia, defined as a haemoglobin less than 11 g/dL. Malaria prevalence ranged from 35-78% over the course of this study. Of the malaria-infected children, 55% were co-infected with Ascaris at baseline, 60% were co-infected four months later and 48% were co-infected eight months later, underlining the persistent prevalence of malaria-nematode co-infections in this population. Over the course of the study the percentage of anaemic subjects in the population ranged between 84% at baseline and 77% at the eight-month time point. The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria. Ascaris infection alone did not increase the odds of being anaemic, indicating that malaria was the main cause of anaemia in this population. There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria and Ascaris. In this cohort of Nigerian preschool children, malaria infection was the major contributor to anaemia status. Ascaris co-infection neither exacerbated nor ameliorated the severity of malarial anaemia.

Major Reduction in Anti-Malarial Drug Consumption in Senegal after Nation-Wide Introduction of Malaria Rapid Diagnostic Tests

PubMed Central

Thiam, Sylla; Thior, Moussa; Faye, Babacar; Ndiop, Médoune; Diouf, Mamadou Lamine; Diouf, Mame Birame; Diallo, Ibrahima; Fall, Fatou Ba; Ndiaye, Jean Louis; Albertini, Audrey; Lee, Evan; Jorgensen, Pernille; Gaye, Oumar; Bell, David

2011-01-01

Background While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. Methods and Findings Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584873 suspect fever cases). An estimated 516576 courses of inappropriate ACT prescription were averted. Conclusions The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement. Programmes need to be allowed flexibility in management of these funds to address increases in other programmatic costs that may accrue from improved diagnosis of febrile disease. PMID:21494674

The Effect of Three-Monthly Albendazole Treatment on Malarial Parasitemia and Allergy: A Household-Based Cluster-Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Kaisar, Maria M. M.; May, Linda; Prasetyani, Margaretta A.; Wahyuni, Sitti; Djuardi, Yenny; Ariawan, Iwan; Wibowo, Heri; Lell, Bertrand; Sauerwein, Robert; Brice, Gary T.; Sutanto, Inge; van Lieshout, Lisette; de Craen, Anton J. M.; van Ree, Ronald; Verweij, Jaco J.; Tsonaka, Roula; Houwing-Duistermaat, Jeanine J.; Luty, Adrian J. F.; Sartono, Erliyani; Supali, Taniawati; Yazdanbakhsh, Maria

2013-01-01

Background Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. Methods and Findings A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5–15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35–12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74–1.86) at 9 months or 1.37 (0.93–2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. Conclusions The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. Trial Registration Controlled-Trials.com ISRCTN83830814 PMID:23526959

Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid.

PubMed

Ro, Dae-Kyun; Ouellet, Mario; Paradise, Eric M; Burd, Helcio; Eng, Diana; Paddon, Chris J; Newman, Jack D; Keasling, Jay D

2008-11-04

Due to the global occurrence of multi-drug-resistant malarial parasites (Plasmodium falciparum), the anti-malarial drug most effective against malaria is artemisinin, a natural product (sesquiterpene lactone endoperoxide) extracted from sweet wormwood (Artemisia annua). However, artemisinin is in short supply and unaffordable to most malaria patients. Artemisinin can be semi-synthesized from its precursor artemisinic acid, which can be synthesized from simple sugars using microorganisms genetically engineered with genes from A. annua. In order to develop an industrially competent yeast strain, detailed analyses of microbial physiology and development of gene expression strategies are required. Three plant genes coding for amorphadiene synthase, amorphadiene oxidase (AMO or CYP71AV1), and cytochrome P450 reductase, which in concert divert carbon flux from farnesyl diphosphate to artemisinic acid, were expressed from a single plasmid. The artemisinic acid production in the engineered yeast reached 250 microg mL(-1) in shake-flask cultures and 1 g L(-1) in bio-reactors with the use of Leu2d selection marker and appropriate medium formulation. When plasmid stability was measured, the yeast strain synthesizing amorphadiene alone maintained the plasmid in 84% of the cells, whereas the yeast strain synthesizing artemisinic acid showed poor plasmid stability. Inactivation of AMO by a point-mutation restored the high plasmid stability, indicating that the low plasmid stability is not caused by production of the AMO protein but by artemisinic acid synthesis or accumulation. Semi-quantitative reverse-transcriptase (RT)-PCR and quantitative real time-PCR consistently showed that pleiotropic drug resistance (PDR) genes, belonging to the family of ATP-Binding Cassette (ABC) transporter, were massively induced in the yeast strain producing artemisinic acid, relative to the yeast strain producing the hydrocarbon amorphadiene alone. Global transcriptional analysis by yeast microarray further demonstrated that the induction of drug-resistant genes such as ABC transporters and major facilitator superfamily (MSF) genes is the primary cellular stress-response; in addition, oxidative and osmotic stress responses were observed in the engineered yeast. The data presented here suggest that the engineered yeast producing artemisinic acid suffers oxidative and drug-associated stresses. The use of plant-derived transporters and optimizing AMO activity may improve the yield of artemisinic acid production in the engineered yeast.

In vitro studies on the sensitivity pattern of Plasmodium falciparum to anti-malarial drugs and local herbal extracts.

PubMed

Olasehinde, Grace I; Ojurongbe, Olusola; Adeyeba, Adegboyega O; Fagade, Obasola E; Valecha, Neena; Ayanda, Isaac O; Ajayi, Adesola A; Egwari, Louis O

2014-02-20

The resistance of human malaria parasites to anti-malarial compounds has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. One way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents. Sensitivity of 100 Plasmodium falciparum isolates to chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, artemisinin, Momordica charantia ('Ejirin') Diospyros monbuttensis ('Egun eja') and Morinda lucida ('Oruwo') was determined using the in vitro microtest (Mark III) technique to determine the IC50 of the drugs. All the isolates tested were sensitive to quinine, mefloquine and artesunate. Fifty-one percent of the isolates were resistant to chloroquine, 13% to amodiaquine and 5% to sulphadoxine/pyrimethamine. Highest resistance to chloroquine (68.9%) was recorded among isolates from Yewa zone while highest resistance to amodiaquine (30%) was observed in Ijebu zone. Highest resistance to sulphadoxine/pyrimethamine was recorded in Yewa and Egba zones, respectively. A positive correlation was observed between the responses to artemisinin and mefloquine (P<0.05), artemisinin and quinine (P<0.05) and quinine and mefloquine (P<0.05). A negative correlation was observed between the responses to chloroquine and mefloquine (P>0.05). Highest anti-plasmodial activity was obtained with the ethanolic extract of D. monbuttensis (IC50 = 3.2 nM) while the lowest was obtained from M. lucida (IC50 = 25 nM). Natural products isolated from plants used in traditional medicine, which have potent anti-plasmodial action in vitro, represent potential sources of new anti-malarial drugs.

Serum sex hormones in men occupationally exposed to dichloro-diphenyl-trichloro ethane (DDT) as young adults.

PubMed

Cocco, Pierluigi; Loviselli, Andrea; Fadda, Domenica; Ibba, Antonio; Melis, Massimo; Oppo, Alessandro; Serra, Stefano; Taberlet, Alessandro; Tocco, Maria Giuseppina; Flore, Costantino

2004-09-01

To explore endocrine effects in relation to para,para'-dichloro-diphenyl-dichloro ethylene (p,p'-DDE) body burden and past occupational exposure to its precursor dichloro-diphenyl-trichloro ethane (DDT), we assayed serum sex hormones, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG), and p,p'-DDE levels in 107 male participants in a 1946-1950 anti-malarial campaign in Sardinia, Italy. Cumulative DDT exposure during the anti-malarial operations was retrospectively estimated from detailed reports of the anti-malarial agency. Ortho,para-DDE, and its precursor ortho,para-DDT were always below the detection limit. p,p'-DDT was detected in 14/107 subjects, and p,p'-DDE in 106/107 subjects. The median lipid-adjusted p,p'-DDE serum concentration over the total study population was 396 parts per billion (interquartile range 157-1045), and it did not vary according to the job at the time of anti-malarial operations, nor was it affected by cumulative DDT exposure. LH, FSH, and SHBG, but not testosterone or E2, showed a significant positive correlation with age. Neither current serum p,p'-DDE nor past cumulative DDT exposure affected sex hormone concentrations. Our results suggest that (1) the low current p,p'-DDE serum concentration does not affect serum hormone levels, and (2) past cumulative DDT exposure is not correlated with the current p,p'-DDE serum level, nor does it show persistent effects on serum hormone levels.

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

An edible vaccine for malaria using transgenic tomatoes of varying sizes, shapes and colors to carry different antigens.

PubMed

Chowdhury, Kamal; Bagasra, Omar

2007-01-01

Malaria, a disease caused by protozoan parasites of genus Plasmodium, is one of the world's biggest scourges. Over two billion individuals reside in the malaria endemic areas and the disease affects 300-500 million people annually. As a result of malarial-infection, an estimated three million lives are lost annually, among them over one million children (majority under 5 years of age). The mortality due to malaria has increased because of the spread of drug-resistant strains of the parasite, the breakdown of health services in many affected areas, the interaction of the disease with human immunodeficiency virus (HIV) infection, and possibly the effects of climate change. Infants and young children with malaria often die from severe anemia, cerebral involvement,or prostration caused by overwhelming infection; many new borns die from complications of low birth weight caused by maternal malaria during pregnancy. The scarce economic resources and lack of communication, infrastructure and adequate means of travel in the endemic areas make it extremely difficult to implement traditional infection control measures (i.e., mosquito control, preventive anti-malarial drugs and nets). To make the matter worse, both malarial parasites and its insect vectors are increasingly becoming resistant to anti-malarial agents (chloroquine) and insecticides (both DDT and melathione and related chemicals), respectively. By conventional wisdom, the immune mechanisms responsible for protection against malaria will require a multiple of 10-15 antigen targets for proper protection against various stages of malarial infection. By standard vaccination protocols, such a large number of targets would not be appropriate to be used for vaccination as a single dose due to antigenic competition. It would be almost impossible to immunize over two billion individuals who live in malaria susceptible areas with several carefully crafted immunization schedules delivered 4-6 weeks apart in the form of two different antigens as a single dose. Besides, if immunization schedules could be arranged, the stability of vaccines carrying different malarial antigens, their transport, and the logistics of vaccination would be an almost impossible task to achieve under the current fiscal constraints. We are proposing a unique way to circumvent these logistical difficulties to deliver the malaria vaccines to every susceptible home at a small fraction of a cost. We hypothesize that the anti-malaria edible vaccines in transgenic tomato plants where different transgenic plants expressing different antigenic type(s). Immunizing individuals against 2-3 antigens and against each stage of the life cycle of the multistage parasites would be an efficient, inexpensive and safe way of vaccination. Tomatoes with varying sizes, shapes and colors carrying different antigens would make the vaccines easily identifiable by lay individuals.

An ethnobotanical study of anti-malarial plants among indigenous people on the upper Negro River in the Brazilian Amazon.

PubMed

Frausin, Gina; Hidalgo, Ari de Freitas; Lima, Renata Braga Souza; Kinupp, Valdely Ferreira; Ming, Lin Chau; Pohlit, Adrian Martin; Milliken, William

2015-11-04

In this article we present the plants used for the treatment of malaria and associated symptoms in Santa Isabel do Rio Negro in the Brazilian Amazon. The region has important biological and cultural diversities including more than twenty indigenous ethnic groups and a strong history in traditional medicine. The aims of this study are to survey information in the Baniwa, Baré, Desana, Piratapuia, Tariana, Tukano, Tuyuca and Yanomami ethnic communities and among caboclos (mixed-ethnicity) on (a) plant species used for the treatment of malaria and associated symptoms, (b) dosage forms and (c) distribution of these anti-malarial plants in the Amazon. Information was obtained through classical ethnobotanical and ethnopharmacological methods from interviews with 146 informants in Santa Isabel municipality on the upper Negro River, Brazil. Fifty-five mainly native neotropical plant species from 34 families were in use. The detailed uses of these plants were documented. The result was 187 records (64.5%) of plants for the specific treatment of malaria, 51 records (17.6%) of plants used in the treatment of liver problems and 29 records (10.0%) of plants used in the control of fevers associated with malaria. Other uses described were blood fortification ('dar sangue'), headache and prophylaxis. Most of the therapeutic preparations were decoctions and infusions based on stem bark, root bark and leaves. These were administered by mouth. In some cases, remedies were prepared with up to three different plant species. Also, plants were used together with other ingredients such as insects, mammals, gunpowder and milk. This is the first study on the anti-malarial plants from this region of the Amazon. Aspidosperma spp. and Ampelozizyphus amazonicus Ducke were the most cited species in the communities surveyed. These species have experimental proof supporting their anti-malarial efficacy. The dosage of the therapeutic preparations depends on the kind of plant, quantity of plant material available, the patient's age (children and adults) and the local expert. The treatment time varies from a single dose to up to several weeks. Most anti-malarial plants are domesticated or grow spontaneously. They are grown in home gardens, open areas near the communities, clearings and secondary forests, and wild species grow in areas of seasonally flooded wetlands and terra firme ('solid ground') forest, in some cases in locations that are hard to access. Traditional knowledge of plants was found to be falling into disuse presumably as a consequence of the local official health services that treat malaria in the communities using commercial drugs. Despite this, some species are used in the prevention of this disease and also in the recovery after using conventional anti-malarial drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ecotope-Based Entomological Surveillance and Molecular Xenomonitoring of Multidrug Resistant Malaria Parasites in Anopheles Vectors

PubMed Central

2014-01-01

The emergence and spread of multidrug resistant (MDR) malaria caused by Plasmodium falciparum or Plasmodium vivax have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease in vitro and in vivo susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in Anopheles vectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation of Anopheles vectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction, Plasmodium- and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence of Anopheles vectors carrying MDR P. vivax in infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notified P. vivax patients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria parasites in hotspots or suspected areas established in most endemic GMS countries implementing the National Malaria Control Programs, in addition to what is guided by the World Health Organization. PMID:25349605

Communicating the AMFm message: exploring the effect of communication and training interventions on private for-profit provider awareness and knowledge related to a multi-country anti-malarial subsidy intervention

PubMed Central

2014-01-01

Background The Affordable Medicines Facility - malaria (AMFm), implemented at national scale in eight African countries or territories, subsidized quality-assured artemisinin combination therapy (ACT) and included communication campaigns to support implementation and promote appropriate anti-malarial use. This paper reports private for-profit provider awareness of key features of the AMFm programme, and changes in provider knowledge of appropriate malaria treatment. Methods This study had a non-experimental design based on nationally representative surveys of outlets stocking anti-malarials before (2009/10) and after (2011) the AMFm roll-out. Results Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5–9 months, 76%-94% awareness of the AMFm ‘green leaf’ logo, 57%-74% awareness of the ACT subsidy programme, and 52%-80% awareness of the correct recommended retail price (RRP) of subsidized ACT were recorded. However, in the remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases of at least 10 percentage points in private for-profit providers’ knowledge of the correct first-line treatment for uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%. Conclusions The results support the interpretation that, in addition to the availability of subsidized ACT, the intensity of communication campaigns may have contributed to the reported levels of AMFm-related awareness and knowledge among private for-profit providers. Future subsidy programmes for anti-malarials or other treatments should similarly include communication activities. PMID:24495691

Macrophage Migration Inhibitory Factor Release by Macrophages after Ingestion of Plasmodium chabaudi-Infected Erythrocytes: Possible Role in the Pathogenesis of Malarial Anemia

PubMed Central

Martiney, James A.; Sherry, Barbara; Metz, Christine N.; Espinoza, Marisol; Ferrer, Angel S.; Calandra, Thierry; Broxmeyer, Hal E.; Bucala, Richard

2000-01-01

Human falciparum malaria, caused by Plasmodium falciparum infection, results in 1 to 2 million deaths per year, mostly children under the age of 5 years. The two main causes of death are severe anemia and cerebral malaria. Malarial anemia is characterized by parasite red blood cell (RBC) destruction and suppression of erythropoiesis (the mechanism of which is unknown) in the presence of a robust host erythropoietin response. The production of a host-derived erythropoiesis inhibitor in response to parasite products has been implicated in the pathogenesis of malarial anemia. The identity of this putative host factor is unknown, but antibody neutralization studies have ruled out interleukin-1β, tumor necrosis factor alpha, and gamma interferon while injection of interleukin-12 protects susceptible mice against lethal P. chabaudi infection. In this study, we report that ingestion of P. chabaudi-infected erythrocytes or malarial pigment (hemozoin) induces the release of macrophage migration inhibitory factor (MIF) from macrophages. MIF, a proinflammatory mediator and counter-regulator of glucocorticoid action, inhibits erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor-derived colony formation. MIF was detected in the sera of P. chabaudi-infected BALB/c mice, and circulating levels correlated with disease severity. Liver MIF immunoreactivity increased concomitant with extensive pigment and parasitized RBC deposition. Finally, MIF was elevated three- to fourfold in the spleen and bone marrow of P. chabaudi-infected mice with active disease, as compared to early disease, or of uninfected controls. In summary, the present results suggest that MIF may be a host-derived factor involved in the pathophysiology of malaria anemia. PMID:10722628

In vitro studies on the sensitivity pattern of Plasmodium falciparum to anti-malarial drugs and local herbal extracts

PubMed Central

2014-01-01

Background The resistance of human malaria parasites to anti-malarial compounds has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. One way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents. Results Sensitivity of 100 Plasmodium falciparum isolates to chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, artemisinin, Momordica charantia (‘Ejirin’) Diospyros monbuttensis (‘Egun eja’) and Morinda lucida (‘Oruwo’) was determined using the in vitro microtest (Mark III) technique to determine the IC50 of the drugs. All the isolates tested were sensitive to quinine, mefloquine and artesunate. Fifty-one percent of the isolates were resistant to chloroquine, 13% to amodiaquine and 5% to sulphadoxine/pyrimethamine. Highest resistance to chloroquine (68.9%) was recorded among isolates from Yewa zone while highest resistance to amodiaquine (30%) was observed in Ijebu zone. Highest resistance to sulphadoxine/pyrimethamine was recorded in Yewa and Egba zones, respectively. A positive correlation was observed between the responses to artemisinin and mefloquine (P<0.05), artemisinin and quinine (P<0.05) and quinine and mefloquine (P<0.05). A negative correlation was observed between the responses to chloroquine and mefloquine (P>0.05). Highest anti-plasmodial activity was obtained with the ethanolic extract of D. monbuttensis (IC50 = 3.2nM) while the lowest was obtained from M. lucida (IC50 =25nM). Conclusions Natural products isolated from plants used in traditional medicine, which have potent anti-plasmodial action in vitro, represent potential sources of new anti-malarial drugs. PMID:24555525

What is the burden of submicroscopic malaria in pregnancy in central India?

PubMed Central

Singh, Neeru; Bharti, Praveen K; Singh, Mrigendra P; Singh, Rajshree; Yeboah-Antwi, Kojo; Desai, Meghna; Udhayakumar, Venkatachalam; Muniyandi, Malaisamy; Hamer, Davidson H; Wylie, Blair J

2015-01-01

Background: Conventional microscopy underestimates the burden of malarial infection when compared with molecular diagnosis using polymerase chain reaction (PCR)-based methods. Lower density parasitemias serve as a reservoir for infection. We evaluated the prevalence of submicroscopic infections in an area of unstable malarial transmission in India and determined whether these infections negatively impacted maternal or fetal outcomes. Methods: This cross-sectional study (2007–2008) was undertaken in two districts of Chhattisgarh, recruiting women from both antenatal clinics (ANCs) and delivery units (DUs). For ANC/DU subjects, peripheral/placental blood, respectively, was obtained for conventional microscopy and collected onto filter paper for PCR analysis. Results: There were 3425 pregnant women, including 2477 ANC subjects and 948 DU subjects who had both microscopic and PCR samples available. Polymerase chain reaction detected significantly more Plasmodium infections than traditional light microscopy both from peripheral (3.4 vs 1.2%; OR 2.9, 95% confidence intervals (CIs) 1.9–4.5) and placental (4.2 vs 1.7%; OR 2.5, 95% CIs 1.4–4.8) blood samples. Submicroscopic infections were not associated with anemia or severe maternal anemia among ANC or DU participants and were not associated with low birth weight (LBW) among DU participants. In contrast, microscopically detected infections were associated with severe anemia and LBW. Conclusions: In this area of unstable malarial transmission from India, submicroscopic infections did not identify a set of pregnant women at increased risk for anemia or LBW. Until PCR techniques become much less expensive and available as a point of care test for the field setting, its use will be limited for malarial detection. PMID:25627878

Does infection with Human Immunodeficiency Virus affect the antibody responses to Plasmodium falciparum antigenic determinants in asymptomatic pregnant women?

PubMed

Ayisi, J G; Branch, OraLee H; Rafi-Janajreh, A; van Eijk, A M; ter Kuile, F O; Rosen, D H; Kager, P A; Lanar, D E; Barbosa, A; Kaslow, D; Nahlen, B L; Lal, A A

2003-04-01

HIV-seropositive pregnant women are more susceptible to malaria than HIV-seronegative women. We assessed whether HIV infection alters maternal and cord plasma malarial antibody responses and the mother-to-infant transfer of malaria antibodies. We determined plasma levels of maternal and cord antibodies [Immunoglobulin (IgG)] to recombinant malarial proteins [merozoite surface protein 1 (MSP-1(19kD)), the erythrocyte binding antigen (EBA-175)], the synthetic peptides [MSP-2, MSP-3, rhoptry associated protein 1 (RAP-1), and the pre-erythrocytic stage, circumsporozoite protein (NANP)(5)] antigenic determinants of Plasmodium falciparum; and tetanus toxoid (TT) by ELISA among samples of 99 HIV-seropositive mothers, 69 of their infants, 102 HIV-seronegative mothers and 62 of their infants. The prevalence of maternal antibodies to the malarial antigenic determinants ranged from 18% on MSP3 to 91% on EBA-175; in cord plasma it ranged from 13% to 91%, respectively. More than 97% of maternal and cord samples had antibodies to TT. In multivariate analysis, HIV infection was only associated with reduced antibodies to (NANP)(5) in maternal (P=0.001) and cord plasma (P=0.001); and reduced mother-to-infant antibody transfer to (NANP)(5) (P=0.012). This effect of HIV was independent of maternal age, gravidity and placental malaria. No consistent HIV-associated differences were observed for other antigenic determinants. An effect of HIV infection was only observed on one malarial antigenic determinant, suggesting that the increased susceptibility to malaria among HIV-infected pregnant women may not be explained on the basis of their reduced antibody response to malaria antigens.

Anti-malarial activity and toxicity assessment of Himatanthus articulatus, a plant used to treat malaria in the Brazilian Amazon.

PubMed

Vale, Valdicley V; Vilhena, Thyago C; Trindade, Rafaela C Santos; Ferreira, Márlia Regina C; Percário, Sandro; Soares, Luciana F; Pereira, Washington Luiz A; Brandão, Geraldo C; Oliveira, Alaíde B; Dolabela, Maria F; De Vasconcelos, Flávio

2015-03-27

Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus. Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity--TEAC; lipid peroxidation--TBARS, and nitrites and nitrates--NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice. Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies. The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.

Malaria diagnostic testing and treatment practices in three different Plasmodium falciparum transmission settings in Tanzania: before and after a government policy change.

PubMed

Bastiaens, Guido J H; Schaftenaar, Erik; Ndaro, Arnold; Keuter, Monique; Bousema, Teun; Shekalaghe, Seif A

2011-04-02

Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African settings. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas. Diagnosis may be facilitated by malaria rapid diagnostic tests (RDTs). In this study, the impact of a government policy change, comprising the provision of RDTs and advice to restrict anti-malarial treatment to RDT-positive individuals, was assessed by describing diagnostic behaviour and treatment decision-making in febrile outpatients <10 years of age in three hospitals in the Kagera and Mwanza Region in northern Tanzania. Prospective data from Biharamulo and Rubya Designated District Hospital (DDH) were collected before and after policy change, in Sumve DDH no new policy was implemented. Diagnosis of malaria was confirmed by RDT; transmission intensity was evaluated by a serological marker of malaria exposure in hospital attendees. Prior to policy change, there was no evident association between the actual level of transmission intensity and drug-prescribing behaviour. After policy change, there was a substantial decrease in anti-malarial prescription and an increase in prescription of antibiotics. The proportion of parasite-negative individuals who received anti-malarials decreased from 89.1% (244/274) to 38.7% (46/119) in Biharamulo and from 76.9% (190/247) to 10.0% (48/479) in Rubya after policy change. This study shows that an official policy change, where RDTs were provided and healthcare providers were advised to adhere to RDT results in prescribing drugs can be followed by more rational drug-prescribing behaviour. The current findings are promising for improving treatment policy in Tanzanian hospitals.

Malaria in India: The Center for the Study of Complex Malaria in India

PubMed Central

Das, Aparup; Anvikar, Anupkumar R.; Cator, Lauren J.; Dhiman, Ramesh C.; Eapen, Alex; Mishra, Neelima; Nagpal, Bhupinder N.; Nanda, Nutan; Raghavendra, Kamaraju; Read, Andrew F.; Sharma, Surya K.; Singh, Om P.; Singh, Vineeta; Sinnis, Photini; Srivastava, Harish C.; Sullivan, Steven A.; Sutton, Patrick L.; Thomas, Matthew B.; Carlton, Jane M.; Valecha, Neena

2012-01-01

Malaria is a major public health problem in India and one which contributes significantly to the overall malaria burden in Southeast Asia. The National Vector Borne Disease Control Program of India reported ~1.6 million cases and ~1100 malaria deaths in 2009. Some experts argue that this is a serious underestimation and that the actual number of malaria cases per year is likely between 9 and 50 times greater, with an approximate 13-fold underestimation of malaria-related mortality. The difficulty in making these estimations is further exacerbated by (i) highly variable malaria eco-epidemiological profiles, (ii) the transmission and overlap of multiple Plasmodium species and Anopheles vectors, (iii) increasing antimalarial drug resistance and insecticide resistance, and (iv) the impact of climate change on each of these variables. Simply stated, the burden of malaria in India is complex. Here we describe plans for a Center for the Study of Complex Malaria in India (CSCMi), one of ten International Centers of Excellence in Malaria Research (ICEMRs) located in malarious regions of the world recently funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The CSCMi is a close partnership between Indian and United States scientists, and aims to address major gaps in our understanding of the complexity of malaria in India, including changing patterns of epidemiology, vector biology and control, drug resistance, and parasite genomics. We hope that such a multidisciplinary approach that integrates clinical and field studies with laboratory, molecular, and genomic methods will provide a powerful combination for malaria control and prevention in India. PMID:22142788

[Sickle-cell crisis in the child and teenager in Brazzaville, Congo. A retrospective study of 587 cases].

PubMed

Babela, J R Mabiala; Nzingoula, S; Senga, P

2005-12-01

Using files related to children admitted at the Brazzaville teaching hospital (Congo) between May 1995 and May 2002, the authors have studied the part of sickle cell crisis (SCC) in the sickle cell disease, have assessed the epidemiological particularities, the relation between some clinical, biological factors as well as the severity of the disease. On the whole, 587 SCC have been observed in homozygous SS children aged 6 to 17. The distribution was as follows: painful osteo-articular crisis (58.6%), abdominal crisis (23.5%), acute chest syndrome (14%), neurological strokes (3.2%) and priapism (0.7%). The neurological strokes (75%) and the hand-foot syndrome (77.8%) were predominant in male. As regards the interaction age-localization of the crisis, the hand-foot syndrome mainly concerned children under five, long bones and rachis impairment those aged 11 to 15; abdominal and neurological crisis were observed especially before the age of 10, the acute chest syndrome after 10 (68.3%). Malaria (48.9%) and bacterial or viral infections (24.5%) proved to be the triggering factors when these are identified (188 cases). SCC occurred in 67.5% of the cases during the hot and rainy seasons. Moreover the haemoglobin F rate above 10% was correlated with a low prevalence of SCC, in particular the potentially severe crisis, revealing at the same time its protective value. These results show that SCC, by their frequency and/or their severity constitute a major handicap when the vital prognosis is not involved. Rigorous health habits, appropriate vaccination programme, adequate malarial prophylaxis, optimal transfusional strategy and especially the use of hydroxyurea, prove to be urgent preventive measures to put into practice. Their efficient implementation will provide a better quality of life to the sickle cell patient and will decrease the risks of severe crisis.

Intensity and Compactness Enabled Saliency Estimation for Leakage Detection in Diabetic and Malarial Retinopathy.

PubMed

Zhao, Yitian; Zheng, Yalin; Liu, Yonghuai; Yang, Jian; Zhao, Yifan; Chen, Duanduan; Wang, Yongtian

2017-01-01

Leakage in retinal angiography currently is a key feature for confirming the activities of lesions in the management of a wide range of retinal diseases, such as diabetic maculopathy and paediatric malarial retinopathy. This paper proposes a new saliency-based method for the detection of leakage in fluorescein angiography. A superpixel approach is firstly employed to divide the image into meaningful patches (or superpixels) at different levels. Two saliency cues, intensity and compactness, are then proposed for the estimation of the saliency map of each individual superpixel at each level. The saliency maps at different levels over the same cues are fused using an averaging operator. The two saliency maps over different cues are fused using a pixel-wise multiplication operator. Leaking regions are finally detected by thresholding the saliency map followed by a graph-cut segmentation. The proposed method has been validated using the only two publicly available datasets: one for malarial retinopathy and the other for diabetic retinopathy. The experimental results show that it outperforms one of the latest competitors and performs as well as a human expert for leakage detection and outperforms several state-of-the-art methods for saliency detection.

Effects of the anti-malarial compound cryptolepine and its analogues in human lymphocytes and sperm in the Comet assay.

PubMed

Gopalan, Rajendran C; Emerce, Esra; Wright, Colin W; Karahalil, Bensu; Karakaya, Ali E; Anderson, Diana

2011-12-15

Malaria is a mosquito-borne infectious disease caused by the genus Plasmodium. It causes one million deaths per year in African children under the age of 5 years. There is an increasing development of resistance of malarial parasites to chloroquine and other currently used anti-malarial drugs. Some plant products such as the indoloquinoline alkaloid cryptolepine have been shown to have potent activity against P. falciparum in vitro. On account of its toxicity, cryptolepine is not suitable for use as an antimalarial drug but a number of analogues of cryptolepine have been synthesised in an attempt to find compounds that have reduced cytotoxicity and these have been investigated in the present study in human sperm and lymphocytes using the Comet assay. The results suggest that cryptolepine and the analogues cause DNA damage in lymphocytes, but appear to have no effect on human sperm at the assessed doses. In the context of antimalarial drug development, the data suggest that all cryptolepine compounds and in particular 2,7-dibromocryptolepine cause DNA damage and therefore may not be suitable for pre clinical development as antimalarial agents. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K as anti-malarial agents

NASA Astrophysics Data System (ADS)

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-06-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents.

PubMed

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-01-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme ( Pf LDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The Pf LDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of Pf LDH, we have used Discovery studio to perform molecular docking in the active binding pocket of Pf LDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q 2 of 0.516. The model has predicted r 2 of 0.91 showing that predicted IC 50 values are in good agreement with experimental IC 50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents

PubMed Central

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-01-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors. PMID:28664157

The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles.

PubMed

Marrelli, Mauro Toledo; Brotto, Marco

2016-11-02

Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.

Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective.

PubMed

Alba, Sandra; Hetzel, Manuel W; Goodman, Catherine; Dillip, Angel; Liana, Jafari; Mshinda, Hassan; Lengeler, Christian

2010-06-15

To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS) and in Ifakara town. Data collection consisted of: 1) yearly censuses of shops selling drugs; 2) collection of monthly data on availability of anti-malarials in public health facilities; and 3) retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008) and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008) of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock), but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock), but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti-malarial sales) The public health and private retail sector are important complementary sources of treatment in rural Tanzania. Ensuring the availability of ALu in the private retail sector is important for its successful uptake.

Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective

PubMed Central

2010-01-01

Background To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. Methods The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS) and in Ifakara town. Data collection consisted of: 1) yearly censuses of shops selling drugs; 2) collection of monthly data on availability of anti-malarials in public health facilities; and 3) retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Results Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008) and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008) of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock), but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock), but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti-malarial sales) Conclusions The public health and private retail sector are important complementary sources of treatment in rural Tanzania. Ensuring the availability of ALu in the private retail sector is important for its successful uptake. PMID:20550654

A pilot study on quality of artesunate and amodiaquine tablets used in the fishing community of Tema, Ghana

PubMed Central

2013-01-01

Background The ineffectiveness of artesunate and amodiaquine tablets in malaria treatment remains a health burden to WHO and governments of malaria-endemic countries, including Ghana. The proliferation of illegitimate anti-malarial drugs and its use by patients is of primary concern to international and local drug regulatory agencies because such drugs are known to contribute to the development of the malaria-resistant parasites in humans. No data exist on quality of these drugs in the fishing village communities in Ghana although the villagers are likely users of such drugs. A pilot study on the quality of anti-malarial tablets in circulation during the major fishing season at a malarious fishing village located along the coast of Tema in southern Ghana was determined. Methods Blisterpacks of anti-malarial tablets were randomly sampled. The International Pharmacopoeia and Global Pharma Health Fund Minilab protocols were used to assess the quality of anti-malarial tablets per blisterpacks allegedly manufactured by Guilin Pharmaceutical Co Ltd, China (GPCL) and Letap Pharmaceuticals Ltd, Ghana (LPL) and sold in chemical sales outlets at Kpone-on–Sea. Ferric chloride and cobaltous thiocyanate tests confirmed the presence of active ingredients in the tablets. A confirmatory test for the active ingredient was achieved with artesunate (ICRS1409) and amodiaquine (ICRS0209) reference standards. A high performance liquid chromatography analysis confirmed the amount of artesunate found in tablets. Results Based on the International Pharmacopoeia acceptable range of 96/98 to 102% for genuine artesunate per tablet, 10% [relative standard deviation (RSD): 3.2%] of field-selected artesunate blisterpack per tablets manufactured by GPCL, and 50% (RSD: 5.1%) of a similar package per tablet by LPL, passed the titrimetric test. However, 100% (RSD: 2.2%) of amodiaquine blisterpack per tablet by GPCL were found to be within the International Pharmacopeia acceptable range of 90 to 110% for genuine amodiaquine in tablet, whilst 17% of a similar package per tablet by LPL failed spectrophotometric testing. Conclusion Inadequate amounts of artesunate and amodiaquine detected in the tablets suggest that both pharmaceutical companies may not be following recommended drug formulation procedures, or the active pharmaceutical ingredients might have been degraded by improper storage conditions. Thus, drugs being sold at Kpone-on-Sea, Ghana may likely be classified as substandard drugs and not suitable for malaria treatment. PMID:23809666

Anti-malarial market and policy surveys in sub-Saharan Africa.

PubMed

Diap, Graciela; Amuasi, John; Boakye, Isaac; Sevcsik, Ann-Marie; Pecoul, Bernard

2010-04-23

At a recent meeting (Sept 18, 2009) in which reasons for the limited access to artemisinin-based combination therapy (ACT) in sub-Saharan Africa were discussed, policy and market surveys on anti-malarial drug availability and accessibility in Burundi and Sierra Leone were presented in a highly interactive brainstorming session among key stakeholders across private, public, and not-for-profit sectors. The surveys, the conduct of which directly involved the national malaria control programme managers of the two countries, provides the groundwork for evidence-based policy implementation. The results of the surveys could be extrapolated to other countries with similar socio-demographic and malaria profiles. The meeting resulted in recommendations on key actions to be taken at the global, national, and community level for better ACT accessibility. At the global level, both public and private sectors have actions to take to strengthen policies that lead to the replacement of loose blister packs with fixed-dose ACT products, develop strategies to ban inappropriate anti-malarials and regulate those bans, and facilitate technology and knowledge transfer to scale up production of fixed-dose ACT products, which should be readily available and affordable to those patients who are in the greatest need of these medicines. At the national level, policies that regulate the anti-malarial medicines market should be enacted and enforced. The public sector, including funding donors, should participate in ensuring that the private sector is engaged in the ACT implementation process. Research similar to the surveys discussed is important for other countries to develop and evaluate the right incentives at a local level. At the community level, community outreach and education about appropriate preventive and treatment measures must continue and be strengthened, with service delivery systems developed within both public and private sectors, among other measures, to decrease access to ineffective and inappropriate anti-malarial medicines. What was clear during the meeting is that continuing commitment, strengthened interaction and transparency among various stakeholders, with focus on communities, national governments, and evidence-based policy and action are the only way to sustainably address the control of malaria, a disease which continues to have a significant health and socio-economic impact worldwide, particularly in sub-Saharan Africa. Details on the methodology employed in carrying out the studies discussed at this meeting, as well as more detailed results, data analysis and discussion of the studies are soon to be published.

Mirincamycin, an old candidate for malaria combination treatment and prophylaxis in the 21st century: in vitro interaction profiles with potential partner drugs in continuous culture and field isolates.

PubMed

Starzengruber, Peter; Fuehrer, Hans-Peter; Swoboda, Paul; Ganesh, Deepa; Haque, Rashidul; Khan, Wasif A; Graninger, Wolfgang; Noedl, Harald

2014-06-10

Spreading resistance of Plasmodium falciparum to existing drugs calls for the search for novel anti-malarial drugs and combinations for the treatment of falciparum malaria. In vitro and ex vivo investigations were conducted with fresh P. falciparum field isolates and culture-adapted P. falciparum clones to evaluate the anti-malarial potential of mirincamycin, a lincosamide, alone and in combination with tafenoquine (TQ), dihydroartemisinin (DHA), and chloroquine (CQ). All samples were tested in a histidine-rich protein 2 (HRP2) drug susceptibility assay. Interaction analysis showed additive to synergistic interaction profiles with these potential partner drugs, with an overall geometric mean fractional inhibitory concentration at 50% inhibition (FIC₅₀) of 0.78, 0.80 and 0.80 for mirincamycin with TQ, DHA, and CQ, respectively. Antagonism was not found in any of the tested field isolates or clones. The strongest tendency toward synergy (i.e. the lowest FIC) was seen with a combination ratio of 1:0.27 to 1:7.2 (mean 1:2.7) for the combination with tafenoquine. The optimal combination ratios for DHA and CQ were 1:444.4 to 1:36,000 (mean 1:10,755.5) and 1:2.7 to 1:216 (mean 1:64.5), respectively. No evidence of an activity correlation (i.e. potential cross-resistance) with DHA, mefloquine, quinine or chloroquine was seen whereas a significant correlation with the activity of clindamycin and azithromycin was detected. Mirincamycin combinations may be promising candidates for further clinical investigations in the therapy and prophylaxis of multidrug-resistant falciparum malaria or in combination with 4 or 8-aminoquinolines for the treatment and relapse prevention of vivax malaria.

Mirincamycin, an old candidate for malaria combination treatment and prophylaxis in the 21st century: in vitro interaction profiles with potential partner drugs in continuous culture and field isolates

PubMed Central

2014-01-01

Background Spreading resistance of Plasmodium falciparum to existing drugs calls for the search for novel anti-malarial drugs and combinations for the treatment of falciparum malaria. Methods In vitro and ex vivo investigations were conducted with fresh P. falciparum field isolates and culture-adapted P. falciparum clones to evaluate the anti-malarial potential of mirincamycin, a lincosamide, alone and in combination with tafenoquine (TQ), dihydroartemisinin (DHA), and chloroquine (CQ). All samples were tested in a histidine-rich protein 2 (HRP2) drug susceptibility assay. Results Interaction analysis showed additive to synergistic interaction profiles with these potential partner drugs, with an overall geometric mean fractional inhibitory concentration at 50% inhibition (FIC50) of 0.78, 0.80 and 0.80 for mirincamycin with TQ, DHA, and CQ, respectively. Antagonism was not found in any of the tested field isolates or clones. The strongest tendency toward synergy (i.e. the lowest FIC) was seen with a combination ratio of 1:0.27 to 1:7.2 (mean 1:2.7) for the combination with tafenoquine. The optimal combination ratios for DHA and CQ were 1:444.4 to 1:36,000 (mean 1:10,755.5) and 1:2.7 to 1:216 (mean 1:64.5), respectively. No evidence of an activity correlation (i.e. potential cross-resistance) with DHA, mefloquine, quinine or chloroquine was seen whereas a significant correlation with the activity of clindamycin and azithromycin was detected. Conclusions Mirincamycin combinations may be promising candidates for further clinical investigations in the therapy and prophylaxis of multidrug-resistant falciparum malaria or in combination with 4 or 8-aminoquinolines for the treatment and relapse prevention of vivax malaria. PMID:24916383

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.

The position of mefloquine as a 21st century malaria chemoprophylaxis

PubMed Central

2010-01-01

Background Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis. Methods A literature search to update the status of mefloquine as a malaria chemoprophylaxis. Results Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerability of mefloquine and the use of this medication by groups at high risk of malaria. Discussion Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors. Conclusion The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline. PMID:21143906

The position of mefloquine as a 21st century malaria chemoprophylaxis.

PubMed

Schlagenhauf, Patricia; Adamcova, Miriam; Regep, Loredana; Schaerer, Martin T; Rhein, Hans-Georg

2010-12-09

Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis. A literature search to update the status of mefloquine as a malaria chemoprophylaxis. Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerability of mefloquine and the use of this medication by groups at high risk of malaria. Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors. The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline.

Artemisinin anti-malarial drugs in China

PubMed Central

Guo, Zongru

2016-01-01

Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the “whole nation” system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. PMID:27006895

Detachment of retinal pigment epithelium in retinopathy due to malaria.

PubMed

Rocha Cabrera, P; Rodríguez Talavera, I; Losada Castillo, M J; Alemán Valls, R; Lorenzo Morales, J

2018-05-25

A 45-year-old man was diagnosed with malaria with neurological involvement. Two months later he referred metamorphopsia in the left eye. Malarial retinopathy was observed in the fundus examination. The Optic Coherence Tomography (OCT) of the macula showed parafoveal pigment epithelium detachment (DEP). Specific anti-malarial treatment was initiated, with the disappearance of the retinopathy being observed. Plasmodium falciparum is responsible for the retinopathy in neurological malaria. A funduscopic examination and macular OCT should be performed in these patients, as it is associated with a higher mortality when there is a retinal involvement. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Tracing investigation and diagnosis of one transfusion-transmitted malaria case in Zhejiang Province].

PubMed

Ruan, Wei; Lei, Yong-Liang; Yao, Li-Nong; Zhang, Ling-Ling; Liu, Xiao-Hong; Xiang, Xiao-Qing; Mei, Jian-Hua; Zhu, Hai-Bo; Yu, Yang; Zeng, Chang-You

2014-02-01

To identify the sources of infection and the mode of transmission of a malaria case with unknown origin. Clinical data of the case were collected and the epidemiological investigation was conducted. The blood samples of the patient and the suspected infection source (blood donor) were detected by microscopy, rapid diagnostic test strip (RDT) and nested PCR. The patient did not visited malaria endemic areas. After a blood transfusion, the patient had chills and fever, and was confirmed as falciparum malaria by microscopy with bone marrow and peripheral blood smears and RDT. The blood donor was a worker returned from Africa. Before blood donation she was sick like malaria carrier, and took anti-malarial drug. She was then confirmed as falciparum malaria by RDT and microscopy. The blood samples from the patient and the blood donor were diagnosed as falciparum malaria by nested PCR, and the similarity of the small subunit rRNA (SSU rRNA) sequence was 100%, showing they were mix-infected with K1 and MAD20 genotypes of Plasmodium falciparum. This patient is confirmed P. falciparum infection via blood transfusion from a donor who returned from Africa.

USP38, FREM3, SDC1, DDC, and LOC727982 Gene Polymorphisms and Differential Susceptibility to Severe Malaria in Tanzania.

PubMed

Manjurano, Alphaxard; Sepúlveda, Nuno; Nadjm, Behzad; Mtove, George; Wangai, Hannah; Maxwell, Caroline; Olomi, Raimos; Reyburn, Hugh; Drakeley, Christopher J; Riley, Eleanor M; Clark, Taane G

2015-10-01

Populations exposed to Plasmodium falciparum infection develop genetic mechanisms of protection against severe malarial disease. Despite decades of genetic epidemiological research, the sickle cell trait (HbAS) sickle cell polymorphism, ABO blood group, and other hemoglobinopathies remain the few major determinants in severe malaria to be replicated across different African populations and study designs. Within a case-control study in a region of high transmission in Tanzania (n = 983), we investigated the role of 40 new loci identified in recent genome-wide studies. In 32 loci passing quality control procedures, we found polymorphisms in USP38, FREM3, SDC1, DDC, and LOC727982 genes to be putatively associated with differential susceptibility to severe malaria. Established candidates explained 7.4% of variation in severe malaria risk (HbAS polymorphism, 6.3%; α-thalassemia, 0.3%; ABO group, 0.3%; and glucose-6-phosphate dehydrogenase deficiency, 0.5%) and the new polymorphisms, another 4.3%. The regions encompassing the loci identified are promising targets for the design of future treatment and control interventions. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Health risks, travel preparation, and illness among public health professionals during international travel.

PubMed

Balaban, Victor; Warnock, Eli; Ramana Dhara, V; Jean-Louis, Lee Ann; Sotir, Mark J; Kozarsky, Phyllis

2014-01-01

Few data currently exist on health risks faced by public health professionals (PHP) during international travel. We conducted pre- and post-travel health surveys to assess knowledge, attitudes, and practices (KAP), and illnesses among PHP international travelers. Anonymous surveys were completed by PHP from a large American public health agency who sought a pre-travel medical consult from September 1, 2009, to September 30, 2010. Surveys were completed by 122 participants; travelers went to 163 countries. Of the 122 respondents, 97 (80%) reported at least one planned health risk activity (visiting rural areas, handling animals, contact with blood or body fluids, visiting malarious areas), and 50 (41%) reported exposure to unanticipated health risks. Of the 62 travelers who visited malarious areas, 14 (23%) reported inconsistent or no use of malaria prophylaxis. Illness during travel was reported by 33 (27%) respondents. Most of the PHP travelers in our study reported at least one planned health risk activity, and almost half reported exposure to unanticipated health risks, and one-quarter of travelers to malarious areas reported inconsistent or no use of malaria chemoprophylaxis. Our findings highlight that communication and education outreach for PHP to prevent travel-associated illnesses can be improved. Published by Elsevier Ltd.

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.

Prevalence of human malaria infection in bordering areas of East Balochistan, adjoining with Punjab: Loralai and Musakhel.

PubMed

Yasinzai, Mohammad Iqbal; Kakarsulemankhel, Juma Khan

2009-03-01

To study the prevalence of malarial infections in human population of districts Loralai and Musakhel areas of Pakistan. Malarial parasites were identified in the blood slides of suspected patients of the disease from July, 2004 to June, 2006, and encompassed 7899 subjects. Out of 7899 suspected cases of malaria, 2275 (28.8%) were found to be positive for malarial parasite in blood smear slides. Out of positive cases, 1633 (71.7%) were identified as Plasmodium falciparum infection, 642 (28.2%) cases with P. vivax. However, seasonal variation was also noted with the highest (83.9%:287/342) infection of P. falciparum in September and lowest (65.3%: 34/52) in January in Loralai area whereas highest (76.9%:30/39) in October and lowest (3/9) in February in Musa Khel area. There was no case of Plasmodium malariae and P. ovale infection observed in the present study. These results are compared with those of other studies done in Pakistan. The high prevalence rate (71.7%:1633/2275) of P. falciparum poses a significant health hazard but 28.2% of P. vivax (642/2275) also may lead to serious complications like cerebral malaria. No association was found between types of infection and age groups.

Methods for implementing a medicine outlet survey: lessons from the anti-malarial market.

PubMed

O'Connell, Kathryn A; Poyer, Stephen; Solomon, Tsione; Munroe, Erik; Patouillard, Edith; Njogu, Julius; Evance, Illah; Hanson, Kara; Shewchuk, Tanya; Goodman, Catherine

2013-02-05

In recent years an increasing number of public investments and policy changes have been made to improve the availability, affordability and quality of medicines available to consumers in developing countries, including anti-malarials. It is important to monitor the extent to which these interventions are successful in achieving their aims using quantitative data on the supply side of the market. There are a number of challenges related to studying supply, including outlet sampling, gaining provider cooperation and collecting accurate data on medicines. This paper provides guidance on key steps to address these issues when conducting a medicine outlet survey in a developing country context. While the basic principles of good survey design and implementation are important for all surveys, there are a set of specific issues that should be considered when conducting a medicine outlet survey. This paper draws on the authors' experience of designing and implementing outlet surveys, including the lessons learnt from ACTwatch outlet surveys on anti-malarial retail supply, and other key studies in the field. Key lessons and points of debate are distilled around the following areas: selecting a sample of outlets; techniques for collecting and analysing data on medicine availability, price and sales volumes; and methods for ensuring high quality data in general. The authors first consider the inclusion criteria for outlets, contrasting comprehensive versus more focused approaches. Methods for developing a reliable sampling frame of outlets are then presented, including use of existing lists, key informants and an outlet census. Specific issues in the collection of data on medicine prices and sales volumes are discussed; and approaches for generating comparable price and sales volume data across products using the adult equivalent treatment dose (AETD) are explored. The paper concludes with advice on practical considerations, including questionnaire design, field worker training, and data collection. Survey materials developed by ACTwatch for investigating anti-malarial markets in sub-Saharan Africa and Asia provide a helpful resource for future studies in this area.

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya.

PubMed

Zhang, Lyna; Prather, Donald; Vanden Eng, Jodi; Crawford, Sara; Kariuki, Simon; ter Kuile, Feiko; Terlouw, Dianne; Nahlen, Bernard; Lal, Altaf A; Slutsker, Laurence; Udhayakumar, Venkatachalam; Shi, Ya Ping

2010-03-29

Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients.

Automated detection of retinal whitening in malarial retinopathy

NASA Astrophysics Data System (ADS)

Joshi, V.; Agurto, C.; Barriga, S.; Nemeth, S.; Soliz, P.; MacCormick, I.; Taylor, T.; Lewallen, S.; Harding, S.

2016-03-01

Cerebral malaria (CM) is a severe neurological complication associated with malarial infection. Malaria affects approximately 200 million people worldwide, and claims 600,000 lives annually, 75% of whom are African children under five years of age. Because most of these mortalities are caused by the high incidence of CM misdiagnosis, there is a need for an accurate diagnostic to confirm the presence of CM. The retinal lesions associated with malarial retinopathy (MR) such as retinal whitening, vessel discoloration, and hemorrhages, are highly specific to CM, and their detection can improve the accuracy of CM diagnosis. This paper will focus on development of an automated method for the detection of retinal whitening which is a unique sign of MR that manifests due to retinal ischemia resulting from CM. We propose to detect the whitening region in retinal color images based on multiple color and textural features. First, we preprocess the image using color and textural features of the CMYK and CIE-XYZ color spaces to minimize camera reflex. Next, we utilize color features of the HSL, CMYK, and CIE-XYZ channels, along with the structural features of difference of Gaussians. A watershed segmentation algorithm is used to assign each image region a probability of being inside the whitening, based on extracted features. The algorithm was applied to a dataset of 54 images (40 with whitening and 14 controls) that resulted in an image-based (binary) classification with an AUC of 0.80. This provides 88% sensitivity at a specificity of 65%. For a clinical application that requires a high specificity setting, the algorithm can be tuned to a specificity of 89% at a sensitivity of 82%. This is the first published method for retinal whitening detection and combining it with the detection methods for vessel discoloration and hemorrhages can further improve the detection accuracy for malarial retinopathy.

Glucose-6-phosphate dehydrogenase deficiency and reduced haemoglobin levels in African children with severe malaria.

PubMed

Nguetse, Christian N; Meyer, Christian G; Adegnika, Ayola Akim; Agbenyega, Tsiri; Ogutu, Bernhards R; Kremsner, Peter G; Velavan, Thirumalaisamy P

2016-07-07

Extensive studies investigating the role of host genetic factors during malaria associate glucose-6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency had been reported to associate with anti-malarial drug induced with haemolytic anaemia. A total of 301 Gabonese, Ghanaian, and Kenyan children aged 6-120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A(+)) and deficient (type A(-)) genotypes were determined by direct sequencing of the common African mutations G202A and A376G. Furthermore, multivariate analyses were executed to associate possible contributions of G6PD deficiency with baseline haemoglobin levels, parasitaemia and with severe malarial anaemia. Two hundred and seventy-eight children (132 females and 146 males) were successfully genotyped for G6PD variants. The overall prevalence of G6PD deficiency was 13 % [36/278; 3 % (4/132) female homozygous and 22 % (32/146) male hemizygous], 14 % (40/278) children were female heterozygous while 73 % (202/278) were G6PD normal [67 % (88/132) females and 78 % (114/146) males] individuals. Multivariate regression revealed a significant association of moderately and severely deficient G6PD genotypes with haemoglobin levels according to the baseline data (p < 0.0001; G6PD heterozygous: p < 0.0001; G6PD deficient: p = 0.009), but not with severe malarial anaemia (p = 0.66). No association of G6PD genotypes with baseline parasitaemia. In this study, moderately (type A(+)) and severely (type A(-)) G6PD deficiency showed significant association with lower haemoglobin concentrations at baseline in African children with severe malaria without leading to severe malarial anaemia. In addition, there was no association of G6PD variant types with parasite densities on admission.

Treatment-seeking patterns for malaria in pharmacies in five sub-Saharan African countries.

PubMed

Ladner, Joël; Davis, Ben; Audureau, Etienne; Saba, Joseph

2017-08-29

Artemisinin-based combination therapy (ACT) is recommended as the first-line anti-malarial treatment strategy in sub-Saharan African countries. WHO policy recommends parasitological confirmation by microscopy or rapid diagnostic test (RDT) in all cases of suspected malaria prior to treatment. Gaps remain in understanding the factors that influence patient treatment-seeking behaviour and anti-malarial drug purchase decisions in the private sector. The objective of this study was to identify patient treatment-seeking behaviour in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Face-to-face patient interviews were conducted at a total of 208 randomly selected retail outlets in five countries. At each outlet, exit interviews were conducted with five patients who indicated they had come seeking anti-malarial treatment. The questionnaire was anonymous and standardized in the five countries and collected data on different factors, including socio-demographic characteristics, history of illness, diagnostic practices (i.e. microscopy or RDT), prescription practices and treatment purchase. The price paid for the treatment was also collected from the outlet vendor. A total of 994 patients were included from the five countries. Location of malaria diagnosis was significantly different in the five countries. A total of 484 blood diagnostic tests were performed, (72.3% with microscopy and 27.7% with RDT). ACTs were purchased by 72.5% of patients who had undergone blood testing and 86.5% of patients without a blood test, regardless of whether the test result was positive or negative (p < 10 -4 ). A total of 531 patients (53.4%) had an anti-malarial drug prescription, of which 82.9% were prescriptions for an ACT. There were significant differences in prescriptions by country. A total of 923 patients (92.9%) purchased anti-malarial drugs in an outlet, including 79.1% of patients purchasing an ACT drug: 98.0% in Ghana, 90.5% in Kenya, 80.4% in Nigeria, 69.2% in Tanzania, and 57.7% in Uganda (p < 10 -4 ). Having a drug prescription was not a significant predictive factor associated with an ACT drug purchase (except in Kenya). The number of ACT drugs purchased with a prescription was greater than the number purchased without a prescription in Kenya, Nigeria and Tanzania. This study highlights differences in drug prescription and purchase patterns in five sub-Saharan African countries. The private sector is playing an increasingly important role in fever case management in sub-Saharan Africa. Understanding the characteristics of private retail outlets and the role they play in providing anti-malaria drugs may support the design of effective malaria interventions.

A cross-sectional study of the availability and price of anti-malarial medicines and malaria rapid diagnostic tests in private sector retail drug outlets in rural Western Kenya, 2013.

PubMed

Kioko, Urbanus; Riley, Christina; Dellicour, Stephanie; Were, Vincent; Ouma, Peter; Gutman, Julie; Kariuki, Simon; Omar, Ahmeddin; Desai, Meghna; Buff, Ann M

2016-07-12

Although anti-malarial medicines are free in Kenyan public health facilities, patients often seek treatment from private sector retail drug outlets. In mid-2010, the Affordable Medicines Facility-malaria (AMFm) was introduced to make quality-assured artemisinin-based combination therapy (ACT) accessible and affordable in private and public sectors. Private sector retail drug outlets stocking anti-malarial medications within a surveillance area of approximately 220,000 people in a malaria perennial high-transmission area in rural western Kenya were identified via a census in September 2013. A cross-sectional study was conducted in September-October 2013 to determine availability and price of anti-malarial medicines and malaria rapid diagnostic tests (RDTs) in drug outlets. A standardized questionnaire was administered to collect drug outlet and personnel characteristics and availability and price of anti-malarials and RDTs. Of 181 drug outlets identified, 179 (99 %) participated in the survey. Thirteen percent were registered pharmacies, 25 % informal drug shops, 46 % general shops, 13 % homesteads and 2 % other. One hundred sixty-five (92 %) had at least one ACT type: 162 (91 %) had recommended first-line artemether-lumefantrine (AL), 22 (12 %) had recommended second-line dihydroartemisinin-piperaquine (DHA-PPQ), 85 (48 %) had sulfadoxine-pyrimethamine (SP), 60 (34 %) had any quinine (QN) formulation, and 14 (8 %) had amodiaquine (AQ) monotherapy. The mean price (range) of an adult treatment course for AL was $1.01 ($0.35-4.71); DHA-PPQ was $4.39 ($0.71-7.06); QN tablets were $2.24 ($0.12-4.71); SP was $0.62 ($0.24-2.35); AQ monotherapy was $0.42 ($0.24-1.06). The mean AL price with or without the AMFm logo did not differ significantly ($1.01 and 1.07, respectively; p = 0.45). Only 17 (10 %) drug outlets had RDTs; 149 (84 %) never stocked RDTs. The mean RDT price was $0.92 ($0.24-2.35). Most outlets never stocked RDTs; therefore, testing prior to treatment was unlikely for customers seeking treatment in the private retail sector. The recommended first-line treatment, AL, was widely available. Although SP and AQ monotherapy are not recommended for treatment, both were less expensive than AL, which might have caused preferential use by customers. Interventions that create community demand for malaria diagnostic testing prior to treatment and that increase RDT availability should be encouraged.

Malaria in India: the center for the study of complex malaria in India.

PubMed

Das, Aparup; Anvikar, Anupkumar R; Cator, Lauren J; Dhiman, Ramesh C; Eapen, Alex; Mishra, Neelima; Nagpal, Bhupinder N; Nanda, Nutan; Raghavendra, Kamaraju; Read, Andrew F; Sharma, Surya K; Singh, Om P; Singh, Vineeta; Sinnis, Photini; Srivastava, Harish C; Sullivan, Steven A; Sutton, Patrick L; Thomas, Matthew B; Carlton, Jane M; Valecha, Neena

2012-03-01

Malaria is a major public health problem in India and one which contributes significantly to the overall malaria burden in Southeast Asia. The National Vector Borne Disease Control Program of India reported ∼1.6 million cases and ∼1100 malaria deaths in 2009. Some experts argue that this is a serious underestimation and that the actual number of malaria cases per year is likely between 9 and 50 times greater, with an approximate 13-fold underestimation of malaria-related mortality. The difficulty in making these estimations is further exacerbated by (i) highly variable malaria eco-epidemiological profiles, (ii) the transmission and overlap of multiple Plasmodium species and Anopheles vectors, (iii) increasing antimalarial drug resistance and insecticide resistance, and (iv) the impact of climate change on each of these variables. Simply stated, the burden of malaria in India is complex. Here we describe plans for a Center for the Study of Complex Malaria in India (CSCMi), one of ten International Centers of Excellence in Malaria Research (ICEMRs) located in malarious regions of the world recently funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The CSCMi is a close partnership between Indian and United States scientists, and aims to address major gaps in our understanding of the complexity of malaria in India, including changing patterns of epidemiology, vector biology and control, drug resistance, and parasite genomics. We hope that such a multidisciplinary approach that integrates clinical and field studies with laboratory, molecular, and genomic methods will provide a powerful combination for malaria control and prevention in India. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic diversity of Plasmodium vivax clinical isolates from southern Pakistan using pvcsp and pvmsp1 genetic markers

PubMed Central

2013-01-01

Background Plasmodium vivax is the prevalent malarial species accounting for 70% of malaria burden in Pakistan; however, there is no baseline data on the circulating genotypes. Studies have shown that polymorphic loci of gene encoding antigens pvcsp and pvmsp1 can be used reliably for conducting molecular epidemiological studies. Therefore, this study aimed to bridge the existing knowledge gap on population structure on P. vivax from Pakistan using these two polymorphic genes. Methods During the period January 2008 to May 2009, a total of 250 blood samples were collected from patients tested slide positive for P. vivax, at the Aga Khan University Hospital, Karachi, or its collection units located in Baluchistan and Sindh Province. Nested PCR/RFLP was performed, using pvcsp and pvmsp1 markers to detect the extent of genetic diversity in clinical isolates of P. vivax from southern Pakistan. Results A total of 227/250 (91%) isolates were included in the analysis while the remainder were excluded due to negative PCR outcome for P.vivax. Pvcsp analysis showed that both VK 210 (85.5%, 194/227) and VK 247 type (14.5%, 33/227) were found to be circulating in P. vivax isolates from southern Pakistan. A total of sixteen and eighty-seven genotypes of pvcsp and pvmsp-1 were detected respectively. Conclusion This is the first report from southern Pakistan on characterization of P. vivax isolates confirming that extensively diverse pvcsp and pvmsp1 variants are present within this region. Results from this study provide valuable data on genetic diversity of P. vivax that will be helpful for further epidemiological studies. PMID:23311628

Successful malaria elimination in the Ecuador-Peru border region: epidemiology and lessons learned.

PubMed

Krisher, Lyndsay K; Krisher, Jesse; Ambuludi, Mariano; Arichabala, Ana; Beltrán-Ayala, Efrain; Navarrete, Patricia; Ordoñez, Tania; Polhemus, Mark E; Quintana, Fernando; Rochford, Rosemary; Silva, Mercy; Bazo, Juan; Stewart-Ibarra, Anna M

2016-11-28

In recent years, malaria (Plasmodium vivax and Plasmodium falciparum) has been successfully controlled in the Ecuador-Peru coastal border region. The aim of this study was to document this control effort and to identify the best practices and lessons learned that are applicable to malaria control and to other vector-borne diseases. A proximal outcome evaluation was conducted of the robust elimination programme in El Oro Province, Ecuador, and the Tumbes Region, Peru. Data collection efforts included a series of workshops with local public health experts who played central roles in the elimination effort, review of epidemiological records from Ministries of Health, and a review of national policy documents. Key programmatic and external factors are identified that determined the success of this eradication effort. From the mid 1980s until the early 2000s, the region experienced a surge in malaria transmission, which experts attributed to a combination of ineffective anti-malarial treatment, social-ecological factors (e.g., El Niño, increasing rice farming, construction of a reservoir), and political factors (e.g., reduction in resources and changes in management). In response to the malaria crisis, local public health practitioners from El Oro and Tumbes joined together in the mid-1990s to forge an unofficial binational collaboration for malaria control. Over the next 20 years, they effectively eradicated malaria in the region, by strengthening surveillance and treatment strategies, sharing of resources, operational research to inform policy, and novel interventions. The binational collaboration at the operational level was the fundamental component of the successful malaria elimination programme. This unique relationship created a trusting, open environment that allowed for flexibility, rapid response, innovation and resilience in times of crisis, and ultimately a sustainable control programme. Strong community involvement, an extensive microscopy network and ongoing epidemiologic investigations at the local level were also identified as crucial programmatic strategies. The results of this study provide key principles of a successful malaria elimination programme that can inform the next generation of public health professionals in the region, and serve as a guide to ongoing and future control efforts of other emerging vector borne diseases globally.

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

PubMed Central

2010-01-01

Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP) is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed. PMID:21029476

Toluidine blue: rapid and simple malaria parasite screening and species identification.

PubMed

Awale, Rupali; Maji, Ratnaprabha; Patil, Parag; Lingiah, Raghavendra; Mukhopadhyay, Ashok Kumar; Sharma, Subhadra

2017-01-01

Malaria, a febrile illness mostly confined to the tropical countries is transmitted by bite of infected female Anopheles mosquito. In 2015 alone, 88% of the malaria burden and 90% deaths due to malaria were confined to the African and Asian countries. Although number of tests are available for rapid diagnosis and screening for malaria, peripheral blood smear examination remains the gold standard. Leishman stain is recommended by WHO however herein we evaluate one of the alternative methods of staining which is simple and rapid. Fifty patients attending the various outpatient departments of the tertiary care hospital with fever and suspected to have malaria were selected. Two thin-air dried smears prepared from the peripheral venous blood from these subjects were stained by Leishman and Toluidine blue method. The findings of the slides by two independent qualified professionals were noted and the results were analyzed. A total of 14% (7/50) cases were diagnosed to have malaria. All the malaria cases which were positive in Leishman stain were also detected in Toluidine blue stain. Malarial parasites were clearly visible against the homogenously light green background in Toluidine blue. The detection of malarial parasite by Toluidine blue was quick, easy and confirmative. Toluidine blue stained peripheral blood smear allows for easy identification and speciation of malarial parasite at low magnification and in shorter period of time.

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

PPARγ Agonists Improve Survival and Neurocognitive Outcomes in Experimental Cerebral Malaria and Induce Neuroprotective Pathways in Human Malaria

PubMed Central

Serghides, Lena; Friedel, Miriam; Cui, Cheryl; Ho, Keith T.; Mount, Howard T. J.; Sled, John G.; Kain, Kevin C.

2014-01-01

Cerebral malaria (CM) is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors. Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone. PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models. Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM. Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brains of infected mice. Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy. In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF. These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM. PMID:24603727

Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon

PubMed Central

Bouyou-Akotet, Marielle K; Dzeing-Ella, Arnaud; Kendjo, Eric; Etoughe, Diane; Ngoungou, Edgard B; Planche, Timothy; Koko, Jean; Kombila, Maryvonne

2009-01-01

Background Improving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies. Methods A prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children. Results The proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36–47 months (54.5%). The proportion of anaemic children increased with parasite density (p < 0.01). Most of infected children were moderately to severely anaemic (69.5%, p < 0.01). Infants aged from one to 11 months had a higher risk of developing severe malarial anaemia. In children over six years of age, anaemia occurrence was high (>60%), but was unrelated to P. falciparum parasitaemia. Conclusion Malaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed. PMID:19619296

Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon.

PubMed

Bouyou-Akotet, Marielle K; Dzeing-Ella, Arnaud; Kendjo, Eric; Etoughe, Diane; Ngoungou, Edgard B; Planche, Timothy; Koko, Jean; Kombila, Maryvonne

2009-07-20

Improving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies. A prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children. The proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36-47 months (54.5%). The proportion of anaemic children increased with parasite density (p < 0.01). Most of infected children were moderately to severely anaemic (69.5%, p < 0.01). Infants aged from one to 11 months had a higher risk of developing severe malarial anaemia. In children over six years of age, anaemia occurrence was high (>60%), but was unrelated to P. falciparum parasitaemia. Malaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed.

Spontaneous fungal peritonitis: Epidemiology, current evidence and future prospective.

PubMed

Fiore, Marco; Leone, Sebastiano

2016-09-14

Spontaneous bacterial peritonitis is a complication of ascitic patients with end-stage liver disease (ESLD); spontaneous fungal peritonitis (SFP) is a complication of ESLD less known and described. ESLD is associated to immunodepression and the resulting increased susceptibility to infections. Recent perspectives of the management of the critically ill patient with ESLD do not specify the rate of isolation of fungi in critically ill patients, not even the antifungals used for the prophylaxis, neither optimal treatment. We reviewed, in order to focus the epidemiology, characteristics, and, considering the high mortality rate of SFP, the use of optimal empirical antifungal therapy the current literature.

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum.

PubMed

Parquet, Véronique; Henry, Maud; Wurtz, Nathalie; Dormoi, Jerome; Briolant, Sébastien; Gil, Marine; Baret, Eric; Amalvict, Rémy; Rogier, Christophe; Pradines, Bruno

2010-05-25

Quinine (QN) remains the first line anti-malarial drug for the treatment of complicated malaria in Europe and Africa. The emergence of QN resistance has been documented. QN resistance is not yet a significant problem, but there is an urgent need to discover partners for use in combination with QN. The aim of the study was to assess the in vitro potentiating effects of atorvastatin (AVA), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with QN against Plasmodium falciparum and to evaluate whether the effects of AVA could be associated with gene copy number or mutations in genes involved in QN resistance, such as pfcrt, pfmdr1, pfmrp and pfnhe. The susceptibilities to combination of AVA with QN were assessed against 21 parasite strains using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfcrt, pfmdr1, pfmdr2, pfmrp genes. In addition, the number of DNNND, DDNHNDNHNN repeats in pfnhe-1 ms4760 and the ms4760 profile were determined for each strains of P. falciparum. AVA demonstrated synergistic effects in combination with QN against 21 P. falciparum strains. The QN IC50 was reduced by 5% (0% to 15%; 95%CI: 1%-8%), 10% (3% to 23%; 95%CI: 7%-14%) and 22% (14% to 40%; 95%CI: 19%-25%) in presence of AVA at concentrations of 0.1, 0.5 and 1.0 microM, respectively. These reductions were all significant (p < 0.009). The reduction in the QN IC50 in presence of AVA was not significantly correlated with the QN IC50 (r = 0.22, P = 0.3288) or the AVA IC50 (r = 0.03, P = 0.8946). The synergistic effect of AVA in combination with QN was not significantly associated with polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes that could be involved in QN resistance. The synergistic effect of AVA on QN responses was not significantly associated with pfmdr1 copy number (P = 0.0428). The synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance. The different mechanisms of drug uptake and/or mode of action for AVA compared to the other anti-malarial drugs, as well as the AVA-mediated synergy of the anti-malarial effect of QN, suggests that AVA will be a good candidate for combinatorial malaria treatment. All of these observations support calls for both an in vivo evaluation with pharmacokinetic component and clinical trials of AVA as an anti-malarial therapy.

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum

PubMed Central

2010-01-01

Background Quinine (QN) remains the first line anti-malarial drug for the treatment of complicated malaria in Europe and Africa. The emergence of QN resistance has been documented. QN resistance is not yet a significant problem, but there is an urgent need to discover partners for use in combination with QN. The aim of the study was to assess the in vitro potentiating effects of atorvastatin (AVA), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with QN against Plasmodium falciparum and to evaluate whether the effects of AVA could be associated with gene copy number or mutations in genes involved in QN resistance, such as pfcrt, pfmdr1, pfmrp and pfnhe. Methods The susceptibilities to combination of AVA with QN were assessed against 21 parasite strains using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfcrt, pfmdr1, pfmdr2, pfmrp genes. In addition, the number of DNNND, DDNHNDNHNN repeats in pfnhe-1 ms4760 and the ms4760 profile were determined for each strains of P. falciparum. Results AVA demonstrated synergistic effects in combination with QN against 21 P. falciparum strains. The QN IC50 was reduced by 5% (0% to 15%; 95%CI: 1%-8%), 10% (3% to 23%; 95%CI: 7%-14%) and 22% (14% to 40%; 95%CI: 19%-25%) in presence of AVA at concentrations of 0.1, 0.5 and 1.0 μM, respectively. These reductions were all significant (p < 0.009). The reduction in the QN IC50 in presence of AVA was not significantly correlated with the QN IC50 (r = 0.22, P = 0.3288) or the AVA IC50 (r = 0.03, P = 0.8946). The synergistic effect of AVA in combination with QN was not significantly associated with polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes that could be involved in QN resistance. The synergistic effect of AVA on QN responses was not significantly associated with pfmdr1 copy number (P = 0.0428). Conclusion The synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance. The different mechanisms of drug uptake and/or mode of action for AVA compared to the other anti-malarial drugs, as well as the AVA-mediated synergy of the anti-malarial effect of QN, suggests that AVA will be a good candidate for combinatorial malaria treatment. All of these observations support calls for both an in vivo evaluation with pharmacokinetic component and clinical trials of AVA as an anti-malarial therapy. PMID:20497586

Insights into the availability and distribution of oral artemisinin monotherapy in Myanmar: evidence from a nationally representative outlet survey.

PubMed

Thein, Si Thu; Khin, Hnin Su Su; Thi, Aung

2017-04-25

The containment of artemisinin resistance in Myanmar, historically an important probable origin and route of anti-malarial resistance to the India sub-continent and beyond, is crucial to global malaria control and elimination. This paper describes what is currently known about the sale and distribution of oral artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly found. A nationally representative 2015 outlet survey was conducted in the private sector, and among community health workers across four geographical domains. A national sample of outlets was screened for availability of malaria testing and treatment, and an audit was completed for all anti-malarials. A total of 3859 outlets across Myanmar had an anti-malarial in stock on the day of survey. Of the 3859 anti-malarial stocking outlets, 988 outlets stocked oral AMT. Availability of oral AMT was highest among outlets in the Western border (36.8%) versus other domains (Eastern, 15.0%; Central, 19.3% Coastal, 10.7%). Over 90% of the oral AMT service delivery points were private sector outlets: general retailers (49.4%), pharmacies (23.5%), and itinerant drug vendors (14.2%). Eleven unique oral AMT products were audited. The most common product audited was Artesunate ® , manufactured by Mediplantex in Vietnam, which accounted for 79.9% of the oral AMT market share. Other oral AMT products were manufactured in China and in Myanmar. Over 60% of oral AMT products had a shelf life at purchase of greater than 2 years and only 14.7% were expired. The median number of oral AMT tablets typically dispensed to treat malaria was two tablets, approximately one tenth of a full adult course. The median price of a 50 mg tablet was $0.16. Given the high availability and distribution of oral AMT, it is possible that Myanmar has become the last remaining viable market for any oral AMT in the region for manufacturers. National and international organizations need to act quickly and effectively to stop the production and distribution to both improve malaria control within Myanmar and reduce risk of artemisinin resistance spreading to India and Africa.

A lactate dehydrogenase ELISA-based assay for the in vitro determination of Plasmodium berghei sensitivity to anti-malarial drugs.

PubMed

Orjuela-Sánchez, Pamela; Duggan, Erika; Nolan, John; Frangos, John A; Carvalho, Leonardo Jm

2012-11-05

Plasmodium berghei rodent malaria is a well-known model for the investigation of anti-malarial drug efficacy in vivo. However, the availability of drug in vitro assays in P. berghei is reduced when compared with the spectrum of techniques existing for Plasmodium falciparum. New alternatives to the current manual or automated methods described for P. berghei are attractive. The present study reports a new ELISA drug in vitro assay for P. berghei using two monoclonal antibodies against the parasite lactate dehydrogenase (pLDH). This procedure includes a short-in vitro culture, the purification of schizonts and the further generation of synchronized mice infections. Early stages of the parasite are then incubated against different concentrations of anti-malarial drugs using micro-plates. The novelty of this procedure in P. berghei relies on the quantification of the drug activity derived from the amount of pLDH estimated by an ELISA assay using two monoclonal antibodies: 14C1 and 19G7. The IC₅₀s obtained through the ELISA assay were compared with those from the micro-test. The initial parameters of the synchronized samples used in the in vitro assays were a parasitaemia of 0.5% and haematocrit of 1%, with an incubation period of 22 hours at 36.5°C. pLDH detection using a 14C1 coating at 10 μg/ml and 19G7 at 2.5 × 10⁻³ μg/ml provided good readouts of optical densities with low background in negative controls and specific detection levels for all parasite stages. IC₅₀s values derived from the ELISA assay for artesunate, chloroquine, amodiaquine and quinine were: 15, 7, 2, and 144 nM, respectively. When artesunate and chloroquine IC₅₀s were evaluated using the micro-test similar values were obtained. This ELISA-based in vitro drug assay is easy to implement, fast, and avoids the use radioisotopes or expensive equipment. The utility of this simple assay for screening anti-malarial drug activity against P. berghei in vitro is demonstrated.

Who continues to stock oral artemisinin monotherapy? Results of a provider survey in Myanmar.

PubMed

Thein, Si Thu; Sudhinaraset, May; Khin, Hnin Su Su; McFarland, Willi; Aung, Tin

2016-06-22

Artemisinin-based combination therapy (ACT) is a key strategy for global malaria elimination efforts. However, the development of artemisinin-resistant malaria parasites threatens progress and continued usage of oral artemisinin monotherapies (AMT) predisposes the selection of drug resistant strains. This is particularly a problem along the Myanmar/Thailand border. The artemisinin monotherapy replacement programme (AMTR) was established in 2012 to remove oral AMT from stocks in Myanmar, specifically by replacing oral AMT with quality-assured ACT and conducting behavioural change communication activities to the outlets dispensing anti-malarial medications. This study attempts to quantify the characteristics of outlet providers who continue to stock oral AMT despite these concerted efforts. A cross-sectional survey of all types of private sector outlets that were stocking anti-malarial drugs in 13 townships of Eastern Myanmar was implemented from July to August 2014. A total of 573 outlets were included. Bivariate and multivariable logistic regressions were conducted to assess outlet and provider-level characteristics associated with stocking oral AMT. In total, 2939 outlets in Eastern Myanmar were screened for presence of any anti-malarial drugs in August 2014. The study found that 573 (19.5 %) had some kind of oral anti-malarial drug in stock at the time of survey and among them, 96 (16.8 %) stocked oral AMT. In bivariate analyses, compared to health care facilities, itinerant drug vendors, retailers and health workers were less likely to stock oral AMT (33.3 vs 12.9, 10.0, 8.1 %, OR = 0.30, 0.22, 0.18, respectively). Providers who cut blister pack or sell partial courses (40.6 vs 11.7 %, OR 5.18, CI 3.18-8.44) and those who based their stock decision on consumer demand (32.8 vs 12.1 %, OR 3.54, CI 2.21-5.63) were more likely to stock oAMT. Multivariate logistic regressions produced similar significant associations. Private healthcare facilities and drug shops and providers who prioritize consumers' demand instead of recommended practices were more likely to stock oral AMT. Malaria elimination strategies should include targeted interventions to effectively reach those outlets.

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

In vivo antiplasmodial and toxicological effect of crude ethanol extract of Echinops kebericho traditionally used in treatment of malaria in Ethiopia.

PubMed

Toma, Alemayehu; Deyno, Serawit; Fikru, Abrham; Eyado, Amalework; Beale, Andrew

2015-05-10

Medicinal plants have contributed significantly to current malaria treatment. Emergence of resistance to currently available drugs has necessitated the search for new plant-based anti-malarial agents and several plant-based, pharmacologically active anti-malarial compounds have been isolated. This study was conducted to validate the traditional usage of Echinops kebericho for treating malaria in the traditional health care system of Ethiopia. The roots of E. kebericho were collected from Masha Woreda, Sheka Zone. After collection, the plant materials were identified by a taxonomist, dried under shade and crushed to powder for extraction. The powdered roots were extracted by maceration using 70 % ethanol. Acute toxicity study of the crude extract was carried out in Swiss albino mice. The in vivo anti-malarial activity of plant extract (200, 350 and 500 mg/kg) of E. kebericho roots against a chloroquine (CQ) sensitive strain of Plasmodium berghei strain ANKA was assessed using the four-day suppressive test procedure. Parameters such as parasitaemia, packed cell volume, body weight and survival time were then determined using standard tests. Oral administration of the ethanol extract showed significant (P<0.001) parasitaemia suppression at dose levels of 350 and 500 mg/kg in dose-related manner compared with the negative control. Five hundred mg/kg showed the highest (57.29±1.76 %) parasitaemia suppression. The survival times of P. berghei-infected mice were also increased in a dose-dependent manner but the test material did not prevent weight loss associated with increased parasitaemia. The result also showed the plant material prevented the loss in packed cell volume associated with increased parasitaemia. Its oral LD50 was found to be greater than 5,000 mg/kg, indicating its wider safety margin in mice. The result revealed the ethanol extract of E. kebericho roots has anti-malarial activity against P. berghei in an animal model and lends support to the use of the plant to combat malaria in Ethiopian folk medicine. Further work is necessary to isolate, identify and characterize the active principles from the plant material.

Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs.

PubMed

Egieyeh, Samuel Ayodele; Syce, James; Malan, Sarel F; Christoffels, Alan

2016-01-29

A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). Natural products with in vitro antiplasmodial activities (NAA) were compiled from various sources. These natural products were sub-divided into four groups based on inhibitory concentration (IC50). Key molecular descriptors and physicochemical properties were computed for these compounds and analysis of variance used to assess statistical significance amongst the sets of compounds. Molecular similarity analysis, estimation of drug-likeness, in silico pharmacokinetic profiling, and exploration of structure-activity landscape were also carried out on these sets of compounds. A total of 1040 natural products were selected and a total of 13 molecular descriptors were analysed. Significant differences were observed among the sub-groups of NAA and CRAD for at least 11 of the molecular descriptors, including number of hydrogen bond donors and acceptors, molecular weight, polar and hydrophobic surface areas, chiral centres, oxygen and nitrogen atoms, and shape index. The remaining molecular descriptors, including clogP, number of rotatable bonds and number of aromatic rings, did not show any significant difference when comparing the two compound sets. Molecular similarity and chemical space analysis identified natural products that were structurally diverse from CRAD. Prediction of the pharmacokinetic properties and drug-likeness of these natural products identified over 50% with desirable drug-like properties. Nearly 70% of all natural products were identified as potentially promiscuous compounds. Structure-activity landscape analysis highlighted compound pairs that form 'activity cliffs'. In all, prioritization strategies for the NAA were proposed. Chemo-informatic profiling of NAA and CRAD have produced a wealth of information that may guide decisions and facilitate anti-malarial drug development from natural products. Articulation of the information provided within an interactive data-mining environment led to a prioritized list of NAA.

Finding parasites and finding challenges: improved diagnostic access and trends in reported malaria and anti-malarial drug use in Livingstone district, Zambia

PubMed Central

2012-01-01

Background Understanding the impact of malaria rapid diagnostic test (RDT) use on management of acute febrile disease at a community level, and on the consumption of anti-malarial medicines, is critical to the planning and success of scale-up to universal parasite-based diagnosis by health systems in malaria-endemic countries. Methods A retrospective study of district-wide community-level RDT introduction was conducted in Livingstone District, Zambia, to assess the impact of this programmed on malaria reporting, incidence of mortality and on district anti-malarial consumption. Results Reported malaria declined from 12,186 cases in the quarter prior to RDT introduction in 2007 to an average of 12.25 confirmed and 294 unconfirmed malaria cases per quarter over the year to September 2009. Reported malaria-like fever also declined, with only 4,381 RDTs being consumed per quarter over the same year. Reported malaria mortality declined to zero in the year to September 2009, and all-cause mortality declined. Consumption of artemisinin-based combination therapy (ACT) dropped dramatically, but remained above reported malaria, declining from 12,550 courses dispensed by the district office in the quarter prior to RDT implementation to an average of 822 per quarter over the last year. Quinine consumption in health centres also declined, with the district office ceasing to supply due to low usage, but requests for sulphadoxine-pyrimethamine (SP) rose to well above previous levels, suggesting substitution of ACT with this drug in RDT-negative cases. Conclusions RDT introduction led to a large decline in reported malaria cases and in ACT consumption in Livingstone district. Reported malaria mortality declined to zero, indicating safety of the new diagnostic regime, although adherence and/or use of RDTs was still incomplete. However, a deficiency is apparent in management of non-malarial fever, with inappropriate use of a low-cost single dose drug, SP, replacing ACT. While large gains have been achieved, the full potential of RDTs will only be realized when strategies can be put in place to better manage RDT-negative cases. PMID:23043557

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.

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

Thalassemia and malaria: new insights into an old problem.

PubMed

Clegg, J B; Weatherall, D J

1999-01-01

The hemoglobinopathies are probably the world's most common genetic diseases: The World Health Organization has estimated that at least 5% of the population are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, which are found at polymorphic frequencies in many countries. All these hemoglobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane. Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa provided support for the "malaria hypothesis," but until recently it has proved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address this old question. Population and molecular genetic analysis of thalassemia variants, and microepidemiological studies of the relationship between alpha-thalassemia and malaria in the southwest Pacific, have provided unequivocal evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposure appears to provide the basis for better protection in later life.

[What's new in clinical dermatology?].

PubMed

Janier, M

2013-11-01

2013 has been the year of large genetic studies of the GWAS type (Genome wide association studies) in common diseases such as psoriasis and atopic dermatitis, aimed at localization of candidate genes. It was also the year of population-based studies from huge public or private registers. Thus, epidemiologic correlations have been put forward: psoriasis and vascular risk, psoriasis and rhinosinusitis, rosacea and migraine, acne and food habits, eczema and basal-cell carcinoma, vitiligo and lower risk of skin cancer, cutaneous Ro/SS-A pos lupus and cancer, chronic eczema and calcium-channel inhlbitors, pemphigoid and loop diuretics. Risk of IBD induced by isotretinoin has not been confirmed but risk of skin cancer under azathioprine is real. New drug reactions have appeared (pigmentation due to interferon, hypodermitis and sarcoidosis to anti-BRAF, vandetanib) and old ones are revisited (patch-testing of Severe Cutaneous adverse cutaneous reactions, pigmentation due to anti-malarial drugs, neutrophilic dermatosis due to azathioprine). Diane35(®) has been transiently withdrawn in January 2013 but tetrazepam has been withdrawn definitively in July 2013. Original aspects of cutaneous infections will be discussed along with new data on STDs (meningococcemia in MSMs, HPV, Herpes, congenital syphilis). Finally, some important papers about dermoscopy, confocal microscopy and aesthetic dermatology will be presented. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia.

PubMed

Valim, Clarissa; Ahmad, Rushdy; Lanaspa, Miguel; Tan, Yan; Acácio, Sozinho; Gillette, Michael A; Almendinger, Katherine D; Milner, Danny A; Madrid, Lola; Pellé, Karell; Harezlak, Jaroslaw; Silterra, Jacob; Alonso, Pedro L; Carr, Steven A; Mesirov, Jill P; Wirth, Dyann F; Wiegand, Roger C; Bassat, Quique

2016-02-15

Plasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy. Using 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses. We selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them. Three proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase-MB. Combinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians.

Cytotoxic effects of inhibitors of de novo pyrimidine biosynthesis upon Plasmodium falciparum.

PubMed

Seymour, K K; Lyons, S D; Phillips, L; Rieckmann, K H; Christopherson, R I

1994-05-03

The malarial parasite Plasmodium falciparum can only synthesize pyrimidine nucleotides via the de novo pathway which is therefore a suitable target for development of antimalarial drugs. New assay procedures have been developed using high-pressure liquid chromatography (HPLC) which enable concurrent measurement of pyrimidine intermediates in malaria. Synchronized parasites growing in erythrocytes were pulse-labeled with [14C]bicarbonate at 6-h intervals around the 48-h asexual life cycle. Analysis of malarial extracts by HPLC showed tht incorporation of [14C]bicarbonate into pyrimidine nucleotides was maximal during the transition from trophozoites to schizonts. The reaction, N-carbamyl-L-aspartate-->L-dihydroorotate (CA-asp-->DHO) catalyzed by malarial dihydroorotase is inhibited by L-6-thiodihydroorotate (TDHO) in vitro (Ki = 6.5 microM), and TDHO, as the free acid or methyl ester, induces a major accumulation of CA-asp in malaria. Atovaquone, a naphthoquinone, is a moderate inhibitor of dihydroorotate dehydrogenase in vitro (Ki = 27 microM) but induces major accumulations of CA-asp and DHO. Pyrazofurin induces accumulation of orotate and orotidine in malaria, consistent with inhibition of orotidine 5'-monophosphate (OMP) decarboxylase with subsequent dephosphorylation of the OMP accumulated. Although TDHO, atovaquone, and pyrazofurin arrest the growth of P. falciparum, only moderate decreases in UTP, CTP, and dTTP were observed. 5-Fluoroorotate also arrests the growth of P. falciparum with major accumulations of 5-fluorouridine mono-, di-, and triphosphates and the most significant inhibition of de novo biosynthesis of pyrimidine nucleotides.

Anaemia prevention for reduction of mortality in mothers and children.

PubMed

Brabin, Bernard; Prinsen-Geerligs, Paul; Verhoeff, Francine; Kazembe, Peter

2003-01-01

The relationship of anaemia as a risk factor for child and maternal mortality is described. Maternal case fatality rates, mainly from hospital studies vary from < 1% to > 50%. These large differences in risk were related primarily to differences in available obstetric care for women living in areas with inadequate antenatal and delivery care facilities. The relative risk of mortality associated with moderate anaemia (haemoglobin [Hb] 40-80 g/L) was 1.35 (95% confidence interval [95% CI] 0.92-2.00) and for severe anaemia (Hb < 47 g/L) was 3.51 (95% CI 2.05-6.00). Nutritional-related anaemia mortality is likely to be greater than malarial anaemia-related mortality. With good antenatal and obstetric care most anaemia-related deaths are preventable, and policies to reduce anaemia prevalence should not be divorced from efforts to provide adequate antenatal and delivery facilities for women in developing countries. In children, although mortality was increased with anaemia (< 50 g/L), the evidence for increased risk with less severe anaemia was inconclusive. A survival analysis of Malawian infants indicated that if Hb decreased by 10 g/L after 6 months of age, the risk of dying before 12 months of age increased 1.72 times. Evidence from a number of studies suggests that mortality due to severe malarial anaemia in children is greater than that due to iron-deficiency anaemia. Primary prevention of nutritional and malarial anaemia in young children could lead to reductions in child mortality.

BDA-410: A novel synthetic calpain inhibitor active against blood stage malaria

PubMed Central

Li, Xuerong; Chen, Huiqing; Jeong, Jong-Jin; Chishti, Athar H.

2007-01-01

Falcipains, the papain-family cysteine proteases of the Plasmodium falciparum, are potential drug targets for malaria parasite. Pharmacological inhibition of falcipains can block the hydrolysis of hemoglobin, parasite development, and egress, suggesting that falcipains play a key role at the blood stage of parasite life cycle. In the present study, we evaluated the anti-malarial effects of BDA-410, a novel cysteine protease inhibitor as a potential antimalarial drug. Recombinant falcipain (MBP-FP-2B) and Plasmodium falciparum trophozoite extract containing native falcipains were used for enzyme inhibition studies in vitro. The effect of BDA-410 on the malaria parasite development in vitro as well as its anti-malarial activity in vivo was evaluated using the Plasmodium chabaudi infection rodent model. The 50% inhibitory concentrations of BDA-410 were determined to be 628 nM and 534 nM for recombinant falcipain-2B and parasite extract, respectively. BDA-410 inhibited the malaria parasite growth in vitro with an IC50 value of 173 nM causing irreversible damage to the intracellular parasite. In vivo, the BDA-410 delayed the progression of malaria infection significantly using a mouse model of malaria pathogenesis. The characterization of BDA-410 as a potent inhibitor of Plasmodium falciparum cysteine proteases, and the demonstration of its efficacy in blocking parasite growth both in vitro and in vivo assays identifies BDA-410 is an important lead compound for the development of novel anti-malarial drugs. PMID:17583361

Plasmodium berghei infection ameliorates atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kishi, C; Amano, H; Suzue, K; Ishikawa, O

2014-10-01

Atopic diseases are more prevalent in industrialized countries than in developing countries. In addition, significant differences in the prevalence of allergic diseases are observed between rural and urban areas within the same country. This difference in prevalence has been attributed to what is called the 'hygiene hypothesis'. Although parasitic infections are known to protect against allergic reactions, the mechanism is still unknown. The aim of this study was to investigate whether or not malarial infections can inhibit atopic dermatitis (AD)-like skin lesions in a mouse model of AD. We used NC/Nga mice which are a model for AD. The NC/Nga mice were intraperitoneally infected with 1 × 10(5) Plasmoduim berghei (Pb) XAT-infected erythrocytes. Malarial infections ameliorated AD-like skin lesions in the NC/Nga mice. This improvement was blocked by the administration of anti-asialo GM1 antibodies, which are anti-natural killer (NK) cells. Additionally, adoptive transfer of NK cells markedly improved AD-like skin lesions in conventional NC/Nga mice; these suggest that the novel protective mechanism associated with malaria parasitic infections is at least, in part, dependent on NK cells. We have experimentally demonstrated for the first time that malarial infections ameliorated AD-like skin lesions in a mouse model of AD. Our study could explain in part the mechanism of the 'hygiene hypothesis', which states that parasitic infections can inhibit the development of allergic diseases. © 2014 The Authors. Allergy Published by John Wiley & Sons Ltd.

Plasmodium falciparum in vitro continuous culture conditions: A comparison of parasite susceptibility and tolerance to anti-malarial drugs throughout the asexual intra-erythrocytic life cycle.

PubMed

Duffy, Sandra; Avery, Vicky M

2017-12-01

The continuous culture of Plasmodium falciparum is often seen as a means to an end, that end being to probe the biology of the parasite in question, and ultimately for many in the malaria drug discovery arena, to identify means of killing the parasite in order to treat malaria. In vitro continuous culture of Plasmodium falciparum is a fundamental requirement when undertaking malaria research where the primary objectives utilise viable parasites of a desired lifecycle stage. This investigation, and resulting data, compared the impact culturing Plasmodium falciparum long term (4 months) in different environmental conditions had on experimental outcomes and thus conclusions. The example presented here focused specifically on the effect culture conditions had on the in vitro tolerance of Plasmodium falciparum to standard anti-malarial drugs, including artemisinin and lumefantrine. Historical data from an independent experiment for 3D7-ALB (5% O 2 ) was also compared with that obtained from this study. We concluded that parasites cultured for several months in media supplemented with a serum substitute such as Albumax II ® or within hyperoxic conditions (21% O 2 ), demonstrate highly variable responses to artemisinin and lumefantrine but not all anti-malarial drugs, when compared to those cultured in human serum in combination with Albumax II ® under normoxic conditions (5% O 2 ) for the parasite. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Is malaria over-diagnosed? A world malaria day 2017 experience by Excellence and Friends Management Care Centre (EFMC) and partners, Abuja Nigeria.

PubMed

Oleribe, Obinna Ositadimma; Osita-Oleribe, Princess; Ekom, Ekei; Ofem, Oriaku; Igwesi, Chidi; Chigozie, Obison Guy; Ekweghariri, Munaonyeso; Iyalla, Grace; Taylor-Robinson, Simon David

2017-01-01

Malaria remains a major cause of mortality across the world, but particularly in sub-Saharan Africa. WHO-sponsored World Malaria Day activity has helped to improve education and has contributed to a reduction in mortality globally in the past decade. However, much needs to be done still in Africa. We report on a World Malaria Day scheme in three primary Healthcare Facilities in and around the Abuja Federal Capital Territory in Nigeria in 2017. Activity included educational talks to pregnant women and nursing mothers of young children, with malarial testing, distribution of free mosquito nets and also medical treatment if needed. We found a large clinical over-diagnosis of malaria with simple fevers of any cause being reported as malaria. None of these cases were found to be due to malaria on formal malarial testing. We conclude that efforts should continue into education and prevention of malaria with insecticide-impregnated mosquito nets a key factor. However, over-diagnosis of malaria and the use of unnecessary antimalarial treatment may lead to parasite resistance to antimalarial treatment, morbidity from drug side-effects and potential mortality from not receiving the right treatment for other febrile illnesses. We recommend that malarial testing, particularly with simple blood film microscopy is implemented more widely across Africa, as it is simple to perform and allows effective management plans to be drawn up for individual patients.

Malaria burden in human population of Quetta, Pakistan

PubMed Central

Tareen, A. M.; Rafique, M.; Wadood, A.; Qasim, M.; Rahman, H.; Shah, S. H.; Khan, K.; Pirkani, G. S.

2012-01-01

Malaria is a serious global health challenge, which is responsible for more than one million deaths a year. Malarial infection is more prevalent in developing countries including Pakistan. Significant efforts have been made to control malaria; however, due to socio-environmental factors, it remains a frequent problem in Quetta. The present study was undertaken to determine the malarial incidence, species prevalence, and its demographic evaluation in human population of Quetta, Pakistan. A total of 1831 subjects, comprising 1072 male and 759 female presenting symptoms of malaria, were included in this study. Blood samples from clinically suspected individuals were subjected to the standard immunochromatographic and malaria parasite smear analysis for malaria diagnosis. Out of 1831 subjects, 338 (18.45%) patients were positive for malarial parasite while the species prevalence was found as 276 (81.66%) and 62 (18.34%) for Plasmodium vivax, and Plasmodium falciparum, respectively. Furthermore, seasonal variations gradual increase in the prevalence rate. The age group of 21–30 years (30.47%) was found more prone to malaria. The suspected malaria cases were found more frequent in rural (72.1%) as compared to urban (27.9%). In addition, the malaria burden was high in urban area (22.89%) population as compared to the rural area (16.74%) population. It was observed that the highest disease occurrence was caused by P. vivax, which reflects a serious threat for public health. The current findings will be helpful to plan effective strategies to prevent and control malaria in this area. PMID:24688766

Prevalence of human malaria infection in Pakistani areas bordering with Iran.

PubMed

Yasinzai, Mohammad Iqbal; Kakarsulemankhel, Juma Khan

2013-03-01

To study the prevalence of malarial infections in human population of district Panjgur in south-western Pakistan. The cross-sectional study identified malarial parasites in the blood slides of 6119 suspected malaria patients from July 2006 to June 2008 through passive and active case detection methods. SPSS 11 was used for statistical analysis. Out of 6119 suspected cases of malaria, 2346 (38.3%) were found to be positive for malarial parasite on blood smear slides. Of these, 1868 (79.6%) cases were due to Plasmodium vivax infection, and 478 (20.3%) had P. falciparum. However, seasonal variation was also noted: P. vivax infection was the highest (n = 131/144, 90.9%) in November and the lowest (n=83/176, 47.1%) in October. The prevalence was higher (n=1831, 78%) in males. Age-wise, the prevalence of the disease was 81.2% (n=334) and 80% (n=860) for age groups 1-10 years and 11-20 years. No case of P. malariae and P. ovale was detected in the study period. No association was found between types of infection and age groups. Human malaria infection was quite frequent in the study region, which is one of the hottest areas of Balochistan, Pakistan. In clinically-suspected cases of malaria, there was a high slide positivity rate. The high prevalence rate of P. vivax poses a significant health hazard but R falciparum also may lead to serious complications, including cerebral malaria.

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

Towards a better understanding of Artemisia vulgaris: Botany, phytochemistry, pharmacological and biotechnological potential.

PubMed

Abiri, Rambod; Silva, Abraão Lincoln Macedo; de Mesquita, Ludmilla Santos Silva; de Mesquita, José Wilson Carvalho; Atabaki, Narges; de Almeida, Eduardo Bezerra; Shaharuddin, Noor Azmi; Malik, Sonia

2018-07-01

Artemisia vulgaris is one of the important medicinal plant species of the genus Artemisia, which is usually known for its volatile oils. The genus Artemisia has become the subject of great interest due to its chemical and biological diversity as well as the discovery and isolation of promising anti-malarial drug artemisinin. A. vulgaris has a long history in treatment of human ailments by medicinal plants in various parts of the world. This medicinal plant possesses a broad spectrum of therapeutic properties including: anti-malarial, anti-inflammatory, anti-hypertensive, anti-oxidant, anti-tumoral, immunomodulatory, hepatoprotective, anti-spasmodic and anti-septic. These activities are mainly attributed to the presence of various classes of secondary metabolites, including flavonoids, sesquiterpene lactones, coumarins, acetylenes, phenolic acids, organic acids, mono- and sesquiterpenes. Studies related to A. vulgaris morphology, anatomy and phytochemistry has gained a significant interest for better understanding of production and accumulation of therapeutic compounds in this species. Recently, phytochemical and pharmacological investigations have corroborated the therapeutic potential of bioactive compounds of A. vulgaris. These findings provided further evidence for gaining deeper insight into the identification and isolation of novel compounds, which act as alternative sources of anti-malarial drugs in a cost-effective manner. Considering the rising demand and various medical applications of A. vulgaris, this review highlights the recent reports on the chemistry, biological activities and biotechnological interventions for controlled and continuous production of bioactive compounds from this plant species. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reverse epidemiology beyond dialysis patients: chronic heart failure, geriatrics, rheumatoid arthritis, COPD, and AIDS.

PubMed

Horwich, Tamara B; Fonarow, Gregg C

2007-01-01

"Reverse epidemiology" refers to paradoxical and counterintuitive epidemiologic associations between survival outcomes and traditional cardiovascular risk factors such as obesity, high blood pressure, and high cholesterol. Reverse epidemiology has been well described in end stage renal disease, but also has been observed in chronic disease states, including chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, and Acquired Immune Deficiency Syndrome, and in elderly populations. This review will highlight the recent medical literature on reverse epidemiology in these populations. Common pathophysiologic underpinnings in these chronic disease states may help explain the reversal of risk factors observed in these diverse populations. Furthermore, guidelines for the general population for optimal goals of weight, cholesterol levels, and blood pressure may not apply to special populations, including patients with chronic diseases or elderly persons.

Capacitive malaria aptasensor using Plasmodium falciparum glutamate dehydrogenase as target antigen in undiluted human serum.

PubMed

Singh, Naveen K; Arya, Sunil K; Estrela, Pedro; Goswami, Pranab

2018-06-08

A capacitive aptasensor for detecting the malaria biomarker, Plasmodium falciparum glutamate dehydrogenase (PfGDH), directly in human serum samples developed. A thiolated ssDNA aptamer (NG3) that binds specifically to PfGDH antigen with high affinity (K d = 79 nM) was used to develop the aptasensor. The aptasensor produced capacitance response at an optimized frequency of 2 Hz in a non-Faradaic electrochemical impedance based signal transduction platform. The aptasensor exhibited a wide dynamic range of 100 fM-100 nM with a limits of detection of 0.77 pM in serum samples. The interference from other predominant malarial biomarkers, namely, Plasmodium falciparum -lactate dehydrogenase and -histidine rich protein-II on the aptasensor was negligible. This PfGDH aptasensor with highly sensitive and label free detection capability has great application potential for diagnosis of asymptotic malaria and monitoring the regression of malaria during treatment regime with antimalarial drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America

PubMed Central

Barlam, Tamar F.; Cosgrove, Sara E.; Abbo, Lilian M.; MacDougall, Conan; Schuetz, Audrey N.; Septimus, Edward J.; Srinivasan, Arjun; Dellit, Timothy H.; Falck-Ytter, Yngve T.; Fishman, Neil O.; Hamilton, Cindy W.; Jenkins, Timothy C.; Lipsett, Pamela A.; Malani, Preeti N.; May, Larissa S.; Moran, Gregory J.; Neuhauser, Melinda M.; Newland, Jason G.; Ohl, Christopher A.; Samore, Matthew H.; Seo, Susan K.; Trivedi, Kavita K.

2016-01-01

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics. PMID:27080992

Treatment of malaria and related symptoms using traditional herbal medicine in Ethiopia.

PubMed

Suleman, Sultan; Beyene Tufa, Takele; Kebebe, Dereje; Belew, Sileshi; Mekonnen, Yimer; Gashe, Fanta; Mussa, Seid; Wynendaele, Evelien; Duchateau, Luc; De Spiegeleer, Bart

2018-03-01

Medicinal plants have always been an integral part of different cultures in Ethiopia in the treatment of different illnesses including malaria and related symptoms. However, due to lack of proper documentation, urbanization, drought, acculturation and deforestation, there is an increased risk of losing this traditional knowledge. Hence, the use of the indigenous knowledge should be well documented and validated for potential future use. To gather and document information on medicinal plants which are used in the traditional treatment of malaria and related symptoms in Ethiopia. First, an ethnomedicinal survey of plants was conducted in 17 districts of Jimma zone, the Oromia national regional state of Ethiopia. Jimma zone is malarious and rich in natural flora. A total of 115 traditional healers were interviewed using a semi-structured questionnaire containing personal data of the respondents, and information on medicinal plants used to treat malaria and related symptoms. In addition, a literature search using Medline/PubMed, Google Scholar, ScienceDirect and HINARI was conducted on the indigenous use, in-vitro/in-vivo anti-malarial activity reports, and the chemical characterization of medicinal plants of Ethiopia used against malaria. From ethnomedicinal survey, a total of 28 species of plants used in the traditional treatment of malaria and related symptoms in Jimma Zone were collected, identified and documented. In addition, the literature search revealed that 124 medicinal plant species were reported to be traditionally used in the treatment of malaria in Ethiopia. From both ethnomedicinal survey and the literature search, Asteraceae and Fabaceae were the most represented families and Allium sativum L., Carica papaya L., Vernonia amygdalina Del., Lepidium sativum L. and Croton macrostachyus Del. were the most frequently reported plant species for their anti-malarial use. The dominant plant parts used in the preparation of remedies were leaves. About 54% of the medicinal plants documented in the survey have been reported as an anti-malarial plant in the literature search. Furthermore, the in-vitro and in-vivo anti-plasmodial activity reports of extracts from some of plant species were found to support the traditional claim of the documented plants. Moreover, literatures indicate that several secondary metabolites isolated from certain plant species that are traditionally used for the treatment of malaria and related symptoms in Ethiopia demonstrate strong anti-plasmodial activity. The result of the current study showed that traditional knowledge is still playing an important role in the management of malaria and related symptoms in Ethiopia. Allium sativum L., Carica papaya L., Vernonia amygdalina Del., and Lepidium sativum L. are the most commonly reported species as anti-malarial plants and the traditional claim of some species was supported by known anti-plasmodial activity and bioactivity reports. The finding of this study is important in the rational prioritization of plant species which are potentially used for investigating new compounds, which could be efficacious for malaria treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The science of epidemiology and the methods needed for public health assessments: a review of epidemiology textbooks.

PubMed

Gouda, Hebe N; Powles, John W

2014-02-10

Epidemiology is often described as 'the science of public health'. Here we aim to assess the extent that epidemiological methods, as covered in contemporary standard textbooks, provide tools that can assess the relative magnitude of public health problems and can be used to help rank and assess public health priorities. Narrative literature review. Thirty textbooks were grouped into three categories; pure, extended or applied epidemiology, were reviewed with attention to the ways the discipline is characterised and the nature of the analytical methods described. Pure texts tend to present a strict hierarchy of methods with those metrics deemed to best serve aetiological inquiry at the top. Extended and applied texts employ broader definitions of epidemiology but in most cases, the metrics described are also those used in aetiological inquiry and may not be optimal for capturing the consequences and social importance of injuries and disease onsets. The primary scientific purpose of epidemiology, even amongst 'applied' textbooks, is aetiological inquiry. Authors do not readily extend to methods suitable for assessing public health problems and priorities.

Mergers and acquisitions: malaria and the great chloroplast heist.

PubMed

McFadden, G I

2000-01-01

The origin of the relict chloroplast recently identified in malarial parasites has been mysterious. Several new papers suggest that the parasites obtained their chloroplasts in an ancient endosymbiotic event that also created some major algal groups.

Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase.

PubMed

Lunev, Sergey; Bosch, Soraya S; Batista, Fernando A; Wang, Chao; Li, Jingyao; Linzke, Marleen; Kruithof, Paul; Chamoun, George; Dömling, Alexander S S; Wrenger, Carsten; Groves, Matthew R

2018-03-11

Aspartate transcarbamoylase catalyzes the second step of de-novo pyrimidine biosynthesis. As malarial parasites lack pyrimidine salvage machinery and rely on de-novo production for growth and proliferation, this pathway is a target for drug discovery. Previously, an apo crystal structure of aspartate transcarbamoylase from Plasmodium falciparum (PfATC) in its T-state has been reported. Here we present crystal structures of PfATC in the liganded R-state as well as in complex with the novel inhibitor, 2,3-napthalenediol, identified by high-throughput screening. Our data shows that 2,3-napthalediol binds in close proximity to the active site, implying an allosteric mechanism of inhibition. Furthermore, we report biophysical characterization of 2,3-napthalenediol. These data provide a promising starting point for structure based drug design targeting PfATC and malarial de-novo pyrimidine biosynthesis. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Validation of the proteasome as a therapeutic target in Plasmodium using an epoxyketone inhibitor with parasite-specific toxicity

PubMed Central

Li, Hao; Ponder, Elizabeth L.; Verdoes, Martijn; Asbjornsdottir, Kristijana H.; Deu, Edgar; Edgington, Laura E.; Lee, Jeong Tae; Kirk, Christopher J.; Demo, Susan D.; Williamson, Kim C.; Bogyo, Matthew

2012-01-01

Summary The Plasmodium proteasome has been suggested to be a potential anti-malarial drug target, however toxicity of inhibitors has prevented validation of this enzyme in vivo. We report here a screen of a library of 670 analogs of the recently FDA approved inhibitor, carfilzomib, to identify compounds that selectively kill parasites. We identified one compound, PR3, that has significant parasite killing activity in vitro but dramatically reduced toxicity in host cells. We found that this parasite-specific toxicity is not due to selective targeting of the Plasmodium proteasome over the host proteasome, but instead is due to a lack of activity against one of the human proteasome subunits. Subsequently, we used PR3 to significantly reduce parasite load in P. berghei infected mice without host toxicity, thus validating the proteasome as a viable anti-malarial drug target. PMID:23142757

Co-incidental Plasmodium Knowlesi and Mucormycosis infections presenting with acute kidney injury and lower gastrointestinal bleeding.

PubMed

Ramaswami, Arunachalam; Pisharam, Jayakrishnan K; Aung, Hla; Ghazala, Kafeel; Maboud, Khalil; Chong, Vui Heng; Tan, Jackson

2013-01-01

Plasmodium knowlesi is frequently reported in Southeast Asian countries and is now widely regarded as the fifth malarial parasite. Mucormycosis is a rare fungal infection that can occur in patients with a weakened immune system. We report a case of acute kidney injury secondary to Plasmodium knowlesi malaria infection and mucormycosis fungal infection. In addition, the patient also had lower gastrointestinal bleeding from invasive gastrointestinal mucormycosis. P. knowlesi infection was diagnosed by blood film and mucormycosis was diagnosed by histopathological examination of biopsy specimen of the colon. The patient recovered with antimalarial treatment (Quinine), antifungal treatment (Lipophilic Amphotericin), and supportive hemodialysis treatment. We hypothesize that P. knowlesi malarial infection can lower the immunologic threshold and predisposes vulnerable individuals to rare disseminated fungal infections. To the best of our knowledge, this is the first P. Knowlesi malaria-associated invasive fungal infection reported in the literature.

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa

PubMed Central

2011-01-01

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed. PMID:21676209

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa.

PubMed

Slavic, Ksenija; Krishna, Sanjeev; Derbyshire, Elvira T; Staines, Henry M

2011-06-15

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed.

Julius Wagner-Jauregg and the Legacy of Malarial Therapy for the Treatment of General Paresis of the Insane

PubMed Central

Tsay, Cynthia J.

2013-01-01

Julius Wagner-Jauregg, a preeminent Austrian psychiatrist was awarded the Nobel Prize in Medicine in 1927 for the development of malaria therapy for the treatment of neurosyphilis, or general paresis of the insane. Despite being only one of three psychiatrists to win a Nobel Prize, he has faded from public consciousness and his name recognition pales in comparison to his contemporary and fellow Austrian, Sigmund Freud. This paper explores his contributions to the field of biological psychiatry and also touches upon reasons, such as the growing bioethics movement, his controversial affiliation with the Nazi Party, and the evolution of neurosyphilis, that explain why Wagner-Jauregg is not more widely celebrated for his contributions to the field of psychiatry, even though his malarial treatment could be considered the earliest triumph of biological psychiatry over psychoanalysis. PMID:23766744

Airport malaria: report of four cases in Tunisia.

PubMed

Siala, Emna; Gamara, Dhikrayet; Kallel, Kalthoum; Daaboub, Jabeur; Zouiten, Faiçal; Houzé, Sandrine; Bouratbine, Aïda; Aoun, Karim

2015-01-28

Four cases of airport malaria were notified for the first time in Tunisia during the summer of 2013. All patients were neighbours living within 2 km of Tunis International Airport. They had no history of travel to malarious countries, of blood transfusion or of intravenous drug use. Although malaria transmission had ceased in Tunisia since 1980, autochthonous infection by local Anopheles mosquitoes was initially considered. However, this diagnostic hypothesis was ruled out due to negative entomological survey and the absence of additional cases.All cases were caused by Plasmodium falciparum. Clinical presentation was severe (important thrombocytopaenia and parasitaemia), because of relatively important delay in diagnosis (average of seven days). This indicates the need to consider malaria while examining airport employees or people living near international airports presenting with fever of unknown origin. It also stresses the need for effective spraying of aircrafts coming from malarious areas.

Ethnography of a parasite: A quantitative ethnographic observation of forest malaria in the Amazon basin.

PubMed

Feged-Rivadeneira, Alejandro; Evans, Sian

2018-05-01

Malaria in the Amazon basin is persistently more prevalent among low density populations (1-4 people/[Formula: see text]). Describing malaria transmission in small populations, such as ethnic minorities in the Amazon basin, living in reserves in groups that amount to 110-450 individuals, is fundamental for the implementation of adequate interventions. Here, we examine malaria transmission in a context of high prevalence in a small population of Nükak ethnicity (ethnic group [Formula: see text] individuals, study group, [Formula: see text] individuals) living in the peri-urban area of a city with [Formula: see text] inhabitants in the Amazon basin. Using methods from behavioral ecology, we conducted a quantitative ethnography and collected data to inform of individual behavioral profiles. Individual malarial infection reports were available from the local public health offices, so each behavioral profile was associated with an epidemic profile for the past 5 years. Our research shows that, in-line with current opinion, malaria among the Nükak is not associated with an occupational hazard risk and follows a holoendemic pattern, where children are most susceptible to the parasite. Parasite loads of malarial infection among the Nükak persist at much higher rates than in any other neighboring ethnicity, which indicates an association between high incidence rates and endemicity. We hypothesize that malarial infection in the forest follows a pattern where the parasite persists in pockets of holoendemicity, and occupational hazard risk for individuals outside those pockets is associated with behaviors that take place in the proximity of the pockets of endemicity.

A Comprehensive Texture Segmentation Framework for Segmentation of Capillary Non-Perfusion Regions in Fundus Fluorescein Angiograms

PubMed Central

Zheng, Yalin; Kwong, Man Ting; MacCormick, Ian J. C.; Beare, Nicholas A. V.; Harding, Simon P.

2014-01-01

Capillary non-perfusion (CNP) in the retina is a characteristic feature used in the management of a wide range of retinal diseases. There is no well-established computation tool for assessing the extent of CNP. We propose a novel texture segmentation framework to address this problem. This framework comprises three major steps: pre-processing, unsupervised total variation texture segmentation, and supervised segmentation. It employs a state-of-the-art multiphase total variation texture segmentation model which is enhanced by new kernel based region terms. The model can be applied to texture and intensity-based multiphase problems. A supervised segmentation step allows the framework to take expert knowledge into account, an AdaBoost classifier with weighted cost coefficient is chosen to tackle imbalanced data classification problems. To demonstrate its effectiveness, we applied this framework to 48 images from malarial retinopathy and 10 images from ischemic diabetic maculopathy. The performance of segmentation is satisfactory when compared to a reference standard of manual delineations: accuracy, sensitivity and specificity are 89.0%, 73.0%, and 90.8% respectively for the malarial retinopathy dataset and 80.8%, 70.6%, and 82.1% respectively for the diabetic maculopathy dataset. In terms of region-wise analysis, this method achieved an accuracy of 76.3% (45 out of 59 regions) for the malarial retinopathy dataset and 73.9% (17 out of 26 regions) for the diabetic maculopathy dataset. This comprehensive segmentation framework can quantify capillary non-perfusion in retinopathy from two distinct etiologies, and has the potential to be adopted for wider applications. PMID:24747681

Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia

PubMed Central

Valim, Clarissa; Ahmad, Rushdy; Lanaspa, Miguel; Tan, Yan; Acácio, Sozinho; Gillette, Michael A.; Almendinger, Katherine D.; Milner, Danny A.; Madrid, Lola; Pellé, Karell; Harezlak, Jaroslaw; Silterra, Jacob; Alonso, Pedro L.; Carr, Steven A.; Mesirov, Jill P.; Wiegand, Roger C.; Bassat, Quique

2016-01-01

Rationale: Plasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy. Objectives: Using 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses. Methods: We selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them. Measurements and Main Results: Three proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase–MB. Conclusions: Combinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians. PMID:26469764

Vessel discoloration detection in malarial retinopathy

NASA Astrophysics Data System (ADS)

Agurto, C.; Nemeth, S.; Barriga, S.; Soliz, P.; MacCormick, I.; Taylor, T.; Harding, S.; Lewallen, S.; Joshi, V.

2016-03-01

Cerebral malaria (CM) is a life-threatening clinical syndrome associated with malarial infection. It affects approximately 200 million people, mostly sub-Saharan African children under five years of age. Malarial retinopathy (MR) is a condition in which lesions such as whitening and vessel discoloration that are highly specific to CM appear in the retina. Other unrelated diseases can present with symptoms similar to CM, therefore the exact nature of the clinical symptoms must be ascertained in order to avoid misdiagnosis, which can lead to inappropriate treatment and, potentially, death. In this paper we outline the first system to detect the presence of discolored vessels associated with MR as a means to improve the CM diagnosis. We modified and improved our previous vessel segmentation algorithm by incorporating the `a' channel of the CIELab color space and noise reduction. We then divided the segmented vasculature into vessel segments and extracted features at the wall and in the centerline of the segment. Finally, we used a regression classifier to sort the segments into discolored and not-discolored vessel classes. By counting the abnormal vessel segments in each image, we were able to divide the analyzed images into two groups: normal and presence of vessel discoloration due to MR. We achieved an accuracy of 85% with sensitivity of 94% and specificity of 67%. In clinical practice, this algorithm would be combined with other MR retinal pathology detection algorithms. Therefore, a high specificity can be achieved. By choosing a different operating point in the ROC curve, our system achieved sensitivity of 67% with specificity of 100%.

Incidence of human malaria infection in northern hilly region of Balochistan, adjoining with NWFP, Pakistan: district Zhob.

PubMed

Yasinzai, Mohammad Iqbal; Kakarsulemankhel, Juma Khan

2008-06-15

This study was conducted to investigate the incidence of malarial infections in human population in 37 localities of district Zhob, Balochistan, Pakistan. Malarial parasites were identified in the blood slides of suspected patients of the disease from July, 2004 to June, 2006 and encompassed 7748 subjects. Out of 7748 suspected cases of malaria, 3240 (41.8%) were found to be positive for malarial parasite in blood smear slides. Out of positive cases, 1681 (51.8%) were identified as Plasmodium vivax infection and 1559 (48.1%) cases with P. falciparum. However, seasonal variation was also noted with the highest (85.4%: 141/165) infection of P. vivax in March and lowest (18.6%: 59/316) in October while infection of P. falciparum was highest (81.3%: 257/316) in October and lowest (14.5%: 24/165) in March. Infection with P. vivax in male was 75.7% (125/165) in March and in female 26.3% (58/220) in May whereas infection of P. falciparum in male was 61.5% (245/398) in July and in female was 20.5% (65/316) in October. These results are compared with those of other studies done in Pakistan. Cases of P. malariae and P. ovale were not found in the present study. In conclusion it can be pointed out that the high incidence rate of P. vivax (51.8%:1681/3240) in Zhob district poses a significant health hazard because it may also lead to cerebral malaria as it was suggested by previous workers.

Anopheles atroparvus density modeling using MODIS NDVI in a former malarious area in Portugal.

PubMed

Lourenço, Pedro M; Sousa, Carla A; Seixas, Júlia; Lopes, Pedro; Novo, Maria T; Almeida, A Paulo G

2011-12-01

Malaria is dependent on environmental factors and considered as potentially re-emerging in temperate regions. Remote sensing data have been used successfully for monitoring environmental conditions that influence the patterns of such arthropod vector-borne diseases. Anopheles atroparvus density data were collected from 2002 to 2005, on a bimonthly basis, at three sites in a former malarial area in Southern Portugal. The development of the Remote Vector Model (RVM) was based upon two main variables: temperature and the Normalized Differential Vegetation Index (NDVI) from the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra satellite. Temperature influences the mosquito life cycle and affects its intra-annual prevalence, and MODIS NDVI was used as a proxy for suitable habitat conditions. Mosquito data were used for calibration and validation of the model. For areas with high mosquito density, the model validation demonstrated a Pearson correlation of 0.68 (p<0.05) and a modelling efficiency/Nash-Sutcliffe of 0.44 representing the model's ability to predict intra- and inter-annual vector density trends. RVM estimates the density of the former malarial vector An. atroparvus as a function of temperature and of MODIS NDVI. RVM is a satellite data-based assimilation algorithm that uses temperature fields to predict the intra- and inter-annual densities of this mosquito species using MODIS NDVI. RVM is a relevant tool for vector density estimation, contributing to the risk assessment of transmission of mosquito-borne diseases and can be part of the early warning system and contingency plans providing support to the decision making process of relevant authorities. © 2011 The Society for Vector Ecology.

Mergers and acquisitions: malaria and the great chloroplast heist

PubMed Central

McFadden, Geoffrey I

2000-01-01

The origin of the relict chloroplast recently identified in malarial parasites has been mysterious. Several new papers suggest that the parasites obtained their chloroplasts in an ancient endosymbiotic event that also created some major algal groups. PMID:11178253

Estimating the burden of scrub typhus: A systematic review.

PubMed

Bonell, Ana; Lubell, Yoel; Newton, Paul N; Crump, John A; Paris, Daniel H

2017-09-01

Scrub typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub typhus remains poorly known. We systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub typhus since the year 2000. In prospective fever studies from Asia, scrub typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%-27.9% (median 22.2% IQR 18.6-25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. Limited evidence suggests high mortality in complicated scrub typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes. Scrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8-10 years from countries with an established surveillance system. A wider distribution of scrub typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.

Estimating the burden of scrub typhus: A systematic review

PubMed Central

Bonell, Ana; Lubell, Yoel; Newton, Paul N.; Crump, John A.

2017-01-01

Background Scrub typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub typhus remains poorly known. Methods We systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub typhus since the year 2000. Findings In prospective fever studies from Asia, scrub typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%–27.9% (median 22.2% IQR 18.6–25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. Limited evidence suggests high mortality in complicated scrub typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes. Interpretation Scrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system. A wider distribution of scrub typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches. PMID:28945755

In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling.

PubMed

Becker, John V W; van der Merwe, Marina M; van Brummelen, Anna C; Pillay, Pamisha; Crampton, Bridget G; Mmutlane, Edwin M; Parkinson, Chris; van Heerden, Fanie R; Crouch, Neil R; Smith, Peter J; Mancama, Dalu T; Maharaj, Vinesh J

2011-10-11

Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis. The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action. The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.

Artemisinin-based combination therapy availability and use in the private sector of five AMFm phase 1 countries

PubMed Central

2013-01-01

Background In 2009, the Global Fund to Fight AIDS, Tuberculosis and Malaria established the Affordable Medicines Facility-malaria (AMFm) in order to increase access to quality-assured artemisinin combination therapy (QAACT). AMFm Phase 1, which includes nine pilot programmes in eight countries, was launched in 2009. The objective of this study was to assess anti-malarial stock and purchase patterns at private outlets in five AMFm Phase 1 countries in regard to three of the core AMFm goals: increase the affordability of QAACT, increase the availability of QAACT, and crowd out artemisinin monotherapies and other substandard therapies. Methods The study was conducted between April and May 2012 and included interviews with personnel in 598 private pharmaceutical outlets in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Questionnaires were administered at private retail outlets and the data were analyzed to assess within- and between-country differences in QAACT price, availability, and popularity. Results AMFm medications were less expensive than their non-AMFm counterparts, yet prices for both types were above country-specific suggested retail prices. Market penetration of AMFm QAACT in both urban and rural areas was high, although stock-outs of both AMFm and non-AMFm products were more common in rural compared with urban outlets in Ghana and Kenya (p = 0.0013). Government recommendation was the most significant factor influencing anti-malarial stock choices in urban (41.5%) and rural (31.9%) outlets. The three top-selling anti-malarials reported for both urban and rural areas in each country were, with the exception of rural Uganda and urban Nigeria, combination therapies. Conclusions Results from this study indicate that the AMFm has not fully achieved its affordability and crowd-out objectives. Still, the final purchase price of AMFm QAACT was substantially lower than non-AMFm equivalents. Moreover, for both urban and rural areas, AMFm QAACT availability was found to be high, and the various forms of QAACT were the best-selling products among all anti-malarials. These findings suggest a continued need for initiatives like the AMFm that improve the affordability and accessibility of QAACT. Similar programmes may be especially effective if employed in combination with rapid diagnostic testing to ensure the appropriate use of these products. PMID:23607504

Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya.

PubMed

Bisanzio, Donal; Mutuku, Francis; LaBeaud, Angelle D; Mungai, Peter L; Muinde, Jackson; Busaidy, Hajara; Mukoko, Dunstan; King, Charles H; Kitron, Uriel

2015-12-01

Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system. Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM). Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012. The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

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.

Natural products as starting points for future anti-malarial therapies: going back to our roots?

PubMed Central

2011-01-01

Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already used by the community. This first step forms a solid basis of observations, before moving to in vivo pharmacological characterization and ultimately identifying the active ingredient. A large part of the population uses herbal medicinal products despite limited numbers of well-controlled clinical studies. Increased awareness by the regulators and public health bodies of the need for safety information on herbal medicinal products also lends support to obtaining more clinical data on such products. Conclusions The relative paucity of new herbal medicinal product scaffolds active against malaria results discovered in recent years suggest it is time to re-evaluate the ‘smash and grab’ approach of randomly testing purified natural products and replace it with a patient-data led approach. This will require a change of perspective form many in the field. It will require an investment in standardisation in several areas, including: the ethnopharmacology and design and reporting of clinical observation studies, systems for characterizing anti-malarial activity of patient plasma samples ex vivo followed by chemical and pharmacological characterisation of extracts from promising sources. Such work falls outside of the core mandate of the product development partnerships, such as MMV, and so will require additional support. This call is timely, given the strong interest from researchers in disease endemic countries to support the research arm of a malaria eradication agenda. Para-national institutions such as the African Network for Drugs and Diagnostics Innovation (ANDi) will play a major role in facilitating the development of their natural products patrimony and possibly clinical best practice to bring forward new therapeutics. As in the past, with quinine, lapinone and artemisinin, once the activity of herbal medicinal products in humans is characterised, it can be used to identify new molecular scaffolds which will form the basis of the next generation of anti-malarial therapies. PMID:21411014

USASOC Injury Prevention/Performance Optimization Musculoskeletal Screening Initiative

DTIC Science & Technology

2014-11-01

Abstract presented at the American College of Sports Medicine 2014. Sell, TC, Abt JP, Lovaleker M, Bozich A, Benson P, Morgan J, Lephart SM, FACSM...Injury Epidemiology of US Army Special Operations Forces. Medicine and Science in Sports and Exercise. 46(5S):759-769, 2014 (Appendix 1); 2) Manuscript...published Military Medicine - Abt JP, Sell TC, Bozich AJ, Lovalekar MT, Kane SF, Benson PJ, Morgan JS, Lephart SM. Injury Epidemiology of US Army

The science of epidemiology and the methods needed for public health assessments: a review of epidemiology textbooks

PubMed Central

2014-01-01

Objectives Epidemiology is often described as ‘the science of public health’. Here we aim to assess the extent that epidemiological methods, as covered in contemporary standard textbooks, provide tools that can assess the relative magnitude of public health problems and can be used to help rank and assess public health priorities. Study Design Narrative literature review. Methods Thirty textbooks were grouped into three categories; pure, extended or applied epidemiology, were reviewed with attention to the ways the discipline is characterised and the nature of the analytical methods described. Results Pure texts tend to present a strict hierarchy of methods with those metrics deemed to best serve aetiological inquiry at the top. Extended and applied texts employ broader definitions of epidemiology but in most cases, the metrics described are also those used in aetiological inquiry and may not be optimal for capturing the consequences and social importance of injuries and disease onsets. Conclusions The primary scientific purpose of epidemiology, even amongst ‘applied’ textbooks, is aetiological inquiry. Authors do not readily extend to methods suitable for assessing public health problems and priorities. PMID:24507570

Helminth-infected patients with malaria: a low profile transmission hub?

PubMed

Nacher, Mathieu

2012-11-15

Eclipsed by the debates about malaria incidence and severity in individual patients, malaria transmission in helminth-infected persons has so far received very little attention. Studies in humans have shown increased malaria incidence and prevalence, and a trend for a reduction of symptoms in patients with malaria. This suggests that such patients could possibly be less likely to seek treatment thus carrying malaria parasites and their gametocytes for longer durations, therefore, being a greater potential source of transmission. In addition, in humans, a study showed increased gametocyte carriage, and in an animal model of helminth-malaria co-infection, there was increased malaria transmission. These elements converge towards the hypothesis that patients co-infected with worms and malaria may represent a hub of malaria transmission. The test of this hypothesis requires verifying, in different epidemiological settings, that helminth-infected patients have more gametocytes, that they have less symptomatic malaria and longer-lasting infections, and that they are more attractive for the vectors. The negative outcome in one setting of one of the above aspects does not necessarily mean that the other two aspects may suffice to increase transmission. If it is verified that patients co-infected by worms and malaria could be a transmission hub, this would be an interesting piece of strategic information in the context of the spread of anti-malarial resistance and the malaria eradication attempts.

A seroprevalence and descriptive epidemiological study of malaria among Indian tribes of the Amazon basin of Brazil.

PubMed

de Arruda, M E; Aragaki, C; Gagliardi, F; Haile, R W

1996-04-01

Data on the seroprevalences of Plasmodium falciparum, P. vivax, and P. malariae in four isolated Indian tribes of the Amazon basin in Brazil, as determined by IFAT, were re-analysed. Age-, sex- and tribe-specific geometric mean antibody titres and externally standardized prevalence ratios were calculated for each parasite species. Correlation coefficients and prevalence odds ratios were also calculated for multiple infections with different combinations of the three Plasmodium species. Titres of all but one of the antibodies studied were similar in males and females; titres of antibodies to the blood stages of P. malariae were slightly higher in females than in males. Titres of antibodies to all three Plasmodium species increased with subject age, and this age effect was not confounded by sex or tribal differences. There were striking differences between tribes, with the Parakana tribe having relatively low titres of antibodies against P. falciparum and P. malariae; these tribal effects were not confounded by sex or age differences between tribes. The results indicate that conditions conductive to the transmission of P. malariae exist in this region of the Amazon. The potential for zoonotic transmission of P. brasilianum, a parasite of monkeys which is morphologically similar to P. malarie, and the generally high rates of seropositivity to all three species of Plasmodium indicate that control measures which are adequate and applicable to the region studied need to be developed.

Whole Genome Sequencing of Field Isolates Reveals Extensive Genetic Diversity in Plasmodium vivax from Colombia

PubMed Central

Winter, David J.; Pacheco, M. Andreína; Vallejo, Andres F.; Schwartz, Rachel S.; Arevalo-Herrera, Myriam; Herrera, Socrates

2015-01-01

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission. Here we analyze whole-genome data from eight field samples from a region in Cordóba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this species. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 polymorphic and easy to score microsatellite loci that can be used in epidemiological investigations in South America. PMID:26709695

Whole Genome Sequencing of Field Isolates Reveals Extensive Genetic Diversity in Plasmodium vivax from Colombia.

PubMed

Winter, David J; Pacheco, M Andreína; Vallejo, Andres F; Schwartz, Rachel S; Arevalo-Herrera, Myriam; Herrera, Socrates; Cartwright, Reed A; Escalante, Ananias A

2015-12-01

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission. Here we analyze whole-genome data from eight field samples from a region in Cordóba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this species. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 polymorphic and easy to score microsatellite loci that can be used in epidemiological investigations in South America.

Optimal control of malaria: combining vector interventions and drug therapies.

PubMed

Khamis, Doran; El Mouden, Claire; Kura, Klodeta; Bonsall, Michael B

2018-04-24

The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes. An optimal control framework based on coupled models of mosquito population dynamics and malaria epidemiology is used to investigate the cost-effectiveness of combining vector control with drug therapies in homogeneous environments with and without vector migration. The costs of endemic malaria are weighed against the costs of administering artemisinin therapies and releasing modified mosquitoes using various cost structures. Larval density dependence is shown to reduce the cost-effectiveness of conventional sterile insect releases compared with transgenic mosquitoes with a late-acting lethal gene. Using drug treatments can reduce the critical vector control release ratio necessary to cause disease fadeout. Combining vector control and drug therapies is the most effective and efficient use of resources, and using optimized implementation strategies can substantially reduce costs.

Structural dynamics of Casein Kinase I (CKI) from malarial parasite Plasmodium falciparum (Isolate 3D7): Insights from theoretical modelling and molecular simulations.

PubMed

Dehury, Budheswar; Behera, Santosh Kumar; Mahapatra, Namita

2017-01-01

The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation. Bi-lobed catalytic domain of PfCKI shares a high degree of secondary structure topology with CKI domains of rice, human, and mouse indicating co-evolution of these kinases. Molecular docking study revealed that ATP binds to the active site where the glycine-rich ATP-binding motif (G16-X-G18-X-X-G21) along with few conserved residues plays a crucial role maintaining stability of the complex. Structural superposition of PfCKI with close structural homologs depicted that the location and length of important loops are different, indicating the dynamic properties of these loops among CKIs, which is consistent with principal component analysis (PCA). PCA displayed that the overall global motion of ATP-bound form is comparatively higher than that of apo form. The present study provides insights into the structural features of PfCKI, which could contribute towards further understanding of related protein structures, dynamics of catalysis and phosphorylation mechanism in these important STKs from malarial parasite in near future. Copyright © 2016 Elsevier Inc. All rights reserved.

Using supply side evidence to inform oral artemisinin monotherapy replacement in Myanmar: a case study.

PubMed

Khin, Hnin Su Su; Aung, Tin; Aung, Moe; Thi, Aung; Boxshall, Matt; White, Chris

2016-08-18

In 2012, alarmingly high rates of oral artemisinin monotherapy availability and use were detected along Eastern Myanmar, threatening efforts to halt the spread of artemisinin resistance in the Greater Mekong Subregion (GMS), and globally. The aim of this paper is to exemplify how the use of supply side evidence generated through the ACTwatch project shaped the artemisinin monotherapy replacement malaria (AMTR) project's design and interventions to rapidly displace oral artemisinin monotherapy with subsidized, quality-assured ACT in the private sector. The AMTR project was implemented as part of the Myanmar artemisinin resistance containment (MARC) framework along Eastern Myanmar. Guided by outlet survey and supply chain evidence, the project implemented a high-level subsidy, including negotiations with a main anti-malarial distributor, with the aim of squeezing oral artemisinin monotherapy out of the market through price competition and increased availability of quality-assured artemisinin-based combinations. This was complemented with a plethora of demand-creation activities targeting anti-malarial providers and consumers. Priority outlet types responsible for the distribution of oral artemisinin monotherapy were identified by the outlet survey, and this evidence was used to target the AMTR project's supporting interventions. The widespread availability and use of oral artemisinin monotherapy in Myanmar has been a serious threat to malaria control and elimination in the country and across the region. Practical anti-malarial market evidence was rapidly generated and used to inform private sector approaches to address these threats. The program design approach outlined in this paper is illustrative of the type of evidence generation and use that will be required to ensure effective containment of artemisinin drug resistance and progress toward regional and global malaria elimination goals.

Combating poor-quality anti-malarial medicines: a call to action.

PubMed

Bassat, Quique; Tanner, Marcel; Guerin, Philippe J; Stricker, Kirstin; Hamed, Kamal

2016-06-01

The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria-endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial-key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development and malaria elimination programmes.

A Population Genetic Model for the Initial Spread of Partially Resistant Malaria Parasites under Anti-Malarial Combination Therapy and Weak Intrahost Competition

PubMed Central

Kim, Yuseob; Escalante, Ananias A.; Schneider, Kristan A.

2014-01-01

To develop public-health policies that extend the lifespan of affordable anti-malarial drugs as effective treatment options, it is necessary to understand the evolutionary processes leading to the origin and spread of mutations conferring drug resistance in malarial parasites. We built a population-genetic model for the emergence of resistance under combination drug therapy. Reproductive cycles of parasites are specified by their absolute fitness determined by clinical parameters, thus coupling the evolutionary-genetic with population-dynamic processes. Initial mutations confer only partial drug-resistance. Therefore, mutant parasites rarely survive combination therapy and within-host competition is very weak among parasites. The model focuses on the early phase of such unsuccessful recurrent mutations. This ends in the rare event of mutants enriching in an infected individual from which the successful spread of resistance over the entire population is initiated. By computer simulations, the waiting time until the establishment of resistant parasites is analysed. Resistance spreads quickly following the first appearance of a host infected predominantly by mutant parasites. This occurs either through a rare transmission of a resistant parasite to an uninfected host or through a rare failure of drugs in removing “transient” mutant alleles. The emergence of resistance is delayed with lower mutation rate, earlier treatment, higher metabolic cost of resistance, longer duration of high drug dose, and higher drug efficacy causing a stronger reduction in the sensitive and resistant parasites’ fitnesses. Overall, contrary to other studies’ proposition, the current model based on absolute fitness suggests that aggressive drug treatment delays the emergence of drug resistance. PMID:25007207

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors

PubMed Central

Alicke, Marie; Boakye-Appiah, Justice K.; Abdul-Jalil, Inusah; Henze, Andrea; van der Giet, Markus; Schulze, Matthias B.; Schweigert, Florian J.; Mockenhaupt, Frank P.; Bedu-Addo, George

2017-01-01

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4–15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38–52%), for malnutrition 50% (43–57%) and for CRFs 16% (11–21%). Infectious diseases and malnutrition frequently co-existed (28%; 21–34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2–9%) or with malnutrition (7%; 3–11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted. PMID:28727775

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors.

PubMed

Alicke, Marie; Boakye-Appiah, Justice K; Abdul-Jalil, Inusah; Henze, Andrea; van der Giet, Markus; Schulze, Matthias B; Schweigert, Florian J; Mockenhaupt, Frank P; Bedu-Addo, George; Danquah, Ina

2017-01-01

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4-15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38-52%), for malnutrition 50% (43-57%) and for CRFs 16% (11-21%). Infectious diseases and malnutrition frequently co-existed (28%; 21-34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2-9%) or with malnutrition (7%; 3-11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted.

The Origin of Malarial Parasites in Orangutans

PubMed Central

Pacheco, M. Andreína; Reid, Michael J. C.; Schillaci, Michael A.; Lowenberger, Carl A.; Galdikas, Biruté M. F.; Jones-Engel, Lisa; Escalante, Ananias A.

2012-01-01

Background Recent findings of Plasmodium in African apes have changed our perspectives on the evolution of malarial parasites in hominids. However, phylogenetic analyses of primate malarias are still missing information from Southeast Asian apes. In this study, we report molecular data for a malaria parasite lineage found in orangutans. Methodology/Principal Findings We screened twenty-four blood samples from Pongo pygmaeus (Kalimantan, Indonesia) for Plasmodium parasites by PCR. For all the malaria positive orangutan samples, parasite mitochondrial genomes (mtDNA) and two antigens: merozoite surface protein 1 42 kDa (MSP-142) and circumsporozoite protein gene (CSP) were amplified, cloned, and sequenced. Fifteen orangutans tested positive and yielded 5 distinct mitochondrial haplotypes not previously found. The haplotypes detected exhibited low genetic divergence among them, indicating that they belong to one species. We report phylogenetic analyses using mitochondrial genomes, MSP-142 and CSP. We found that the orangutan malaria parasite lineage was part of a monophyletic group that includes all the known non-human primate malaria parasites found in Southeast Asia; specifically, it shares a recent common ancestor with P. inui (a macaque parasite) and P. hylobati (a gibbon parasite) suggesting that this lineage originated as a result of a host switch. The genetic diversity of MSP-142 in orangutans seems to be under negative selection. This result is similar to previous findings in non-human primate malarias closely related to P. vivax. As has been previously observed in the other Plasmodium species found in non-human primates, the CSP shows high polymorphism in the number of repeats. However, it has clearly distinctive motifs from those previously found in other malarial parasites. Conclusion The evidence available from Asian apes indicates that these parasites originated independently from those found in Africa, likely as the result of host switches from other non-human primates. PMID:22536346

Glucose-6-phosphate dehydrogenase status and severity of malarial anaemia in Nigerian children.

PubMed

Orimadegun, Adebola Emmanuel; Sodeinde, Olugbemiro

2011-11-15

Glucose-6-phosphate dehydrogenase (G6PD) deficiency (Gd-) contributes to morbidity and mortality in sub-Saharan Africa but recent data on the interaction between Gd- and malaria among children is scarce. We hypothesised that, being a haemolytic factor, Gd- makes severe malarial anaemia (SMA) more common and even more severe. We selected 930 children aged 0.5-12 years attending a reference hospital with microscopically proven falciparum malaria. G6PD and haemoglobin were typed by the fluorescent spot test and electrophoresis, respectively. Molecular typing by PCR and restriction enzyme digestion was also performed on 15% of randomly selected samples. Haematocrit (PCV) values, haemoglobin type, blood group, presence of sickle cell trait (HbAS), and parasite counts were compared between G6PD-normal and deficient children. Prevalence of Gd- was 16.4% and 8.1% among boys and girls with malaria, respectively. Mean PCV was 22.8% in deficient children compared with 21.0% in normal children (p = 0.041). In boys, 2.7% of Gd- had PCV ≤ 10%, as compared to 13.6% in Gd+ (p = 0.005). Similarly, 21.3% of Gd- had PCV ≤ 15% compared with 39.4% in Gd+ (p = 0.003). No such difference was found among girls. Overall, HbAS was typed in 7.6% and was more common in Gd- (13.0%) than in Gd+ (6.8%), but the difference was not statistically significant (p = 0.058). The mean parasite counts were significantly lower in Gd- (15477.5/µl) than in Gd+ (19784.4/µl; p = 0.013), and it was independent from HbAS. Gd- males but not females were significantly less likely to develop severe malarial anaemia.

Seeing is believing: the nocturnal malarial mosquito Anopheles coluzzii responds to visual host-cues when odour indicates a host is nearby.

PubMed

Hawkes, Frances; Gibson, Gabriella

2016-06-03

The immediate aim of our study was to analyse the behaviour of the malarial mosquito Anopheles coluzzii (An. gambiae species complex) near a human host with the ultimate aim of contributing to our fundamental understanding of mosquito host-seeking behaviour and the overall aim of identifying behaviours that could be exploited to enhance sampling and control strategies. Based on 3D video recordings of individual host-seeking females in a laboratory wind-tunnel, we found that despite being a nocturnal species, An. coluzzii is highly responsive to a visually conspicuous object, but only in the presence of host-odour. Female mosquitoes approached and abruptly veered away from a dark object, which suggests attraction to visual cues plays a role in bringing mosquitoes to the source of host odour. It is worth noting that the majority of our recorded flight tracks consisted of highly stereotyped 'dipping' sequences near the ground, which have been mentioned in the literature, but never before quantified. Our quantitative analysis of female mosquito flight patterns within ~1.5 m of a host has revealed highly relevant information about responsiveness to visual objects and flight height that could revolutionise the efficacy of sampling traps; the capturing device of a trap should be visually conspicuous and positioned near the ground where the density of host-seeking mosquitoes would be greatest. These characteristics are not universally present in current traps for malarial mosquitoes. The characterisation of a new type of flight pattern that is prevalent in mosquitoes suggests that there is still much that is not fully understood about mosquito flight behaviour.

Effect of Preventive Supplementation with Zinc and Other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial

PubMed Central

Veenemans, Jacobien; Schouten, Laura R. A.; Ottenhof, Maarten J.; Mank, Theo G.; Uges, Donald R. A.; Mbugi, Erasto V.; Demir, Ayşe Y.; Kraaijenhagen, Rob J.; Savelkoul, Huub F. J.; Verhoef, Hans

2012-01-01

Background The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity. Methods and Findings Rural Tanzanian children (n = 612) aged 6–60 months and with height-for-age z-score < –1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%–40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94–1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24–3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57–0.96), but we found no evidence that it reduced the overall number of clinic visits. Conclusions We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics. Trial Registration ClinicalTrials.gov NCT00623857 PMID:22870238

Epidemiology of Injuries and Prevention Strategies in Competitive Swimmers

PubMed Central

Wanivenhaus, Florian; Fox, Alice J. S.; Chaudhury, Salma; Rodeo, Scott A.

2012-01-01

Context: Competitive swimmers are predisposed to musculoskeletal injuries of the upper limb, knee, and spine. This review discusses the epidemiology of these injuries, in addition to prevention strategies that may assist the physician in formulating rehabilitation programs for the swimmer following an injury. Evidence Acquisition: A literature search was performed by a review of Google Scholar, OVID, and PubMed articles published from 1972 to 2011. Results: This study highlights the epidemiology of injuries common to competitive swimmers and provides prevention strategies for the sports health professional. Conclusions: An understanding of swimming biomechanics and typical injuries in swimming aids in early recognition of injury, initiation of treatment, and design of optimal prevention and rehabilitation strategies. PMID:23016094

Applying a Geospatial Visualization Based on USSD Messages to Real Time Identification of Epidemiological Risk Areas in Developing Countries: A Case of Study of Paraguay.

PubMed

Ochoa, Silvia; Talavera, Julia; Paciello, Julio

2015-01-01

The identification of epidemiological risk areas is one of the major problems in public health. Information management strategies are needed to facilitate prevention and control of disease in the affected areas. This paper presents a model to optimize geographical data collection of suspected or confirmed disease occurrences using the Unstructured Supplementary Service Data (USSD) mobile technology, considering its wide adoption even in developing countries such as Paraguay. A Geographic Information System (GIS) is proposed for visualizing potential epidemiological risk areas in real time, that aims to support decision making and to implement prevention or contingency programs for public health.

Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

PubMed Central

Chiang, Annette N.; Valderramos, Juan-Carlos; Balachandran, Raghavan; Chovatiya, Raj J.; Mead, Brian P.; Schneider, Corinne; Bell, Samantha L.; Klein, Michael G.; Huryn, Donna M.; Chen, Xiaojiang S.; Day, Billy W.; Fidock, David A.; Wipf, Peter; Brodsky, Jeffrey L.

2009-01-01

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 μM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. PMID:19195901

Immunogenicity and protective efficacy of a recombinant yellow fever vaccine against the murine malarial parasite Plasmodium yoelii.

PubMed

Stoyanov, Cristina T; Boscardin, Silvia B; Deroubaix, Stephanie; Barba-Spaeth, Giovanna; Franco, David; Nussenzweig, Ruth S; Nussenzweig, Michel; Rice, Charles M

2010-06-23

The live-attenuated yellow fever vaccine (YF17D) is one of the safest and most effective vaccines available today. Here, YF17D was genetically altered to express the circumsporozoite protein (CSP) from the murine malarial parasite Plasmodium yoelii. Reconstituted recombinant virus was viable and exhibited robust CSP expression. Immunization of naïve mice resulted in extensive proliferation of adoptively transferred CSP-specific transgenic CD8(+) T-cells. A single immunization of naïve mice with recombinant YF17D resulted in robust production of IFN-gamma by CD8(+) T-cells and IFN-gamma and IL-2 by CD4(+) T-cells. A prime-boost regimen consisting of recombinant virus followed by a low-dose of irradiated sporozoites conferred protection against challenge with P. yoelii. Taken together, these results show that recombinant YF17D can efficiently express CSP in culture, and prime a protective immune response in vivo. (c) 2010 Elsevier Ltd. All rights reserved.

A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax

PubMed Central

March, Sandra; Ng, Shengyong; Velmurugan, Soundarapandian; Galstian, Ani; Shan, Jing; Logan, David; Carpenter, Anne; Thomas, David; Lee Sim, B. Kim; Mota, Maria M.; Hoffman, Stephen L.; Bhatia, Sangeeta N.

2013-01-01

SUMMARY The Plasmodium liver stage is an attractive target for the development of anti-malarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable and reproducible in vitro liver stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum including the release of infected merozoites and infection of overlaid erythrocytes, and also the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput anti-malarial drug screening and vaccine development. PMID:23870318

Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria.

PubMed

Small, Dylan S; Taylor, Terrie E; Postels, Douglas G; Beare, Nicholas Av; Cheng, Jing; MacCormick, Ian Jc; Seydel, Karl B

2017-06-07

Cerebral malaria (CM) can be classified as retinopathy-positive or retinopathy-negative, based on the presence or absence of characteristic retinal features. While malaria parasites are considered central to the pathogenesis of retinopathy-positive CM, their contribution to retinopathy-negative CM is largely unknown. One theory is that malaria parasites are innocent bystanders in retinopathy-negative CM and the etiology of the coma is entirely non-malarial. Because hospitals in malaria-endemic areas often lack diagnostic facilities to identify non-malarial causes of coma, it has not been possible to evaluate the contribution of malaria infection to retinopathy-negative CM. To overcome this barrier, we studied a natural experiment involving genetically inherited traits, and find evidence that malaria parasitemia does contribute to the pathogenesis of retinopathy-negative CM. A lower bound for the fraction of retinopathy-negative CM that would be prevented if malaria parasitemia were to be eliminated is estimated to be 0.93 (95% confidence interval: 0.68, 1).

Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia.

PubMed

Fernandez-Arias, Cristina; Rivera-Correa, Juan; Gallego-Delgado, Julio; Rudlaff, Rachel; Fernandez, Clemente; Roussel, Camille; Götz, Anton; Gonzalez, Sandra; Mohanty, Akshaya; Mohanty, Sanjib; Wassmer, Samuel; Buffet, Pierre; Ndour, Papa Alioune; Rodriguez, Ana

2016-02-10

Plasmodium species, the parasitic agents of malaria, invade erythrocytes to reproduce, resulting in erythrocyte loss. However, a greater loss is caused by the elimination of uninfected erythrocytes, sometimes long after infection has been cleared. Using a mouse model, we found that Plasmodium infection induces the generation of anti-self antibodies that bind to the surface of uninfected erythrocytes from infected, but not uninfected, mice. These antibodies recognize phosphatidylserine, which is exposed on the surface of a fraction of uninfected erythrocytes during malaria. We find that phosphatidylserine-exposing erythrocytes are reticulocytes expressing high levels of CD47, a "do-not-eat-me" signal, but the binding of anti-phosphatidylserine antibodies mediates their phagocytosis, contributing to anemia. In human patients with late postmalarial anemia, we found a strong inverse correlation between the levels of anti-phosphatidylserine antibodies and plasma hemoglobin, suggesting a similar role in humans. Inhibition of this pathway may be exploited for treating malarial anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of the capacity between public and private health facilities to manage under-five children with febrile illnesses in Uganda.

PubMed

Buregyeya, Esther; Rutebemberwa, Elizeus; LaRussa, Phillip; Lal, Sham; Clarke, Sîan E; Hansen, Kristian S; Magnussen, Pascal; Mbonye, Anthony K

2017-05-02

Public health facilities are usually the first to receive interventions compared to private facilities, yet majority of health seeking care is first done with the latter. This study compared the capacity to manage acute febrile illnesses in children below 5 years in private vs public health facilities in order to design interventions to improve quality of care. A survey was conducted within 57 geographical areas (parishes), from August to October 2014 in Mukono district, central Uganda. The survey comprised both facility and health worker assessment. Data were collected on drug stocks, availability of treatment guidelines, diagnostic equipment, and knowledge in management of malaria, pneumonia and diarrhoea, using a structured questionnaire. A total of 53 public and 241 private health facilities participated in the study. While similar proportions of private and public health facilities stocked Coartem, the first-line anti-malarial drug, (98 vs 95%, p = 0.22), significantly more private than public health facilities stocked quinine (85 vs 53%, p < 0.01). Stocks of obsolete anti-malarial drugs, such as chloroquine, were reported in few public and private facilities (3.7 vs 12.5%, p = 0.06). Stocks of antibiotics-amoxycillin and gentamycin were similar in both sectors (≥90% for amoxicillin; ≥50 for gentamycin). Training in malaria was reported by 65% of public health facilities vs 56% in the private sector, p = 0.25), while, only 21% in the public facility and 12% in the private facilities, p = 0.11, reported receiving training in pneumonia. Only 55% of public facilities had microscopes. Malaria treatment guidelines were significantly lacking in the private sector, p = 0.01. Knowledge about first-line management of uncomplicated malaria, pneumonia and diarrhoea was significantly better in the public facilities compared to the private ones, though still sub-optimal. Deficiencies of equipment, supplies and training exist even in public health facilities. In order to significantly improve the capacity to handle acute febrile illness among children under five, training in proper case management, availability of supplies and diagnostics need to be addressed in both sectors.

Netting the malaria menace: Distribution and utilization of long-lasting insecticidal net in a malaria endemic area in Bankura, West Bengal.

PubMed

Mukhopadhyay, D K; Basu, S S; Roy, D; Das, N; Akbar, F; Sarkar, G N

2016-03-01

Long-lasting insecticidal net (LLIN) is considered to be a highly effective intervention against malaria under National Vector Borne Disease Control Programme in India. A cross-sectional study was undertaken to assess the coverage and utilization of LLIN and the factors related thereto. A survey of 1300 households was carried out in Ranibandh block of Bankura district in West Bengal, India, using lot quality assurance sampling (LQAS) method. Coverage/utilization of 80% was considered as minimum acceptable norm. The weighted sample size was calculated from each village of the block. The sociodemographic, economic information of the household along with the availability and use of LLIN was collected through interview and observation. In total, 7320 individuals including 840 children ≤ 5 yr were visited. Overall coverage of adequate LLIN was 65.4% (± 1.5%) and for children ≤ 5 yr, it was 60.5% (± 1.3%). Overall, 66.1% (± 1.4%) people of all ages and 63.7% (± 1.4%) children ≤ 5 yr slept under LLINs in the night before the survey. Out of 26 sub-centres, distribution of LLINs in 10 sub-centres was below the accepted norm, whereas utilization was sub-optimal in 19 sub-centres. In only 18.2% (± 0.5%) households, LLINs remained hanging during daytime. Poverty, caste, education, perception regarding malarial morbidity and preventive action of LLIN were associated significantly with the distribution of LLIN. Similarly, poverty (AOR = 2.14), threat perception regarding malarial morbidity (AOR = 1.51) and mortality (AOR = 2.52) were positively associated with the use of LLIN. Full utilization of bednets by under-fives of the households was higher in villages with sub-centres. Around two-third population of the study area was effectively covered with LLIN. Higher proportion of socially marginalized people received LLIN. Threat perception regarding malaria was directly associated with both receipt and use of LLIN. Behaviour change communication on utilization along with adequate access to LLIN needs to be strengthened.

Cynaropicrin: A Comprehensive Research Review and Therapeutic Potential As an Anti-Hepatitis C Virus Agent

PubMed Central

Elsebai, Mahmoud F.; Mocan, Andrei; Atanasov, Atanas G.

2016-01-01

The different pharmacologic properties of plants-containing cynaropicrin, especially artichokes, have been known for many centuries. More recently, cynaropicrin exhibited a potential activity against all genotypes of hepatitis C virus (HCV). Cynaropicrin has also shown a wide range of other pharmacologic properties such as anti-hyperlipidemic, anti-trypanosomal, anti-malarial, antifeedant, antispasmodic, anti-photoaging, and anti-tumor action, as well as activation of bitter sensory receptors, and anti-inflammatory properties (e.g., associated with the suppression of the key pro-inflammatory NF-κB pathway). These pharmacological effects are very supportive factors to its outstanding activity against HCV. Structurally, cynaropicrin might be considered as a potential drug candidate, since it has no violations for the rule of five and its water-solubility could allow formulation as therapeutic injections. Moreover, cynaropicrin is a small molecule that can be easily synthesized and as the major constituent of the edible plant artichoke, which has a history of safe dietary use. In summary, cynaropicrin is a promising bioactive natural product that, with minor hit-to-lead optimization, might be developed as a drug for HCV. PMID:28008316

Optimising and communicating options for the control of invasive plant disease when there is epidemiological uncertainty.

PubMed

Cunniffe, Nik J; Stutt, Richard O J H; DeSimone, R Erik; Gottwald, Tim R; Gilligan, Christopher A

2015-04-01

Although local eradication is routinely attempted following introduction of disease into a new region, failure is commonplace. Epidemiological principles governing the design of successful control are not well-understood. We analyse factors underlying the effectiveness of reactive eradication of localised outbreaks of invading plant disease, using citrus canker in Florida as a case study, although our results are largely generic, and apply to other plant pathogens (as we show via our second case study, citrus greening). We demonstrate how to optimise control via removal of hosts surrounding detected infection (i.e. localised culling) using a spatially-explicit, stochastic epidemiological model. We show how to define optimal culling strategies that take account of stochasticity in disease spread, and how the effectiveness of disease control depends on epidemiological parameters determining pathogen infectivity, symptom emergence and spread, the initial level of infection, and the logistics and implementation of detection and control. We also consider how optimal culling strategies are conditioned on the levels of risk acceptance/aversion of decision makers, and show how to extend the analyses to account for potential larger-scale impacts of a small-scale outbreak. Control of local outbreaks by culling can be very effective, particularly when started quickly, but the optimum strategy and its performance are strongly dependent on epidemiological parameters (particularly those controlling dispersal and the extent of any cryptic infection, i.e. infectious hosts prior to symptoms), the logistics of detection and control, and the level of local and global risk that is deemed to be acceptable. A version of the model we developed to illustrate our methodology and results to an audience of stakeholders, including policy makers, regulators and growers, is available online as an interactive, user-friendly interface at http://www.webidemics.com/. This version of our model allows the complex epidemiological principles that underlie our results to be communicated to a non-specialist audience.

Optimising and Communicating Options for the Control of Invasive Plant Disease When There Is Epidemiological Uncertainty

PubMed Central

Cunniffe, Nik J.; Stutt, Richard O. J. H.; DeSimone, R. Erik; Gottwald, Tim R.; Gilligan, Christopher A.

2015-01-01

Although local eradication is routinely attempted following introduction of disease into a new region, failure is commonplace. Epidemiological principles governing the design of successful control are not well-understood. We analyse factors underlying the effectiveness of reactive eradication of localised outbreaks of invading plant disease, using citrus canker in Florida as a case study, although our results are largely generic, and apply to other plant pathogens (as we show via our second case study, citrus greening). We demonstrate how to optimise control via removal of hosts surrounding detected infection (i.e. localised culling) using a spatially-explicit, stochastic epidemiological model. We show how to define optimal culling strategies that take account of stochasticity in disease spread, and how the effectiveness of disease control depends on epidemiological parameters determining pathogen infectivity, symptom emergence and spread, the initial level of infection, and the logistics and implementation of detection and control. We also consider how optimal culling strategies are conditioned on the levels of risk acceptance/aversion of decision makers, and show how to extend the analyses to account for potential larger-scale impacts of a small-scale outbreak. Control of local outbreaks by culling can be very effective, particularly when started quickly, but the optimum strategy and its performance are strongly dependent on epidemiological parameters (particularly those controlling dispersal and the extent of any cryptic infection, i.e. infectious hosts prior to symptoms), the logistics of detection and control, and the level of local and global risk that is deemed to be acceptable. A version of the model we developed to illustrate our methodology and results to an audience of stakeholders, including policy makers, regulators and growers, is available online as an interactive, user-friendly interface at http://www.webidemics.com/. This version of our model allows the complex epidemiological principles that underlie our results to be communicated to a non-specialist audience. PMID:25874622

Cellular engineering of Artemisia annua and Artemisia dubia with the rol ABC genes for enhanced production of potent anti-malarial drug artemisinin.

PubMed

Kiani, Bushra Hafeez; Suberu, John; Mirza, Bushra

2016-05-04

Malaria is causing more than half of a million deaths and 214 million clinical cases annually. Despite tremendous efforts for the control of malaria, the global morbidity and mortality have not been significantly changed in the last 50 years. Artemisinin, extracted from the medicinal plant Artemisia sp. is an effective anti-malarial drug. In 2015, elucidation of the effectiveness of artemisinin as a potent anti-malarial drug was acknowledged with a Nobel prize. Owing to the tight market and low yield of artemisinin, an economical way to increase its production is to increase its content in Artemisia sp. through different biotechnological approaches including genetic transformation. Artemisia annua and Artemisia dubia were transformed with rol ABC genes through Agrobacterium tumefacienes and Agrobacterium rhizogenes methods. The artemisinin content was analysed and compared between transformed and untransformed plants with the help of LC-MS/MS. Expression of key genes [Cytochrome P450 (CYP71AV1), aldehyde dehydrogenase 1 (ALDH1), amorpha-4, 11 diene synthase (ADS)] in the biosynthetic pathway of artemisinin and gene for trichome development and sesquiterpenoid biosynthetic (TFAR1) were measured using Quantitative real time PCR (qRT-PCR). Trichome density was analysed using confocal microscope. Artemisinin content was significantly increased in transformed material of both Artemisia species when compared to un-transformed plants. The artemisinin content within leaves of transformed lines was increased by a factor of nine, indicating that the plant is capable of synthesizing much higher amounts than has been achieved so far through traditional breeding. Expression of all artemisinin biosynthesis genes was significantly increased, although variation between the genes was observed. CYP71AV1 and ALDH1 expression levels were higher than that of ADS. Levels of the TFAR1 expression were also increased in all transgenic lines. Trichome density was also significantly increased in the leaves of transformed plants, but no trichomes were found in control roots or transformed roots. The detection of significantly raised levels of expression of the genes involved in artemisinin biosynthesis in transformed roots correlated with the production of significant amounts of artemisinin in these tissues. This suggests that synthesis is occurring in tissues other than the trichomes, which contradicts previous theories. Transformation of Artemisia sp. with rol ABC genes can lead to the increased production of artemisinin, which will help to meet the increasing demand of artemisinin because of its diverse pharmacological and anti-malarial importance.

[Exposure to CT scans in childhood and long-term cancer risk: A review of epidemiological studies].

PubMed

Baysson, Hélène; Journy, Neige; Roué, Tristan; Ducou-Lepointe, Hubert; Etard, Cécile; Bernier, Marie-Odile

2016-02-01

Amongst medical exams requiring ionizing radiation, computed tomography (CT) scans are used more frequently, including in children. These CT examinations are associated with absorbed doses that are much higher than those associated with conventional radiology. In comparison to adults, children have a greater sensitivity to radiation and a longer life span with more years at cancer risks. Five epidemiological studies on cancer risks after CT scan exposure during childhood were published between 2012 and 2015. The results of these studies are consistent and show an increase of cancer risks in children who have been exposed to several CT scans. However, methodological limits due to indication bias, retrospective assessment of radiation exposure from CT scans and lack of statistical power are to be taken into consideration. International projects such as EPI-CT (Epidemiological study to quantify risks for pediatric computerized tomography and to optimize dose), with a focus on dosimetric reconstruction and minimization of bias will provide more precise results. In the meantime, available results reinforce the necessity of justification and optimization of doses. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Adaption and agronomic performance of Artemisia annua L. under lowland humid tropical conditions

USDA-ARS?s Scientific Manuscript database

Demand for new chemotherapies against malaria is increasing as Plasmodium, the causative organism of the disease, has shown a high degree of resistance against most standard anti-malarial drugs. One the few highly effective compounds is artemisinin, the major sesquiterpene for the production of art...

Naval Medical Research and Development News. Volume 7, Issue 10

DTIC Science & Technology

2015-10-01

SR) product against adult Aedes aegypti the primary vector for DENV. The goal of this project is to obtain evidence that SRs lessen contact between...multi-site project designated to test the SR against the dengue vector Aedes aegypti. Four other sites will evaluate its impact against malarial

Research Methods in Healthcare Epidemiology: Survey and Qualitative Research.

PubMed

Safdar, Nasia; Abbo, Lilian M; Knobloch, Mary Jo; Seo, Susan K

2016-11-01

Surveys are one of the most frequently employed study designs in healthcare epidemiology research. Generally easier to undertake and less costly than many other study designs, surveys can be invaluable to gain insights into opinions and practices in large samples and may be descriptive and/or be used to test associations. In this context, qualitative research methods may complement this study design either at the survey development phase and/or at the interpretation/extension of results stage. This methods article focuses on key considerations for designing and deploying surveys in healthcare epidemiology and antibiotic stewardship, including identification of whether or not de novo survey development is necessary, ways to optimally lay out and display a survey, denominator measurement, discussion of biases to keep in mind particularly in research using surveys, and the role of qualitative research methods to complement surveys. We review examples of surveys in healthcare epidemiology and antimicrobial stewardship and review the pros and cons of methods used. A checklist is provided to help aid design and deployment of surveys in healthcare epidemiology and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;1-6.

Research Methods in Healthcare Epidemiology: Survey and Qualitative Research

PubMed Central

Safdar, Nasia; Abbo, Lilian M.; Knobloch, Mary Jo; Seo, Susan K.

2017-01-01

Surveys are one of the most frequently employed study designs in healthcare epidemiology research. Generally easier to undertake and less costly than many other study designs, surveys can be invaluable to gain insights into opinions and practices in large samples and may be descriptive and/or be used to test associations. In this context, qualitative research methods may complement this study design either at the survey development phase and/or at the interpretation/extension of results stage. This methods article focuses on key considerations for designing and deploying surveys in healthcare epidemiology and antibiotic stewardship, including identification of whether or not de novo survey development is necessary, ways to optimally lay out and display a survey, denominator measurement, discussion of biases to keep in mind particularly in research using surveys, and the role of qualitative research methods to complement surveys. We review examples of surveys in healthcare epidemiology and antimicrobial stewardship and review the pros and cons of methods used. A checklist is provided to help aid design and deployment of surveys in healthcare epidemiology and antimicrobial stewardship. PMID:27514583

Optimal sampling strategies for detecting zoonotic disease epidemics.

PubMed

Ferguson, Jake M; Langebrake, Jessica B; Cannataro, Vincent L; Garcia, Andres J; Hamman, Elizabeth A; Martcheva, Maia; Osenberg, Craig W

2014-06-01

The early detection of disease epidemics reduces the chance of successful introductions into new locales, minimizes the number of infections, and reduces the financial impact. We develop a framework to determine the optimal sampling strategy for disease detection in zoonotic host-vector epidemiological systems when a disease goes from below detectable levels to an epidemic. We find that if the time of disease introduction is known then the optimal sampling strategy can switch abruptly between sampling only from the vector population to sampling only from the host population. We also construct time-independent optimal sampling strategies when conducting periodic sampling that can involve sampling both the host and the vector populations simultaneously. Both time-dependent and -independent solutions can be useful for sampling design, depending on whether the time of introduction of the disease is known or not. We illustrate the approach with West Nile virus, a globally-spreading zoonotic arbovirus. Though our analytical results are based on a linearization of the dynamical systems, the sampling rules appear robust over a wide range of parameter space when compared to nonlinear simulation models. Our results suggest some simple rules that can be used by practitioners when developing surveillance programs. These rules require knowledge of transition rates between epidemiological compartments, which population was initially infected, and of the cost per sample for serological tests.

Testing times: trends in availability, price, and market share of malaria diagnostics in the public and private healthcare sector across eight sub-Saharan African countries from 2009 to 2015.

PubMed

Hanson, Kara; Goodman, Catherine

2017-05-19

The World Health Organization guidelines have recommended that all cases of suspected malaria should receive a confirmatory test with microscopy or a malaria rapid diagnostic test (RDT), however evidence from sub-Saharan Africa (SSA) illustrates that only one-third of children under five with a recent fever received a test. The aim of this study was to evaluate availability, price and market share of microscopy and RDT from 2009/11 to 2014/15 in 8 SSA countries, to better understand barriers to improving access to malaria confirmatory testing in the public and private health sectors. Repeated national cross-sectional quantitative surveys were conducted among a sample of outlets stocking anti-malarial medicines and/or diagnostics. In total, 169,655 outlets were screened. Availability of malaria blood testing among all screened public health facilities increased significantly between the first survey wave in 2009/11 and the most recent in 2014/15 in Benin (36.2, 85.4%, p < 0.001), Kenya (53.8, 93.0%, p < 0.001), mainland Tanzania (46.9, 89.9%, p < 0.001), Nigeria (28.5, 86.2%, p < 0.001), Katanga, the Democratic Republic of the Congo (DRC) (76.0, 88.2%, p < 0.05), and Uganda (38.9, 95.6%, p < 0.001). These findings were attributed to an increase in availability of RDTs. Diagnostic availability remained high in Kinshasa (the DRC) (87.6, 97.6%) and Zambia (87.9, 91.6%). Testing availability in public health facilities significantly decreased in Madagascar (88.1, 73.1%, p < 0.01). In the most recent survey round, the majority of malaria testing was performed in the public sector in Zambia (90.9%), Benin (90.3%), Madagascar (84.5%), Katanga (74.3%), mainland Tanzania (73.5%), Uganda (71.8%), Nigeria (68.4%), Kenya (53.2%) and Kinshasa (51.9%). In the anti-malarial stocking private sector, significant increases in availability of diagnostic tests among private for-profit facilities were observed between the first and final survey rounds in Kinshasa (82.1, 94.0%, p < 0.05), Nigeria (37.0, 66.0%, p < 0.05), Kenya (52.8, 74.3%, p < 0.001), mainland Tanzania (66.8, 93.5%, p < 0.01), Uganda (47.1, 70.1%, p < 0.001), and Madagascar (14.5, 45.0%, p < 0.01). Blood testing availability remained low over time among anti-malarial stocking private health facilities in Benin (33.1, 20.7%), and high over time in Zambia (94.4, 87.5%), with evidence of falls in availability in Katanga (72.7, 55.6%, p < 0.05). Availability among anti-malarial stocking pharmacies and drug stores-which are the most common source of anti-malarial medicines-was rare in all settings, and highest in Uganda in 2015 (21.5%). Median private sector price of RDT for a child was equal to the price of pre-packaged quality-assured artemisinin-based combination therapy (QAACT) treatment for a two-year old child in some countries, and 1.5-2.5 times higher in others. Median private sector QAACT price for an adult varied from having parity with an RDT for an adult to being up to 2 times more expensive. The exception was in both Kinshasa and Katanga, where the median price of QAACT was less expensive than RDTs. Significant strides have been made in the availability of testing, mainly through the widespread distribution of RDT, and especially in public health facilities. Significant barriers to universal coverage of diagnostic testing can be attributed to very low availability in the private sector, particularly among pharmacies and drug stores, which are responsible for most anti-malarial distribution. Where tests are available, price may serve as a barrier to uptake, particularly for young children. Several initiatives that have introduced RDT into the private sector can be modified and expanded as a means to close this gap in malaria testing availability and promote universal diagnosis.

Transforming Epidemiology for 21st Century Medicine and Public Health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khoury, Muin J; Lam, Tram Kim; Ioannidis, John

2013-01-01

n 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving toward more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and acceleratemore » translation; (iii) expanding cohort studies to collect exposure, clinical, and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating big data science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy, and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology, in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits.« less

Transforming Epidemiology for 21st Century Medicine and Public Health

PubMed Central

Khoury, Muin J.; Lam, Tram Kim; Ioannidis, John P.A.; Hartge, Patricia; Spitz, Margaret R.; Buring, Julie E.; Chanock, Stephen J.; Croyle, Robert T.; Goddard, Katrina A.; Ginsburg, Geoffrey S.; Herceg, Zdenko; Hiatt, Robert A.; Hoover, Robert N.; Hunter, David J.; Kramer, Barnet S.; Lauer, Michael S.; Meyerhardt, Jeffrey A.; Olopade, Olufunmilayo I.; Palmer, Julie R.; Sellers, Thomas A.; Seminara, Daniela; Ransohoff, David F.; Rebbeck, Timothy R.; Tourassi, Georgia; Winn, Deborah M.; Zauber, Ann; Schully, Sheri D.

2013-01-01

In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving towards more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating “big data” science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits. PMID:23462917

Describing the epidemiology of rheumatic diseases: methodological aspects.

PubMed

Guillemin, Francis

2012-03-01

Producing descriptive epidemiology data is essential to understand the burden of rheumatic diseases (prevalence) and their dynamic in the population (incidence). No matter how simple such indicators may look, the correct collection of data and the appropriate interpretation of the results face several challenges: distinguishing indicators, facing the costs of obtaining data, using appropriate definition, identifying optimal sources of data, choosing among many survey methods, dealing with estimates precision, and standardizing results. This study describes the underlying methodological difficulties to be overcome so as to make descriptive indicators reliable and interpretable.

Epidemiology of Posttraumatic Osteoarthritis.

PubMed

Thomas, Abbey C; Hubbard-Turner, Tricia; Wikstrom, Erik A; Palmieri-Smith, Riann M

2017-06-02

Osteoarthritis is a leading cause of disability whose prevalence and incidence continue to increase. History of joint injury represents an important risk factor for posttraumatic osteoarthritis and is a significant contributor to the rapidly growing percentage of the population with osteoarthritis. This review will present the epidemiology associated with posttraumatic osteoarthritis, with particular emphasis on the knee and ankle joints. It is important to understand the effect of posttraumatic osteoarthritis on the population so that sufficient resources can be devoted to countering the disease and promoting optimal long-term health for patients after joint injury.

Decision making with regard to antiviral intervention during an influenza pandemic.

PubMed

Shim, Eunha; Chapman, Gretchen B; Galvani, Alison P

2010-01-01

Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might be aligned through subsidization.

Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

PubMed Central

Shim, Eunha; Chapman, Gretchen B.; Galvani, Alison P.

2012-01-01

Background Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). Methods We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. Results At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. Conclusions The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might be aligned through subsidization. PMID:20634545

Chinese version of the Optimism and Pessimism Scale: Psychometric properties in mainland China and development of a short form.

PubMed

Xia, Jie; Wu, Daxing; Zhang, Jibiao; Xu, Yuanchao; Xu, Yunxuan

2016-06-01

This study aimed to validate the Chinese version of the Optimism and Pessimism Scale in a sample of 730 adult Chinese individuals. Confirmatory factor analyses confirmed the bidimensionality of the scale with two factors, optimism and pessimism. The total scale and optimism and pessimism factors demonstrated satisfactory reliability and validity. Population-based normative data and mean values for gender, age, and education were determined. Furthermore, we developed a 20-item short form of the Chinese version of the Optimism and Pessimism Scale with structural validity comparable to the full form. In summary, the Chinese version of the Optimism and Pessimism Scale is an appropriate and practical tool for epidemiological research in mainland China. © The Author(s) 2014.

Predictors of knowledge towards malaria of rural tribal communities in Dhalai District of Tripura, India.

PubMed

Kumar, S; Debbarma, A

2013-10-01

Reduction of malarial morbidity and mortality is one of the top public health priorities in Tripura and the Country. To achieve these targets it is imperative to have active community participation to control malaria. Community participation in turn depends on people's knowledge and attitude towards the disease. This study was conducted to examine the factors that predict the knowledge of rural tribal communities in Dhalai district of Tripura towards malaria. This community based epidemiological cross-sectional descriptive study was carried out in Dhalai district of Tripura. A pre-tested structured questionnaire collecting socio-demographic and malaria-related KAP information was administered to the 216 adult respondents from a representative sample of households. As a whole, there were 147(68.1%) illiterate respondents. Out of them, 89(41.2%) persons were male and 58(26.9%) were female. Correct knowledge about the cause of malaria was 2.77 times higher in males than females and 11.53 times higher in literate tribal people than in illiterate. Correct knowledge about the symptoms fever, chills, and rigors of malaria were also higher in male sex and in literate tribal people. Use of smoke as preventive measure was very high among the respondents. Common predictors of correct knowledge about etiology and clinical features of malaria were in male Tripuri and Reang community. Use of smoke for killing of adult mosquito was predicted by illiteracy. Promotion of literacy and participation in health education are vital component in terms of knowledge and practice.

Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT)

PubMed Central

Boggild, A; Brophy, J; Charlebois, P; Crockett, M; Geduld, J; Ghesquiere, W; McDonald, P; Plourde, P; Teitelbaum, P; Tepper, M; Schofield, S; McCarthy, A

2014-01-01

Background On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. These recommendations aim to achieve appropriate diagnosis and management of malaria, a disease that is still uncommon in Canada. Objective To provide recommendations on the appropriate diagnosis and treatment of malaria. Methods CATMAT reviewed all major sources of information on malaria diagnosis and treatment, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. Recommendations Malarial management depends on rapid identification of the disease, as well as identification of the malaria species and level of parasitemia. Microscopic identification of blood samples is both rapid and accurate but can be done only by trained laboratory technicians. Rapid diagnostic tests are widely available, are simple to use and do not require specialized laboratory equipment or training; however, they do not provide the level of parasitemia and do require verification. Polymerase chain reaction (PCR), although still limited in availability, is emerging as the gold standard for high sensitivity and specificity in identifying the species. PMID:29769894

Clinical Survey of Dengue Virus Circulation in the Republic of Djibouti between 2011 and 2014 Identifies Serotype 3 Epidemic and Recommends Clinical Diagnosis Guidelines for Resource Limited Settings.

PubMed

Le Gonidec, Erwan; Maquart, Marianne; Duron, Sandrine; Savini, Hélène; Cazajous, Geraldine; Vidal, Pierre-Olivier; Chenilleau, Marie-Caroline; Roseau, Jean-Baptiste; Benois, Alain; Dehan, Céline; Kugelman, Jeffrey; Leparc-Goffart, Isabelle; Védy, Serge

2016-06-01

Dengue virus is endemic globally, throughout tropical and sub-tropical regions. While the number of epidemics due to the four DENV serotypes is pronounced in East Africa, the total number of cases reported in Africa (16 million infections) remained at low levels compared to Asia (70 million infections). The French Armed forces Health Service provides epidemiological surveillance support in the Republic of Djibouti through the Bouffard Military hospital. Between 2011 and 2014, clinical and biological data of suspected dengue syndromes were collected at the Bouffard Military hospital and analyzed to improve Dengue clinical diagnosis and evaluate its circulation in East Africa. Examining samples from patients that presented one or more Dengue-like symptoms the study evidenced 128 Dengue cases among 354 suspected cases (36.2% of the non-malarial Dengue-like syndromes). It also demonstrated the circulation of serotypes 1 and 2 and reports the first epidemic of serotype 3 infections in Djibouti which was found in all of the hospitalized patients in this study. Based on these results we have determined that screening for Malaria and the presence of the arthralgia, gastro-intestinal symptoms and lymphopenia < 1,000cell/ mm3 allows for negative predictive value and specificity of diagnosis in isolated areas superior to 80% up to day 6. This study also provides evidence for an epidemic of Dengue virus serotype 3 previously not detected in Djibouti.

Clinical Survey of Dengue Virus Circulation in the Republic of Djibouti between 2011 and 2014 Identifies Serotype 3 Epidemic and Recommends Clinical Diagnosis Guidelines for Resource Limited Settings

PubMed Central

Duron, Sandrine; Savini, Hélène; Cazajous, Geraldine; Vidal, Pierre-Olivier; Chenilleau, Marie-Caroline; Roseau, Jean-Baptiste; Benois, Alain; Dehan, Céline; Kugelman, Jeffrey; Leparc-Goffart, Isabelle; Védy, Serge

2016-01-01

Dengue virus is endemic globally, throughout tropical and sub-tropical regions. While the number of epidemics due to the four DENV serotypes is pronounced in East Africa, the total number of cases reported in Africa (16 million infections) remained at low levels compared to Asia (70 million infections). The French Armed forces Health Service provides epidemiological surveillance support in the Republic of Djibouti through the Bouffard Military hospital. Between 2011 and 2014, clinical and biological data of suspected dengue syndromes were collected at the Bouffard Military hospital and analyzed to improve Dengue clinical diagnosis and evaluate its circulation in East Africa. Examining samples from patients that presented one or more Dengue-like symptoms the study evidenced 128 Dengue cases among 354 suspected cases (36.2% of the non-malarial Dengue-like syndromes). It also demonstrated the circulation of serotypes 1 and 2 and reports the first epidemic of serotype 3 infections in Djibouti which was found in all of the hospitalized patients in this study. Based on these results we have determined that screening for Malaria and the presence of the arthralgia, gastro-intestinal symptoms and lymphopenia < 1,000cell/ mm3 allows for negative predictive value and specificity of diagnosis in isolated areas superior to 80% up to day 6. This study also provides evidence for an epidemic of Dengue virus serotype 3 previously not detected in Djibouti. PMID:27322644

Workbook on the Identification of Anopheles Larvae. Preliminary Issue.

ERIC Educational Resources Information Center

Pratt, Harry D.; Stojanovich, Chester J.

This self-instructional booklet is designed to enable malarial control workers to identify the larvae of "Anopheles" species that are important malaria vectors. The morphological features of the larvae are illustrated in a programed booklet, which also contains an illustrated taxonomic key to 25 species of anopheline larvae. A glossary and a short…

Recent and projected increases in atmospheric carbon dioxide are associated with enhanced concentration of the anti-malarial compound, artemesinin

USDA-ARS?s Scientific Manuscript database

Although direct impacts on plant biology, in response to projected increases in atmospheric carbon dioxide [CO2], have been well established experimentally, data quantifying recent (20th century) impacts of [CO2] on plant chemical composition are undocumented. Yet, such impacts could include change...

Production of a Recombinant E. coli Expressed Malarial Vaccine from the C-Terminal Fragment of Plasmodium Falciparum 3D7 Merozoite Surface Protein-1.

DTIC Science & Technology

2000-04-01

Reportable Outcomes 1. Manuscript in preparation: Evelina Angov, Barbara Aufiero, Michel Van Handenhove, Christian Ockenhouse, Kent Kester, Doug Walsh, Jana...Burnouf, T., Ouattara, D., Attanath, P., Bouharoun-Tayoun, H., Chantavanich, P., Foucault , C., Chongsuphajaisiddhi, T., and Druilhe, P. (1991

Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density

PubMed Central

Betancourt, Michael; Upton, Leanna M; Angrisano, Fiona; Morin, Merribeth J

2018-01-01

Anti-malarial pre-erythrocytic vaccines (PEV) target transmission by inhibiting human infection but are currently partially protective. It has been posited, but never demonstrated, that co-administering transmission-blocking vaccines (TBV) would enhance malaria control. We hypothesized a mechanism that TBV could reduce parasite density in the mosquito salivary glands, thereby enhancing PEV efficacy. This was tested using a multigenerational population assay, passaging Plasmodium berghei to Anopheles stephensi mosquitoes. A combined efficacy of 90.8% (86.7–94.2%) was observed in the PEV +TBV antibody group, higher than the estimated efficacy of 83.3% (95% CrI 79.1–87.0%) if the two antibodies acted independently. Higher PEV efficacy at lower mosquito parasite loads was observed, comprising the first direct evidence that co-administering anti-sporozoite and anti-transmission interventions act synergistically, enhancing PEV efficacy across a range of TBV doses and transmission intensities. Combining partially effective vaccines of differing anti-parasitic classes is a pragmatic, powerful way to accelerate malaria elimination efforts. PMID:29914622

Economic transformation and biological welfare in colonial Burma: regional differentiation in the evolution of average height.

PubMed

Bassino, Jean-Pascal; Coclanis, Peter A

2008-07-01

Did economic development result in an improvement in biological welfare in the tropics before the diffusion of modern public health techniques in the 1950s and 1960s? Between the mid-19th and early 20th century, Lower Burma experienced a rapid rise in population and became increasingly commercialized as a major rice exporter. Land reclamation on a massive scale in the Irrawaddy delta required an arduous process of jungle clearance, land drainage and preparation, and canal and bund construction, mostly in malarial swamps. Once paddy lands were created, rice was grown with rudimentary tools in malarial zones. By contrast, in most parts of Upper Burma the economy remained more subsistence-oriented, and less commercialized. In this paper, we investigate changes in physical stature by processing and analyzing data reported in two anthropometric surveys conducted in various regions of Upper and Lower Burma in 1904 and in 1938-1941. An inverted U curve is observed in the evolution of average height in Lower Burma, while stature remained fairly stable in Upper Burma until the 1930s.

The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer

PubMed Central

Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A.

2013-01-01

Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein—a finding that correlates with increased numbers of autophagosomes—and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of “autophagy addiction” because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer. PMID:23965851

In vitro synergistic effect of fluoroquinolone analogues in combination with artemisinin against Plasmodium falciparum; their antiplasmodial action in rodent malaria model.

PubMed

Agarwal, Drishti; Sharma, Manish; Dixit, Sandeep K; Dutta, Roshan K; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

2015-02-05

Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. Current treatment regimen of malaria relies on the concept of artemisinin-based combination therapy (ACT). Fluoroquinolone analogues, compounds 10, 12 and 18 were investigated for their anti-malarial interaction in combination with artemisinin in vitro, against Plasmodium falciparum 3D7 strain, employing fixed-ratio combination isobologram method. In addition, the efficacy of these compounds was evaluated intraperitoneally in BALB/c mice infected with chloroquine-resistant Plasmodium berghei ANKA strain in the Peters' four-day suppressive test. Promising results were obtained in the form of synergistic or additive interactions. Compounds 10 and 12 were found to have highly synergistic interactions with artemisinin. Antiplasmodial effect was further verified by the convincing ED50 values of these compounds, which ranged between 2.31 and 3.09 (mg/kg BW). In vivo studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.

Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

PubMed

McGowan, Sheena; Porter, Corrine J; Lowther, Jonathan; Stack, Colin M; Golding, Sarah J; Skinner-Adams, Tina S; Trenholme, Katharine R; Teuscher, Franka; Donnelly, Sheila M; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; Degori, Ross; Buckle, Ashley M; Gardiner, Donald L; Whisstock, James C; Dalton, John P

2009-02-24

Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH(2)]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite.

Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

PubMed Central

McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan; Stack, Colin M.; Golding, Sarah J.; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Teuscher, Franka; Donnelly, Sheila M.; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; DeGori, Ross; Buckle, Ashley M.; Gardiner, Donald L.; Whisstock, James C.; Dalton, John P.

2009-01-01

Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. PMID:19196988

Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

PubMed

Boyle, Michelle J; Reiling, Linda; Feng, Gaoqian; Langer, Christine; Osier, Faith H; Aspeling-Jones, Harvey; Cheng, Yik Sheng; Stubbs, Janine; Tetteh, Kevin K A; Conway, David J; McCarthy, James S; Muller, Ivo; Marsh, Kevin; Anders, Robin F; Beeson, James G

2015-03-17

Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The effect of persistent malarial infections on haemoglobin A2 levels in Liberian children.

PubMed

Willcox, M C; Björkman, A; Brohult, J

1985-01-01

Children two to nine years old from an area of holoendemic malaria in northern Liberia had mean HbA2 and haematocrit values significantly (P less than 0.001) lower than others from a neighbouring town where malaria is hypoendemic. After regular administration of chloroquine over two years to 38 children living in a holoendemic village, their mean HbA2 rose from 2.1%, SE +/- 0.04, to 2.6%, SE +/- 0.08 (P less than 0.001) and their mean haematocrit from 0.348, SEM +/- 0.004, to 0.382, SE +/- 0.004 (P less than 0.001), values similar to those of children from the neighbouring town. In another village where chloroquine was not given regularly, mean HbA2, haematocrit and malariometric indices were little changed at the end of the two-year period. We conclude that persistent malarial parasitaemia was the main factor in the relatively low values of the village children. Although it is not clear how malaria depresses HbA, the findings were consistent with the hypothesis that chronic malaria induces iron-deficiency.

Receptor for Activated C-Kinase 1 (PfRACK1) is required for Plasmodium falciparum intra-erythrocytic proliferation.

PubMed

Blomqvist, Karin; DiPetrillo, Christen; Streva, Vincent A; Pine, Stewart; Dvorin, Jeffrey D

2017-01-01

Emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of Plasmodium falciparum proliferation, thus allowing identification of new drug targets. The well-conserved protein Receptor for Activated C-Kinase 1 (RACK1) was originally identified in mammalian cells as an anchoring protein for protein kinase C (PKC) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. The P. falciparum ortholog, PfRACK1, is expressed in blood stages of the parasite and is diffusely localized in the parasite cytoplasm. Using a destabilizing domain to allow inducible knockdown of the endogenous protein level, we evaluated the requirement for PfRACK1 during blood-stage replication. Following destabilization, the parasites demonstrate a nearly complete growth arrest at the trophozoite stage. The essential nature of PfRACK1 suggests that the protein itself or the pathways regulated by the protein are potential targets for novel anti-malarial therapeutics. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

PubMed

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy Me; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris Ca; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-09

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria

PubMed Central

Small, Dylan S; Taylor, Terrie E; Postels, Douglas G; Beare, Nicholas AV; Cheng, Jing; MacCormick, Ian JC; Seydel, Karl B

2017-01-01

Cerebral malaria (CM) can be classified as retinopathy-positive or retinopathy-negative, based on the presence or absence of characteristic retinal features. While malaria parasites are considered central to the pathogenesis of retinopathy-positive CM, their contribution to retinopathy-negative CM is largely unknown. One theory is that malaria parasites are innocent bystanders in retinopathy-negative CM and the etiology of the coma is entirely non-malarial. Because hospitals in malaria-endemic areas often lack diagnostic facilities to identify non-malarial causes of coma, it has not been possible to evaluate the contribution of malaria infection to retinopathy-negative CM. To overcome this barrier, we studied a natural experiment involving genetically inherited traits, and find evidence that malaria parasitemia does contribute to the pathogenesis of retinopathy-negative CM. A lower bound for the fraction of retinopathy-negative CM that would be prevented if malaria parasitemia were to be eliminated is estimated to be 0.93 (95% confidence interval: 0.68, 1). DOI: http://dx.doi.org/10.7554/eLife.23699.001 PMID:28590246

The anti-malarial chloroquine overcomes primary resistance and restores sensitivity to trastuzumab in HER2-positive breast cancer.

PubMed

Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

2013-01-01

Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein--a finding that correlates with increased numbers of autophagosomes--and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of "autophagy addiction" because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer.

Patient-, health worker-, and health facility-level determinants of correct malaria case management at publicly funded health facilities 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

2014-02-20

Prompt and effective case management is needed to reduce malaria morbidity and mortality. However, malaria diagnosis and treatment is a multistep process that remains problematic in many settings, resulting in missed opportunities for effective treatment as well as overtreatment of patients without malaria. Prior to the widespread roll-out of malaria rapid diagnostic tests (RDTs) in late 2011, a national, cross-sectional, complex-sample, health facility survey was conducted in Malawi to assess patient-, health worker-, and health facility-level factors associated with malaria case management quality using multivariate Poisson regression models. Among the 2,019 patients surveyed, 34% had confirmed malaria defined as presence of fever and parasitaemia on a reference blood smear. Sixty-seven per cent of patients with confirmed malaria were correctly prescribed the first-line anti-malarial, with most cases of incorrect treatment due to missed diagnosis; 31% of patients without confirmed malaria were overtreated with an anti-malarial. More than one-quarter of patients were not assessed for fever or history of fever by health workers. The most important determinants of correct malaria case management were patient-level clinical symptoms, such as spontaneous complaint of fever to health workers, which increased both correct treatment and overtreatment by 72 and 210%, respectively (p<0.0001). Complaint of cough was associated with a 27% decreased likelihood of correct malaria treatment (p=0.001). Lower-level cadres of health workers were more likely to prescribe anti-malarials for patients, increasing the likelihood of both correct treatment and overtreatment, but no other health worker or health facility-level factors were significantly associated with case management quality. Introduction of RDTs holds potential to improve malaria case management in Malawi, but health workers must systematically assess all patients for fever, and then test and treat accordingly, otherwise, malaria control programmes might miss an opportunity to dramatically improve malaria case management, despite better diagnostic tools.

Structure and function based design of Plasmodium-selective proteasome inhibitors

PubMed Central

Li, Hao; O'Donoghue, Anthony J.; van der Linden, Wouter A.; Xie, Stanley C.; Yoo, Euna; Foe, Ian T.; Tilley, Leann; Craik, Charles S.; da Fonseca, Paula C. A.; Bogyo, Matthew

2016-01-01

The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation1. Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle2-5. Most compounds that have been tested against the parasite also inhibit the mammalian proteasome resulting in toxicity that precludes their use as therapeutic agents2,6. Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, we used a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We designed inhibitors based on amino acid preferences specific to the parasite proteasome, and found that they preferentially inhibit the β 2 subunit. We determined the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryo-electron microscopy (cryo-EM) and single particle analysis, to a resolution of 3.6 Å. These data reveal the unusually open P. falciparum β2 active site and provide valuable information regarding active site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin (ART) family anti-malarials7,8, we observed growth inhibition synergism with low doses of this β 2 selective inhibitor in ART sensitive and resistant parasites. Finally, we demonstrated that a parasite selective inhibitor could be used to attenuate parasite growth in vivo without significant toxicity to the host. Thus, the Plasmodium proteasome is a chemically tractable target that could be exploited by next generation anti-malarial agents. PMID:26863983

Characterizing Pediatric Non-Malarial Fever and Identifying the At-Risk Child in Rural Malawi.

PubMed

Kortz, Teresa Bleakly; Blair, Alden; Scarr, Ellen; Mguntha, Andrew Masozi; Bandawe, Gama; Schell, Ellen; Rankin, Sally; Baltzell, Kimberly

2018-01-01

Objective . To characterize children with non-malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods . This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non-malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results . A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion . Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.

A retrospective analysis of the change in anti-malarial treatment policy: Peru.

PubMed

Williams, Holly Ann; Vincent-Mark, Arlene; Herrera, Yenni; Chang, O Jaime

2009-04-28

National malaria control programmes must deal with the complex process of changing national malaria treatment guidelines, often without guidance on the process of change. Selecting a replacement drug is only one issue in this process. There is a paucity of literature describing successful malaria treatment policy changes to help guide control programs through this process. To understand the wider context in which national malaria treatment guidelines were formulated in a specific country (Peru). Using qualitative methods (individual and focus group interviews, stakeholder analysis and a review of documents), a retrospective analysis of the process of change in Peru's anti-malarial treatment policy from the early 1990's to 2003 was completed. The decision to change Peru's policies resulted from increasing levels of anti-malarial drug resistance, as well as complaints from providers that the drugs were no longer working. The context of the change occurred in a time in which Peru was changing national governments, which created extreme challenges in moving the change process forward. Peru utilized a number of key strategies successfully to ensure that policy change would occur. This included a) having the process directed by a group who shared a common interest in malaria and who had long-established social and professional networks among themselves, b) engaging in collaborative teamwork among nationals and between nationals and international collaborators, c) respect for and inclusion of district-level staff in all phases of the process, d) reliance on high levels of technical and scientific knowledge, e) use of standardized protocols to collect data, and f) transparency. Although not perfectly or fully implemented by 2003, the change in malaria treatment policy in Peru occurred very quickly, as compared to other countries. They identified a problem, collected the data necessary to justify the change, utilized political will to their favor, approved the policy, and moved to improve malaria control in their country. As such, they offer an excellent example for other countries as they contemplate or embark on policy changes.

Structure- and function-based design of Plasmodium-selective proteasome inhibitors.

PubMed

Li, Hao; O'Donoghue, Anthony J; van der Linden, Wouter A; Xie, Stanley C; Yoo, Euna; Foe, Ian T; Tilley, Leann; Craik, Charles S; da Fonseca, Paula C A; Bogyo, Matthew

2016-02-11

The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation. Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle. Most compounds that have been tested against the parasite also inhibit the mammalian proteasome, resulting in toxicity that precludes their use as therapeutic agents. Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, here we use a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We design inhibitors based on amino-acid preferences specific to the parasite proteasome, and find that they preferentially inhibit the β2-subunit. We determine the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryo-electron microscopy and single-particle analysis, to a resolution of 3.6 Å. These data reveal the unusually open P. falciparum β2 active site and provide valuable information about active-site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin family anti-malarials, we observe growth inhibition synergism with low doses of this β2-selective inhibitor in artemisinin-sensitive and -resistant parasites. Finally, we demonstrate that a parasite-selective inhibitor could be used to attenuate parasite growth in vivo without appreciable toxicity to the host. Thus, the Plasmodium proteasome is a chemically tractable target that could be exploited by next-generation anti-malarial agents.

Coma Associated with Microscopy-Diagnosed Plasmodium vivax: A Prospective Study in Papua, Indonesia

PubMed Central

Hardianto, Setiawan O.; Tjitra, Emiliana; Kenangalem, Enny; Sugiarto, Paulus; Price, Ric N.; Anstey, Nicholas M.

2011-01-01

Background Coma complicates Plasmodium falciparum infection but is uncommonly associated with P. vivax. Most series of vivax coma have been retrospective and have not utilized molecular methods to exclude mixed infections with P. falciparum. Methods We prospectively enrolled patients hospitalized in Timika, Indonesia, with a Glasgow Coma Score (GCS) ≤10 and P. vivax monoinfection on initial microscopy over a four year period. Hematological, biochemical, serological, radiological and cerebrospinal fluid (CSF) examinations were performed to identify other causes of coma. Repeat microscopy, antigen detection and polymerase chain reaction (PCR) were performed to exclude infections with other Plasmodium species. Results Of 24 patients fulfilling enrolment criteria, 5 had clear evidence for other non-malarial etiologies. PCR demonstrated 10 mixed infections and 3 P. falciparum monoinfections. 6 (25%) patients had vivax monoinfection and no apparent alternative cause, with a median GCS of 9 (range 8–10) and a median coma duration of 42 (range 36–48) hours. CSF leukocyte counts were <10/ul (n = 3); 2 of the 3 patients without CSF examination recovered with antimalarial therapy alone. One patient had a tremor on discharge consistent with a post-malarial neurological syndrome. No patient had other organ dysfunction. The only death was associated with pure P. falciparum infection by PCR. Vivax monoinfection-associated risk of coma was estimated at 1 in 29,486 clinical vivax infections with no deaths. In comparison, the risk of falciparum-associated coma was estimated at 1 in 1,276 clinical infections with an 18.5% mortality rate. Conclusions P. vivax-associated coma is rare, occurring 23 times less frequently than that seen with falciparum malaria, and is associated with a high proportion of non-malarial causes and mixed infections using PCR. The pathogenesis of coma associated with vivax malaria, particularly the role of comorbidities, is uncertain and requires further investigation. PMID:21666785

Plasmodium falciparum infection and age influence parasite growth inhibition mediated by IgG in Beninese infants.

PubMed

Adamou, Rafiou; Chénou, Francine; Sadissou, Ibrahim; Sonon, Paulin; Dechavanne, Célia; Djilali-Saïah, Abdelkader; Cottrell, Gilles; Le Port, Agnès; Massougbodji, Achille; Remarque, Edmond J; Luty, Adrian J F; Sanni, Ambaliou; Garcia, André; Migot-Nabias, Florence; Milet, Jacqueline; Courtin, David

2016-07-01

Antibodies that impede the invasion of Plasmodium falciparum (P. falciparum) merozoites into erythrocytes play a critical role in anti-malarial immunity. The Growth Inhibition Assay (GIA) is an in vitro measure of the functional capacity of such antibodies to limit erythrocyte invasion and/or parasite growth. Up to now, it is unclear whether growth-inhibitory activity correlates with protection from clinical disease and there are inconsistent results from studies performed with GIA. Studies that have focused on the relationship between IgGs and their in vitro parasite Growth Inhibition Activity (GIAc) in infants aged less than two years old are rare. Here, we used clinical and parasitological data to precisely define symptomatic or asymptomatic infection with P. falciparum in groups of infants followed-up actively for 18 months post-natally. We quantified the levels of IgG1 and IgG3 directed to a panel of candidate P. falciparum vaccine antigens (AMA-1, MSP1, 2, 3 and GLURP) using ELISA and the functional activity of IgG was quantified using GIA. Data were then correlated with individuals' infection status. At 18 months of age, infants harbouring infections at the time of blood sampling had an average 19% less GIAc than those not infected (p=0.004, multivariate linear regression). GIAc decreased from 12 to 18 months of age (p=0.003, Wilcoxon matched pairs test). Antibody levels quantified at 18 months in infants were strongly correlated with their exposure to malarial infection, however GIAc was not correlated with malaria infectious status (asymptomatic and symptomatic groups). In conclusion, both infection status at blood draw and age influence parasite growth inhibition mediated by IgG in the GIA. Both factors must be taken into account when correlations between GIAc and anti-malarial protection or vaccine efficacy have to be made. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical and epidemiological characteristics of imported infectious diseases in Spanish travelers.

PubMed

Zamarrón Fuertes, Pilar; Pérez-Ayala, Ana; Pérez Molina, José A; Norman, Francesca F; Monge-Maíllo, Begoña; Navarro, Miriam; López-Vélez, Rogelio

2010-01-01

Spain could be a potential area in Europe for the development and spread of emerging diseases from the tropics due to its geoclimatic characteristics, but there is little information on infectious diseases imported by travelers. The aim of this article was to analyze clinical-epidemiological characteristics of infectious diseases imported by Spanish travelers from the tropics. A retrospective descriptive study of 2,982 travelers seeking medical advice who return ill from the tropics was conducted. Demographic data, details of travel (destination, type, and duration), preventive measures, clinical syndromes, and diagnoses were analyzed. Nearly half (46.5%) the travelers had traveled to sub-Saharan Africa; 46.5% reported a stay exceeding 1 month (and almost a quarter more than 6 months). Following pre-travel advice, 69.1% received at least one vaccine and 35.5% took malarial chemoprophylaxis with variations according to geographical area of travel. In all, 58.8% of this took chemoprophylaxis correctly. Most common syndromes were fever 1,028 (34.5%), diarrhea 872 (29.3%), and cutaneous syndrome 684 (22.9%). Most frequent diagnoses were traveler's diarrhea (17.2%), malaria (17%), and intestinal parasites (10.4%). The three main syndromes in travelers to the Caribbean-Central America, Indian subcontinent-Southeast Asia, and other areas were diarrhea, fever, and cutaneous syndrome (p < 0.05); in sub-Saharan Africa were fever, cutaneous syndrome, and diarrhea (p < 0.05); and in South America were cutaneous syndrome, diarrhea, and fever (p < 0.05). Travelers to sub-Saharan Africa showed a higher frequency of malaria, rickettsiosis, filariasis, and schistosomiasis (p < 0.05); those to South America showed cutaneous larva migrants, other ectoparasitosis, and cutaneous/mucocutaneous leishmaniasis; and those to the Indian subcontinent-Southeast Asia showed intestinal parasitosis, arboviriasis, and enteric fever (p < 0.05). Increased international travel is a key factor for the development and spread of emerging pathogens. Information on these diseases is essential to establish early warning mechanisms and action plans. Spain represents a unique setting for this. © 2010 International Society of Travel Medicine.

Imported malaria in Spain (2009-2016): results from the +REDIVI Collaborative Network.

PubMed

Norman, Francesca F; López-Polín, Ana; Salvador, Fernando; Treviño, Begoña; Calabuig, Eva; Torrús, Diego; Soriano-Arandes, Antonio; Ruíz-Giardín, Jose-Manuel; Monge-Maillo, Begoña; Pérez-Molina, Jose-Antonio; Perez-Ayala, Ana; García, Magdalena; Rodríguez, Azucena; Martínez-Serrano, María; Zubero, Miren; López-Vélez, Rogelio

2017-10-10

Imported malaria is a frequent diagnosis in travellers and migrants. The objective of this study was to describe the epidemiological and clinical characteristics of patients diagnosed with imported malaria within a Spanish collaborative network registering imported diseases (+REDIVI). In addition, the possible association between malaria and type of case, gender, age or area of exposure was explored. Cases of imported malaria were identified among all cases registered in the +REDIVI database during the period October 2009-October 2016. Demographic, epidemiological and clinical characteristics were analysed. In total, 11,816 cases of imported infectious diseases were registered in +REDIVI's database between October 2009 and October 2016. Immigrants seen for the first time after migration accounted for 60.2% of cases, 21.0% of patients were travellers, and 18.8% were travellers/immigrants visiting friends and relatives (VFRs). There were 850 cases of malaria (850/11,816, 7.2%). Malaria was significantly more frequent in men than in women (56.8% vs 43.2%) and in VFR-immigrants (52.6%) as compared to travellers (21.3%), immigrants (20.7%) and VFR-travellers (5.4%) (p < 0.001). Although this data was not available for most patients with malaria, only a minority (29/217, 13.4%) mentioned correct anti-malarial prophylaxis. Sub-Saharan Africa was found to be the most common region of acquisition of malaria. Most common reason for consultation after travel was a febrile syndrome although an important proportion of immigrants were asymptomatic and presented only for health screening (27.3%). Around 5% of travellers presented with severe malaria. The most prevalent species of Plasmodium diagnosed was Plasmodium falciparum (81.5%). Malaria due to Plasmodium ovale/Plasmodium vivax was frequent among travellers (17%) and nearly 5% of all malaria cases in immigrants were caused by Plasmodium malariae. Malaria was among the five most frequent diagnoses registered in +REDIVI's database. Some significant differences were found in the distribution of malaria according to gender, type of case, species. Among all malaria cases, the most frequent diagnosis was P. falciparum infection in VFR-immigrant men.

Competency in health care management: a training model in epidemiologic methods for assessing and improving the quality of clinical practice through evidence-based decision making.

PubMed

Hudak, R P; Jacoby, I; Meyer, G S; Potter, A L; Hooper, T I; Krakauer, H

1997-01-01

This article describes a training model that focuses on health care management by applying epidemiologic methods to assess and improve the quality of clinical practice. The model's uniqueness is its focus on integrating clinical evidence-based decision making with fundamental principles of resource management to achieve attainable, cost-effective, high-quality health outcomes. The target students are current and prospective clinical and administrative executives who must optimize decision making at the clinical and managerial levels of health care organizations.

An Analysis of the Health Service Support to the Centennial Campaign of 1876

DTIC Science & Technology

2015-06-12

and it will be a wonder if they don’t get typhoid fever when the rains begin.”28 Paulding stated his concerns, but he did not take any actions or...malarial fever , smallpox and other types of febricula.22 These conditions doubtfully improved greatly in the year preceding the Centennial Campaign. This

Incidence of diseases primarily affecting the skin by age group: population-based epidemiologic study in Olmsted County, Minnesota, and comparison with age-specific incidence rates worldwide.

PubMed

Wessman, Laurel L; Andersen, Louise K; Davis, Mark D P

2018-01-29

Understanding the effects of age on the epidemiology of diseases primarily affecting the skin is important to the practice of dermatology, both for proper allocation of resources and for optimal patient-centered care. To fully appreciate the effect that age may have on the population-based calculations of incidence of diseases primarily affecting the skin in Olmsted County, Minnesota, and worldwide, we performed a review of all relevant Rochester Epidemiology Project-published data and compared them to similar reports in the worldwide English literature. Using the Rochester Epidemiology Project, population-based epidemiologic studies have been performed to estimate the incidence of specific skin diseases over the past 50 years. In older persons (>65 years), nonmelanoma skin cancer, lentigo maligna, herpes zoster, delusional infestation, venous stasis syndrome, venous ulcer, and burning mouth syndrome were more commonly diagnosed. In those younger than 65 years, atypical nevi, psoriatic arthritis, pityriasis rosea, herpes progenitalis, genital warts, alopecia areata, hidradenitis suppurativa, infantile hemangioma, Behçet's disease, and sarcoidosis (isolated cutaneous, with sarcoidosis-specific cutaneous lesions and with erythema nodosum) had a higher incidence. Many of the incidence rates by age group of diseases primarily affecting the skin derived from the Rochester Epidemiology Project were similar to those reported elsewhere. © 2018 The International Society of Dermatology.

Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia's southern province: a simulation study.

PubMed

Stuckey, Erin M; Miller, John M; Littrell, Megan; Chitnis, Nakul; Steketee, Rick

2016-03-09

Malaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. To achieve this goal in Southern province, Zambia a mass test and treat (MTAT) campaign was conducted from 2011-2013 to complement high coverage of long-lasting insecticide-treated nets (LLIN). To identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operational strategies for parasite clearance in southern province. OpenMalaria, a discrete-time, individual-based stochastic model of malaria, was parameterized for the study area to simulate anti-malarial drug administration for interruption of transmission. Simulations were run for scenarios with a range of artemisinin-combination therapies, proportion of the population reached by the campaign, targeted age groups, time between campaign rounds, Plasmodium falciparum test protocols, and the addition of drugs aimed at preventing onward transmission. A sensitivity analysis was conducted to assess uncertainty of simulation results. Scenarios were evaluated based on the reduction in all-age parasite prevalence during the peak transmission month one year following the campaign, compared to the currently-implemented strategy of MTAT 19 % population coverage at pilot and 40 % coverage during the first year of implementation in the presence of 56 % LLIN use and 18 % indoor residual spray coverage. Simulation results suggest the most important determinant of success in reducing prevalence is the population coverage achieved in the campaign, which would require more than 1 year of campaign implementation for elimination. The inclusion of single low-dose primaquine, which acts as a gametocytocide, or ivermectin, which acts as an endectocide, to the drug regimen did not further reduce parasite prevalence one year following the campaign compared to the currently-implemented strategy. Simulation results indicate a high proportion of low-density infections were missed by rapid diagnostic tests that would be treated and cleared with mass drug administration (MDA). The optimal implementation strategy for MTAT or MDA will vary by background level of prevalence, by rate of infections imported to the area, and by ability to operationally achieve high population coverage. Overall success with new parasite clearance strategies depends on continued coverage of vector control interventions to ensure sustained gains in reduction of disease burden.

Management of invading pathogens should be informed by epidemiology rather than administrative boundaries.

PubMed

Thompson, Robin N; Cobb, Richard C; Gilligan, Christopher A; Cunniffe, Nik J

2016-03-24

Plant and animal disease outbreaks have significant ecological and economic impacts. The spatial extent of control is often informed solely by administrative geography - for example, quarantine of an entire county or state once an invading disease is detected - with little regard for pathogen epidemiology. We present a stochastic model for the spread of a plant pathogen that couples spread in the natural environment and transmission via the nursery trade, and use it to illustrate that control deployed according to administrative boundaries is almost always sub-optimal. We use sudden oak death (caused by Phytophthora ramorum ) in mixed forests in California as motivation for our study, since the decision as to whether or not to deploy plant trade quarantine is currently undertaken on a county-by-county basis for that system. However, our key conclusion is applicable more generally: basing management of any disease entirely upon administrative borders does not balance the cost of control with the possible economic and ecological costs of further spread in the optimal fashion.

Integrating epidemiology, psychology, and economics to achieve HPV vaccination targets.

PubMed

Basu, Sanjay; Chapman, Gretchen B; Galvani, Alison P

2008-12-02

Human papillomavirus (HPV) vaccines provide an opportunity to reduce the incidence of cervical cancer. Optimization of cervical cancer prevention programs requires anticipation of the degree to which the public will adhere to vaccination recommendations. To compare vaccination levels driven by public perceptions with levels that are optimal for maximizing the community's overall utility, we develop an epidemiological game-theoretic model of HPV vaccination. The model is parameterized with survey data on actual perceptions regarding cervical cancer, genital warts, and HPV vaccination collected from parents of vaccine-eligible children in the United States. The results suggest that perceptions of survey respondents generate vaccination levels far lower than those that maximize overall health-related utility for the population. Vaccination goals may be achieved by addressing concerns about vaccine risk, particularly those related to sexual activity among adolescent vaccine recipients. In addition, cost subsidizations and shifts in federal coverage plans may compensate for perceived and real costs of HPV vaccination to achieve public health vaccination targets.

Optimizing Health Care Environmental Hygiene.

PubMed

Carling, Philip C

2016-09-01

This article presents a review and perspectives on aspects of optimizing health care environmental hygiene. The topics covered include the epidemiology of environmental surface contamination, a discussion of cleaning health care patient area surfaces, an overview of disinfecting health care surfaces, an overview of challenges in monitoring cleaning versus cleanliness, a description of an integrated approach to environmental hygiene and hand hygiene as interrelated disciplines, and an overview of the research opportunities and challenges related to health care environmental hygiene. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimizing Burn Treatment in Developing Low-and Middle-Income Countries with Limited Health Care Resources (Part 2)

PubMed Central

Atiyeh, B.; Masellis, A.; Conte, C.

2009-01-01

Summary The present review of the literature aims at analysing the challenges facing burn management in low- and middleincome countries (LMICs) and exploring probable modalities to optimize burn management in these countries. In Part 1, the epidemiology of burn injuries and the formidable challenges for proper management due to limited resources and inaccessibility to sophisticated skills and technologies in LMICs were presented. Part II will discuss the actual state of burn injuries management in LMICs. PMID:21991180

[THE OPTIMIZATION OF THE ACTIVITY OF ORGANS OF FEDERAL SERVICE FOR SUPERVISION OF CONSUMER RIGHTS PROTECTION AND HUMAN WELFARE IN THE SVERDLOVSK REGION].

PubMed

Kuz'min, S V; Gurvich, V B; Romanov, S V; Dikonskaia, O V; Iarushin, S V; Malykh, O L

2015-01-01

In the Sverdlovsk region there have developed and implemented methodological approaches to the optimization oj the activity of the Directorate and the Centre directed to the improvement of the sanitary and epidemiological surveillance and in the sphere of the protection of the rights of consumers in the framework of the development of an comprehensive regional system of risk management for the population's health in the Sverdlovsk region.

[Human African trypanosomiasis in Côte d'Ivoire and Burkina Faso: optimization of epidemiologic surveillance strategies].

PubMed

Kambiré, R; Lingué, K; Courtin, F; Sidibé, I; Kiendrébéogo, D; N'gouan, K E; Blé, L; Kaba, D; Koffi, M; Solano, P; Bucheton, B; Jamonneau, V

2012-11-01

The objective of this paper was to describe recent data from Burkina Faso and Côte d'Ivoire on Human African Trypanosomosis medical monitoring in order to (i) update the disease situation in these two countries that have been sharing important migratory, economic and epidemiological links for more than a century and (ii) to define the future strategic plans to achieve the goal of a sustainable control/elimination process. Results of active and passive surveillance indicate that all sleeping sickness patients diagnosed these last years in Burkina Faso were imported cases from Côte d'Ivoire. Nevertheless the re-introduction of the parasite is effective and the risk of a resumption of transmission exists. In Côte d'Ivoire, few cases are still diagnosed in several historical foci and the fear exists that the disease could reemerge in these foci or spread to other areas. In order to achieve a sustainable elimination of sleeping sickness in these two countries, control entities have to adapt their strategy to the different epidemiological contexts. At the exception of specific cases, the current disease prevalence no longer justifies the use of expensive medical surveys by exhaustive screening of the population. New disease control strategies, based on the exchange of epidemiological information between the two countries and integrated to the regular national health systems are required to target priority intervention areas. Follow-up in time of both treated patients and serological suspects that are potential asymptomatic carriers of parasite is also important. In parallel, researchers need to better characterize the respective roles of the human and animal reservoir in the maintenance of transmission and evaluate the different control strategies taken by National Control Programs in term of cost/effectiveness to help optimize them.

Asymptomatic Plasmodium Infections in Children in Low Malaria Transmission Setting, Southwestern Uganda(1).

PubMed

Roh, Michelle E; Oyet, Caesar; Orikiriza, Patrick; Wade, Martina; Kiwanuka, Gertrude N; Mwanga-Amumpaire, Juliet; Parikh, Sunil; Boum, Yap

2016-08-01

A survey of asymptomatic children in Uganda showed Plasmodium malariae and P. falciparum parasites in 45% and 55% of microscopy-positive samples, respectively. Although 36% of microscopy-positive samples were negative by rapid diagnostic test, 75% showed P. malariae or P. ovale parasites by PCR, indicating that routine diagnostic testing misses many non-P. falciparum malarial infections.

Mutasynthesis of fluorinated pactamycin analogues and their antimalarial activity.

PubMed

Almabruk, Khaled H; Lu, Wanli; Li, Yuexin; Abugreen, Mostafa; Kelly, Jane X; Mahmud, Taifo

2013-04-05

A mutasynthetic strategy has been used to generate fluorinated TM-025 and TM-026, two biosynthetically engineered pactamycin analogues produced by Streptomyces pactum ATCC 27456. The fluorinated compounds maintain excellent activity and selectivity toward chloroquine-sensitive and multidrug-resistant strains of malarial parasites as the parent compounds. The results also provide insights into the biosynthesis of 3-aminobenzoic acid in S. pactum.

Challenges facing drug development for malaria.

PubMed

Craft, J Carl

2008-10-01

Malaria is a significant cause of morbidity and mortality in the developing world. Until recently malaria was winning but with increase in funding particularly from philanthropic groups the ability to control malaria is again possible. There are still many challenges to developing the next generations of anti-malarials. This article will briefly discuss the challenges and the advance that are being made.

A Computer-Assisted Instruction Course on Laboratory Detection of Malarial Parasites in Human Blood. Interim Report.

ERIC Educational Resources Information Center

Mitzel, Harold E.

In cooperation with the United States Navy, this project was undertaken to examine the feasibility of computer assisted instruction in clinical malaria recognition, to train a small group of Naval personnel in techniques of creating and presenting such material, and to evaluate the course by giving it to a representative sample of Naval medical…

The Impact of School Based Anti-Malarial Treatment on Adolescents' Cognition: Evidence from a Cluster-Randomized Intervention in Kenya

ERIC Educational Resources Information Center

Gee, Kevin A.

2010-01-01

Children's health is an important factor that influences their success in education--poor health, especially when induced by disease, has been linked to poorer cognitive performance, particularly among children across the developing world (Behrman, 1996; UNESCO, 2008; Jukes et al., 2008). One health concern, particularly for sub-Saharan Africa,…

Repellent activity of selected plant essential oils against the malarial fever mosquito Anopheles stephensi.

PubMed

Rajkumar, S; Jebanesan, A

2007-12-01

In recent years, use of environment friendly and biodegradable natural insecticides of plant origin have received renewed attention as agents for vector control. In this study, essential oils extracted by steam distillation from leaves of five plant species Centella asiatica L., Ipomoea cairica L., Momordica charantia L., Psidium guajava L. and Tridax procumbens L. were evaluated for their topical repellency effects against malarial vector Anopheles stephensi in mosquito cages. All essential oils were tested at three different concentrations (2, 4 and 6%). Of these, the essential oils of I. cairica, M. charantia and T. procumbens exhibited relatively high repellency effect (>300 minutes at 6% concentration), followed by C. asiatica and P. guajava which showed less effective (< 150 minutes at 6 % concentration). However, the ethanol applied arm served as control provided maximum 8.0 minutes repellency in this study. In general, clear dose-response relationships were established in all essential oils, with the highest concentration of 6% provided high repellency effect. The results obtained from this study suggest that essential oils of I. cairica, M. charantia and T. procumbens are promising as repellents at 6% concentration against An. stephensi and could be useful in the search for new natural repellent compounds.

Falcipain inhibitors as potential therapeutics for resistant strains of malaria: a patent review.

PubMed

Mane, Uttam Rajaram; Gupta, Ramesh C; Nadkarni, Sunil Sadanand; Giridhar, Rajani R; Naik, Prashant Prakash; Yadav, Mange R

2013-02-01

There is an urgent need to discover new antimalarial drugs due to emergence of resistance in the parasite to the existing drugs. Malarial cysteine proteases falcipin-2 (FP-2) and falcipain-3 (FP-3) are attractive targets for antimalarial chemotherapy. The structures and functions of FP-2/3, their binding domains and their interactions with small- and macro-molecules are well studied. These studies could provide important insight into rational designing of FP inhibitors as potential antimalarial drugs. This review is focused on a selection of interesting patents published during 1999 - 2011 on peptidic and nonpeptidic chemotypes of the FP-2/FP-3 inhibitors. It is a known fact that malaria is a serious health problem worldwide due to the emergence of resistant strains. Hence, development of novel, potent and affordable antimalarial drugs devoid of side effects is of great significance and in great demand. FPs, the malarial cysteine proteases are potential targets for development of new antimalarial drugs. Assessing the available literature on FP-2/3 and their inhibitors it could be speculated that these inhibitors have the potential to enter the clinical stages of development for the treatment of malaria in the years to come.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

PubMed Central

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy ME; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris CA; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations. DOI: http://dx.doi.org/10.7554/eLife.15085.001 PMID:28067620

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

Advances in the Treatment of Malaria

PubMed Central

Castelli, Francesco; Tomasoni, Lina Rachele; Matteelli, Alberto

2012-01-01

Malaria still claims a heavy toll of deaths and disabilities even at the beginning of the third millennium. The inappropriate sequential use of drug monotherapy in the past has facilitated the spread of drug-resistant P. falciparum, and to a lesser extend P. vivax, strains in most of the malaria endemic areas, rendering most anti-malarial ineffective. In the last decade, a new combination strategy based on artemisinin derivatives (ACT) has become the standard of treatment for most P. falciparum malaria infections. This strategy could prevent the selection of resistant strains by rapidly decreasing the parasitic burden (by the artemisinin derivative, mostly artesunate) and exposing the residual parasite to effective concentrations of the partner drug. The widespread use of this strategy is somehow constrained by cost and by the inappropriate use of artemisinin, with possible impact on resistance, as already sporadically observed in South East Asia. Parenteral artesunate has now become the standard of care for severe malaria, even if quinine still retains its value in case artesunate is not immediately available. The appropriateness of pre-referral use of suppository artesunate is under close monitoring, while waiting for an effective anti-malarial vaccine to be made available. PMID:23170193

Reproductive outcomes in DDT applicators.

PubMed

Cocco, Pierluigi; Fadda, Domenica; Ibba, Antonio; Melis, Massimo; Tocco, Maria Giuseppina; Atzeri, Sergio; Avataneo, Giuseppe; Meloni, Michele; Monni, Filippo; Flore, Costantino

2005-05-01

To explore reproductive outcomes in relation to occupational exposure to DDT. We inquired into the reproductive history, including total number of children, sex distribution in the offspring, time-to-pregnancy, and number of spontaneous abortions and stillbirths, of the spouses of 105 men first exposed to DDT in a 1946-1950 anti-malarial campaign in Sardinia, Italy. The time-to-pregnancy in months at the first successful conception was estimated from population Registrars. Cumulative DDT exposure during the anti-malarial campaign was retrospectively estimated. The stillbirth rate was elevated and the male/female ratio in the offspring was reversed among DDT-exposed workers, and particularly among DDT applicators, compared to the unexposed subjects. Among DDT applicators, the stillbirth rate increased and the male/female ratio decreased by the tertile of cumulative DDT exposure. The fecundity ratio among spouses of DDT applicators was 0.72 (95% CI, 0.41,1.21) compared to the unexposed. The average number of children and abortion rate were unaffected by DDT exposure. The low statistical power of our study does not allow definitive conclusions. However, the results prompt further in-depth research into adverse reproductive outcomes and reduced fertility among men heavily exposed to DDT.

Case Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors

PubMed Central

Herrera, Sócrates; Fernández, Olga; Manzano, María R.; Murrain, Bermans; Vergara, Juana; Blanco, Pedro; Palacios, Ricardo; Vélez, Juan D.; Epstein, Judith E.; Chen-Mok, Mario; Reed, Zarifah H.; Arévalo-Herrera, Myriam

2010-01-01

Successful establishment of a Plasmodium vivax sporozoite challenge model in humans is described. Eighteen healthy adult, malaria-naïve volunteers were randomly allocated to Groups A–C and exposed to 3 ± 1, 6 ± 1, and 9 ± 1 bites of Anopheles albimanus mosquitoes infected with P. vivax, respectively. Seventeen volunteers developed signs and symptoms consistent with malaria, and geometric mean prepatent periods of 11.1 days (9.3–11) for Group A; 10.8 days (9.8–11.9) for Group B; and 10.6 days (8.7–12.4) for Group C, with no statistically significant difference among groups (Kruskal-Wallis, P = 0.70). One volunteer exposed to eight mosquito bites did not develop a parasitemia. No differences in parasite density were observed and all individuals successfully recovered after anti-malarial treatment. None of the volunteers developed parasite relapses within an 18-month follow-up. In conclusion, malaria-naive volunteers can be safely and reproducibly infected with bites of 2–10 An. albimanus mosquitoes carrying P. vivax sporozoites. This challenge method is suitable for vaccine and anti-malarial drug testing. PMID:19861603

The Plasma Concentration of the B Cell Activating Factor Is Increased in Children With Acute Malaria

PubMed Central

Nduati, Eunice; Gwela, Agnes; Karanja, Henry; Mugyenyi, Cleopatra; Langhorne, Jean; Marsh, Kevin

2011-01-01

Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF) and its receptors expressed on B cells with antibody responses during and after acute malaria in children. Our results demonstrate that BAFF plasma levels increased during acute malarial disease and reflected disease severity. The expression profiles for BAFF receptors on B cells agreed with rapid activation and differentiation of a proportion of B cells to plasma cells. However, BAFF receptor (BAFF-R) expression was reduced on all peripheral blood B cells during acute infection, but those children with the highest level of BAFF-R expression on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4 months, indicating that dysregulation of BAFF-R expression on B cells may contribute to short-lived antibody responses to malarial antigens in children. In summary, this study suggests a potential role for BAFF during malaria disease, both as a marker for disease severity and in shaping the differentiation pattern of antigen-specific B cells. PMID:21849293

Protective immunity provided by a new modified SERA protein peptide: its immunogenetic characteristics and correlation with 3D structure.

PubMed

Bermúdez, Adriana; Moreno-Vranich, Armando; Patarroyo, Manuel E

2012-07-01

The serine repeat antigen (SERA) protein is a leading candidate molecule for inclusion as a component in a multi-antigen, multi-stage, minimal subunit-based, chemically synthesised anti-malarial vaccine. Peptides having high red blood cell binding affinity (known as HABPs) have been identified in this protein. The 6733 HABP was located in the C-terminal portion of the 47-kDa fragment while HABP 6754 was located in the C-terminal region of the 56-kDa fragment. These conserved HABPs failed to induce an immune response. Critical red blood cell binding residues and/or their neighbours (assessed by glycine-analogue scanning) were replaced by others having the same mass, volume and surface but different polarity, rendering some of them highly immunogenic when assessed by antibody production against the parasite or its proteins and protection-inducers against experimental challenge with a highly infectious Aotus monkey-adapted Plasmodium falciparum strain. This manuscript presents some modified HABPs as vaccine candidate components for enriching our tailor-made anti-malarial vaccine repertoire, as well as their 3D structure obtained by 1H-NMR displaying a short-structured region, differently from the native ones having random structures.

Linking remote sensing, land cover and disease.

PubMed

Curran, P J; Atkinson, P M; Foody, G M; Milton, E J

2000-01-01

Land cover is a critical variable in epidemiology and can be characterized remotely. A framework is used to describe both the links between land cover and radiation recorded in a remotely sensed image, and the links between land cover and the disease carried by vectors. The framework is then used to explore the issues involved when moving from remotely sensed imagery to land cover and then to vector density/disease risk. This exploration highlights the role of land cover; the need to develop a sound knowledge of each link in the predictive sequence; the problematic mismatch between the spatial units of the remotely sensed and epidemiological data and the challenges and opportunities posed by adding a temporal mismatch between the remotely sensed and epidemiological data. The paper concludes with a call for both greater understanding of the physical components of the proposed framework and the utilization of optimized statistical tools as prerequisites to progress in this field.

Estimation of an optimal chemotherapy utilisation rate for cancer: setting an evidence-based benchmark for quality cancer care.

PubMed

Jacob, S A; Ng, W L; Do, V

2015-02-01

There is wide variation in the proportion of newly diagnosed cancer patients who receive chemotherapy, indicating the need for a benchmark rate of chemotherapy utilisation. This study describes an evidence-based model that estimates the proportion of new cancer patients in whom chemotherapy is indicated at least once (defined as the optimal chemotherapy utilisation rate). The optimal chemotherapy utilisation rate can act as a benchmark for measuring and improving the quality of care. Models of optimal chemotherapy utilisation were constructed for each cancer site based on indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient- and tumour-related attributes for which chemotherapy was indicated were obtained, using population-based data where possible. Treatment indications and epidemiological data were merged to calculate the optimal chemotherapy utilisation rate. Monte Carlo simulations and sensitivity analyses were used to assess the effect of controversial chemotherapy indications and variations in epidemiological data on our model. Chemotherapy is indicated at least once in 49.1% (95% confidence interval 48.8-49.6%) of all new cancer patients in Australia. The optimal chemotherapy utilisation rates for individual tumour sites ranged from a low of 13% in thyroid cancers to a high of 94% in myeloma. The optimal chemotherapy utilisation rate can serve as a benchmark for planning chemotherapy services on a population basis. The model can be used to evaluate service delivery by comparing the benchmark rate with patterns of care data. The overall estimate for other countries can be obtained by substituting the relevant distribution of cancer types. It can also be used to predict future chemotherapy workload and can be easily modified to take into account future changes in cancer incidence, presentation stage or chemotherapy indications. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Radiotherapy utilization in developing countries: An IAEA study.

PubMed

Rosenblatt, Eduardo; Fidarova, Elena; Zubizarreta, Eduardo H; Barton, Michael B; Jones, Glenn W; Mackillop, William J; Cordero, Lisbeth; Yarney, Joel; Lim, Gerard; Gan, John V; Cernea, Valentin; Stojanovic-Rundic, Suzana; Strojan, Primoz; Kochbati, Lotfi; Quarneti, Aldo

2018-05-30

The planning of national radiotherapy (RT) services requires a thorough knowledge of the country's cancer epidemiology profile, the radiotherapy utilization (RTU) rates and a future projection of these data. Previous studies have established RTU rates in high-income countries. Optimal RTU (oRTU) rates were determined for nine middle-income countries, following the epidemiological evidence-based method. The actual RTU (aRTU) rates were calculated dividing the total number of new notifiable cancer patients treated with radiotherapy in 2012 by the total number of cancer patients diagnosed in the same year in each country. An analysis of the characteristics of patients and treatments in a series of 300 consecutive radiotherapy patients shed light on the particular patient and treatments profile in the participating countries. The median oRTU rate for the group of nine countries was 52% (47-56%). The median aRTU rate for the nine countries was 28% (9-46%). These results show that the real proportion of cancer patients receiving RT is lower than the optimal RTU with a rate difference between 10-42.7%. The median percent-unmet need was 47% (18-82.3%). The optimal RTU rate in middle-income countries did not differ significantly from that previously found in high-income countries. The actual RTU rates were consistently lower than the optimal, in particular in countries with limited resources and a large population. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Optimizing cost-efficiency in mean exposure assessment - cost functions reconsidered

PubMed Central

2011-01-01

Background Reliable exposure data is a vital concern in medical epidemiology and intervention studies. The present study addresses the needs of the medical researcher to spend monetary resources devoted to exposure assessment with an optimal cost-efficiency, i.e. obtain the best possible statistical performance at a specified budget. A few previous studies have suggested mathematical optimization procedures based on very simple cost models; this study extends the methodology to cover even non-linear cost scenarios. Methods Statistical performance, i.e. efficiency, was assessed in terms of the precision of an exposure mean value, as determined in a hierarchical, nested measurement model with three stages. Total costs were assessed using a corresponding three-stage cost model, allowing costs at each stage to vary non-linearly with the number of measurements according to a power function. Using these models, procedures for identifying the optimally cost-efficient allocation of measurements under a constrained budget were developed, and applied on 225 scenarios combining different sizes of unit costs, cost function exponents, and exposure variance components. Results Explicit mathematical rules for identifying optimal allocation could be developed when cost functions were linear, while non-linear cost functions implied that parts of or the entire optimization procedure had to be carried out using numerical methods. For many of the 225 scenarios, the optimal strategy consisted in measuring on only one occasion from each of as many subjects as allowed by the budget. Significant deviations from this principle occurred if costs for recruiting subjects were large compared to costs for setting up measurement occasions, and, at the same time, the between-subjects to within-subject variance ratio was small. In these cases, non-linearities had a profound influence on the optimal allocation and on the eventual size of the exposure data set. Conclusions The analysis procedures developed in the present study can be used for informed design of exposure assessment strategies, provided that data are available on exposure variability and the costs of collecting and processing data. The present shortage of empirical evidence on costs and appropriate cost functions however impedes general conclusions on optimal exposure measurement strategies in different epidemiologic scenarios. PMID:21600023

Optimizing cost-efficiency in mean exposure assessment--cost functions reconsidered.

PubMed

Mathiassen, Svend Erik; Bolin, Kristian

2011-05-21

Reliable exposure data is a vital concern in medical epidemiology and intervention studies. The present study addresses the needs of the medical researcher to spend monetary resources devoted to exposure assessment with an optimal cost-efficiency, i.e. obtain the best possible statistical performance at a specified budget. A few previous studies have suggested mathematical optimization procedures based on very simple cost models; this study extends the methodology to cover even non-linear cost scenarios. Statistical performance, i.e. efficiency, was assessed in terms of the precision of an exposure mean value, as determined in a hierarchical, nested measurement model with three stages. Total costs were assessed using a corresponding three-stage cost model, allowing costs at each stage to vary non-linearly with the number of measurements according to a power function. Using these models, procedures for identifying the optimally cost-efficient allocation of measurements under a constrained budget were developed, and applied on 225 scenarios combining different sizes of unit costs, cost function exponents, and exposure variance components. Explicit mathematical rules for identifying optimal allocation could be developed when cost functions were linear, while non-linear cost functions implied that parts of or the entire optimization procedure had to be carried out using numerical methods.For many of the 225 scenarios, the optimal strategy consisted in measuring on only one occasion from each of as many subjects as allowed by the budget. Significant deviations from this principle occurred if costs for recruiting subjects were large compared to costs for setting up measurement occasions, and, at the same time, the between-subjects to within-subject variance ratio was small. In these cases, non-linearities had a profound influence on the optimal allocation and on the eventual size of the exposure data set. The analysis procedures developed in the present study can be used for informed design of exposure assessment strategies, provided that data are available on exposure variability and the costs of collecting and processing data. The present shortage of empirical evidence on costs and appropriate cost functions however impedes general conclusions on optimal exposure measurement strategies in different epidemiologic scenarios.

Optimal strategies for the eradication of Asiatic citrus canker in heterogeneous host landscapes

USDA-ARS?s Scientific Manuscript database

The eradication of non-native plant pathogens is a key challenge in plant disease epidemiology. Asiatic citrus canker is an economically significant disease of citrus caused by the bacterial plant pathogen Xanthomonas citri subsp. citri. The pathogen is a major exotic disease problem in many citru...

Sharka epidemiology and worldwide management strategies: learning lessons to optimize disease control in perennial plants

USDA-ARS?s Scientific Manuscript database

Many plant epidemics that cause major economic losses cannot be controlled with pesticides. Among them, sharka epidemics severely affect prunus trees worldwide. Its causal agent, Plum pox virus (PPV;, genus Potyvirus), has been classified as a quarantine pathogen in numerous countries. As a result, ...

Vaccination in pulses: a strategy for global eradication of measles and polio?

PubMed

Nokes, D J; Swinton, J

1997-01-01

Recent American successes against poliomyelitis and measles have been attributed to repeated 'pulse' vaccination campaigns. Whilst logistic and economic constraints will be crucial, a deeper epidemiological understanding of the mechanism, strengths and weaknesses of pulse vaccination will optimize the chances of success elsewhere in the world.

[Current malaria situation in the Republic of Kazakhstan].

PubMed

Bismil'din, F B; Shapieva, Zh Zh; Anpilova, E N

2001-01-01

The Republic of Kazakhstan is situated in the northern hemisphere on the boundary of two continents--Europe and Asia--at a longitude of 45 degrees E--87 degrees E and a latitude of 40 degrees N--55 degrees N. The total area of the republic is 2,724,900 square kilometers. Kazakhstan shares a border with the Russian Federation to the north-west, north and east: the border between the two countries is almost 6500 km long. To the south, Kazakhstan shares a border with the Central Asian states of Turkmenistan (380 km), Uzbekistan (2300 km) and Kyrgystan (980 km). To the south-east, it shares a border with China (1460 km): to the west is the Caspian Sea (600 km). Thus, the total length of Kazakhstan's external borders is 12,000 km. Because of the geographical, natural and climatic features prevailing throughout most of the Republic, there is a potential danger that local transmission of malaria may begin again if the disease is imported from abroad. The areas most at risk are the Panfilov and Uigur raions of Almaty oblast, which share a border with malaria-endemic regions of China, and the Saryagash and Makhtaral' raions of South Kazakhstan oblast along the border with Uzbekistan. The Government of the Republic of Kazakhstan places particular emphasis on malaria prevention and control, taking into account the historical data about the prevalence of malaria from the late 1920s to the early 1940s, amounting to hundreds of thousands of cases every year. Government Decree No. 840 entitled "Urgent Measures to Protect the Population from Blood-Sucking Insects and Ticks Dangerous to Humans", which lays down measures for the control of malarial mosquitoes in the areas most susceptible to malaria resurgence, was adopted in 1996. The Ministry of Health of the Republic of Kazakhstan issued instructions in 1998 and 1999 which were designed to motivate all health facilities in the field of malaria prevention and control. At present, as part of the directives developed by the Republican Health Epidemiology Posts, work is being done on the planning of malaria control measures in Kazakhstan for the period 2001-2003. In 1994 a programme of epidemiological malaria surveillance was introduced, which has enabled us to improve our monitoring of the epidemiological situation of malaria. The number of cases of imported malaria has declined: in 1997, there were 102 cases, in 1998-87 and in 1999-52. There have been occasional local cases in some years, and in 1998 there were four local cases in the south and north-west of the country: two cases in Almaty oblast, one case in Zhambyl oblast and one in West Kazakhstan oblast (see Fig. 1). Most malaria infections are imported from Tajikistan and Azerbaijan, with occasional cases from Pakistan, India, Turkey and Afghanistan. Analysis of the occupational status of patients shows that around 45% are military personnel who have served on the Tajik-Afghan border. The others are refugees, merchants, unemployed people or students. The overall aetiological structure of malaria cases is dominated by P. vivax malaria. For example, in 1999, there were 48 cases of P. vivax malaria (90.5% of the total), one case of tropical malaria (1.9%), two cases of quartan malaria (3.8%) and two cases of P. vivax + P. malariae (3.8%). In order to prevent indigenous malaria occurring within the country, a system of malaria screening has been set up; screening is carried out every year on groups who have visited neighbouring or more distant malaria-endemic countries and for patients with a persistent fever who are suspected of suffering from malaria. The area of water throughout the country within communities or within a 3-5 km radius of them which is susceptible to colonization by the Anopheles mosquito amounts to over 5000 hectares, according to the certification system in force. In addition, approximately 70,000 hectares in three oblasts used for rice cultivation also provide a habitat for Anopheles. The main malaria vector, An. messeae, is found throughout the country: in a few areas An. hyrcanus and An. claviger are found and, in the south, An. pulcherrimus. Data from recent years show the presence of An. superpictus, An. plumbeus and An. algeriensis. In 1999, from data collected during systematic observations of the phenology and seasonal variations in the number of Anopheles at 114 observation posts, the average seasonal numerical indicators for the mosquito imago reached a maximum of between 21 and 46.5 adult mosquitoes per cattle shed, up to 2.7-3.3 adult mosquitoes per residential building and 30-67.3 larvae per square metre of surface water. According to the results of large scale trapping programmes (486 communities were screened in 1999), the maximum value of the numerical indicator was 16.8-74.1 adult mosquitoes per cattle shed and 4.1-3.8 adult mosquitoes per residential building. In 1999, compared with 1998, the number of malarial mosquitoes detected throughout the country declined encouragingly, or stayed at the same level, which is one of the factors responsible for the country's favourable epidemiological situation with regard to malaria. According to data going back many years, there has been a significant increase in the number of mosquitoes at some observation posts in Almaty, East Kazakhstan and Kyzlorda oblasts. There is a tendency everywhere for the numbers of imagos detected in residential buildings to increase, which presents a definite epidemiological risk that indigenous malaria will re-emerge if the disease is imported into Kazakhstan from countries which suffer from it. If we consider the species of mosquito present in the country and the temperature factor (the number of days in the year when the average daily temperature is over 16 degrees C), the country can be divided, on the basis of incomplete 1999 data, into zones at very high risk of re-emergence of malaria (Almaty, Zhambyl and South Kazakhstan oblasts), high risk (Karaganda oblasts and Almaty city), medium risk (Aktyubinsk and Akmolinsk oblasts), and low risk (Kostanay oblast). The malaria risk of the other oblasts has been calculated using data from earlier years (map attached) [Translator's Note: map missing]. Preventive malaria control measures in Kazakhstan are divided into three categories to suit three different groups of communities. One hundred and seventy-nine communities have been allocated to the first group, at high risk of malaria resurgence; 1377 communities to the second group, at medium risk; and the remainder to the third group, at little or no risk of malaria resurgence. The following factors were used to categorize communities according to the risk that malaria might become reestablished if the disease should be imported from elsewhere: species of malarial mosquito present; changes in mosquito numbers and in the area of water susceptible to population by Anopheles; temperature conditions and, consequently, the length of the malaria transmission season and the season of effective susceptibility of the mosquito to infection; population migration; quality of laboratory testing for the diagnosis of malaria. Measures aimed at the destruction of mosquitoes are intended to reduce the numbers of Anopheles in the communities most at risk of malaria resurgence, i.e. those in group 1 above and the actual foci of malaria infection. Because of the economic crisis and financial difficulties, fewer areas have been treated in recent years. In 1999, 1387 hectares of water and 450,000 square metres of buildings were treated (see Fig. 2). Measures to control biting flies in health establishments, recreation areas, etc. Certainly also help to protect people from malarial mosquitoes. In 1999, 12,501 hectares of water and land were treated from the ground or the air (see Fig. 3). In the present situation, the main reasons for the difficulties affecting the malaria control and prevention campaign are as follows. Staff numbers in the Republic's parasitology service have been unjustifiably reduced. For example, the number of entomologists and entomology assistants employed is 58% and 48%, respectively, of the number laid down in Ministry of Health directives. At the health epidemiology posts, the number of disinfectors has been reduced to a minimum, and practically all engineer/water engineer posts have been abolished. The country does not possess the necessary education base for initial training or continuing education of staff for the parasitology service. The lack of basic scientific information about the problems of malaria control and prevention and parasitology in general. There is no research to test or introduce the most effective, safe and low-cost malaria control products and insecticides. The methodological literature required to use certain modern insecticides is not available. Entomologists are not provided with specialist insect control equipment. Entomological surveys are left incomplete because of shortages of transport and fuel at the health epidemiology posts. Because of the economic crisis and the high cost of the radical water engineering measures necessary to combat malaria, these measures cannot be implemented on the scale required. The equipment and materials stocks of the parasitology laboratories are highly inadequate: there is a lack of modern laboratory equipment, as well as a lack of opportunities for high-level professional training for staff. The exchange of information between the CIS countries is unsatisfactory, and there is no common information space: nor is there any systematic data available from other foreign countries. In the period 2000-2003, Kazakhstan plans to carry out malaria control activities (mosquito destruction) over an area of 2000 hectares of water and 1.5 million square metres of buildings.

Malaria

DTIC Science & Technology

2011-06-01

terms tertian and quartan describe the usual periodicity of the fever . General Considerations In the mid-19th century Meckel and others discovered...cyclic fever . Fever peaks around the time of schizogony and is more severe in naive patients than in those who have had previous infections. Malarial...majority undergo schizogony at approximately the same time and fever periodicity is determined by the length of the asexual cycle (Table 10.3

The Strategic Implications of China’s Expanding Presence in Africa

DTIC Science & Technology

2011-03-24

cooperation, debt relief, tourism; migration, agriculture, natural resources and energy, science and technology, medical care and public health, education...technicians 8  Deepen cooperation in medical and health care by providing approximately $76.2 million in equipment and anti-malarial materials and...in exchange for mineral concessions.47 China expects one pyrometallurgic plant, constructed through a Chinese-Congolese joint venture in DRC, to

Nature's Chiral Catalyst and Anti-Malarial Agent: Isolation and Structure Elucidation of Cinchonine and Quinine from "Cinchona calisaya"

ERIC Educational Resources Information Center

Carroll, Anne-Marie; Kavanagh, David J.; McGovern, Fiona P.; Reilly, Joe W.; Walsh, John J.

2012-01-01

Nature is a well-recognized source of compounds of interest, but access is often an issue. One pertinent example is the cinchona alkaloids from the bark of "Cinchona calisaya." In this experiment, students at the third-year undergraduate level undertake the selective isolation and characterization of two of the four main alkaloids present in the…

Metabolic Host Responses to Malarial Infection during the Intraerythrocytic Developmental Cycle

DTIC Science & Technology

2016-08-08

by reproducing the experimentally determined 1) stage-specific production of biomass components and their precursors in the parasite and 2) metabolite...uptake, allow for the prediction of cellular growth ( biomass accumulation) and other phenotypic functions related to metabolism [9]. For example...our group to capture stage-specific growth phenotypes and biomass metabolite production [15]. Among these metabolic descriptions, only the network

Incestuous gene in consanguinophilia and incest: toward a consilience theory of incest taboo.

PubMed

Denic, Srdjan; Nicholls, M Gary

2006-01-01

Westermarck's theory of incest taboo states that inhibition of sexual attraction between biologically close relatives is situational and develops during co-residence in early childhood. By contrast, the biological (genetic) basis of incest taboo is presumed from its universality in all human societies and animals and teleologically, from the need to prevent the detrimental effects of inbreeding. As incest taboo violation is infrequent, the frequency of the presumed gene in the population is believed to be near 100%. We present arguments which suggest that the incestuous gene may exist in all populations and could play an important role in evolution. When malaria emerged 10,000 years ago, human adaptation proceeded by the selection of protective genotypes. Among them, homozygotes for alpha-thalassemia, hemoglobin C, and Duffy antigen negative blood group, have better survival odds in malarious regions than heterozygotes and those with normal genotypes. Since consanguinity increases homozygosity, it increases the number of persons who are resistant to malaria. To pro-create, however, biologically close individuals must not feel sexual aversion that normally develops between those who spend their early childhood together (Westermarck effect). It is reasonable to assume, therefore, that mutation of the gene that discourages inbreeding may have appeared at an early time in evolution, and produced a weak Westermarck effect. This gene (we will call it anti-w) failed to inhibit mating between kins. Inbred offspring of anti-w carriers, would statistically, more likely carry both anti-w and homozygote genotypes which increase fitness in the presence of malaria. Today, alpha-thalassemia is the single most common monogenetic disorders in man with over 500 millions carriers concentrated in malarious regions of the world. The world's consanguineous population is some 500-800 millions and is also concentrated in malarious regions. Population migration has spread the gene outside areas of high malaria endemicity. However, endemicity of malaria provides a worldwide gradient of genotype frequencies which makes the incestuous gene hypothesis testable. We propose that the incestuous anti-w allele was co-selected with some of the genes protective against malaria because anti-w facilitates mating between genetically close individuals whose offspring better survive malaria.

Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses.

PubMed

Mtove, George; Hendriksen, Ilse Ce; Amos, Ben; Mrema, Hedwiga; Mandia, Victor; Manjurano, Alphaxard; Muro, Florida; Sykes, Alma; Hildenwall, Helena; Whitty, Christopher J M; Reyburn, Hugh

2011-10-06

WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT). However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. Over the course of one year, 965 children were enrolled; 158 (16.4%) were RDT-positive and treated with artemether-lumefantrine and 807 (83.4%) were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6%) children became RDT-positive after enrollment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrollment. In addition, 12 (1.2%) children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9%) children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤ 12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95% CI 96.9-98.7) and specificity of 96.3% (95% CI 96.3-98.4). Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive bacterial disease is uncommon in children with non-severe illness and most cases occurred in infants with a current fever.

Malarial Anaemia and Anaemia Severity in Apparently Healthy Primary School Children in Urban and Rural Settings in the Mount Cameroon Area: Cross Sectional Survey

PubMed Central

Ndamukong-Nyanga, Judith Lum; Nweboh, Malaika; Anchang-Kimbi, Judith Kuoh; Lum, Emmaculate; Nana, Yannick; Ndamukong, Kenneth K. J.; Lehman, Leopold G.

2015-01-01

Background This study examines the relative importance of living in an urban versus rural setting and malaria in contributing to the public health problem of malarial anaemia (MA) and anaemia respectively in apparently healthy primary school children. Methods A cross-sectional study was conducted among 727 school children aged between four and 15 years living in an urban (302) and rural (425) settings in the Mount Cameroon area. Blood sample collected from each child was used for the preparation of blood films for detection of malaria parasites and assessment of malaria parasite density as well as full blood count determination using an automated haematology analyzer. Based on haemoglobin (Hb) measurements, children with malaria parasitaemia were stratified into MA (Hb<11g/dL); mild MA (Hb of 8–10.9g/dL); moderate MA (Hb of 6.1–7.9g/dL) and severe MA (Hb≤6g/dL). Evaluation of potential determinants of MA and anaemia was performed by multinomial logistic-regression analysis and odds ratios used to evaluate risk factors. Results Out of the 727 children examined, 72 (9.9%) had MA. The prevalence of MA and anaemia were significantly higher (χ2 = 36.5, P <0.001; χ2 = 16.19, P <0.001 respectively) in children in the urban (17.9%; 26.8% respectively) than in the rural area (4.2%; 14.8% respectively). Majority of the MA cases were mild (88.9%), with moderate (5.6%) and severe MA (5.6%) occurring in the urban area only. The age group ≤6years was significantly (P <0.05) associated with both MA and anaemia. In addition, low parasite density was associated with MA while malaria parasite negative and microcytosis were associated with anaemia. Conclusions Malarial anaemia and anaemia display heterogeneity and complexity that differ with the type of settlement. The presence of severe MA and the contributions of the age group ≤6 years, low parasite density and microcytosis to the public health problem of MA and anaemia are noteworthy. PMID:25893500

Malarial anaemia and anaemia severity in apparently healthy primary school children in urban and rural settings in the Mount Cameroon area: cross sectional survey.

PubMed

Sumbele, Irene Ule Ngole; Kimbi, Helen Kuokuo; Ndamukong-Nyanga, Judith Lum; Nweboh, Malaika; Anchang-Kimbi, Judith Kuoh; Lum, Emmaculate; Nana, Yannick; Ndamukong, Kenneth K J; Lehman, Leopold G

2015-01-01

This study examines the relative importance of living in an urban versus rural setting and malaria in contributing to the public health problem of malarial anaemia (MA) and anaemia respectively in apparently healthy primary school children. A cross-sectional study was conducted among 727 school children aged between four and 15 years living in an urban (302) and rural (425) settings in the Mount Cameroon area. Blood sample collected from each child was used for the preparation of blood films for detection of malaria parasites and assessment of malaria parasite density as well as full blood count determination using an automated haematology analyzer. Based on haemoglobin (Hb) measurements, children with malaria parasitaemia were stratified into MA (Hb<11 g/dL); mild MA (Hb of 8-10.9 g/dL); moderate MA (Hb of 6.1-7.9 g/dL) and severe MA (Hb≤6 g/dL). Evaluation of potential determinants of MA and anaemia was performed by multinomial logistic-regression analysis and odds ratios used to evaluate risk factors. Out of the 727 children examined, 72 (9.9%) had MA. The prevalence of MA and anaemia were significantly higher (χ2 = 36.5, P <0.001; χ2 = 16.19, P <0.001 respectively) in children in the urban (17.9%; 26.8% respectively) than in the rural area (4.2%; 14.8% respectively). Majority of the MA cases were mild (88.9%), with moderate (5.6%) and severe MA (5.6%) occurring in the urban area only. The age group ≤6 years was significantly (P <0.05) associated with both MA and anaemia. In addition, low parasite density was associated with MA while malaria parasite negative and microcytosis were associated with anaemia. Malarial anaemia and anaemia display heterogeneity and complexity that differ with the type of settlement. The presence of severe MA and the contributions of the age group ≤6 years, low parasite density and microcytosis to the public health problem of MA and anaemia are noteworthy.

The challenge to avoid anti-malarial medicine stock-outs in an era of funding partners: the case of Tanzania.

PubMed

Mikkelsen-Lopez, Inez; Shango, Winna; Barrington, Jim; Ziegler, Rene; Smith, Tom; deSavigny, Don

2014-05-11

Between 2007 and 2013, the Tanzanian public sector received 93.1 million doses of first-line anti-malarial artemisinin-based combination therapy (ACT) in the form of artemether-lumefantrine entirely supplied by funding partners. The introduction of a health facility ACT stock monitoring system using SMS technology by the National Malaria Control Programme in mid 2011 revealed a high frequency of stock-outs of ACT in primary care public health facilities. The objective of this study was to determine the pattern of availability of ACT and possible causes of observed stock-outs across public health facilities in Tanzania since mid-2011. Data were collected weekly by the mobile phone reporting tool SMS for Life on ACT availability from over 5,000 public health facilities in Tanzania starting from September 2011 to December 2012. Stock data for all four age-dose levels of ACT across health facilities were summarized and supply of ACT at the national level was also documented. Over the period of 15 months, on average 29% of health facilities in Tanzania were completely stocked out of all four-age dose levels of the first-line anti-malarial with a median duration of total stock-out of six weeks. Patterns of total stock-out by region ranged from a low of 9% to a high of 52%. The ACT stock-outs were most likely caused by: a) insufficient ACT supplies entering Tanzania (e.g. in 2012 Tanzania received 10.9 million ACT doses compared with a forecast demand of 14.4 million doses); and b) irregular pattern of ACT supply (several months with no ACT stock). The reduced ACT availability and irregular pattern of supply were due to cumbersome bureaucratic processes and delays both within the country and from the main donor, the Global Fund to Fight AIDS, Tuberculosis and Malaria. Tanzania should invest in strengthening both the supply system and the health information system using mHealth solutions such as SMS for Life. This will continue to assist in tracking ACT availability across the country where all partners work towards more streamlined, demand driven and accountable procurement and supply chain systems.

Accuracy of a Plasmodium falciparum specific histidine-rich protein 2 rapid diagnostic test in the context of the presence of non-malaria fevers, prior anti-malarial use and seasonal malaria transmission.

PubMed

Kiemde, Francois; Bonko, Massa Dit Achille; Tahita, Marc Christian; Lompo, Palpouguini; Rouamba, Toussaint; Tinto, Halidou; van Hensbroek, Michael Boele; Mens, Petra F; Schallig, Henk D F H

2017-07-20

It remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. This study was designed to determine the influence of other causes of fever, prior anti-malarial treatment, and a possible seasonality of the performance of a PfHRP2 RDT for the diagnosis of malaria in children under-5 years of age living in a malaria endemic area. A prospective etiology study was conducted in 2015 among febrile children under 5 years of age in Burkina Faso. In order to assess the influence of other febrile illnesses, prior treatment and seasonality on the performance of a PfHRP2 RDT in diagnosing malaria, the RDT results were compared with the gold standard (expert microscopic diagnosis of Plasmodium falciparum) and test results were analysed by assuming that prior anti-malarial use and bacterial/viral infection status would have been known prior to testing. To assess bacterial and viral infection status blood, urine and stool samples were analysed. In total 683 blood samples were analysed with microscopy and RDT-PfHRP2. Plasmodium falciparum malaria was diagnosed in 49.8% (340/683) by microscopy compared to 69.5% (475/683) by RDT-PfHRP2. The RDT-PfHRP2 reported 29.7% (141/475) false positive results and 1.8% (6/340) false negative cases. The RDT-PfHRP2 had a high sensitivity (98.2%) and negative predictive value (97.1%), but a low specificity (58.9%) and positive predictive value (70.3%). Almost 50% of the alternative cause of fever were diagnosed by laboratory testing in the RDT false positive malaria group. The use of a malaria RDT-PfHRP2 in a malaria endemic area may cause misdiagnosis of the actual cause of fever due to false positive test results. The development of a practical diagnostic tool to screen for other causes of fever in malaria endemic areas is required to save lives.

Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience

PubMed Central

2011-01-01

Background This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field. Case description In 2002, DNDi created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DNDi and sanofi-aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam®/Artesunate Amodiaquine Winthrop® ("ASAQ Winthrop") which was prequalified by the WHO in 2008. Additional partnerships have since been established by DNDi and sanofi-aventis to ensure: 1) the adoption of this new medicine by malaria-endemic countries, 2) its appropriate usage through a broad range of information tools, and 3) the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan. Discussion and evaluation The partnership between DNDi and sanofi-aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan. Conclusions The speed at which ASAQ Winthrop was adopted in the field shows that this drug fits the needs of patients and health authorities. It also demonstrates the power of partnerships that combine different sets of strengths and skills, and that evolve to include additional actors to meet new global health challenges for poverty-related diseases. PMID:21605364

Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience.

PubMed

Bompart, François; Kiechel, Jean-René; Sebbag, Robert; Pecoul, Bernard

2011-05-23

This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field. In 2002, DNDi created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-Aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DNDi and Sanofi-Aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam®/Artesunate Amodiaquine Winthrop® ("ASAQ Winthrop") which was prequalified by the WHO in 2008. Additional partnerships have since been established by DNDi and Sanofi-Aventis to ensure: 1) the adoption of this new medicine by malaria-endemic countries, 2) its appropriate usage through a broad range of information tools, and 3) the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan. The partnership between DNDi and Sanofi-Aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan. The speed at which ASAQ Winthrop was adopted in the field shows that this drug fits the needs of patients and health authorities. It also demonstrates the power of partnerships that combine different sets of strengths and skills, and that evolve to include additional actors to meet new global health challenges for poverty-related diseases.

“We have become doctors for ourselves”: motives for malaria self-care among adults in southeastern Tanzania

PubMed Central

2014-01-01

Background Prompt and appropriate treatment of malaria with effective medicines remains necessary if malaria control goals are to be achieved. The theoretical concepts from self-care and the health belief model were used to examine the motivations for malaria self-care among the adult population. Methods A qualitative study was conducted through eight focus group discussions with adult community members to explore their general opinions, views and perceptions of malaria and of its treatments. These groups were followed by 15 in-depth interviews of participants with a recent malaria experience to allow for an in-depth exploration of their self-care practices. The analysis followed principles of grounded theory and was conducted using Nvivo 9 qualitative data management software. Results The self-treatment of malaria at home was found to be a common practice among the study participants. The majority of the participants practiced self-medication with a painkiller as an initial response. The persistence and the worsening of the disease symptoms prompted participants to consider other self-care options. Perceptions that many malaria symptoms are suggestive of other conditions motivated participants to self-refer for malaria test. The accessibility of private laboratory facilities and drug shops motivated their use for malaria tests and for obtaining anti-malarial medicines, respectively. Self-treatment with anti-malarial monotherapy was common, motivated by their perceived effectiveness and availability. The perceived barriers to using the recommended combination treatment, artemether-lumefantrine, were related to the possible side-effects and to uncertainty about their effectiveness, and these doubts motivated some participants to consider self-medication with local herbs. Several factors were mentioned as motivating people for self-care practices. These included poor patient provider relationship, unavailability of medicine and the costs associated with accessing treatments from the health facilities. Conclusions Malaria self-care and self-treatment with anti-malarial monotherapy are common among adults, and are motivated by both individual characteristics and the limitations of the existing health care facilities. There is a need for public health interventions to take into account community perceptions and cultural schemas on malaria self-care practices. PMID:24986165

Computational prediction of protein interactions related to the invasion of erythrocytes by malarial parasites.

PubMed

Liu, Xuewu; Huang, Yuxiao; Liang, Jiao; Zhang, Shuai; Li, Yinghui; Wang, Jun; Shen, Yan; Xu, Zhikai; Zhao, Ya

2014-11-30

The invasion of red blood cells (RBCs) by malarial parasites is an essential step in the life cycle of Plasmodium falciparum. Human-parasite surface protein interactions play a critical role in this process. Although several interactions between human and parasite proteins have been discovered, the mechanism related to invasion remains poorly understood because numerous human-parasite protein interactions have not yet been identified. High-throughput screening experiments are not feasible for malarial parasites due to difficulty in expressing the parasite proteins. Here, we performed computational prediction of the PPIs involved in malaria parasite invasion to elucidate the mechanism by which invasion occurs. In this study, an expectation maximization algorithm was used to estimate the probabilities of domain-domain interactions (DDIs). Estimates of DDI probabilities were then used to infer PPI probabilities. We found that our prediction performance was better than that based on the information of D. melanogaster alone when information related to the six species was used. Prediction performance was assessed using protein interaction data from S. cerevisiae, indicating that the predicted results were reliable. We then used the estimates of DDI probabilities to infer interactions between 490 parasite and 3,787 human membrane proteins. A small-scale dataset was used to illustrate the usability of our method in predicting interactions between human and parasite proteins. The positive predictive value (PPV) was lower than that observed in S. cerevisiae. We integrated gene expression data to improve prediction accuracy and to reduce false positives. We identified 80 membrane proteins highly expressed in the schizont stage by fast Fourier transform method. Approximately 221 erythrocyte membrane proteins were identified using published mass spectral datasets. A network consisting of 205 interactions was predicted. Results of network analysis suggest that SNARE proteins of parasites and APP of humans may function in the invasion of RBCs by parasites. We predicted a small-scale PPI network that may be involved in parasite invasion of RBCs by integrating DDI information and expression profiles. Experimental studies should be conducted to validate the predicted interactions. The predicted PPIs help elucidate the mechanism of parasite invasion and provide directions for future experimental investigations.

Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa.

PubMed

Zwang, Julien; Ndiaye, Jean-Louis; Djimdé, Abdoulaye; Dorsey, Grant; Mårtensson, Andreas; Karema, Corine; Olliaro, Piero

2012-01-25

Artesunate-amodiaquine (AS&AQ) is a widely used artemisinin combination therapy (ACT) for falciparum malaria. A comprehensive appreciation of its effects on haematology vs other anti-malarials is needed in view of potential safety liabilities. Individual-patient data analysis conducted on a database from seven randomized controlled trials conducted in sub-Saharan African comparing AS&AQ to reference treatments in uncomplicated falciparum malaria patients of all ages. Haematologic values (white cells total and neutrophil counts, haemoglobin/haematocrit, platelets) were analysed as both continuous and categorical variables for their occurrence, (severity grade 1-4) and changes during follow-up. Risks and trends were calculated using multivariate logistic random effect models. 4,502 patients (72% < 5 years old), from 13 sites in nine countries with 28-day follow-up were treated with AS&AQ (45%) or a comparator (other forms of ACT accounted for 27%, other combination 12%, mono-therapies 16%). Pre-treatment leucopaenia (3%) and neutropaenia (6%) were infrequent; anaemia was common (39%). The treatment-emergent adverse events incidence (TEAE = condition not present or less severe pre-treatment) was 11% for neutropaenia, 6% for thrombocytopaenia with AS&AQ and not different from treatment groups; anaemia was higher with AS&AQ (20%) or other forms of ACT (22%) than in non-artemisinin groups (4%, p = 0.001). Multivariate analysis showed that the risk of anaemia, thrombocytopaenia, and leucopaenia decreased with follow-up time, while neutropaenia increased; the risk of anaemia and thrombocytopaenia increased with higher baseline parasitaemia and parasitological reappearance. White cells total count was not a good surrogate for neutropaenia. No systematic significant difference between treatments was detected. Older patients were at lower risks. The effects of AS&AQ on haematologic parameters were not different from those of other anti-malarial treatments used in sub-Saharan Africa. This analysis provides the basis for a broader evaluation of haematology following anti-malarial treatment. Continuing monitoring of haematologic safety on larger databases is required.

Synthesizing epidemiological and economic optima for control of immunizing infections.

PubMed

Klepac, Petra; Laxminarayan, Ramanan; Grenfell, Bryan T

2011-08-23

Epidemic theory predicts that the vaccination threshold required to interrupt local transmission of an immunizing infection like measles depends only on the basic reproductive number and hence transmission rates. When the search for optimal strategies is expanded to incorporate economic constraints, the optimum for disease control in a single population is determined by relative costs of infection and control, rather than transmission rates. Adding a spatial dimension, which precludes local elimination unless it can be achieved globally, can reduce or increase optimal vaccination levels depending on the balance of costs and benefits. For weakly coupled populations, local optimal strategies agree with the global cost-effective strategy; however, asymmetries in costs can lead to divergent control optima in more strongly coupled systems--in particular, strong regional differences in costs of vaccination can preclude local elimination even when elimination is locally optimal. Under certain conditions, it is locally optimal to share vaccination resources with other populations.

Corporation-induced Diseases, Upstream Epidemiologic Surveillance, and Urban Health

PubMed Central

2008-01-01

Corporation-induced diseases are defined as diseases of consumers, workers, or community residents who have been exposed to disease agents contained in corporate products. To study the epidemiology and to guide expanded surveillance of these diseases, a new analytical framework is proposed. This framework is based on the agent–host–environment model and the upstream multilevel epidemiologic approach and posits an epidemiologic cascade starting with government-sanctioned corporate profit making and ending in a social cost, i.e., harm to population health. Each of the framework’s levels addresses a specific level of analysis, including government, corporations, corporate conduits, the environment of the host, and the host. The explained variable at one level is also the explanatory variable at the next lower level. In this way, a causal chain can be followed along the epidemiologic cascade from the site of societal power down to the host. The framework thus describes the pathways by which corporate decisions filter down to disease production in the host and identifies opportunities for epidemiologic surveillance. Since the environment of city dwellers is strongly shaped by corporations that are far upstream and several levels away, the framework has relevance for the study of urban health. Corporations that influence the health of urban populations include developers and financial corporations that determine growth or decay of urban neighborhoods, as well as companies that use strategies based on neighborhood characteristics to sell products that harm consumer health. Epidemiological inquiry and surveillance are necessary at all levels to provide the knowledge needed for action to protect the health of the population. To achieve optimal inquiry and surveillance at the uppermost levels, epidemiologists will have to work with political scientists and other social scientists and to utilize novel sources of information. PMID:18437580

Lack of evidence for intergenerational reproductive effects due to prenatal and postnatal undernutrition in the female CD-1 mouse

EPA Science Inventory

The impacts of adverse environments during the prenatal and/or early postnatal periods may be manifested as functional deficits that occur later in life. Epidemiological studies have shown an association of sub-optimal pregnancy outcomes in one generation with similar events in t...

The epidemiology of a specialist neurorehabilitation clinic: implications for clinical practice and regional service development.

PubMed

Seeley, Helen; Pickard, John; Allanson, Judith; Hutchinson, Peter

2014-01-01

To examine the epidemiology of referrals to a specialist neurotrauma clinic and explore and highlight implications for clinical practice and service development for persons with head injury/traumatic brain injury (HI/TBI). A retrospective population-based cohort study of all referrals to a specialist neurotrauma clinic over a 9-year period. Data from a specialist head injury database (which included all persons presenting to hospital with traumatic brain injury) were analysed. In total, 1235 new patients of all ages, severities of injury, both admitted and non-admitted were referred. Referrals have increased due to successful integration with new service developments and resulting optimization of resources. Data gathered from the cohort gives increased understanding of the characteristics and numbers of patients requiring rehabilitation and adds to the evidence-base. Integration with new and complementary service developments has optimized the function/aims of the clinic and enhanced its role in terms of patient service and outcome and as a research resource. The model provides principles which may be applied to planning, organizing and providing follow-up/rehabilitation services for HI/TBI.

tuf-PCR-temporal temperature gradient gel electrophoresis for molecular detection and identification of staphylococci: application to breast milk and neonate gut microbiota.

PubMed

Filleron, Anne; Simon, Margaux; Hantova, Stefaniya; Jacquot, Aurélien; Cambonie, Gilles; Marchandin, Hélène; Jumas-Bilak, Estelle

2014-03-01

Coagulase negative staphylococci (CoNS) are a leading cause of infections in preterm infants, mostly involved in late-onset infection in low birth weight neonates. The epidemiology and pathophysiology of these infections remain unclear, notably because the causing agents are gathered in the artificial CoNS group. The aim of this work was to optimize the study of Staphylococcus species diversity in human breast milk and neonate stool, two sample types with bacterial communities dominated by CoNS, using PCR-temporal temperature gel electrophoresis based on the tuf gene. The optimized protocol identified 18 Staphylococcus species involved in neonate gut microbiota and infections and was applied to cultivation-independent study of breast milk and neonate stool. The efficiency, sensitivity, specificity and species discrimination of the proposed protocol appears suitable for patient follow-up in order to link microbiological data at the community level in milk and stool and interpret them from epidemiological and pathophysiological points of view. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular basis of the potential of vitamin D to prevent cancer.

PubMed

Ingraham, Betty A; Bragdon, Beth; Nohe, Anja

2008-01-01

To review current research findings in cell biology, epidemiology, preclinical, and clinical trials on the protective effects of vitamin D against the development of cancers of the breast, colon, prostate, lung, and ovary. Current recommendations for optimal vitamin D status, the movement towards revision of standards, and reflections on healthy exposure to sunlight are also reviewed. Search methodology: A literature search was conducted in April and updated in September 2007. The Medline and Web of Knowledge databases were searched for primary and review articles published between 1970 and 2007, using the search terms 'vitamin D', 'calcitriol', 'cancer', 'chemoprevention', 'nuclear receptor', 'vitamin D receptor', 'apoptosis', 'cell cycle', 'epidemiology', and 'cell adhesion molecule'. Articles that focused on epidemiological, preclinical, and clinical evidence for vitamin D's effects were selected and additional articles were obtained from reference lists of the retrieved articles. An increasing body of research supports the hypothesis that the active form of vitamin D has significant, protective effects against the development of cancer. Epidemiological studies show an inverse association between sun exposure, serum levels of 25(OH)D, and intakes of vitamin D and risk of developing and/or surviving cancer. The protective effects of vitamin D result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. A significant number of individuals have serum vitamin D levels lower than what appears to protect against cancer, and the research community is currently revising the guidelines for optimal health. This will lead to improved public health policies and to reduced risk of cancer. Research strongly supports the view that efforts to improve vitamin D status would have significant protective effects against the development of cancer. The clinical research community is currently revising recommendations for optimal serum levels and for sensible levels of sun exposure, to levels greater than previously thought. Currently, most experts in the field believe that intakes of between 1000 and 4000 IU will lead to a more healthy level of serum 25(OH)D, at approximately 75 nmol/L that will offer significant protection effects against cancers of the breast, colon, prostate, ovary, lungs, and pancreas. The first randomized trial has shown significant protection against breast cancer, and other clinical trials will follow and ultimately lead to improved public health policies and significantly fewer cancers.

Epidemiology of hypertension in Northern Tanzania: a community-based mixed-methods study.

PubMed

Galson, Sophie W; Staton, Catherine A; Karia, Francis; Kilonzo, Kajiru; Lunyera, Joseph; Patel, Uptal D; Hertz, Julian T; Stanifer, John W

2017-11-09

Sub-Saharan Africa is particularly vulnerable to the growing global burden of hypertension, but epidemiological studies are limited and barriers to optimal management are poorly understood. Therefore, we undertook a community-based mixed-methods study in Tanzania to investigate the epidemiology of hypertension and barriers to care. In Northern Tanzania, between December 2013 and June 2015, we conducted a mixed-methods study, including a cross-sectional household epidemiological survey and qualitative sessions of focus groups and in-depth interviews. For the survey, we assessed for hypertension, defined as a single blood pressure ≥160/100 mm Hg, a two-time average of ≥140/90 mm Hg or current use of antihypertensive medications. To investigate relationships with potential risk factors, we used adjusted generalised linear models. Uncontrolled hypertension was defined as a two-time average measurement of ≥160/100 mm Hg irrespective of treatment status. Hypertension awareness was defined as a self-reported disease history in a participant with confirmed hypertension. To explore barriers to care, we identified emerging themes using an inductive approach within the framework method. We enrolled 481 adults (median age 45 years) from 346 households, including 123 men (25.6%) and 358 women (74.4%). Overall, the prevalence of hypertension was 28.0% (95% CI 19.4% to 38.7%), which was independently associated with age >60 years (prevalence risk ratio (PRR) 4.68; 95% CI 2.25 to 9.74) and alcohol use (PRR 1.72; 95% CI 1.15 to 2.58). Traditional medicine use was inversely associated with hypertension (PRR 0.37; 95% CI 0.26 to 0.54). Nearly half (48.3%) of the participants were aware of their disease, but almost all (95.3%) had uncontrolled hypertension. In the qualitative sessions, we identified barriers to optimal care, including poor point-of-care communication, poor understanding of hypertension and structural barriers such as long wait times and undertrained providers. In Northern Tanzania, the burden of hypertensive disease is substantial, and optimal hypertension control is rare. Transdisciplinary strategies sensitive to local practices should be explored to facilitate early diagnosis and sustained care delivery. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Relating phylogenetic trees to transmission trees of infectious disease outbreaks.

PubMed

Ypma, Rolf J F; van Ballegooijen, W Marijn; Wallinga, Jacco

2013-11-01

Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.

Bronchiolitis caused by respiratory syncytial virus in an area of portugal: epidemiology, clinical features, and risk factors.

PubMed

Flores, P; Rebelo-de-Andrade, H; Gonçalves, P; Guiomar, R; Carvalho, C; Sousa, E N; Noronha, F T; Palminha, J M

2004-01-01

The aim of the present study was to analyse the clinical and epidemiological characteristics of bronchiolitis caused by respiratory syncytial virus (RSV) in 225 children observed in a paediatric hospital in Lisbon, Portugal, and to determine the clinical, epidemiological, or laboratory parameters that correlate with greater severity of the disease. This prospective study included hospitalised and ambulatory children younger than 36 months of age with a diagnosis of bronchiolitis and was conducted during two consecutive RSV epidemiological seasons (November-March 2000/01 and 2001/02). The median age of the patients was 5 months, and the male-to-female ratio was 1.6:1. RSV was isolated in 60.9% of patients, predominantly in the hospitalised group. The subtype A:B ratio was 7.4:1 and was similar in both seasons. RSV-positive patients were younger, had more severe clinical forms of bronchiolitis, and fewer changes in leucocyte total and differential counts. Among infected patients, higher clinical severity scores occurred in association with first wheezing episodes, overcrowded households, attendance at day-care centres, or prematurity (<36 weeks). This first prospective study of RSV epidemiology in Portugal provides a foundation for appropriate surveillance programmes of RSV infection in this country. A multicentre study is desirable in order to delineate optimal prophylactic and therapeutic guidelines for RSV infection in Portugal.

[Safe drinking water supply to the Vologda Region's population using risk assessment methodology].

PubMed

Kuznetsova, I A; Figurina, T Ia; Shadrina, S Iu

2011-01-01

To supply the population with qualitative potable water is a priority problem in the provision of sanitary-and-epidemiologic well-being and in the prevention of disease in the Vologda Region. The monitoring of the results of laboratory control over the quality of drinking-water and the assessment of health risk enabled a package of measures to be proposed to optimize the conditions of drinking water supply in the Vologda Region. The risk assessment technology used by a state agency for sanitary-and-epidemiological surveillance makes it possible to substantiate a system of actions to organize household water use and to include scientifically grounded proposals into the developed regional and local programs.

nanos-Driven expression of piggyBac transposase induces mobilization of a synthetic autonomous transposon in the malaria vector mosquito, Anopheles stephensi.

PubMed

Macias, Vanessa M; Jimenez, Alyssa J; Burini-Kojin, Bianca; Pledger, David; Jasinskiene, Nijole; Phong, Celine Hien; Chu, Karen; Fazekas, Aniko; Martin, Kelcie; Marinotti, Osvaldo; James, Anthony A

2017-08-01

Transposons are a class of selfish DNA elements that can mobilize within a genome. If mobilization is accompanied by an increase in copy number (replicative transposition), the transposon may sweep through a population until it is fixed in all of its interbreeding members. This introgression has been proposed as the basis for drive systems to move genes with desirable phenotypes into target species. One such application would be to use them to move a gene conferring resistance to malaria parasites throughout a population of vector mosquitos. We assessed the feasibility of using the piggyBac transposon as a gene-drive mechanism to distribute anti-malarial transgenes in populations of the malaria vector, Anopheles stephensi. We designed synthetic gene constructs that express the piggyBac transposase in the female germline using the control DNA of the An. stephensi nanos orthologous gene linked to marker genes to monitor inheritance. Two remobilization events were observed with a frequency of one every 23 generations, a rate far below what would be useful to drive anti-pathogen transgenes into wild mosquito populations. We discuss the possibility of optimizing this system and the impetus to do so. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electron Microscopy to Correlate Cell Structures and Biochemical Activity

DTIC Science & Technology

1991-06-15

1991 A,.G2_ 1 I TYPE OF REPORT: Midterm - PREPARED FOR: U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND FORT DETRICK FREDERICK, MARYLAND 21702-5012... biochemistry , WRAIR, we studied intracellular localization ahd fate of liposomes and liposome- encapsulated malarial antigen after phagocytosis by...Parasitology Vol. 29 (ed. J. R. Baker), Academic Press, London p. 151- * 214. 10. Keberle, H. 1964. The biochemistry of desferrioxamine and its relation

JPRS Report, East Asia, Southeast Asia.

DTIC Science & Technology

1988-11-04

contrary to the views and interests of Indonesia. Foreign Impact The PANGAB noted in his lecture that while foreign social, economic, and cultural ...each country control of one area and joint control of a third . /9604 ROK Loan for West Sumatra Bypass 42000002/Jakarta BUSINESS NEWS in English 2...and Order] following the MALARI [15 January Disaster] incident in early 1974. Amelia Yani (40), the third daughter of the late General (posthumous

Studies on larvicidal and pupicidal activity of Leucas aspera Willd. (Lamiaceae) and bacterial insecticide, Bacillus sphaericus, against malarial vector, Anopheles stephensi Liston (Diptera: Culicidae)

USDA-ARS?s Scientific Manuscript database

The efficacy of whole plant ethanolic extracts of Leucas aspera and of Bacillus sphaericus was determined for larvae and pupae of Anopheles stephensi. When larvae were exposed to one of five concentrations of plant extract (6%, 8%, 10%, 12%, and 14%) for 24 h, mortality in 4th instars ranged from 1...

Repurposing the anti-malarial drug dihydroartemisinin suppresses metastasis of non-small-cell lung cancer via inhibiting NF-κB/GLUT1 axis

PubMed Central

Jiang, Jie; Geng, Guojun; Yu, Xiuyi; Liu, Hongming; Gao, Jing; An, Hanxiang; Cai, Chengfu; Li, Ning; Shen, Dongyan; Wu, Xiaoqiang; Zheng, Lisheng; Mi, Yanjun; Yang, Shuyu

2016-01-01

Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells. DHA inhibited in vitro migration and invasion of NSCLC cells even in low concentration with little cytotoxicity. Additionally, low concentration DHA also inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates NF-κB signaling to inhibit the GLUT1 translocation. Blocking the NF-κB signaling largely abolishes the inhibitory effects of DHA on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown significantly decreased the inhibition of invasion, and migration by DHA. Our results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose metabolism via inhibiting NF-κB signaling pathway and DHA may deserve further investigation in NSCLC treatment. PMID:27895313

Automated Detection of Malarial Retinopathy in Digital Fundus Images for Improved Diagnosis in Malawian Children with Clinically Defined Cerebral Malaria.

PubMed

Joshi, Vinayak; Agurto, Carla; Barriga, Simon; Nemeth, Sheila; Soliz, Peter; MacCormick, Ian J; Lewallen, Susan; Taylor, Terrie E; Harding, Simon P

2017-02-15

Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages. The individual lesion detection algorithms were combined using a partial least square classifier to determine the presence or absence of MR. We used a retrospective retinal image dataset of 86 pediatric patients with clinically defined CM (70 with MR and 16 without) to evaluate the algorithm performance. Our goal was to reduce the false positive rate of CM diagnosis, and so the algorithms were tuned at high specificity. This yielded sensitivity/specificity of 95%/100% for the detection of MR overall, and 65%/94% for retinal whitening, 62%/100% for vessel discoloration, and 73%/96% for hemorrhages. This automated system for detecting MR using retinal color images has the potential to improve the accuracy of CM diagnosis.

Malaria prevention in the pregnant traveller: a review.

PubMed

Roggelin, Louise; Cramer, Jakob P

2014-01-01

Malaria is still a major threat to health in tropical regions. Particular attention should be directed to malaria prevention in infants and pregnant women as they are at high risk for plasmodial infection and complicated malaria. In this review, we summarize and discuss current evidence on malaria prevention in pregnant travellers. As neither anti-mosquito measures nor anti-malarial drugs have been proven to be unequivocally safe or toxic in pregnant women, the individual risk assessment should take into account the risk of transmission at the destination, the benefit of travelling despite being pregnant as well as the individual risk perception. All three factors may differ in various groups of travellers like tourist travellers, expatriate travellers as well as those visiting friends and relatives. For pregnant women, mefloquine appears to be the drug of choice for prophylaxis and stand by-therapy if no contraindications exist - despite recent renewed warnings related to prolonged side effects. In areas with high resistance against mefloquine or in women with contraindications to mefloquine, atovaquone-proguanil or artemether-lumefantrine should be considered as an option for stand-by emergency therapy. Nevertheless, evidence on the safety of anti-malarials especially during the first trimester is still insufficient. Copyright © 2014 Elsevier Ltd. All rights reserved.

Malaria-Associated l-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia

PubMed Central

Chau, Jennifer Y.; Tiffany, Caitlin M.; Nimishakavi, Shilpa; Lawrence, Jessica A.; Pakpour, Nazzy; Mooney, Jason P.; Lokken, Kristen L.; Caughey, George H.; Tsolis, Renee M.

2013-01-01

Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop l-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of l-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with l-arginine or l-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with l-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing l-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans. PMID:23690397

Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

PubMed Central

Moore, Julie M.; Chaisavaneeyakorn, Sujittra; Perkins, Douglas J.; Othoro, Caroline; Otieno, Juliana; Nahlen, Bernard L.; Shi, Ya Ping; Udhayakumar, Venkatachalam

2004-01-01

Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-γ), with less of an effect on tumor necrosis factor alpha (TNF-α) and interleukin-10, in human immunodeficiency virus-seronegative (HIV−) women. In contrast, IFN-γ and TNF-α production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-γ in HIV− women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women. PMID:15557625

Puzzling and ambivalent roles of malarial infections in cancer development and progression.

PubMed

Faure, Eric

2016-12-01

Scientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth. Plasmodium protozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans, Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

A potent series targeting the malarial cGMP-dependent protein kinase clears infection and blocks transmission.

PubMed

Baker, David A; Stewart, Lindsay B; Large, Jonathan M; Bowyer, Paul W; Ansell, Keith H; Jiménez-Díaz, María B; El Bakkouri, Majida; Birchall, Kristian; Dechering, Koen J; Bouloc, Nathalie S; Coombs, Peter J; Whalley, David; Harding, Denise J; Smiljanic-Hurley, Ela; Wheldon, Mary C; Walker, Eloise M; Dessens, Johannes T; Lafuente, María José; Sanz, Laura M; Gamo, Francisco-Javier; Ferrer, Santiago B; Hui, Raymond; Bousema, Teun; Angulo-Barturén, Iñigo; Merritt, Andy T; Croft, Simon L; Gutteridge, Winston E; Kettleborough, Catherine A; Osborne, Simon A

2017-09-05

To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC 50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC 50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P. falciparum SCID mouse model. The series targets both merozoite egress and erythrocyte invasion, but crucially, also blocks transmission of mature P. falciparum gametocytes to Anopheles stephensi mosquitoes. A co-crystal structure of PvPKG bound to ML10, reveals intimate molecular contacts that explain the high levels of potency and selectivity we have measured. The properties of this series warrant consideration for further development to produce an antimalarial drug.Protein kinases are promising drug targets for treatment of malaria. Here, starting with a medicinal chemistry approach, Baker et al. generate an imidazopyridine that selectively targets Plasmodium falciparum PKG, inhibits blood stage parasite growth in vitro and in mice and blocks transmission to mosquitoes.

Identification of Anti-Malarial Compounds as Novel Antagonists to Chemokine Receptor CXCR4 in Pancreatic Cancer Cells

PubMed Central

Kim, Joseph; Yip, M. L. Richard; Shen, Xiaoming; Li, Hubert; Hsin, Li-Yu Charlie; Labarge, Samuel; Heinrich, Eileen L.; Lee, Wendy; Lu, Jianming; Vaidehi, Nagarajan

2012-01-01

Despite recent advances in targeted therapies, patients with pancreatic adenocarcinoma continue to have poor survival highlighting the urgency to identify novel therapeutic targets. Our previous investigations have implicated chemokine receptor CXCR4 and its selective ligand CXCL12 in the pathogenesis and progression of pancreatic intraepithelial neoplasia and invasive pancreatic cancer; hence, CXCR4 is a promising target for suppression of pancreatic cancer growth. Here, we combined in silico structural modeling of CXCR4 to screen for candidate anti-CXCR4 compounds with in vitro cell line assays and identified NSC56612 from the National Cancer Institute's (NCI) Open Chemical Repository Collection as an inhibitor of activated CXCR4. Next, we identified that NSC56612 is structurally similar to the established anti-malarial drugs chloroquine and hydroxychloroquine. We evaluated these compounds in pancreatic cancer cells in vitro and observed specific antagonism of CXCR4-mediated signaling and cell proliferation. Recent in vivo therapeutic applications of chloroquine in pancreatic cancer mouse models have demonstrated decreased tumor growth and improved survival. Our results thus provide a molecular target and basis for further evaluation of chloroquine and hydroxychloroquine in pancreatic cancer. Historically safe in humans, chloroquine and hydroxychloroquine appear to be promising agents to safely and effectively target CXCR4 in patients with pancreatic cancer. PMID:22319600

Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems.

PubMed Central

Dietz, V.; Galazka, A.; van Loon, F.; Cochi, S.

1997-01-01

An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989 WHO adopted the goal of eliminating NT as a public health problem worldwide. To achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that newborns be passively protected at birth by the antepartum administration of at least two doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP) vaccine. For this strategy to be effective, the TT used must be immunogenic. Potential factors that may affect TT immunogenicity need to be evaluated if NT is to be eliminated and if non-NT is to be controlled. Although data are conflicting, concurrent malarial infection may decrease the immune response to TT; however, malarial chemoprophylaxis may enhance the immune response. Malnutrition does not appear to affect immunogenicity; nevertheless, one study suggests that vitamin A deficiency is associated with an impaired immune response. Although it has been postulated that placental transfer of tetanus antibody is impaired in African women, a survey of the published literature suggests that this is not the case. Freezing TT has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation. PMID:9141753

The end of a dogma: the safety of doxycycline use in young children for malaria treatment.

PubMed

Gaillard, Tiphaine; Briolant, Sébastien; Madamet, Marylin; Pradines, Bruno

2017-04-13

Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.

PCR diagnostics underestimate the prevalence of avian malaria (Plasmodium relictum) in experimentally-infected passerines

USGS Publications Warehouse

Jarvi, Susan I.; Schultz, Jeffrey J.; Atkinson, Carter T.

2002-01-01

Several polymerase chain reaction (PCR)-based methods have recently been developed for diagnosing malarial infections in both birds and reptiles, but a critical evaluation of their sensitivity in experimentally-infected hosts has not been done. This study compares the sensitivity of several PCR-based methods for diagnosing avian malaria (Plasmodium relictum) in captive Hawaiian honeycreepers using microscopy and a recently developed immunoblotting technique. Sequential blood samples were collected over periods of up to 4.4 yr after experimental infection and rechallenge to determine both the duration and detectability of chronic infections. Two new nested PCR approaches for detecting circulating parasites based on P. relictum 18S rRNA genes and the thrombospondin-related anonymous protein (TRAP) gene are described. The blood smear and the PCR tests were less sensitive than serological methods for detecting chronic malarial infections. Individually, none of the diagnostic methods was 100% accurate in detecting subpatent infections, although serological methods were significantly more sensitive (97%) than either nested PCR (61–84%) or microscopy (27%). Circulating parasites in chronically infected birds either disappear completely from circulation or to drop to intensities below detectability by nested PCR. Thus, the use of PCR as a sole means of detection of circulating parasites may significantly underestimate true prevalence.

Pathogenicity, serological responses, and diagnosis of experimental and natural malarial infections in native Hawaiian thrushes

USGS Publications Warehouse

Atkinson, C.T.; Lease, J.K.; Drake, B.M.; Shema, N.P.

2001-01-01

Omao (Myadestes obscurus) from the Hawaiian Islands typically have very low prevalences of infection with avian malaria (Plasmodium relictum) and it is not clear whether they share the same high susceptibility to this parasite that has been documented in native Hawaiian honeycreepers. We exposed four captive Omao to single infective mosquito bites and measured parasitemia, serological responses, and mortality over time. All four birds experienced transient infections with low parasitemias and were immune when rechallenged with multiple infective mosquito bites. By contrast, three of four honeycreepers (Maui Alauahio, Paroreomyza montana) that were exposed to the same dose and parasite isolate succumbed to infection. All four Omao developed antibodies to a common suite of malarial antigens that were detectable on immunoblots of a crude red blood cell extract of P. relictum. We used this technique to screen plasma samples from wild Omao and endangered Puaiohi (Myadestes palmeri) that were captured at elevations between 900 and 1300 m on the islands of Hawaii and Kauai. We found that the true prevalence of infection at elevations where active malaria transmission occurs is much higher than estimates based on blood smears alone. Hawaiian thrushes appear to have a high tolerance for malaria, with most individuals developing chronic, low-level infections after exposure that cannot be diagnosed accurately by blood smears.

Bioavailability enhancement of atovaquone using hot melt extrusion technology.

PubMed

Kate, Laxman; Gokarna, Vinod; Borhade, Vivek; Prabhu, Priyanka; Deshpande, Vinita; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

2016-04-30

Emerging parasite resistance and poor oral bioavailability of anti-malarials are the two cardinal issues which hinder the clinical success of malaria chemotherapy. Atovaquone-Proguanil is a WHO approved fixed dose combination used to tackle the problem of emerging resistance. However, Atovaquone is a highly lipophilic drug having poor aqueous solubility (less than 0.2 μg/ml) thus reducing its oral bioavailability. The aim of the present investigation was to explore hot melt extrusion (HME) as a solvent-free technique to enhance solubility and oral bioavailability of Atovaquone and to develop an oral dosage form for Atovaquone-Proguanil combination. Solid dispersion of Atovaquone was successfully developed using HME. The solid dispersion was characterized for DSC, FTIR, XRD, SEM, and flow properties. It was filled in size 2 hard gelatin capsules. The formulation showed better release as compared to Malarone® tablets, and 3.2-fold and 4.6-fold higher bioavailability as compared to Malarone® tablets and Atovaquone respectively. The enhanced bioavailability also resulted in 100% anti-malarial activity in murine infection model at 1/8(th) therapeutic dose. Thus the developed methodology shows promising potential to solve the problems associated with Atovaquone therapy, namely its high cost and poor oral bioavailability, resulting in increased therapeutic efficacy of Atovaquone. Copyright © 2016 Elsevier B.V. All rights reserved.

Geophagy: soil consumption enhances the bioactivities of plants eaten by chimpanzees

NASA Astrophysics Data System (ADS)

Klein, Noémie; Fröhlich, François; Krief, Sabrina

2008-04-01

Geophagy, the deliberate ingestion of soil, is a widespread practice among animals, including humans. Although some cases are well documented, motivations and consequences of this practice on the health status of the consumer remain unclear. In this paper, we focused our study on chimpanzees ( Pan troglodytes schweinfurthii) of the Kibale National Park, Uganda, after observing they sometimes ingest soil shortly before or after consuming some plant parts such as leaves of Trichilia rubescens, which have in vitro anti-malarial properties. Chemical and mineralogical analyses of soil eaten by chimpanzees and soil used by the local healer to treat diarrhoea revealed similar composition, the clay mineralogy being dominated by kaolinite. We modelled the interaction between samples of the two types of soil and the leaves of T. rubescens in gastric and intestinal compartments and assayed the anti-malarial properties of these solutions. Results obtained for both soil samples are similar and support the hypothesis that soil enhances the pharmacological properties of the bio-available gastric fraction. The adaptive function of geophagy is likely to be multi-factorial. Nevertheless, the medical literature and most of occidental people usually consider geophagy in humans as an aberrant behaviour, symptomatic of metabolic dysfunction. Our results provide a new evidence to view geophagy as a practice for maintaining health, explaining its persistence through evolution.

Synthesis, in vitro and in silico antimalarial activity of 7-chloroquinoline and 4H-chromene conjugates.

PubMed

Parthiban, A; Muthukumaran, J; Manhas, Ashan; Srivastava, Kumkum; Krishna, R; Rao, H Surya Prakash

2015-10-15

A new series of chloroquinoline-4H-chromene conjugates incorporating piperizine or azipane tethers were synthesized and their anti-malarial activity were evaluated against two Plasmodium falciparum strains namely 3D7 chloroquine sensitive (CQS) and K1 chloroquine resistant (CQR). Chloroquine was used as the standard and also reference for comparison. The conjugates exhibit intense UV absorption with λmax located at 342 nm (log ε=4.0), 254 nm (log ε=4.2), 223 nm (log ε=4.4) which can be used to spectrometrically track the molecules even in trace amounts. Among all the synthetic compounds, two molecules namely 6-nitro and N-piperazine groups incorporated 7d and 6-chloro and N-azapane incorporated 15b chloroquinoline-4H-chromene conjugates showed significant anti-malarial activity against two strains (3D7 and K1) of P. falciparum. These values are lesser than the values of standard antimalarial compound. Molecular docking results suggested that these two compounds showing strong binding affinity with P. falciparum lactate dehydrogenase (PfLDH) and also they occupy the co-factor position which indicated that they could be the potent inhibitors for dreadful disease malaria and specifically attack the glycolytic pathway in parasite for energy production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Malaria notifications in the Australian Defence Force from 1998 to 2007.

PubMed

Elmes, Nathan J

2010-06-01

We report here a retrospective analysis of all malaria cases in military personnel reported to the Australian Defence Force (ADF) Central Malaria Register from 1998 to 2007. A total of 637 cases of malaria were notified affecting 487 individuals. Of these 85.9% (547) were infected with Plasmodium vivax malaria and 10.2% (65) with P. falciparum malaria. The majority of cases were from Timor Leste (78.5%, 501/637). Malaria attack rates of 0.9% (369/40 571), 1.1% (52/4776) and 0.4% (20/5345) were seen in Timor Leste, Bougainville and the Solomon Islands, respectively. The median period following departure from a malarious country to presentation of P. falciparum was 17 d (range 1-47 d) and for a primary presentation of P. vivax malaria was 86 d (range 1-505 d). Increasing the dose of primaquine from 22.5 mg daily to 30 mg daily for 14 d for radical cure of P. vivax malaria reduced the failure rate from 46.6% (35/75) to 9.4% (17/181) in subjects returning from Timor Leste. Malaria remains a serious problem for ADF soldiers deploying to malarious areas, particularly the incidence of relapsing vivax malaria and the tolerance of these vivax strains to primaquine.

Simultaneous capture and sequential detection of two malarial biomarkers on magnetic microparticles.

PubMed

Markwalter, Christine F; Ricks, Keersten M; Bitting, Anna L; Mudenda, Lwiindi; Wright, David W

2016-12-01

We have developed a rapid magnetic microparticle-based detection strategy for malarial biomarkers Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein II (PfHRPII). In this assay, magnetic particles functionalized with antibodies specific for pLDH and PfHRPII as well as detection antibodies with distinct enzymes for each biomarker are added to parasitized lysed blood samples. Sandwich complexes for pLDH and PfHRPII form on the surface of the magnetic beads, which are washed and sequentially re-suspended in detection enzyme substrate for each antigen. The developed simultaneous capture and sequential detection (SCSD) assay detects both biomarkers in samples as low as 2.0parasites/µl, an order of magnitude below commercially available ELISA kits, has a total incubation time of 35min, and was found to be reproducible between users over time. This assay provides a simple and efficient alternative to traditional 96-well plate ELISAs, which take 5-8h to complete and are limited to one analyte. Further, the modularity of the magnetic bead-based SCSD ELISA format could serve as a platform for application to other diseases for which multi-biomarker detection is advantageous. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Potential impact of global climate change on malaria risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martens, W.J.M.; Rotmans, J.; Niessen, L.W.

The biological activity and geographic distribution of the malarial parasite and its vector are sensitive to climatic influences, especially temperature and precipitation. We have incorporated General Circulation Model-based scenarios of anthropogenic global climate change in an integrated linked-system model for predicting changes in malaria epidemic potential in the next century. The concept of the disability-adjusted life years is included to arrive at a single measure of the effect of anthropogenic climate change on the health impact of malaria. Assessment of the potential impact of global climate change on the incidence of malaria suggests a widespread increase of risk due tomore » expansion of the areas suitable for malaria transmission. This predicted increase is most pronounced at the borders of endemic malaria areas and at higher altitudes within malarial areas. The incidence of infection is sensitive to climate changes in areas of Southeast Asia, South America, and parts of Africa where the disease is less endemic; in these regions the numbers of years of healthy life lost may increase significantly. However, the simulated changes in malaria risk must be interpreted on the basis of local environmental conditions, the effects of socioeconomic developments, and malaria control programs or capabilities. 33 refs., 5 figs., 1 tab.« less

Automated Detection of Malarial Retinopathy in Digital Fundus Images for Improved Diagnosis in Malawian Children with Clinically Defined Cerebral Malaria

NASA Astrophysics Data System (ADS)

Joshi, Vinayak; Agurto, Carla; Barriga, Simon; Nemeth, Sheila; Soliz, Peter; MacCormick, Ian J.; Lewallen, Susan; Taylor, Terrie E.; Harding, Simon P.

2017-02-01

Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages. The individual lesion detection algorithms were combined using a partial least square classifier to determine the presence or absence of MR. We used a retrospective retinal image dataset of 86 pediatric patients with clinically defined CM (70 with MR and 16 without) to evaluate the algorithm performance. Our goal was to reduce the false positive rate of CM diagnosis, and so the algorithms were tuned at high specificity. This yielded sensitivity/specificity of 95%/100% for the detection of MR overall, and 65%/94% for retinal whitening, 62%/100% for vessel discoloration, and 73%/96% for hemorrhages. This automated system for detecting MR using retinal color images has the potential to improve the accuracy of CM diagnosis.

Initiating malaria control programs in the third world: directives for short- and long-term solutions.

PubMed

Basu, Sanjay

2002-01-01

Although malaria is a growing problem affecting several hundred million people each year, many malarial countries lack successful disease control programs. Worldwide malaria incidence rates are dramatically increasing, generating fear among many people who are witnessing malaria control initiatives fail. In this paper, we explore two options for malaria control in poor countries: (1) the production and distribution of a malaria vaccine and (2) the control of mosquitoes that harbor the malaria parasite. We first demonstrate that the development of a malaria vaccine is indeed likely, although it will take several years to produce because of both biological obstacles and insufficient research support. The distribution of such a vaccine, as suggested by some economists, will require that wealthy states promise a market to pharmaceutical companies who have traditionally failed to investigate diseases affecting the poorest of nations. But prior to the development of a malaria vaccine, we recommend the implementation of vector control pro- grams, such as those using Bti toxin, in regions with low vector capacity. Our analysis indicates that both endogenous programs in malarial regions and molecular approaches to parasite control will provide pragmatic solutions to the malaria problem. But the successful control of malaria will require sustained support from wealthy nations, without whom vaccine development and vector control programs will likely fail.

Getting it right when budgets are tight: Using optimal expansion pathways to prioritize responses to concentrated and mixed HIV epidemics.

PubMed

Stuart, Robyn M; Kerr, Cliff C; Haghparast-Bidgoli, Hassan; Estill, Janne; Grobicki, Laura; Baranczuk, Zofia; Prieto, Lorena; Montañez, Vilma; Reporter, Iyanoosh; Gray, Richard T; Skordis-Worrall, Jolene; Keiser, Olivia; Cheikh, Nejma; Boonto, Krittayawan; Osornprasop, Sutayut; Lavadenz, Fernando; Benedikt, Clemens J; Martin-Hughes, Rowan; Hussain, S Azfar; Kelly, Sherrie L; Kedziora, David J; Wilson, David P

2017-01-01

Prioritizing investments across health interventions is complicated by the nonlinear relationship between intervention coverage and epidemiological outcomes. It can be difficult for countries to know which interventions to prioritize for greatest epidemiological impact, particularly when budgets are uncertain. We examined four case studies of HIV epidemics in diverse settings, each with different characteristics. These case studies were based on public data available for Belarus, Peru, Togo, and Myanmar. The Optima HIV model and software package was used to estimate the optimal distribution of resources across interventions associated with a range of budget envelopes. We constructed "investment staircases", a useful tool for understanding investment priorities. These were used to estimate the best attainable cost-effectiveness of the response at each investment level. We find that when budgets are very limited, the optimal HIV response consists of a smaller number of 'core' interventions. As budgets increase, those core interventions should first be scaled up, and then new interventions introduced. We estimate that the cost-effectiveness of HIV programming decreases as investment levels increase, but that the overall cost-effectiveness remains below GDP per capita. It is important for HIV programming to respond effectively to the overall level of funding availability. The analytic tools presented here can help to guide program planners understand the most cost-effective HIV responses and plan for an uncertain future.

Global Health: Pediatric Neurology.

PubMed

Bearden, David R; Ciccone, Ornella; Patel, Archana A

2018-04-01

Neurologic disorders contribute significantly to both morbidity and mortality among children in resource-limited settings, but there are a few succinct studies summarizing the epidemiology of neurologic disorders in these settings. A review of available literature was performed to identify data on the prevalence, etiology, outcomes, and treatment of neurologic disorders in children in resource-limited settings. The burden of neurologic disorders in children is high in resource-limited settings. Barriers to optimal care include lack of trained personnel, limited access to diagnostic technology, and limited availability of drugs used to treat common conditions. Several solutions have been suggested to deal with these challenges including increased collaborations to train neurologists willing to practice in resource-limited settings and increased training of physician extenders or community health workers. Further studies are necessary to improve our understanding of the epidemiology of neurologic disorders in resource-limited settings. Future epidemiologic studies should incorporate multiple countries in resource-limited settings and utilize standardized definitions and methodologies to enable comparison across regions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Influenza in the Asia-Pacific region: Findings and recommendations from the Global Influenza Initiative.

PubMed

Cowling, Benjamin J; Caini, Saverio; Chotpitayasunondh, Tawee; Djauzi, Samsuridjal; Gatchalian, Salvacion R; Huang, Q Sue; Koul, Parvaiz A; Lee, Ping-Ing; Muttalif, Abdul Razak; Plotkin, Stanley

2017-02-07

The fourth roundtable meeting of the Global Influenza Initiative (GII) was held in Hong Kong, China, in July 2015. An objective of this meeting was to gain a broader understanding of the epidemiology, surveillance, vaccination policies and programs, and obstacles to vaccination of influenza in the Asia-Pacific region through presentations of data from Australia, Hong Kong, India, Indonesia, Malaysia, New Zealand, the Philippines, Taiwan, Thailand, and Vietnam. As well as a need for improved levels of surveillance in some areas, a range of factors were identified that act as barriers to vaccination in some countries, including differences in climate and geography, logistical challenges, funding, lack of vaccine awareness and education, safety concerns, perceived lack of vaccine effectiveness, and lack of inclusion in national guidelines. From the presentations at the meeting, the GII discussed a number of recommendations for easing the burden of influenza and overcoming the current challenges in the Asia-Pacific region. These recommendations encompass the need to improve surveillance and availability of epidemiological data; the development and publication of national guidelines, where not currently available and/or that are in line with those proposed by the World Health Organization; the requirement for optimal timing of vaccination programs according to local or country-specific epidemiology; and calls for advocacy and government support of vaccination programs in order to improve availability and uptake and coverage. In conclusion, in addition to the varied epidemiology of seasonal influenza across this diverse region, there are a number of logistical and resourcing issues that present a challenge to the development of optimally effective vaccination strategies and that need to be overcome to improve access to and uptake of seasonal influenza vaccines. The GII has developed a number of recommendations to address these challenges and improve the control of influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cost-effective control of plant disease when epidemiological knowledge is incomplete: modelling Bahia bark scaling of citrus.

PubMed

Cunniffe, Nik J; Laranjeira, Francisco F; Neri, Franco M; DeSimone, R Erik; Gilligan, Christopher A

2014-08-01

A spatially-explicit, stochastic model is developed for Bahia bark scaling, a threat to citrus production in north-eastern Brazil, and is used to assess epidemiological principles underlying the cost-effectiveness of disease control strategies. The model is fitted via Markov chain Monte Carlo with data augmentation to snapshots of disease spread derived from a previously-reported multi-year experiment. Goodness-of-fit tests strongly supported the fit of the model, even though the detailed etiology of the disease is unknown and was not explicitly included in the model. Key epidemiological parameters including the infection rate, incubation period and scale of dispersal are estimated from the spread data. This allows us to scale-up the experimental results to predict the effect of the level of initial inoculum on disease progression in a typically-sized citrus grove. The efficacies of two cultural control measures are assessed: altering the spacing of host plants, and roguing symptomatic trees. Reducing planting density can slow disease spread significantly if the distance between hosts is sufficiently large. However, low density groves have fewer plants per hectare. The optimum density of productive plants is therefore recovered at an intermediate host spacing. Roguing, even when detection of symptomatic plants is imperfect, can lead to very effective control. However, scouting for disease symptoms incurs a cost. We use the model to balance the cost of scouting against the number of plants lost to disease, and show how to determine a roguing schedule that optimises profit. The trade-offs underlying the two optima we identify-the optimal host spacing and the optimal roguing schedule-are applicable to many pathosystems. Our work demonstrates how a carefully parameterised mathematical model can be used to find these optima. It also illustrates how mathematical models can be used in even this most challenging of situations in which the underlying epidemiology is ill-understood.

SIS epidemiological model for adaptive RT: Forecasting the parotid glands shrinkage during tomotherapy treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maffei, Nicola; Guidi, Gabriele, E-mail: guidi.gab

Purpose: A susceptible-infected-susceptible (SIS) epidemic model was applied to radiation therapy (RT) treatments to predict morphological variations in head and neck (H&N) anatomy. Methods: 360 daily MVCT images of 12 H&N patients treated by tomotherapy were analyzed in this retrospective study. Deformable image registration (DIR) algorithms, mesh grids, and structure recontouring, implemented in the RayStation treatment planning system (TPS), were applied to assess the daily organ warping. The parotid’s warping was evaluated using the epidemiological approach considering each vertex as a single subject and its deformed vector field (DVF) as an infection. Dedicated IronPython scripts were developed to export dailymore » coordinates and displacements of the region of interest (ROI) from the TPS. MATLAB tools were implemented to simulate the SIS modeling. Finally, the fully trained model was applied to a new patient. Results: A QUASAR phantom was used to validate the model. The patients’ validation was obtained setting 0.4 cm of vertex displacement as threshold and splitting susceptible (S) and infectious (I) cases. The correlation between the epidemiological model and the parotids’ trend for further optimization of alpha and beta was carried out by Euclidean and dynamic time warping (DTW) distances. The best fit with experimental conditions across all patients (Euclidean distance of 4.09 ± 1.12 and DTW distance of 2.39 ± 0.66) was obtained setting the contact rate at 7.55 ± 0.69 and the recovery rate at 2.45 ± 0.26; birth rate was disregarded in this constant population. Conclusions: Combining an epidemiological model with adaptive RT (ART), the authors’ novel approach could support image-guided radiation therapy (IGRT) to validate daily setup and to forecast anatomical variations. The SIS-ART model developed could support clinical decisions in order to optimize timing of replanning achieving personalized treatments.« less

[Clinical economics: a concept to optimize healthcare services].

PubMed

Porzsolt, F; Bauer, K; Henne-Bruns, D

2012-03-01

Clinical economics strives to support healthcare decisions by economic considerations. Making economic decisions does not mean saving costs but rather comparing the gained added value with the burden which has to be accepted. The necessary rules are offered in various disciplines, such as economy, epidemiology and ethics. Medical doctors have recognized these rules but are not applying them in daily clinical practice. This lacking orientation leads to preventable errors. Examples of these errors are shown for diagnosis, screening, prognosis and therapy. As these errors can be prevented by application of clinical economic principles the possible consequences for optimization of healthcare are discussed.

Size and sequence polymorphisms in the glutamate-rich protein gene of the human malaria parasite Plasmodium falciparum in Thailand.

PubMed

Pattaradilokrat, Sittiporn; Trakoolsoontorn, Chawinya; Simpalipan, Phumin; Warrit, Natapot; Kaewthamasorn, Morakot; Harnyuttanakorn, Pongchai

2018-01-22

The glutamate-rich protein (GLURP) of the malaria parasite Plasmodium falciparum is a key surface antigen that serves as a component of a clinical vaccine. Moreover, the GLURP gene is also employed routinely as a genetic marker for malarial genotyping in epidemiological studies. While extensive size polymorphisms in GLURP are well recorded, the extent of the sequence diversity of this gene is rarely investigated. The present study aimed to explore the genetic diversity of GLURP in natural populations of P. falciparum. The polymorphic C-terminal repetitive R2 region of GLURP sequences from 65 P. falciparum isolates in Thailand were generated and combined with the data from 103 worldwide isolates to generate a GLURP database. The collection was comprised of 168 alleles, encoding 105 unique GLURP subtypes, characterized by 18 types of amino acid repeat units (AAU). Of these, 28 GLURP subtypes, formed by 10 AAU types, were detected in P. falciparum in Thailand. Among them, 19 GLURP subtypes and 2 AAU types are described for the first time in the Thai parasite population. The AAU sequences were highly conserved, which is likely due to negative selection. Standard Fst analysis revealed the shared distributions of GLURP types among the P. falciparum populations, providing evidence of gene flow among the different demographic populations. Sequence diversity causing size variations in GLURP in Thai P. falciparum populations were detected, and caused by non-synonymous substitutions in repeat units and some insertion/deletion of aspartic acid or glutamic acid codons between repeat units. The P. falciparum population structure based on GLURP showed promising implications for the development of GLURP-based vaccines and for monitoring vaccine efficacy.

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

Use of Antimalarial in the Management of Fever during a Community Survey in the Kintampo Districts of Ghana.

PubMed

Abokyi, Livesy Naafoe; Asante, Kwaku Poku; Mahama, Emmanuel; Gyaase, Stephaney; Sulemana, Abubakari; Kwarteng, Anthony; Ayaam, Jennifer; Dosoo, David; Adu-Gyasi, Dennis; Amenga Etego, Seeba; Ogutu, Bernhards; Akweongo, Patricia; Owusu-Agyei, Seth

2015-01-01

Epidemiology of malaria and related fevers in most parts of Africa is changing due to scale up of interventions such as appropriate use of ACTs in the effort towards sustained control and eventual elimination of malaria. The use of ACTs in the management of malaria-associated fever was evaluated in the Kintampo districts of Ghana. Household survey was conducted between October 2009 and February, 2011. A random selection of 370 households was generated from 25,000 households existing within the Health and Demographic Surveillance Systems in Kintampo, Ghana at the time. All household members present at the time of survey in the eligible households were interviewed based on a two weeks reported fever recall and the use of antimalarial for the management of fever. A finger-prick blood sample was also obtained from each member of the household present and later examined for malaria parasites using microscopy. Descriptive analysis was performed, with univariate and multivariate analysis used to identify predictors of fever and malaria parasitemia. A total of 1436 individuals were interviewed from 370 households. Overall, fever prevalence was 23.8% (341/1436) and was 38.8% (77/198) in children < 5 years, 21.3% (264/1238) in older children plus adults. Participants who sought treatment for fever were 84% (285/341) with 47.7% (136/285) using any anti-malarial. Artemisinin-based Combination Therapy use was in 69.1% (94/136) of cases while 30.9% used mono-therapies. Malaria parasitaemia rate was 28.2% (397/1407). The study reports high community fever prevalence, frequent use of antimalarials for fever treatment and relatively high use of mono-therapies especially in children < 5 years in an area with high malaria parasite prevalence in Ghana.

Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria

PubMed Central

Fry, Andrew E.; Griffiths, Michael J.; Auburn, Sarah; Diakite, Mahamadou; Forton, Julian T.; Green, Angela; Richardson, Anna; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Peshu, Norbert; Williams, Thomas N.; Marsh, Kevin; Molyneux, Malcolm E.; Taylor, Terrie E.; Rockett, Kirk A.; Kwiatkowski, Dominic P.

2009-01-01

There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across 3 African populations. Using population- and family-based tests we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: Case-control allelic odds ratio (OR) 1.2, 95% confidence interval (CI) 1.09 – 1.32, P=0.0003; Family-studies allelic OR 1.19, CI 1.08 – 1.32, P=0.001; Pooled across all studies allelic OR 1.18, CI 1.11 - 1.26, P=2×10−7. Analyzing the family trios we found suggestive evidence of a parent-of-origin effect at the ABO locus. Non-O haplotypes inherited from mothers, but not fathers, are significantly associated with severe malaria (likelihood ratio test of Weinberg, P=0.046). Finally we used HapMap data to demonstrate a region of low FST (−0.001) between the three main HapMap population groups across the ABO locus, an outlier in the empirical distribution of FST across chromosome 9 (~99.5 – 99.9th centile). This low FST region may be a signal of longstanding balancing selection at the ABO locus, caused by multiple infectious pathogens including P. falciparum. PMID:18003641

PCR/RFLP-based analysis of genetically distinct Plasmodium vivax population of Pvmsp-3α and Pvmsp-3β genes in Pakistan.

PubMed

Khan, Shahid Niaz; Khan, Asif; Khan, Sanaullah; Ayaz, Sultan; Attaullah, Sobia; Khan, Jabbar; Khan, Muhammad Asim; Ali, Ijaz; Shah, Abdul Haleem

2014-09-09

Plasmodium vivax is one of the widespread human malarial parasites accounting for 75% of malaria epidemics. However, there is no baseline information about the status and nature of genetic variation of Plasmodium species circulating in various parts of Pakistan. The present study was aimed at observing the molecular epidemiology and genetic variation of Plasmodium vivax by analysing its merozoite surface protein-3α (msp-3α) and merozoite surface protein-3β (msp-3β) genes, by using suballele, species-specific, combined nested PCR/RFLP detection techniques. A total of 230 blood samples from suspected subjects tested slide positive for vivax malaria were collected from Punjab, Sindh, Khyber Pakhtunkhwa, and Balochistan during the period May 2012 to December 2013. Combined nested PCR/RFLP technique was conducted using Pvmsp-3α and Pvmsp-3β genetic markers to detect extent of genetic variation in clinical isolates of P. vivax in the studied areas of Pakistan. By PCR, P. vivax, 202/230 (87.82%), was found to be widely distributed in the studied areas. PCR/RFLP analysis showed a high range of allelic variations for both msp-3α and msp-3β genetic markers of P. vivax, i.e., 21 alleles for msp-3α and 19 for msp-3β. Statistically a significant difference (p ≤ 0.05) was observed in the genetic diversity of the suballelic variants of msp-3α and msp-3β genes of P. vivax. It is concluded that P. vivax populations are highly polymorphic and diverse allelic variants of Pvmsp-3α and Pvmsp-3β are present in Pakistan.

Potency assay design for adjuvanted recombinant proteins as malaria vaccines.

PubMed

Giersing, Birgitte K; Dubovsky, Filip; Saul, Allan; Denamur, Francoise; Minor, Philip; Meade, Bruce

2006-05-15

Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modern vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development.

A longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural Tanzania.

PubMed

Simmons, Ryan A; Mboera, Leonard; Miranda, Marie Lynn; Morris, Alison; Stresman, Gillian; Turner, Elizabeth L; Kramer, Randall; Drakeley, Chris; O'Meara, Wendy P

2017-08-02

Measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses. The occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time. While the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event. While the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes.

Policy analysis for deciding on a malaria vaccine RTS,S in Tanzania.

PubMed

Romore, Idda; Njau, Ritha J A; Semali, Innocent; Mwisongo, Aziza; Ba Nguz, Antoinette; Mshinda, Hassan; Tanner, Marcel; Abdulla, Salim

2016-03-08

Traditionally, it has taken decades to introduce new interventions in low-income countries. Several factors account for these delays, one of which is the absence of a framework to facilitate comprehensive understanding of policy process to inform policy makers and stimulate the decision-making process. In the case of the proposed introduction of malaria vaccines in Tanzania, a specific framework for decision-making will speed up the administrative process and shorten the time until the vaccine is made available to the target population. Qualitative research was used as a basis for developing the Policy Framework. Interviews were conducted with government officials, bilateral and multilateral partners and other stakeholders in Tanzania to assess malaria treatment policy changes and to draw lessons for malaria vaccine adoption. The decision-making process for adopting malaria interventions and new vaccines in general takes years, involving several processes: meetings and presentations of scientific data from different studies with consistent results, packaging and disseminating evidence and getting approval for use by the Ministry of Health and Social Welfare (MOHSW). It is influenced by contextual factors; Promoting factors include; epidemiological and intervention characteristics, country experiences of malaria treatment policy change, presentation and dissemination of evidence, coordination and harmonization of the process, use of international scientific evidence. Barriers factors includes; financial sustainability, competing health and other priorities, political will and bureaucratic procedures, costs related to the adoption and implementations of interventions, supply and distribution and professional compliance with anti-malarial drugs. The framework facilitates the synthesis of information in a coherent way, enabling a clearer understanding of the policy process, thereby speeding up the policy decision-making process and shortening the time for a malaria vaccine to become available.

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.

A Course in Air Force Logistics History Since 1940

DTIC Science & Technology

1984-09-01

malarial procedures: long pants and sleeve-, repellents , sleeping under mosquito nets, takirg quinine or atabrine 48 --- Medical services heavily tasked...logistics forms a coequal triumvirate with strategy and tactics, recommend that students be given an overview course in strategic and tactical...Lesson 2: Overview of AF logistics history before WW II and beginning WW II. Lesson 3: WW II. Lesson 4: WW II. Lesson 5: WW II. 18 Lesson 6: Between WW

Reversibility of Retinal Microvascular Changes in Severe Falciparum Malaria

PubMed Central

Maude, Richard J.; Kingston, Hugh W. F.; Joshi, Sonia; Mohanty, Sanjib; Mishra, Saroj K.; White, Nicholas J.; Dondorp, Arjen M.

2014-01-01

Malarial retinopathy allows detailed study of central nervous system vascular pathology in living patients with severe malaria. An adult with cerebral malaria is described who had prominent retinal whitening with corresponding retinal microvascular obstruction, vessel dilatation, increased vascular tortuosity, and blood retinal barrier leakage with decreased visual acuity, all of which resolved on recovery. Additional study of these features and their potential role in elucidating the pathogenesis of cerebral malaria is warranted. PMID:24935949

Is the Optimal Level of Protein Intake for Older Adults Greater Than the Recommended Dietary Allowance?

PubMed Central

2013-01-01

Background. Protein is a macronutrient essential for growth, muscle function, immunity and overall tissue homeostasis. Suboptimal protein intake can significantly impact physical function and overall health in older adults. Methods. This article reviews the literature on the recommendations for protein intake in older adults in light of the new evidence linking protein intake with sarcopenia and physical function. Challenges and opportunities for optimal protein nutrition in older persons are discussed. Results. Recent metabolic and epidemiological studies suggest that the current recommendations of protein intake may not be adequate for maintenance of physical function and optimal health in older adults. Methodological limitations and novel concepts in protein nutrition are also discussed. Conclusion. We conclude that new research and novel research methodologies are necessary to establish the protein needs and optimal patterns of protein intake for older persons. PMID:23183903

Optimal control of vaccination rate in an epidemiological model of Clostridium difficile transmission.

PubMed

Stephenson, Brittany; Lanzas, Cristina; Lenhart, Suzanne; Day, Judy

2017-12-01

The spore-forming, gram-negative bacteria Clostridium difficile can cause severe intestinal illness. A striking increase in the number of cases of C. difficile infection (CDI) among hospitals has highlighted the need to better understand how to prevent the spread of CDI. In our paper, we modify and update a compartmental model of nosocomial C. difficile transmission to include vaccination. We then apply optimal control theory to determine the time-varying optimal vaccination rate that minimizes a combination of disease prevalence and spread in the hospital population as well as cost, in terms of time and money, associated with vaccination. Various hospital scenarios are considered, such as times of increased antibiotic prescription rate and times of outbreak, to see how such scenarios modify the optimal vaccination rate. By comparing the values of the objective functional with constant vaccination rates to those with time-varying optimal vaccination rates, we illustrate the benefits of time-varying controls.

Molecular Epidemiology of Pulmonary Tuberculosis in Belgrade, Central Serbia

PubMed Central

Vuković, Dragana; Rüsch-Gerdes, Sabine; Savić, Branislava; Niemann, Stefan

2003-01-01

In order to gain precise data on the actual epidemiology of tuberculosis (TB) in Belgrade, central Serbia, we conducted the molecular epidemiological investigation described herein. IS6110 restriction fragment length polymorphism (RFLP) typing of 176 Mycobacterium tuberculosis isolates was performed. These strains were obtained from 48.4% of all patients diagnosed with culture-proven pulmonary TB from April through September 1998 and from May through October 1999. Clusters containing strains with identical RFLP IS6110 patterns were assumed to have arisen from recent transmission. Of the 176 cases, 55 (31.2%) were grouped into 23 clusters ranging in size from two to six patients. Nearly 80% of clustered patients were directly interviewed, and transmission between family-unrelated contacts was found to be predominant in the study population. Classical contact investigation identified only 2 (3.6%) of the 55 clustered patients. The clustering of TB patients was not associated with any demographic or clinical characteristic other than infection with multidrug-resistant (MDR) M. tuberculosis strains. Nearly 70% of MDR strains were clustered, which indicates active transmission of MDR TB in Belgrade. However, this was not observed by conventional epidemiologic surveillance. In conclusion, the first molecular epidemiologic analysis of TB in the region revealed frequent recent transmission of TB and pointed out significant shortcomings of the current concept for conventional contact tracing. The results presented also demonstrate that transmission of MDR TB in Belgrade is not optimally controlled, and they provide support for the development of improved control strategies, including application of molecular methods. PMID:12958271

A simplified method of performance indicators development for epidemiological surveillance networks--application to the RESAPATH surveillance network.

PubMed

Sorbe, A; Chazel, M; Gay, E; Haenni, M; Madec, J-Y; Hendrikx, P

2011-06-01

Develop and calculate performance indicators allows to continuously follow the operation of an epidemiological surveillance network. This is an internal evaluation method, implemented by the coordinators in collaboration with all the actors of the network. Its purpose is to detect weak points in order to optimize management. A method for the development of performance indicators of epidemiological surveillance networks was developed in 2004 and was applied to several networks. Its implementation requires a thorough description of the network environment and all its activities to define priority indicators. Since this method is considered to be complex, our objective consisted in developing a simplified approach and applying it to an epidemiological surveillance network. We applied the initial method to a theoretical network model to obtain a list of generic indicators that can be adapted to any surveillance network. We obtained a list of 25 generic performance indicators, intended to be reformulated and described according to the specificities of each network. It was used to develop performance indicators for RESAPATH, an epidemiological surveillance network of antimicrobial resistance in pathogenic bacteria of animal origin in France. This application allowed us to validate the simplified method, its value in terms of practical implementation, and its level of user acceptance. Its ease of use and speed of application compared to the initial method argue in favor of its use on broader scale. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Optimal reconstruction of historical water supply to a distribution system: A. Methodology.

PubMed

Aral, M M; Guan, J; Maslia, M L; Sautner, J B; Gillig, R E; Reyes, J J; Williams, R C

2004-09-01

The New Jersey Department of Health and Senior Services (NJDHSS), with support from the Agency for Toxic Substances and Disease Registry (ATSDR) conducted an epidemiological study of childhood leukaemia and nervous system cancers that occurred in the period 1979 through 1996 in Dover Township, Ocean County, New Jersey. The epidemiological study explored a wide variety of possible risk factors, including environmental exposures. ATSDR and NJDHSS determined that completed human exposure pathways to groundwater contaminants occurred in the past through private and community water supplies (i.e. the water distribution system serving the area). To investigate this exposure, a model of the water distribution system was developed and calibrated through an extensive field investigation. The components of this water distribution system, such as number of pipes, number of tanks, and number of supply wells in the network, changed significantly over a 35-year period (1962--1996), the time frame established for the epidemiological study. Data on the historical management of this system was limited. Thus, it was necessary to investigate alternative ways to reconstruct the operation of the system and test the sensitivity of the system to various alternative operations. Manual reconstruction of the historical water supply to the system in order to provide this sensitivity analysis was time-consuming and labour intensive, given the complexity of the system and the time constraints imposed on the study. To address these issues, the problem was formulated as an optimization problem, where it was assumed that the water distribution system was operated in an optimum manner at all times to satisfy the constraints in the system. The solution to the optimization problem provided the historical water supply strategy in a consistent manner for each month of the study period. The non-uniqueness of the selected historical water supply strategy was addressed by the formulation of a second model, which was based on the first solution. Numerous other sensitivity analyses were also conducted using these two models. Both models are solved using a two-stage progressive optimality algorithm along with genetic algorithms (GAs) and the EPANET2 water distribution network solver. This process reduced the required solution time and generated a historically consistent water supply strategy for the water distribution system.

Market analyses of livestock trade networks to inform the prevention of joint economic and epidemiological risks.

PubMed

Moslonka-Lefebvre, Mathieu; Gilligan, Christopher A; Monod, Hervé; Belloc, Catherine; Ezanno, Pauline; Filipe, João A N; Vergu, Elisabeta

2016-03-01

Conventional epidemiological studies of infections spreading through trade networks, e.g., via livestock movements, generally show that central large-size holdings (hubs) should be preferentially surveyed and controlled in order to reduce epidemic spread. However, epidemiological strategies alone may not be economically optimal when costs of control are factored in together with risks of market disruption from targeting core holdings in a supply chain. Using extensive data on animal movements in supply chains for cattle and swine in France, we introduce a method to identify effective strategies for preventing outbreaks with limited budgets while minimizing the risk of market disruptions. Our method involves the categorization of holdings based on position along the supply chain and degree of market share. Our analyses suggest that trade has a higher risk of propagating epidemics through cattle networks, which are dominated by exchanges involving wholesalers, than for swine. We assess the effectiveness of contrasting interventions from the perspectives of regulators and the market, using percolation analysis. We show that preferentially targeting minor, non-central agents can outperform targeting of hubs when the costs to stakeholders and the risks of market disturbance are considered. Our study highlights the importance of assessing joint economic-epidemiological risks in networks underlying pathogen propagation and trade. © 2016 The Authors.

Market analyses of livestock trade networks to inform the prevention of joint economic and epidemiological risks

PubMed Central

Gilligan, Christopher A.; Belloc, Catherine; Filipe, João A. N.; Vergu, Elisabeta

2016-01-01

Conventional epidemiological studies of infections spreading through trade networks, e.g. via livestock movements, generally show that central large-size holdings (hubs) should be preferentially surveyed and controlled in order to reduce epidemic spread. However, epidemiological strategies alone may not be economically optimal when costs of control are factored in together with risks of market disruption from targeting core holdings in a supply chain. Using extensive data on animal movements in supply chains for cattle and swine in France, we introduce a method to identify effective strategies for preventing outbreaks with limited budgets while minimizing the risk of market disruptions. Our method involves the categorization of holdings based on position along the supply chain and degree of market share. Our analyses suggest that trade has a higher risk of propagating epidemics through cattle networks, which are dominated by exchanges involving wholesalers, than for swine. We assess the effectiveness of contrasting interventions from the perspectives of regulators and the market, using percolation analysis. We show that preferentially targeting minor, non-central agents can outperform targeting of hubs when the costs to stakeholders and the risks of market disturbance are considered. Our study highlights the importance of assessing joint economic–epidemiological risks in networks underlying pathogen propagation and trade. PMID:26984191

Current approaches used in epidemiologic studies to examine short-term multipollutant air pollution exposures.

PubMed

Davalos, Angel D; Luben, Thomas J; Herring, Amy H; Sacks, Jason D

2017-02-01

Air pollution epidemiology traditionally focuses on the relationship between individual air pollutants and health outcomes (e.g., mortality). To account for potential copollutant confounding, individual pollutant associations are often estimated by adjusting or controlling for other pollutants in the mixture. Recently, the need to characterize the relationship between health outcomes and the larger multipollutant mixture has been emphasized in an attempt to better protect public health and inform more sustainable air quality management decisions. New and innovative statistical methods to examine multipollutant exposures were identified through a broad literature search, with a specific focus on those statistical approaches currently used in epidemiologic studies of short-term exposures to criteria air pollutants (i.e., particulate matter, carbon monoxide, sulfur dioxide, nitrogen dioxide, and ozone). Five broad classes of statistical approaches were identified for examining associations between short-term multipollutant exposures and health outcomes, specifically additive main effects, effect measure modification, unsupervised dimension reduction, supervised dimension reduction, and nonparametric methods. These approaches are characterized including advantages and limitations in different epidemiologic scenarios. By highlighting the characteristics of various studies in which multipollutant statistical methods have been used, this review provides epidemiologists and biostatisticians with a resource to aid in the selection of the most optimal statistical method to use when examining multipollutant exposures. Published by Elsevier Inc.

Modeling urban air pollution with optimized hierarchical fuzzy inference system.

PubMed

Tashayo, Behnam; Alimohammadi, Abbas

2016-10-01

Environmental exposure assessments (EEA) and epidemiological studies require urban air pollution models with appropriate spatial and temporal resolutions. Uncertain available data and inflexible models can limit air pollution modeling techniques, particularly in under developing countries. This paper develops a hierarchical fuzzy inference system (HFIS) to model air pollution under different land use, transportation, and meteorological conditions. To improve performance, the system treats the issue as a large-scale and high-dimensional problem and develops the proposed model using a three-step approach. In the first step, a geospatial information system (GIS) and probabilistic methods are used to preprocess the data. In the second step, a hierarchical structure is generated based on the problem. In the third step, the accuracy and complexity of the model are simultaneously optimized with a multiple objective particle swarm optimization (MOPSO) algorithm. We examine the capabilities of the proposed model for predicting daily and annual mean PM2.5 and NO2 and compare the accuracy of the results with representative models from existing literature. The benefits provided by the model features, including probabilistic preprocessing, multi-objective optimization, and hierarchical structure, are precisely evaluated by comparing five different consecutive models in terms of accuracy and complexity criteria. Fivefold cross validation is used to assess the performance of the generated models. The respective average RMSEs and coefficients of determination (R (2)) for the test datasets using proposed model are as follows: daily PM2.5 = (8.13, 0.78), annual mean PM2.5 = (4.96, 0.80), daily NO2 = (5.63, 0.79), and annual mean NO2 = (2.89, 0.83). The obtained results demonstrate that the developed hierarchical fuzzy inference system can be utilized for modeling air pollution in EEA and epidemiological studies.

Computer-Aided Lead Optimization: Improved Small-Molecule Inhibitor of the Zinc Endopeptidase of Botulinum Neurotoxin Serotype A

DTIC Science & Technology

2007-08-01

doi:10.1371/journal.pone.0000761.s004 (1.33 MB TIF) ACKNOWLEDGMENTS The authors thank Steve Whiting and Seth Swaii for their assistance in preparing...clinical and epidemiologic review. Ann Intern Med 129: 221–228. 2. Kessler KR, Benecke R (1997) Botulinum toxin—from poison to remedy. Neurotoxicology 18

Standardizing Plasmodium falciparum infection prevalence measured via microscopy versus rapid diagnostic test.

PubMed

Mappin, Bonnie; Cameron, Ewan; Dalrymple, Ursula; Weiss, Daniel J; Bisanzio, Donal; Bhatt, Samir; Gething, Peter W

2015-11-17

Large-scale mapping of Plasmodium falciparum infection prevalence relies on opportunistic assemblies of infection prevalence data arising from thousands of P. falciparum parasite rate (PfPR) surveys conducted worldwide. Variance in these data is driven by both signal, the true underlying pattern of infection prevalence, and a range of factors contributing to 'noise', including sampling error, differing age ranges of subjects and differing parasite detection methods. Whilst the former two noise components have been addressed in previous studies, the effect of different diagnostic methods used to determine PfPR in different studies has not. In particular, the majority of PfPR data are based on positivity rates determined by either microscopy or rapid diagnostic test (RDT), yet these approaches are not equivalent; therefore a method is needed for standardizing RDT and microscopy-based prevalence estimates prior to use in mapping. Twenty-five recent Demographic and Health surveys (DHS) datasets from sub-Saharan Africa provide child diagnostic test results derived using both RDT and microscopy for each individual. These prevalence estimates were aggregated across level one administrative zones and a Bayesian probit regression model fit to the microscopy- versus RDT-derived prevalence relationship. An errors-in-variables approach was employed to account for sampling error in both the dependent and independent variables. In addition to the diagnostic outcome, RDT type, fever status and recent anti-malarial treatment were extracted from the datasets in order to analyse their effect on observed malaria prevalence. A strong non-linear relationship between the microscopy and RDT-derived prevalence was found. The results of regressions stratified by the additional diagnostic variables (RDT type, fever status and recent anti-malarial treatment) indicate that there is a distinct and consistent difference in the relationship when the data are stratified by febrile status and RDT brand. The relationships defined in this research can be applied to RDT-derived PfPR data to effectively convert them to an estimate of the parasite prevalence expected using microscopy (or vice versa), thereby standardizing the dataset and improving the signal-to-noise ratio. Additionally, the results provide insight on the importance of RDT brands, febrile status and recent anti-malarial treatment for explaining inconsistencies between observed prevalence derived from different diagnostics.

Evaluation of SMS reminder messages for altering treatment adherence and health seeking perceptions among malaria care-seekers in Nigeria.

PubMed

Liu, Jenny X; Modrek, Sepideh

2016-12-01

In Nigeria, access to malaria diagnostics may be expanded if drug retailers were allowed to administer malaria rapid diagnostic tests (RDTs). A 2012 pilot intervention showed that short message service (SMS) reminder messages could boost treatment adherence to RDT results by 10-14% points. This study aimed to replicate the SMS intervention in a different population, and additionally test the effect of an expanded message about anticipated RDT access policy change on customers' acceptability for drug retailers' administration of RDTs. One day after being tested with an RDT, participants who purchased malaria treatment from drug shops were randomized to receive (1) a basic SMS reminder repeating the RDT result and appropriate treatment actions, (2) an expanded SMS reminder additionally saying that the 'government might allow pharmacists/chemists to do RDTs' or (3) no SMS reminders (i.e. control). Using regression analysis, we estimate intent-to-treat (ITT) and treatment effects on the treated for 686 study participants. Results corroborate previous findings that a basic SMS reminder increased treatment adherence [odds ratio (OR) = 1.53, 95% CI 0.96-2.44] and decreased use of unnecessary anti-malarials for RDT-negative adults [OR = 0.63, 95% CI 0.39-1.00]. The expanded SMS also increased adherence for adults [OR = 1.42, 95% CI 0.97-2.07], but the effects for sick children differed-the basic SMS did not have any measurable impact on treatment adherence [OR = 0.87, 95% CI 0.24-3.09] or use of unnecessary anti-malarials [OR = 1.27, 95% CI 0.32-1.93], and the expanded SMS actually led to poorer treatment adherence [OR = 0.26, 95% CI 0.10-0.66] and increased use of unnecessary anti-malarials [OR = 4.67, 95% CI 1.76-12.43]. Further, the targeted but neutral message in the expanded SMS lowered acceptance for drug retailers' administration of RDTs [OR = 0.55, 95% CI 0.10-2.93], counter to what we hypothesized. Future SMS interventions should show consistent positive results across populations and be attuned to message length and content before initiating a larger messaging campaign. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

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.

The challenge to avoid anti-malarial medicine stock-outs in an era of funding partners: the case of Tanzania

PubMed Central

2014-01-01

Background Between 2007 and 2013, the Tanzanian public sector received 93.1 million doses of first-line anti-malarial artemisinin-based combination therapy (ACT) in the form of artemether-lumefantrine entirely supplied by funding partners. The introduction of a health facility ACT stock monitoring system using SMS technology by the National Malaria Control Programme in mid 2011 revealed a high frequency of stock-outs of ACT in primary care public health facilities. The objective of this study was to determine the pattern of availability of ACT and possible causes of observed stock-outs across public health facilities in Tanzania since mid-2011. Methods Data were collected weekly by the mobile phone reporting tool SMS for Life on ACT availability from over 5,000 public health facilities in Tanzania starting from September 2011 to December 2012. Stock data for all four age-dose levels of ACT across health facilities were summarized and supply of ACT at the national level was also documented. Results Over the period of 15 months, on average 29% of health facilities in Tanzania were completely stocked out of all four-age dose levels of the first-line anti-malarial with a median duration of total stock-out of six weeks. Patterns of total stock-out by region ranged from a low of 9% to a high of 52%. The ACT stock-outs were most likely caused by: a) insufficient ACT supplies entering Tanzania (e.g. in 2012 Tanzania received 10.9 million ACT doses compared with a forecast demand of 14.4 million doses); and b) irregular pattern of ACT supply (several months with no ACT stock). Conclusion The reduced ACT availability and irregular pattern of supply were due to cumbersome bureaucratic processes and delays both within the country and from the main donor, the Global Fund to Fight AIDS, Tuberculosis and Malaria. Tanzania should invest in strengthening both the supply system and the health information system using mHealth solutions such as SMS for Life. This will continue to assist in tracking ACT availability across the country where all partners work towards more streamlined, demand driven and accountable procurement and supply chain systems. PMID:24885420

Causes of non-malarial fever in Laos: a prospective study

PubMed Central

Mayxay, Mayfong; Castonguay-Vanier, Josée; Chansamouth, Vilada; Dubot-Pérès, Audrey; Paris, Daniel H; Phetsouvanh, Rattanaphone; Tangkhabuanbutra, Jarasporn; Douangdala, Phouvieng; Inthalath, Saythong; Souvannasing, Phoutthalavanh; Slesak, Günther; Tongyoo, Narongchai; Chanthongthip, Anisone; Panyanouvong, Phonepasith; Sibounheuang, Bountoy; Phommasone, Koukeo; Dohnt, Michael; Phonekeo, Darouny; Hongvanthong, Bouasy; Xayadeth, Sinakhone; Ketmayoon, Pakapak; Blacksell, Stuart D; Moore, Catrin E; Craig, Scott B; Burns, Mary-Anne; von Sonnenburg, Frank; Corwin, Andrew; de Lamballerie, Xavier; González, Iveth J; Christophel, Eva Maria; Cawthorne, Amy; Bell, David; Newton, Paul N

2013-01-01

Summary Background Because of reductions in the incidence of Plasmodium falciparum malaria in Laos, identification of the causes of fever in people without malaria, and discussion of the best empirical treatment options, are urgently needed. We aimed to identify the causes of non-malarial acute fever in patients in rural Laos. Methods For this prospective study, we recruited 1938 febrile patients, between May, 2008, and December, 2010, at Luang Namtha provincial hospital in northwest Laos (n=1390), and between September, 2008, and December, 2010, at Salavan provincial hospital in southern Laos (n=548). Eligible participants were aged 5–49 years with fever (≥38°C) lasting 8 days or less and were eligible for malaria testing by national guidelines. Findings With conservative definitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion of influenza, the top five diagnoses when only one aetiological agent per patient was identified were dengue (156 [8%] of 1927 patients), scrub typhus (122 [7%] of 1871), Japanese encephalitis virus (112 [6%] of 1924), leptospirosis (109 [6%] of 1934), and bacteraemia (43 [2%] of 1938). 115 (32%) of 358 patients at Luang Namtha hospital tested influenza PCR-positive between June and December, 2010, of which influenza B was the most frequently detected strain (n=121 [87%]). Disease frequency differed significantly between the two sites: Japanese encephalitis virus infection (p=0·04), typhoid (p=0·006), and leptospirosis (p=0·001) were more common at Luang Namtha, whereas dengue and malaria were more common at Salavan (all p<0·0001). With use of evidence from southeast Asia when possible, we estimated that azithromycin, doxycycline, ceftriaxone, and ofloxacin would have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively. Interpretation Our findings suggest that a wide range of treatable or preventable pathogens are implicated in non-malarial febrile illness in Laos. Empirical treatment with doxycycline for patients with undifferentiated fever and negative rapid diagnostic tests for malaria and dengue could be an appropriate strategy for rural health workers in Laos. Funding Wellcome Trust, WHO–Western Pacific Region, Foundation for Innovative New Diagnostics, US Centers for Disease Control and Prevention. PMID:24748368

Health service providers in Somalia: their readiness to provide malaria case-management

PubMed Central

Noor, Abdisalan M; Rage, Ismail A; Moonen, Bruno; Snow, Robert W

2009-01-01

Background Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. Methods Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. Results There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT) or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53.1% prescribed chloroquine as first-line therapy. 31.4% of private pharmacies also provided malaria diagnosis using RDT or microscopy. Conclusion Geographic access to public health sector is relatively low and there were major shortages of appropriate guidelines, anti-malarials and diagnostic tests required for appropriate malaria case management. Efforts to strengthen the readiness of the health sector in Somalia to provide malaria case management should improve availability of drugs and diagnostic kits; provide appropriate information and training; and engage and regulate the private sector to scale up malaria control. PMID:19439097

Ethnomedicinal uses of plants for the treatment of malaria in Soon Valley, Khushab, Pakistan.

PubMed

Shah, Amin; Rahim, Sarvat

2017-03-22

To best of our knowledge this is the first quantitative ethno-medicinal study with the aim of documenting the indigenous knowledge and practices of using plants for malarial therapy in Soon Valley, Khushab, Pakistan. In this Valley, malaria is among the major public health problems but, until now, the population still mostly relies on herbal medicine for treatment. Ethno-medicinal data were documented from 63 informants by using semi-structured questionnaires and interviewing the informants about their knowledge of plants regarding malaria and related symptoms. Documented data were evaluated using the quantitative ethno-botanical indices of frequency citation (FC), relative frequency of citation (RFC), percentage of respondents having knowledge (PRK) and Jaccard index (JI). A total of 70 plant species belonging to 62 genera and 34 families were recorded as anti-malarial in the study area. Solanaceae was found to be the most cited family with 7 species, followed by Fabaceae, Rutaceae and Lamiaceae with 5 species each. Ocimum americanum and Solanum incanum were the species with the highest relative frequency of citation (RFC =0.25 each) and percentage of respondents having knowledge (PRK =25.4% each), followed by Grewia tenax (RFC =0.23, PRK =23.8%), which indicates that these plants are the best species with anti-malarial properties. The most highly cited life form was found to be herbs (56%). The dominant plant part used in preparations were leaves (49%). The main mode of utilization was decoction (47%) followed by infusion (29%). In comparison, maximum similarity index is found in our study with JI (16.83) followed by (13.13). Similarity percentage of plants uses ranges from 0.81 to 16.83 while dissimilarity percentage varies from 0% to 17.65%. To the best of our knowledge seven plant species, viz. Withania coagulans, Fagonia cretica, Carthamus oxyacantha, Ehretia obtusifolia, Helianthus annuus, Olea ferruginea and Vitex trifolia, are reported from this region for the first time for the treatment of malaria. This first ethno-medicinal study highlights potential sources for the development of new antimalarial drugs from indigenous knowledge of medicinal plants found in the Soon Valley, Pakistan. Such investigations could be a subject for in vitro and in vivo anti-plasmodial screening to develop new plant-based antimalarial drugs and can also be evaluated for other biological activities and novel drug discoveries. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Analysis of polymorphisms in Plasmodium falciparum genes related to drug resistance: a survey over four decades under different treatment policies in Brazil.

PubMed

Inoue, Juliana; Lopes, Dinora; do Rosário, Virgílio; Machado, Marta; Hristov, Angélica D; Lima, Giselle Fmc; Costa-Nascimento, Maria J; Segurado, Aluísio C; Di Santi, Silvia M

2014-09-19

Anti-malarial resistance in Plasmodium falciparum remains an obstacle for malaria control. Resistance-associated genes were analysed in Brazilian samples over four decades to evaluate the impact of different treatment regimens on the parasite genetic profile. Samples were collected on filter paper from patients infected in the Amazon region from 1984 to 2011. DNA was extracted with Chelex® 100 and monoinfection confirmed by PCR. SNPs in the pfcrt, pfmdr1, pfdhfr and pfdhps genes were assessed by PCR-RFLP. The pfmdr1 copy number was estimated using real time quantitative PCR with SYBR® Green. Parasite response was assessed ex vivo with seven concentrations of each anti-malarial. Patients were treated according to Brazilian guidelines: quinine plus tetracycline or mefloquine in period 1 and ACT in period 2. All 96 samples presented the pfcrt 76T mutant throughout the assessed periods. In addition, all isolates showed ex vivo chloroquine resistance. The pfmdr1 86Y was detected in 1.5% of samples in period 1, and in 25% in period 2. All samples presented the pfmdr1 1246Y. The analysis of pfmdr1 copy number showed amplification in 37.3% in period 1 and in 42% in period 2. Mutations in pfdhfr were shown as follows: 51I in all samples in period 1 and in 81.2% in period 2; 59R in 6.4% in period 2. The pfdhfr 108N and the pfdhps 437G were seen in all samples along time; the pfdhps 540E in 93.7% in period 1 and in 75% in period 2. The 76T mutation associated to chloroquine resistance is still present in the parasite population, although this anti-malarial was withdrawn from the chemotherapy of P. falciparum in Brazil in the mid-1980s. All isolates assayed ex vivo for chloroquine showed resistant phenotype and 76T. No association was observed between pfmdr1 mutations and resistance to quinine, mefloquine and artemisinin derivatives. Additionally, the pfdhfr 108N mutation was detected in all samples throughout the evaluated periods, demonstrating fixation of the mutant allele in the parasite population. Changes in Brazilian national guidelines for the malaria chemotherapy in the last 27 years yielded a discreet genetic impact in the parasite population.

Health service providers in Somalia: their readiness to provide malaria case-management.

PubMed

Noor, Abdisalan M; Rage, Ismail A; Moonen, Bruno; Snow, Robert W

2009-05-13

Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT) or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53.1% prescribed chloroquine as first-line therapy. 31.4% of private pharmacies also provided malaria diagnosis using RDT or microscopy. Geographic access to public health sector is relatively low and there were major shortages of appropriate guidelines, anti-malarials and diagnostic tests required for appropriate malaria case management. Efforts to strengthen the readiness of the health sector in Somalia to provide malaria case management should improve availability of drugs and diagnostic kits; provide appropriate information and training; and engage and regulate the private sector to scale up malaria control.

Evaluation of SMS reminder messages for altering treatment adherence and health seeking perceptions among malaria care-seekers in Nigeria

PubMed Central

Liu, Jenny X.; Modrek, Sepideh

2016-01-01

In Nigeria, access to malaria diagnostics may be expanded if drug retailers were allowed to administer malaria rapid diagnostic tests (RDTs). A 2012 pilot intervention showed that short message service (SMS) reminder messages could boost treatment adherence to RDT results by 10–14% points. This study aimed to replicate the SMS intervention in a different population, and additionally test the effect of an expanded message about anticipated RDT access policy change on customers’ acceptability for drug retailers’ administration of RDTs. One day after being tested with an RDT, participants who purchased malaria treatment from drug shops were randomized to receive (1) a basic SMS reminder repeating the RDT result and appropriate treatment actions, (2) an expanded SMS reminder additionally saying that the ‘government might allow pharmacists/chemists to do RDTs’ or (3) no SMS reminders (i.e. control). Using regression analysis, we estimate intent-to-treat (ITT) and treatment effects on the treated for 686 study participants. Results corroborate previous findings that a basic SMS reminder increased treatment adherence [odds ratio (OR) = 1.53, 95% CI 0.96–2.44] and decreased use of unnecessary anti-malarials for RDT-negative adults [OR = 0.63, 95% CI 0.39–1.00]. The expanded SMS also increased adherence for adults [OR = 1.42, 95% CI 0.97–2.07], but the effects for sick children differed—the basic SMS did not have any measurable impact on treatment adherence [OR = 0.87, 95% CI 0.24–3.09] or use of unnecessary anti-malarials [OR = 1.27, 95% CI 0.32–1.93], and the expanded SMS actually led to poorer treatment adherence [OR = 0.26, 95% CI 0.10–0.66] and increased use of unnecessary anti-malarials [OR = 4.67, 95% CI 1.76–12.43]. Further, the targeted but neutral message in the expanded SMS lowered acceptance for drug retailers' administration of RDTs [OR = 0.55, 95% CI 0.10–2.93], counter to what we hypothesized. Future SMS interventions should show consistent positive results across populations and be attuned to message length and content before initiating a larger messaging campaign. PMID:27315831

Rural households at risk of malaria did not own sufficient insecticide treated nets at Dabat HDSS site: evidence from a cross sectional re-census.

PubMed

Muchie, Kindie Fentahun; Alemu, Kassahun; Tariku, Amare; Tsegaye, Adino Tesfahun; Abebe, Solomon Mekonnen; Yitayal, Mezgebu; Awoke, Tadesse; Biks, Gashaw Andargie

2017-11-21

Malaria is the leading cause of disease burden across the world, especially in African countries. Ethiopia has designed a five year (2011-2015) plan to cover 100% of the households in malarious areas with one insecticide treated net (ITN) for every two persons, and to raise consistent ITN utilization to at least 80%. However, evidence on ownership of ITN among malarious rural households in northwest Ethiopia is quite limited. Hence, the present study aimed at assessing ownership of ITN and associated factors among rural households at risk of malaria at Dabat Health and Demographic Surveillance System site, northwest Ethiopia. A cross sectional re-census was carried out in Dabat Health and Demographic Surveillance System site during peak malaria seasons from October to December, 2014. Data for 15,088 households at Dabat Health and Demographic Surveillance System site were used for the analysis. Descriptive measures and binary logistic regression were carried out. Among those who owned at least one ITN, 53.4% were living at an altitude >2500 m above sea level. However, out of households living at an altitude <2000 m above sea level, 15.8% (95% CI 14.4%, 17.3%) owned ITN at an average of 4.3 ± 2.1 persons per ITN. Of these, 69.5% (95% CI 64.7%, 74.1%) used the ITN. Among utilizing households at malarious areas, 23.7% prioritized pregnant women and 31.4% children to use ITN. The availability of radio receiver/mobile (AOR 1.60, 95%CI 1.08, 2.35) and secondary/above educational status of household member (AOR 1.54, 95%CI 1.19, 2.04) were predictors of ownership of ITN. Rural households at risk of malaria did not own a sufficient number of ITN though the utilization is promising. Moreover, prioritizing children and pregnant women to sleep under ITN remains public health problems. Programmers, partners and implementers should consider tailored intervention strategy stratified by altitude in distributing ITN. ITN distribution should also be accompanied by using exhaustive promotion strategies that consider people without access to any source of information, and educating households to prioritize pregnant and under five children to sleep under ITN.

Epidemiology, Etiology, Diagnosis, and Management of Placenta Accreta

PubMed Central

Garmi, Gali; Salim, Raed

2012-01-01

Placenta accreta is a severe pregnancy complication and is currently the most common indication for peripartum hysterectomy. It is becoming an increasingly common complication mainly due to the increasing rate of cesarean delivery. Main risk factor for placenta accreta is a previous cesarean delivery particularly when accompanied with a coexisting placenta previa. Antenatal diagnosis seems to be a key factor in optimizing maternal outcome. Diagnosis can be achieved by ultrasound in the majority of cases. Women with placenta accreta are usually delivered by a cesarean section. In order to avoid an emergency cesarean and to minimize complications of prematurity it is acceptable to schedule cesarean at 34 to 35 weeks. A multidisciplinary team approach and delivery at a center with adequate resources, including those for massive transfusion are both essential to reduce neonatal and maternal morbidity and mortality. The optimal management after delivery of the neonate is vague since randomized controlled trials and large cohort studies are lacking. Cesarean hysterectomy is probably the preferable treatment. In carefully selected cases, when fertility is desired, conservative management may be considered with caution. The current review discusses the epidemiology, predisposing factors, pathogenesis, diagnostic methods, clinical implications and management options of this condition. PMID:22645616

Getting it right when budgets are tight: Using optimal expansion pathways to prioritize responses to concentrated and mixed HIV epidemics

PubMed Central

Kerr, Cliff C.; Haghparast-Bidgoli, Hassan; Estill, Janne; Grobicki, Laura; Baranczuk, Zofia; Prieto, Lorena; Montañez, Vilma; Reporter, Iyanoosh; Gray, Richard T.; Skordis-Worrall, Jolene; Keiser, Olivia; Cheikh, Nejma; Boonto, Krittayawan; Osornprasop, Sutayut; Lavadenz, Fernando; Benedikt, Clemens J.; Martin-Hughes, Rowan; Hussain, S. Azfar; Kelly, Sherrie L.; Kedziora, David J.; Wilson, David P.

2017-01-01

Background Prioritizing investments across health interventions is complicated by the nonlinear relationship between intervention coverage and epidemiological outcomes. It can be difficult for countries to know which interventions to prioritize for greatest epidemiological impact, particularly when budgets are uncertain. Methods We examined four case studies of HIV epidemics in diverse settings, each with different characteristics. These case studies were based on public data available for Belarus, Peru, Togo, and Myanmar. The Optima HIV model and software package was used to estimate the optimal distribution of resources across interventions associated with a range of budget envelopes. We constructed “investment staircases”, a useful tool for understanding investment priorities. These were used to estimate the best attainable cost-effectiveness of the response at each investment level. Findings We find that when budgets are very limited, the optimal HIV response consists of a smaller number of ‘core’ interventions. As budgets increase, those core interventions should first be scaled up, and then new interventions introduced. We estimate that the cost-effectiveness of HIV programming decreases as investment levels increase, but that the overall cost-effectiveness remains below GDP per capita. Significance It is important for HIV programming to respond effectively to the overall level of funding availability. The analytic tools presented here can help to guide program planners understand the most cost-effective HIV responses and plan for an uncertain future. PMID:28972975

Mössbauer studies of malaria

NASA Astrophysics Data System (ADS)

Bauminger, E. R.; Ginsburg, H.; Ofer, S.; Yayon, A.

1983-12-01

Mössbauer studies of rat and human erythrocytes infected by malarial parasites have been carried out. Different parameters of the pigment iron were obtained in human and rat infected red blood cells. No difference was found between the parameters obtained in rat erythrocytes infected by drug sensitive and drug resistant strains of p. berghei, both before and after the treatment with chloroquine. The pigment was shown to contain a trivalent, high spin iron compound, which is different from hematin.

Seasonal Distribution, Biology, and Human Attraction Patterns of Mosquitoes (Diptera: Culicidae) in a Rural Village and Adjacent Forested Site Near Iquitos, Peru

DTIC Science & Technology

2008-11-01

and malarial activity in the Amazon Basin, Loreto Department, Peru , to determine the relative abundance, species diversity, and seasonal and vertical...populations. KEY WORDS Anopheles, bionomics, mosquito ecology, Amazon Basin, Peru Malaria and other arthropod-vectored diseases are on the increase...in the Amazon Basin region of Peru to date. The Puerto Almendra area was selected because human cases of dengue, malaria, Mayaro, Oropouche

Aquatic Plant Control Research Program. Ecological Assessment of Kirk Pond

DTIC Science & Technology

1994-03-01

Botany 60, 1216-21. Bamickol, P. G. (1941). "Food habits of Gambusia affinis from Reelfoot Lake , Tennessee, with special reference to malarial control...34 Report of the Reelfoot Lake Biological Station 5, 5-13. Barwick, D. H., and Holcomb, D. E. (1976). "Relation of largemouth bass reproduction to crowded...1991 (Figure 3). Pond elevation at all in- lake stations remained constant throughout the study. Station I represents the inflow to the impoundment

The Fate of the Red Cells: Insights from Two Models of Severe Malarial Anemia

DTIC Science & Technology

2011-03-07

approximately 1%. The reticulocyte levels in these animals elevated to approximately 35% 2 days after the anemic crisis and then returned to basal...cells are destroyed for every parasitized red cell22. A prospective study in a Karen community on the western border of Thailand showed that in anemia...activation in severe Plasmodium falciparum malaria. Clin.Immunol.Immunopathol. 1997;85:166-171. 136. Facer CA, Bray RS, Brown J. Direct Coombs

Computational and Experimental Validation of B and T-Cell Epitopes of the In Vivo Immune Response to a Novel Malarial Antigen

DTIC Science & Technology

2013-08-16

approach in the context of a novel, immunologically relevant antigen. The limited accuracy of the tested algorithms to predict the in vivo immune responses...overlapping peptides spanning the entire sequence are individually tested for antibody interacting residues. Conformational B cell epitopes, in contrast...a blind assessment of this approach in the context of a novel, immunologically relevant antigen. The limited accuracy of the tested algorithms to

Malaria in the United Kingdom

PubMed Central

Bruce-Chwatt, L. J.; Southgate, B. A.; Draper, C. C.

1974-01-01

Over the past decade the United Kingdom had the second highest number of cases of imported malaria among European countries. There has been a substantial rise in recorded cases of malaria during the past three years though some of it may be due to improved notification. Fatal cases of malaria in visitors to Africa have averaged 6.5% of reported infections due to Plasmodium falciparum. Attacks of vivax malaria may occur several months after travellers return from a malarious country. PMID:4604717

Epidemic pox and malaria in native forest birds

USGS Publications Warehouse

Atkinson, C. T.; Dusek, R. J.; Iko, W. M.

1993-01-01

Studies by Warner in the 1950’s and van Riper in the 1970’s identified disease as a potential limiting factor in the distribution and abundance of Hawaii’s native forest birds. Mosquito-transmitted protozoan and viral infections caused by malarial parasites and pox virus were especially significant. Both organisms were introduced to the islands after the arrival of Europeans and are thought to have affected avian communities the same way that measles devastated native Hawaiian peoples.

Mosquito adulticidal and repellent activities of botanical extracts against malarial vector, Anopheles stephensi Liston (Diptera: Culicidae).

PubMed

Govindarajan, Marimuthu; Sivakumar, Rajamohan

2011-12-01

To determine the adulticidal and repellent activities of different solvent leaf extracts of Eclipta alba (E. alba) and Andrographis paniculata (A. paniculata) against malarial vector, Anopheles stephensi (An. stephensi). Adulticidal efficacy of the crude leaf extracts of E. alba and A. paniculata with five different solvents like benzene, hexane, ethyl acetate, methanol and chloroform was tested against the five to six day old adult female mosquitoes of An. stephensi. The adult mortality was observed after 24 h under the laboratory conditions. The repellent efficacy was determined against An. stephensi mosquito species at three concentrations viz., 1.0, 2.5 and 5.0 mg/cm(2) under laboratory conditions. Among the tested solvents the maximum efficacy was observed in the methanol extract. The LC(50) and LC(90) values of E. alba and A. paniculata against adults of An. stephensi were 150.36, 130.19 ppm and 285.22, 244.16 ppm, respectively. No mortality was observed in controls. The chi-square values were significant at P<0.05 level. Methanol extract of E. alba and A. paniculata was produce maximum repellency against An. stephensi. From the results it can be concluded the crude extract of E. alba and A. paniculata was an excellent potential for controlling An. stephensi mosquitoes. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Targeting histone deacetylase inhibitors for anti-malarial therapy.

PubMed

Andrews, Katherine T; Tran, Thanh N; Wheatley, Nicole C; Fairlie, David P

2009-01-01

It is now clear that histone acetylation plays key roles in regulating gene transcription in both eukaryotes and prokaryotes, the acetylated form inducing gene expression while deacetylation silences genes. Recent studies have identified roles for histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) in a number of parasites including Entamoeba histolytica, Toxoplasma gondii, Schistosoma mansoni, Cryptosporidium sp., Leishmania donovani, Neospora caninum, and Plasmodium falciparum. Here we survey fairly limited efforts to date in profiling antimalarial activities of HDAC inhibitors, showing that such compounds are potent inhibitors of the growth of P. falciparum in vitro and in vivo. Most of the compounds evaluated so far have borne a zinc-binding hydroxamate group that tends to be metabolized in vivo, and thus new zinc-binding groups need to be incorporated into second generation inhibitors in order to mask the catalytic zinc in the active site of HDACs. Also the development of compounds that are selective for parasitic HDACs over mammalian HDACs is still in relative infancy and it will take some time to derive antiparasitic HDAC inhibitor compounds with minimal toxicity for the host and acceptable pharmacokinetic and pharmacodynamic profiles for human treatment. Nevertheless, results to date suggest that HDAC inhibitor development represents a promising new approach to the potential treatment of parasitic infections, including those induced by malaria protozoa, and may offer new therapeutic targets within increasingly drug-resistant malarial parasites.

Prevention and treatment strategies used for the community management of childhood fever in Kampala, Uganda.

PubMed

Kemble, Sarah K; Davis, Jennifer C; Nalugwa, Talemwa; Njama-Meya, Denise; Hopkins, Heidi; Dorsey, Grant; Staedke, Sarah G

2006-06-01

To assess malaria-related prevention and treatment strategies in an urban parish of Kampala, Uganda, a questionnaire was administered to 339 randomly selected primary caregivers of children 1-10 years of age. Our study population was relatively stable and well educated, with better access to health services than many in Africa. Ownership of an insecticide-treated net (ITN) was reported by 11% of households and was predicted only by greater household wealth (highest quartile versus lowest quartile: odds ratio [OR] 21.8; 95% confidence interval [CI], 2.74-173). Among women, 5% reported use of an ITN and 11% used intermittent preventive therapy (IPT) during their last pregnancy. Use of appropriate IPT during pregnancy was predicted only by completion of secondary education or higher (OR, 2.87; 95% CI, 1.13-7.21). Children of 123 (36%) caregivers had experienced an episode of fever in the past 2 weeks. Of these, 22% received an anti-malarial that could be considered "adequate" (combination therapy or quinine). Only 1% of febrile children received adequate treatment at the correct dose within 24 hours of onset of fever. The only independent predictor of treatment with an adequate anti-malarial was accessing a clinic or hospital as the first source of care. In this urban area, use of appropriate malaria control measures occurs uncommonly.

Development, malaria and adaptation to climate change: a case study from India.

PubMed

Garg, Amit; Dhiman, R C; Bhattacharya, Sumana; Shukla, P R

2009-05-01

India has reasons to be concerned about climate change. Over 650 million people depend on climate-sensitive sectors, such as rain-fed agriculture and forestry, for livelihood and over 973 million people are exposed to vector borne malarial parasites. Projection of climatic factors indicates a wider exposure to malaria for the Indian population in the future. If precautionary measures are not taken and development processes are not managed properly some developmental activities, such as hydro-electric dams and irrigation canal systems, may also exacerbate breeding grounds for malaria. This article integrates climate change and developmental variables in articulating a framework for integrated impact assessment and adaptation responses, with malaria incidence in India as a case study. The climate change variables include temperature, rainfall, humidity, extreme events, and other secondary variables. Development variables are income levels, institutional mechanisms to implement preventive measures, infrastructure development that could promote malarial breeding grounds, and other policies. The case study indicates that sustainable development variables may sometimes reduce the adverse impacts on the system due to climate change alone, while it may sometimes also exacerbate these impacts if the development variables are not managed well and therefore they produce a negative impact on the system. The study concludes that well crafted and well managed developmental policies could result in enhanced resilience of communities and systems, and lower health impacts due to climate change.

Molecular analysis demonstrates high prevalence of chloroquine resistance but no evidence of artemisinin resistance in Plasmodium falciparum in the Chittagong Hill Tracts of Bangladesh.

PubMed

Alam, Mohammad Shafiul; Ley, Benedikt; Nima, Maisha Khair; Johora, Fatema Tuj; Hossain, Mohammad Enayet; Thriemer, Kamala; Auburn, Sarah; Marfurt, Jutta; Price, Ric N; Khan, Wasif A

2017-08-15

Artemisinin resistance is present in the Greater Mekong region and poses a significant threat for current anti-malarial treatment guidelines in Bangladesh. The aim of this molecular study was to assess the current status of drug resistance in the Chittagong Hill Tracts of Bangladesh near the Myanmar border. Samples were obtained from patients enrolled into a Clinical Trial (NCT02389374) conducted in Alikadam, Bandarban between August 2014 and January 2015. Plasmodium falciparum infections were confirmed by PCR and all P. falciparum positive isolates genotyped for the pfcrt K76T and pfmdr1 N86Y markers. The propeller region of the kelch 13 (k13) gene was sequenced from isolates from patients with delayed parasite clearance. In total, 130 P. falciparum isolates were available for analysis. The pfcrt mutation K76T, associated with chloroquine resistance was found in 81.5% (106/130) of cases and the pfmdr1 mutation N86Y in 13.9% (18/130) cases. No single nucleotide polymorphisms were observed in the k13 propeller region. This study provides molecular evidence for the ongoing presence of chloroquine resistant P. falciparum in Bangladesh, but no evidence of mutations in the k13 propeller domain associated with artemisinin resistance. Monitoring for artemisinin susceptibility in Bangladesh is needed to ensure early detection and containment emerging anti-malarial resistance.

The green vaccine: A global strategy to combat infectious and autoimmune diseases

PubMed Central

Davoodi-Semiromi, Abdoreza; Samson, Nalapalli; Daniell, Henry

2009-01-01

Plant derived oral green vaccines eliminate expenses associated with fermenters, purification, cold storage/transportation and sterile delivery. Green vaccines are expressed via the plant nuclear or chloroplast genomes. Chloroplast expression has advantages of hyper-expression of therapeutic proteins (10,000 copies of trans-gene per cell), efficient oral delivery and transgene containment via maternal inheritance. To date, 23 vaccine antigens against 16 different bacterial, viral or protozoan pathogens have been expressed in chloroplasts. Mice subcutaneously immunized with the chloroplast derived anthrax protective antigen conferred 100% protection against lethal doses of the anthrax toxin. Oral immunization (ORV) of F1-V antigens without adjuvant conferred greater protection (88%) against 50-fold lethal dose of aerosolized plague (Yersinia pestis) than subcutaneous (SQV) immunization (33%). Oral immunization of malarial vaccine antigens fused to the cholera antigen (CTB-AMA1/CTB-Msp1) conferred prolonged immunity (50% life span), 100% protection against cholera toxin challenge and inhibited proliferation of the malarial parasite. Protection was correlated with antigen-specific titers of intestinal, serum IgA & IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. High level expression in edible plant chloroplasts ideal for oral delivery and long-term immunity observed should facilitate development of low cost human vaccines for large populations, at times of outbreak. PMID:19430198

Development, Malaria and Adaptation to Climate Change: A Case Study from India

NASA Astrophysics Data System (ADS)

Garg, Amit; Dhiman, R. C.; Bhattacharya, Sumana; Shukla, P. R.

2009-05-01

India has reasons to be concerned about climate change. Over 650 million people depend on climate-sensitive sectors, such as rain-fed agriculture and forestry, for livelihood and over 973 million people are exposed to vector borne malarial parasites. Projection of climatic factors indicates a wider exposure to malaria for the Indian population in the future. If precautionary measures are not taken and development processes are not managed properly some developmental activities, such as hydro-electric dams and irrigation canal systems, may also exacerbate breeding grounds for malaria. This article integrates climate change and developmental variables in articulating a framework for integrated impact assessment and adaptation responses, with malaria incidence in India as a case study. The climate change variables include temperature, rainfall, humidity, extreme events, and other secondary variables. Development variables are income levels, institutional mechanisms to implement preventive measures, infrastructure development that could promote malarial breeding grounds, and other policies. The case study indicates that sustainable development variables may sometimes reduce the adverse impacts on the system due to climate change alone, while it may sometimes also exacerbate these impacts if the development variables are not managed well and therefore they produce a negative impact on the system. The study concludes that well crafted and well managed developmental policies could result in enhanced resilience of communities and systems, and lower health impacts due to climate change.

Simultaneous detection of Plasmodium vivax dhfr, dhps, mdr1 and crt-o resistance-associated mutations in the Colombian Amazonian region.

PubMed

Cubides, Juan Ricardo; Camargo-Ayala, Paola Andrea; Niño, Carlos Hernando; Garzón-Ospina, Diego; Ortega-Ortegón, Anggie; Ospina-Cantillo, Estefany; Orduz-Durán, María Fernanda; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

2018-03-27

Malaria continues being a public health problem worldwide. Plasmodium vivax is the species causing the largest number of cases of malaria in Asia and South America. Due to the lack of a completely effective anti-malarial vaccine, controlling this disease has been based on transmission vector management, rapid diagnosis and suitable treatment. However, parasite resistance to anti-malarial drugs has become a major yet-to-be-overcome challenge. This study was thus aimed at determining pvmdr1, pvdhfr, pvdhps and pvcrt-o gene mutations and haplotypes from field samples obtained from an endemic area in the Colombian Amazonian region. Fifty samples of parasite DNA infected by a single P. vivax strain from symptomatic patients from the Amazonas department in Colombia were analysed by PCR and the pvdhfr, pvdhps, pvmdr1 and pvcrt-o genes were sequenced. Diversity estimators were calculated from the sequences and the haplotypes circulating in the Colombian Amazonian region were obtained. pvdhfr, pvdhps, pvmdr1 and pvcrt-o genes in the Colombian Amazonian region are characterized by low genetic diversity. Some resistance-associated mutations were found circulating in this population. New variants are also being reported. A selective sweep signal was located in pvdhfr and pvmdr1 genes, suggesting that these mutations (or some of them) could be providing an adaptive advantage.

Pernicious plans revealed: Plasmodium falciparum genome wide expression analysis.

PubMed

Llinás, Manuel; DeRisi, Joseph L

2004-08-01

The asexual intraerythrocytic developmental cycle (IDC) of Plasmodium falciparum is responsible for the majority of the clinical manifestations of malaria in humans. Although malaria has been studied for over a century, the elucidation of the full genome sequence of P. falciparum has now allowed for in-depth studies of gene expression throughout the entire intraerythrocytic stage. As the mainstays of anti-malarial chemotherapy become increasingly ineffective, we need a deeper understanding of fundamental plasmodial bioregulatory mechanisms to successfully subvert them. Recent gene expression studies have begun to examine different aspects of the IDC and are providing key insights into the basic mechanisms of Plasmodium gene regulation and are helping to define gene functions. However, to date, no transcription factor has been fully characterized from Plasmodium and the definitive identification of cis-acting regulatory elements along with their corresponding trans-acting partners is still lacking. The characterization of the transcriptome of P. falciparum is the first major step towards the understanding of the genome wide regulation of gene expression in this parasite. IDC expression data for almost every gene in the P. falciparum genome can now be publicly queried at and. The results of these studies suggest promising leads for identifying novel targets for anti-malarial therapeutics and vaccines in addition to providing a solid foundation for the ongoing elucidation of plasmodial gene expression.

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC-MS/MS.

PubMed

Pandey, Saurabh; Gautam, Nagsen; Kushwaha, Hari Narayan; Singh, Shio Kumar

2016-12-01

The pharmacokinetic profile of 99/411, a novel anti-malarial drug, was established in rats (12 mg/kg of body weight) and monkeys (20 mg/kg of body weight). Following oral administration, the presence of 99/411 was rapidly determined in rat plasma, tissues, urine, feces and monkey plasma using a validated LC-MS/MS method. The tissue distribution studies in rats indicated that the drug was partially distributed in all major tissues and plasma, and peak concentration levels were achieved within 0.5-4 h. Area under the curve in different rat tissues and plasma was found in order of blood > lung > intestine > heart > muscle > brain > kidney > spleen > liver. The total recoveries (within 86 h) of 99/411 were <0.0017% and <0.08% in urine and feces, respectively. The peak plasma concentration was 3499 ng/mL in rats after ~2 h of oral administration and 697-767 ng/mL in monkeys after ~6 h of oral administration. No plasma accumulation was observed in both male and female monkeys, even after multiple dosing. The preclinical pharmacokinetic profile and tissue distribution data are expected to assist in future clinical explorations of 99/411 as a promising anti-malarial agent. Copyright © 2016 John Wiley & Sons, Ltd.

Novel Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Anti-malarial Activity in the Mouse Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Booker, Michael L.; Bastos, Cecilia M.; Kramer, Martin L.

Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. A high throughput screen and subsequent medicinal chemistry program identified a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH from P. falciparum, P. vivax, and P. berghei. The compounds were selective for the parasite enzymes over human DHODH, and x-ray structural data on the analog Genz-667348, demonstrated that species selectivitymore » could be attributed to amino acid differences in the inhibitor-binding site. Compounds from this series demonstrated in vitro potency against the 3D7 and Dd2 strains of P. falciparum, good tolerability and oral exposure in the mouse, and ED{sub 50} values in the 4-day murine P. berghei efficacy model of 13-21 mg/kg/day with oral twice-daily dosing. In particular, treatment with Genz-667348 at 100 mg/kg/day resulted in sterile cure. Two recent analogs of Genz-667348 are currently undergoing pilot toxicity testing to determine suitability as clinical development candidates.« less

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria.

PubMed

Varo, Rosauro; Crowley, Valerie M; Sitoe, Antonio; Madrid, Lola; Serghides, Lena; Bila, Rubao; Mucavele, Helio; Mayor, Alfredo; Bassat, Quique; Kain, Kevin C

2017-05-23

Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention. In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem ® ) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations. Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters. Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874.

Assessment of dual life stage antiplasmodial activity of british seaweeds.

PubMed

Spavieri, Jasmine; Allmendinger, Andrea; Kaiser, Marcel; Itoe, Maurice Ayamba; Blunden, Gerald; Mota, Maria M; Tasdemir, Deniz

2013-10-22

Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC(50)s around 3 μg/mL). The extracts generally had high selectivity indices (>10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 μg/mL). The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II) pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds.

Assessment of Dual Life Stage Antiplasmodial Activity of British Seaweeds

PubMed Central

Spavieri, Jasmine; Allmendinger, Andrea; Kaiser, Marcel; Itoe, Maurice Ayamba; Blunden, Gerald; Mota, Maria M.; Tasdemir, Deniz

2013-01-01

Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC50s around 3 μg/mL). The extracts generally had high selectivity indices (>10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 μg/mL). The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II) pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds. PMID:24152562

Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens.

PubMed

Ateba-Ngoa, Ulysse; Jones, Sophie; Zinsou, Jeannot Fréjus; Honkpehedji, Josiane; Adegnika, Ayola Akim; Agobe, Jean-Claude Dejon; Massinga-Loembe, Marguerite; Mordmüller, Benjamin; Bousema, Teun; Yazdanbakhsh, Maria

2016-08-03

Infections with helminths and Plasmodium spp. overlap in their geographical distribution. It has been postulated that helminth infections may influence malarial transmission by altering Plasmodium falciparum gametocytogenesis. This cross-sectional study assessed the effect of helminth infections on P. falciparum gametocyte carriage and on humoral immune responses to sexual stage antigens in Gabon. Schistosoma haematobium and filarial infections as well as P. falciparum asexual forms and gametocyte carriage were determined. The antibody responses measured were to sexual (Pfs230, Pfs48/45) and asexual P. falciparum antigens (AMA1, MSP1, and GLURP). A total of 287 subjects were included. The prevalence of microscopically detectable P. falciparum asexual parasites was higher in S. haematobium-infected subjects in comparison to their uninfected counterparts (47% versus 26%, P = 0.003), but this was not different when filarial infections were considered. Plasmodium falciparum gametocyte carriage was similar between Schistosoma- or filaria-infected and uninfected subjects. We observed a significant decrease of Pfs48/45 immunoglobulin G titer in S. haematobium-infected subjects (P = 0.037), whereas no difference was seen for Pfs230 antibody titer, nor for antibodies to AMA1, MSP1, or GLURP. Our findings suggest an effect of S. haematobium on antibody responses to some P. falciparum gametocyte antigens that may have consequences for transmission-blocking immunity. © The American Society of Tropical Medicine and Hygiene.

Optimizing Burn Treatment in Developing Low-and Middle-Income Countries with Limited Health Care Resources (Part 3)

PubMed Central

Atiyeh, B.; Masellis, A.; Conte, F.

2010-01-01

Summary The present review of the literature aims at analysing the challenges facing burn management in low- and middleincome countries and exploring probable modalities to optimize burn management in these countries. In Part I, epidemiology of burns injuries and the formidable challenges for proper management due to limited resources and inaccessibility to sophisticated skills and technologies in low- and middle income countries (LMICs) were presented. Part II discussed the actual state of burn injuries management in LMICs. In Part III of this review strategies for proper prevention and burn care in LMICs will be presented. PMID:21991190

[PRIORITY TECHNOLOGIES OF THE MEDICAL WASTE DISPOSAL SYSTEM].

PubMed

Samutin, N M; Butorina, N N; Starodubova, N Yu; Korneychuk, S S; Ustinov, A K

2015-01-01

The annual production of waste in health care institutions (HCI) tends to increase because of the growth of health care provision for population. Among the many criteria for selecting the optimal treatment technologies HCI is important to provide epidemiological and chemical safety of the final products. Environmentally friendly method of thermal disinfection of medical waste may be sterilizators of medical wastes intended for hospitals, medical centers, laboratories and other health care facilities that have small and medium volume of processing of all types of waste Class B and C. The most optimal method of centralized disposal of medical waste is a thermal processing method of the collected material.

Nutrition and the science of disease prevention: a systems approach to support metabolic health

PubMed Central

Bennett, Brian J.; Hall, Kevin D.; Hu, Frank B.; McCartney, Anne L.; Roberto, Christina

2017-01-01

Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene–diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. PMID:26415028

[Syndromic surveillance in circumstances of bioterrorism threat--the essence, application abilities and superiority over a traditional epidemiological surveillance].

PubMed

Osemek, Paweł; Kocik, Janusz; Paśnik, Krzysztof

2009-12-01

This article provides a short review about trends of developing current syndromic surveillance systems. To improve methods of early detection of natural or bioterrorism-related outbreaks, it has to be established a new way of epidemiological thinking, which uses innovative real-time surveillance systems. Syndromic surveillance has been created for an early detection, to monitor the temporo-spatial spread of an outbreak, and to provide prompt data for immediate analysis and feedback to public health authorities. It supports timely decision making process for countermeasure procedures. Framework of syndromic surveillance system requires a proper electronic infrastructure to be build up. Optimal syndrome definitions and data sources for continuing specific diseases outbreak surveillance have not been determined so far. Systems of interest might enhance collaboration among clinical providers, primary care providers, emergency services, information-systems professionals and public health agencies. However economic scope of this undertakings effectively limits ability to implement it in Polish public health service right now. Besides, syndromic surveillance cannot replace traditional public health surveillance with a post-factum epidemiological investigation and laboratory analysis. It can be a useful supplement.

The conservation relevance of epidemiological research into carnivore viral diseases in the serengeti.

PubMed

Cleaveland, Sarah; Mlengeya, Titus; Kaare, Magai; Haydon, Dan; Lembo, Tiziana; Laurenson, M Karen; Packer, Craig

2007-06-01

Recent outbreaks of rabies and canine distemper in wildlife populations of the Serengeti show that infectious disease constitutes a significant cause of mortality that can result in regional extirpation of endangered species even within large, well-protected areas. Nevertheless, effective management of an infectious disease depends critically on understanding the epidemiological dynamics of the causative pathogen. Pathogens with short infection cycles cannot persist in small populations in the absence of a more permanent reservoir of infection. Development of appropriate interventions requires detailed data on transmission pathways between reservoirs and wildlife populations of conservation concern. Relevant data can be derived from long-term population monitoring, epidemic and case-surveillance patterns, genetic analyses of rapidly evolving pathogens, serological surveys, and intervention studies. We examined studies of carnivore diseases in the Serengeti. Epidemiological research contributes to wildlife conservation policy in terms of management of endangered populations and the integration of wildlife conservation with public health interventions. Long-term, integrative, cross-species research is essential for formulation of effective policy for disease control and optimization of ecosystem health.

Acute respiratory infections among returning Hajj pilgrims-Jordan, 2014.

PubMed

Al-Abdallat, Mohammad Mousa; Rha, Brian; Alqasrawi, Sultan; Payne, Daniel C; Iblan, Ibrahim; Binder, Alison M; Haddadin, Aktham; Nsour, Mohannad Al; Alsanouri, Tarek; Mofleh, Jawad; Whitaker, Brett; Lindstrom, Stephen L; Tong, Suxiang; Ali, Sami Sheikh; Dahl, Rebecca Moritz; Berman, LaShondra; Zhang, Jing; Erdman, Dean D; Gerber, Susan I

2017-04-01

The emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the Hajj, one of the largest annual mass gatherings in the world. To describe the epidemiology and etiologies of respiratory illnesses among pilgrims returning to Jordan after the 2014 Hajj. Surveillance for respiratory illness among pilgrims returning to Jordan after the 2014 Hajj was conducted at sentinel health care facilities using epidemiologic surveys and molecular diagnostic testing of upper respiratory specimens for multiple respiratory pathogens, including MERS-CoV. Among the 125 subjects, 58% tested positive for at least one virus; 47% tested positive for rhino/enterovirus. No cases of MERS-CoV were detected. The majority of pilgrims returning to Jordan from the 2014 Hajj with respiratory illness were determined to have a viral etiology, but none were due to MERS-CoV. A greater understanding of the epidemiology of acute respiratory infections among returning travelers to other countries after Hajj should help optimize surveillance systems and inform public health response practices. Published by Elsevier B.V.

Monitoring Bone Health after Spaceflight: Data Mining to Support an Epidemiological Analysis of Age-related Bone Loss in Astronauts

NASA Technical Reports Server (NTRS)

Baker, K. S,; Amin, S.; Sibonga, Jean D.

2009-01-01

Through the epidemiological analysis of bone data, HRP is seeking evidence as to whether the prolonged exposure to microgravity of low earth orbit predisposes crewmembers to an earlier onset of osteoporosis. While this collaborative Epidemiological Project may be currently limited by the number of ISS persons providing relevant spaceflight medical data, a positive note is that it compares medical data of astronauts to data of an age-matched (not elderly) population that is followed longitudinally with similar technologies. The inclusion of data from non-ISS and non-NASA crewmembers is also being pursued. The ultimate goal of this study is to provide critical information for NASA to understand the impact of low physical or minimal weight-bearing activity on the aging process as well as to direct its development of countermeasures and rehabilitation programs to influence skeletal recovery. However, in order to optimize these results NASA needs to better define the requirements for long term monitoring and encourage both active and retired astronauts to contribute to a legacy of data that will define human health risks in space.

Liver fungal infections: an overview of the etiology and epidemiology in patients affected or not affected by oncohematologic malignancies

PubMed Central

Bimonte, Sabrina; Maraolo, Alberto Enrico; Gentile, Ivan; Schiavone, Vincenzo; Pace, Maria Caterina

2018-01-01

Fungal infections of the liver, most commonly caused by Candida spp., often occur in patients with hematologic malignancies treated with chemotherapy. Colonization of the gastrointestinal tract is thought to be the main origin of dissemination of Candida; mucositis and neutropenia facilitate the spread of Candida from the gastrointestinal tract to the liver. Hepatic involvement due to other fungi is a less common infectious complication in this setting. Fungal infections represent a less common cause of hepatic abscesses in non-oncohematologic population and the trend appears to be decreasing in recent years. Understanding of the etiology and epidemiology of fungal infections of the liver is indicated for an appropriate antimicrobial therapy and an overall optimal management of fungal liver infections. PMID:29416363

Malaria indicator survey 2007, Ethiopia: coverage and use of major malaria prevention and control interventions.

PubMed

Jima, Daddi; Getachew, Asefaw; Bilak, Hana; Steketee, Richard W; Emerson, Paul M; Graves, Patricia M; Gebre, Teshome; Reithinger, Richard; Hwang, Jimee

2010-02-24

In 2005, a nationwide survey estimated that 6.5% of households in Ethiopia owned an insecticide-treated net (ITN), 17% of households had been sprayed with insecticide, and 4% of children under five years of age with a fever were taking an anti-malarial drug. Similar to other sub-Saharan African countries scaling-up malaria interventions, the Government of Ethiopia set an ambitious national goal in 2005 to (i) provide 100% ITN coverage in malarious areas, with a mean of two ITNs per household; (ii) to scale-up indoor residual spraying of households with insecticide (IRS) to cover 30% of households targeted for IRS; and (iii) scale-up the provision of case management with rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT), particularly at the peripheral level. A nationally representative malaria indicator survey (MIS) was conducted in Ethiopia between September and December 2007 to determine parasite and anaemia prevalence in the population at risk and to assess coverage, use and access to scaled-up malaria prevention and control interventions. The survey used a two-stage random cluster sample of 7,621 households in 319 census enumeration areas. A total of 32,380 people participated in the survey. Data was collected using standardized Roll Back Malaria Monitoring and Evaluation Reference Group MIS household and women's questionnaires, which were adapted to the local context. Data presented is for households in malarious areas, which according to the Ethiopian Federal Ministry of Health are defined as being located <2,000 m altitude. Of 5,083 surveyed households, 3,282 (65.6%) owned at least one ITN. In ITN-owning households, 53.2% of all persons had slept under an ITN the prior night, including 1,564/2,496 (60.1%) children <5 years of age, 1,891/3,009 (60.9%) of women 15 - 49 years of age, and 166/266 (65.7%) of pregnant women. Overall, 906 (20.0%) households reported to have had IRS in the past 12 months. Of 747 children with reported fever in the two weeks preceding the survey, 131 (16.3%) sought medical attention within 24 hours. Of those with fever, 86 (11.9%) took an anti-malarial drug and 41 (4.7%) took it within 24 hours of fever onset. Among 7,167 surveyed individuals of all ages, parasitaemia as estimated by microscopy was 1.0% (95% CI 0.5 - 1.5), with 0.7% and 0.3% due to Plasmodium falciparum and Plasmodium vivax, respectively. Moderate-severe anaemia (haemoglobin <8 g/dl) was observed in 239/3,366 (6.6%, 95% CI 4.9-8.3) children <5 years of age. Since mid-2005, the Ethiopian National Malaria Control Programme has considerably scaled-up its malaria prevention and control interventions, demonstrating the impact of strong political will and a committed partnership. The MIS showed, however, that besides sustaining and expanding malaria intervention coverage, efforts will have to be made to increase intervention access and use. With ongoing efforts to sustain and expand malaria intervention coverage, to increase intervention access and use, and with strong involvement of the community, Ethiopia expects to achieve its targets in terms of coverage and uptake of interventions in the coming years and move towards eliminating malaria.

Malaria indicator survey 2007, Ethiopia: coverage and use of major malaria prevention and control interventions

PubMed Central

2010-01-01

Background In 2005, a nationwide survey estimated that 6.5% of households in Ethiopia owned an insecticide-treated net (ITN), 17% of households had been sprayed with insecticide, and 4% of children under five years of age with a fever were taking an anti-malarial drug. Similar to other sub-Saharan African countries scaling-up malaria interventions, the Government of Ethiopia set an ambitious national goal in 2005 to (i) provide 100% ITN coverage in malarious areas, with a mean of two ITNs per household; (ii) to scale-up indoor residual spraying of households with insecticide (IRS) to cover 30% of households targeted for IRS; and (iii) scale-up the provision of case management with rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT), particularly at the peripheral level. Methods A nationally representative malaria indicator survey (MIS) was conducted in Ethiopia between September and December 2007 to determine parasite and anaemia prevalence in the population at risk and to assess coverage, use and access to scaled-up malaria prevention and control interventions. The survey used a two-stage random cluster sample of 7,621 households in 319 census enumeration areas. A total of 32,380 people participated in the survey. Data was collected using standardized Roll Back Malaria Monitoring and Evaluation Reference Group MIS household and women's questionnaires, which were adapted to the local context. Results Data presented is for households in malarious areas, which according to the Ethiopian Federal Ministry of Health are defined as being located <2,000 m altitude. Of 5,083 surveyed households, 3,282 (65.6%) owned at least one ITN. In ITN-owning households, 53.2% of all persons had slept under an ITN the prior night, including 1,564/2,496 (60.1%) children <5 years of age, 1,891/3,009 (60.9%) of women 15 - 49 years of age, and 166/266 (65.7%) of pregnant women. Overall, 906 (20.0%) households reported to have had IRS in the past 12 months. Of 747 children with reported fever in the two weeks preceding the survey, 131 (16.3%) sought medical attention within 24 hours. Of those with fever, 86 (11.9%) took an anti-malarial drug and 41 (4.7%) took it within 24 hours of fever onset. Among 7,167 surveyed individuals of all ages, parasitaemia as estimated by microscopy was 1.0% (95% CI 0.5 - 1.5), with 0.7% and 0.3% due to Plasmodium falciparum and Plasmodium vivax, respectively. Moderate-severe anaemia (haemoglobin <8 g/dl) was observed in 239/3,366 (6.6%, 95% CI 4.9-8.3) children <5 years of age. Conclusions Since mid-2005, the Ethiopian National Malaria Control Programme has considerably scaled-up its malaria prevention and control interventions, demonstrating the impact of strong political will and a committed partnership. The MIS showed, however, that besides sustaining and expanding malaria intervention coverage, efforts will have to be made to increase intervention access and use. With ongoing efforts to sustain and expand malaria intervention coverage, to increase intervention access and use, and with strong involvement of the community, Ethiopia expects to achieve its targets in terms of coverage and uptake of interventions in the coming years and move towards eliminating malaria. PMID:20178654

Medical coverage of gymnastics competitions.

PubMed

Hecht, Suzanne S; Burton, Monique S

2009-01-01

Medical coverage of gymnastics competitions can be a challenging task for the sports medicine physician and other medical personnel because of the complexity and aerial nature of the sport. A broad understanding of the six gymnastics disciplines, along with the type of competitions, injury epidemiology, and the common acute gymnastics injuries will help sports medicine professionals in planning and delivering optimal care to the injured or ill gymnast.

Unappreciated epidemiology: the churn effect in a regional HIV care programme.

PubMed

Gill, M J; Krentz, H B

2009-08-01

High levels of geographic mobility in and out of HIV care centres (i.e. the churn effect) can disrupt the continuity of patient care, misalign prevention services, impact local prevalence data perturbing optimal allocation of resources, and contribute to logical challenges in repeated transfer of health records. We report on the clinical, demographic, and administrative impact of high population turnover within HIV populations.

Evaluation of an Optimal Epidemiological Typing Scheme for Legionella pneumophila with Whole-Genome Sequence Data Using Validation Guidelines

PubMed Central

Mentasti, Massimo; Tewolde, Rediat; Aslett, Martin; Harris, Simon R.; Afshar, Baharak; Underwood, Anthony; Harrison, Timothy G.

2016-01-01

Sequence-based typing (SBT), analogous to multilocus sequence typing (MLST), is the current “gold standard” typing method for investigation of legionellosis outbreaks caused by Legionella pneumophila. However, as common sequence types (STs) cause many infections, some investigations remain unresolved. In this study, various whole-genome sequencing (WGS)-based methods were evaluated according to published guidelines, including (i) a single nucleotide polymorphism (SNP)-based method, (ii) extended MLST using different numbers of genes, (iii) determination of gene presence or absence, and (iv) a kmer-based method. L. pneumophila serogroup 1 isolates (n = 106) from the standard “typing panel,” previously used by the European Society for Clinical Microbiology Study Group on Legionella Infections (ESGLI), were tested together with another 229 isolates. Over 98% of isolates were considered typeable using the SNP- and kmer-based methods. Percentages of isolates with complete extended MLST profiles ranged from 99.1% (50 genes) to 86.8% (1,455 genes), while only 41.5% produced a full profile with the gene presence/absence scheme. Replicates demonstrated that all methods offer 100% reproducibility. Indices of discrimination range from 0.972 (ribosomal MLST) to 0.999 (SNP based), and all values were higher than that achieved with SBT (0.940). Epidemiological concordance is generally inversely related to discriminatory power. We propose that an extended MLST scheme with ∼50 genes provides optimal epidemiological concordance while substantially improving the discrimination offered by SBT and can be used as part of a hierarchical typing scheme that should maintain backwards compatibility and increase discrimination where necessary. This analysis will be useful for the ESGLI to design a scheme that has the potential to become the new gold standard typing method for L. pneumophila. PMID:27280420