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Sample records for acute malaria infection

  1. Acute pancreatitis, ascites, and acute renal failure in Plasmodium vivax malaria infection, a rare complication.

    PubMed

    Lakhotia, Manoj; Pahadiya, Hans Raj; Kumar, Harish; Singh, Jagdish; Sangappa, Jainapur Ravi; Choudhary, Prakash Kumar

    2015-01-01

    A 22-year-old male presented with 6 days history of intermittent fever with chills, 2 days history of upper abdomen pain, distension of abdomen, and decreased urine output. He was diagnosed to have Plasmodium vivax malaria, acute pancreatitis, ascites, and acute renal failure. These constellations of complications in P. vivax infection have never been reported in the past. The patient responded to intravenous chloroquine and supportive treatment. For renal failure, he required hemodialysis. Acute pancreatitis, ascites, and acute renal failure form an unusual combination in P. vivax infection. PMID:26629455

  2. Complication of Corticosteroid Treatment by Acute Plasmodium malariae Infection Confirmed by Small-Subunit rRNA Sequencing▿

    PubMed Central

    To, Kelvin K. W.; Teng, Jade L. L.; Wong, Samson S. Y.; Ngan, Antonio H. Y.; Yuen, Kwok-Yung; Woo, Patrick C. Y.

    2010-01-01

    We report a case of acute Plasmodium malariae infection complicating corticosteroid treatment for membranoproliferative glomerulonephritis in a patient from an area where P. malariae infection is not endemic. A peripheral blood smear showed typical band-form trophozoites compatible with P. malariae or Plasmodium knowlesi. SSU rRNA sequencing confirmed the identity to be P. malariae. PMID:20739487

  3. Anesthetic management of urgent cesarean delivery in a parturient with acute malaria infection: a case report

    PubMed Central

    Dell'Anna, Antonio Maria; Catarci, Stefano; Frassanito, Luciano; Vagnoni, Salvatore; Draisci, Gaetano

    2016-01-01

    Malaria is associated with high rates of morbidity and mortality worldwide, particularly in Africa, Southeast Asia and South America. Nonetheless, several cases of malaria have been reported in Western countries involving travelers from endemic areas, though very few involve pregnant women. In this article, we report a case of a young woman born in Sierra Leone who had been living in Italy for two years. She was admitted to our hospital with malaise; worsening of her condition led to Plasmodium falciparum infection diagnosis early during her hospital stay, as well as an urgent cesarean delivery. We briefly discuss the features of malaria in pregnancy, the difficulties associated with early diagnosis, and the possible fetal and maternal implications, and also consider how the disease may affect anesthetic management. PMID:27066212

  4. Anesthetic management of urgent cesarean delivery in a parturient with acute malaria infection: a case report.

    PubMed

    Zanfini, Bruno Antonio; Dell'Anna, Antonio Maria; Catarci, Stefano; Frassanito, Luciano; Vagnoni, Salvatore; Draisci, Gaetano

    2016-04-01

    Malaria is associated with high rates of morbidity and mortality worldwide, particularly in Africa, Southeast Asia and South America. Nonetheless, several cases of malaria have been reported in Western countries involving travelers from endemic areas, though very few involve pregnant women. In this article, we report a case of a young woman born in Sierra Leone who had been living in Italy for two years. She was admitted to our hospital with malaise; worsening of her condition led to Plasmodium falciparum infection diagnosis early during her hospital stay, as well as an urgent cesarean delivery. We briefly discuss the features of malaria in pregnancy, the difficulties associated with early diagnosis, and the possible fetal and maternal implications, and also consider how the disease may affect anesthetic management. PMID:27066212

  5. Idiopathic acute myocarditis during treatment for controlled human malaria infection: a case report

    PubMed Central

    2014-01-01

    A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between

  6. Malaria

    MedlinePlus

    Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium ... Malaria is caused by a parasite that is passed to humans by the bite of infected Anopheles ...

  7. A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever.

    PubMed

    Ahmad, S; Dhar, M; Mittal, G; Bhat, N K; Shirazi, N; Kalra, V; Sati, H C; Gupta, V

    2016-04-01

    Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono-infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co-infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono-infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross-reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection. PMID:26851948

  8. Malaria infection and human evolution.

    PubMed

    Sabbatani, Sergio; Manfredi, Roberto; Fiorino, Sirio

    2010-03-01

    During the evolution of the genus Homo, with regard to the species habilis, erectus and sapiens, malaria has played a key biological role in influencing human development. The plasmodia causing malaria have evolved in two ways, in biological and phylogenetic terms: Plasmodium vivax, Plasmodium malariae and Plasmodium ovale appear to have either coevolved with human mankind, or encountered human species during the most ancient phases of Homo evolution; on the other hand, Plasmodium falciparum has been transmitted to humans by monkeys in a more recent period, probably between the end of the Mesolithic and the beginning of the Neolithic age. The authors show both direct and indirect biomolecular evidence of malarial infection, detected in buried subjects, dating to ancient times and brought to light in the course of archaeological excavations in major Mediterranean sites. In this review of the literature the authors present scientific evidence confirming the role of malaria in affecting the evolution of populations in Mediterranean countries. The people living in several different Mediterranean regions, the cradle of western civilization, have been progressively influenced by malaria in the course of the spread of this endemic disease in recent millennia. In addition, populations affected by endemic malaria progressively developed cultural, dietary and behavioural adaptation mechanisms, which contributed to diminish the risk of disease. These habits were probably not fully conscious. Nevertheless it may be thought that both these customs and biological modifications, caused by malarial plasmodia, favoured the emergence of groups of people with greater resistance to malaria. All these factors have diminished the unfavourable demographic impact of the disease, also positively influencing the general development and growth of civilization. PMID:20424529

  9. Acute renal failure due to falciparum malaria.

    PubMed

    Habte, B

    1990-01-01

    Seventy-two patients with severe falciparum malaria are described. Twenty-four (33.3%) were complicated by acute renal failure. Comparing patients with renal failure and those without, statistically significant differences occurred regarding presence of cerebral malaria (83% vs 46%), jaundice (92% vs 33%), and death (54% vs 17%). A significantly higher number of patients with renal failure were nonimmune visitors to malaria endemic regions. Renal failure was oliguric in 45% of cases. Dialysis was indicated in 38%, 29% died in early renal failure, and 33% recovered spontaneously. It is concluded that falciparum malaria is frequently complicated by cerebral malaria and renal failure. As nonimmune individuals are prone to develop serious complications, malaria prophylaxis and vigorous treatment of cases is mandatory. PMID:2236718

  10. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.

    PubMed

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi

    2016-03-01

    In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. PMID:26755155

  11. Acute Pancreatitis in a Patient with Complicated Falciparum Malaria

    PubMed Central

    Bhattacharya, Prasanta Kumar; Lynrah, Kryshan G; Ete, Tony; Issar, Neel Kanth

    2016-01-01

    Malaria is one of the most common protozoan diseases, especially in tropical countries. The clinical manifestation of malaria, especially falciparum malaria varies from mild acute febrile illness to life threatening severe systemic complications involving one or more organ systems. We would like to report a case of complicated falciparum malaria involving cerebral, renal, hepatic system along with acute pancreatitis. The patient was successfully treated with anti malarial and other supportive treatment. To the best of our knowledge there are very few reports of acute pancreatitis due to malaria. Falciparum malaria therefore should be added to the list of infectious agents causing acute pancreatitis especially in areas where malaria is endemic. PMID:26894117

  12. Ear infection - acute

    MedlinePlus

    Otitis media - acute; Infection - inner ear; Middle ear infection - acute ... Casselbrandt ML, Mandel EM. Acute otitis media and otitis media with effusion. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  13. Relation between Vitamin B12 and Folate Status, and Hemoglobin Concentration and Parasitemia during Acute Malaria Infections in Colombia

    PubMed Central

    Caicedo, Olga; Villamor, Eduardo; Forero, Yibby; Ziade, José; Pérez, Pilar; Quiñones, Francisco; Arévalo-Herrera, Myriam; Herrera, Sócrates

    2010-01-01

    Anemia is a common complication of human malaria. Since micronutrient deficiencies are highly prevalent in malaria-endemic areas and appear to contribute to anemia etiology, we conducted a cross-sectional study in Tumaco, Colombia, to examine the associations between plasma vitamin B12 or erythrocyte folate concentrations and hemoglobin (Hb) among 96 adults with predominantly Plasmodium falciparum malaria. Prevalence of folate and vitamin B12 deficiencies were 26.0% and 26.6%, respectively. There was an inverse, linear relation between folate and Hb concentrations. Adjusted difference in Hb between lowest and highest folate quartiles was 1 g/dL (p = 0.04; p, test for trend = 0.01). Vitamin B12 was not associated with Hb concentrations and did not modify the associations between folate and Hb. Incidentally, body mass index (BMI) was inversely associated with parasitemia and risk of clinical malaria. Future longitudinal studies are warranted to determine the potential pathophysiological role of folate in malaria-related anemia. PMID:19931503

  14. Cardiac complication after experimental human malaria infection: a case report

    PubMed Central

    2009-01-01

    A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear. PMID:19958549

  15. Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections.

    PubMed

    Kung'u, Jacqueline K; Wright, Victoria J; Haji, Hamad J; Ramsan, Mahdi; Goodman, David; Tielsch, James M; Bickle, Quentin D; Raynes, John G; Stoltzfus, Rebecca J

    2009-11-01

    The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever. We then examined the influence of the APR on each iron status indicator using regression analysis with Hb as the outcome variable. Ferritin was inversely related to Hb in the APR-unadjusted model. Adjusting for the APR using reported recent fever alone was not sufficient to reverse the inverse Hb-ferritin relationship. However, using CRP and/or AGP resulted in the expected positive relationship. The best fit model included reported recent fever, AGP and CRP (R(2) = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models included reported recent fever and AGP but not CRP (R(2) = 0.253, 0.310, and 0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by the APR, whereas ferritin was immensely affected. Reported recent fever alone cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting if only 1 APP can be measured. However, AGP best predicted the APR in this population. PMID:19741202

  16. Dynamic alteration in splenic function during acute falciparum malaria

    SciTech Connect

    Looareesuwan, S.; Ho, M.; Wattanagoon, Y.; White, N.J.; Warrell, D.A.; Bunnag, D.; Harinasuta, T.; Wyler, D.J.

    1987-09-10

    Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated /sup 51/Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes (mean +/- SD) vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

  17. The Avian Transcriptome Response to Malaria Infection

    PubMed Central

    Videvall, Elin; Cornwallis, Charlie K.; Palinauskas, Vaidas; Valkiūnas, Gediminas; Hellgren, Olof

    2015-01-01

    Malaria parasites are highly virulent pathogens which infect a wide range of vertebrates. Despite their importance, the way different hosts control and suppress malaria infections remains poorly understood. With recent developments in next-generation sequencing techniques, however, it is now possible to quantify the response of the entire transcriptome to infections. We experimentally infected Eurasian siskins (Carduelis spinus) with avian malaria parasites (Plasmodium ashfordi), and used high-throughput RNA-sequencing to measure the avian transcriptome in blood collected before infection (day 0), during peak parasitemia (day 21 postinfection), and when parasitemia was decreasing (day 31). We found considerable differences in the transcriptomes of infected and uninfected individuals, with a large number of genes differentially expressed during both peak and decreasing parasitemia stages. These genes were overrepresented among functions involved in the immune system, stress response, cell death regulation, metabolism, and telomerase activity. Comparative analyses of the differentially expressed genes in our study to those found in other hosts of malaria (human and mouse) revealed a set of genes that are potentially involved in highly conserved evolutionary responses to malaria infection. By using RNA-sequencing we gained a more complete view of the host response, and were able to pinpoint not only well-documented host genes but also unannotated genes with clear significance during infection, such as microRNAs. This study shows how the avian blood transcriptome shifts in response to malaria infection, and we believe that it will facilitate further research into the diversity of molecular mechanisms that hosts utilize to fight malaria infections. PMID:25636457

  18. ASSESSMENT OF HOST RESISTANCE TO INFECTION WITH RODENT MALARIA

    EPA Science Inventory

    Resistance to malaria infection is known to require an intact immune system. his chapter presents an overview of rodent malaria, the host response to infection and methods for assessing infection in rats and mice.

  19. Pathogenesis of acute avian malaria. II. Anemia mediated by a cold-active autohemagglutinin from the blood of chickens with acute Plasmodium gallinaceum infection.

    PubMed

    Soni, J L; Cox, H W

    1975-03-01

    A cold-active hemagglutinin for trypsinized human type "O" erythrocytes (CAH) from blood of chickens with acute Plasmodium gallinaceum malaria was found to be associated with 19 S and 7 S globulin fractions of malarious chicken blood, but cleavage with 2-mercaptoethanol indicated that it was primarily of the IgM class of antibody. In serologic tests CAH reacted with trypsinized erythrocytes, and anti-chicken globulin. It did not react with other of the antigens or antibodies detected in the blood of malarious chickens. When the absorbed and eluted CAH was injected into normal chickens it produced an anaphylactic-like shock and caused a 25% reduction in red blood cell counts within 48 hours. Plasma samples collected during this interval showed signs of hemolysis. Reactions of blood cells from the recipient birds with fluorescein conjugated anti-chicken globulin indicated that CAH reacted with erythrocytes. The absence of fluorescent activity 3 days after injection suggested that these erythrocytes had been removed from the circulation. When normal chickens were injected with trypsinized autologous blood cells, CAH was detected within 3 days. The agglutination test again was active at temperatures below 22 degrees C and was negative when tested at 37 degrees C. In these birds the appearance of CAH was accompanied by reductions in red blood cell counts and by hemolysis. The results of these experiments suggest that CAH was not stimulated by plasmodial parasite antigen, but rather by autoantigens, which appear to be common to heterologous animal species, and which were in some manner expressed by the presence of the intracellular parasites, or by trypsin treatment. The experiments further suggest that this autohemagglutinin was partially causal of malarial anemia. The presence of other anemia factor(s) was indicated by anemia following injection of plasma that had been absorbed free of CAH. PMID:804265

  20. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  1. Malaria

    MedlinePlus

    MENU Return to Web version Malaria Overview What is malaria? Malaria is an infection of a part of the blood called the red blood cells. It is ... by mosquitoes that carry a parasite that causes malaria. If a mosquito carrying this parasite bites you, ...

  2. Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

    PubMed Central

    Carmona-Fonseca, Jaime; Arango, Eliana; Maestre, Amanda

    2013-01-01

    Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive. PMID:23546807

  3. A High Malaria Prevalence Identified by PCR among Patients with Acute Undifferentiated Fever in India

    PubMed Central

    Haanshuus, Christel Gill; Chandy, Sara; Manoharan, Anand; Vivek, Rosario; Mathai, Dilip; Xena, Deepika; Singh, Ashita; Langeland, Nina; Blomberg, Bjørn; Vasanthan, George; Sitaram, Usha; Appasamy, Jonathan; Nesaraj, Joel; Henry, Anil; Patil, Suvarna; Alvarez-Uria, Gerardo; Armstrong, Lois; Mørch, Kristine

    2016-01-01

    Background Approximately one million malaria cases were reported in India in 2015, based on microscopy. This study aims to assess the malaria prevalence among hospitalised fever patients in India identified by PCR, and to evaluate the performance of routine diagnostic methods. Methods During June 2011-December 2012, patients admitted with acute undifferentiated fever to seven secondary level community hospitals in Assam (Tezpur), Bihar (Raxaul), Chhattisgarh (Mungeli), Maharashtra (Ratnagiri), Andhra Pradesh (Anantapur) and Tamil Nadu (Oddanchatram and Ambur) were included. The malaria prevalence was assessed by polymerase chain reaction (PCR), routine microscopy, and a rapid diagnostic test (RDT) with PCR as a reference method. Results The malaria prevalence by PCR was 19% (268/1412) ranging from 6% (Oddanchatram, South India) to 35% (Ratnagiri, West India). Among malaria positive patients P. falciparum single infection was detected in 46%, while 38% had P. vivax, 11% mixed infections with P. falciparum and P. vivax, and 5% P. malariae. Compared to PCR, microscopy had sensitivity of 29% and specificity of 98%, while the RDT had sensitivity of 24% and specificity of 99%. Conclusions High malaria prevalence was identified by PCR in this cohort. Routine diagnostic methods had low sensitivity compared to PCR. The results suggest that malaria is underdiagnosed in rural India. However, low parasitaemia controlled by immunity may constitute a proportion of PCR positive cases, which calls for awareness of the fact that other pathogens could be responsible for the febrile disease in submicroscopic malaria. PMID:27389396

  4. Malaria

    PubMed Central

    Suh, Kathryn N.; Kain, Kevin C.; Keystone, Jay S.

    2004-01-01

    Malaria is a parasitic infection of global importance. Although relatively uncommon in developed countries, where the disease occurs mainly in travellers who have returned from endemic regions, it remains one of the most prevalent infections of humans worldwide. In endemic regions, malaria is a significant cause of morbidity and mortality and creates enormous social and economic burdens. Current efforts to control malaria focus on reducing attributable morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated bed nets have been successful in some endemic areas. For travellers to malaria-endemic regions, personal protective measures and appropriate chemoprophylaxis can significantly reduce the risk of infection. Prompt evaluation of the febrile traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis, and appropriate antimalarial therapy are essential in order to optimize clinical outcomes of infected patients. Additional approaches to malaria control, including genetic manipulation of mosquitoes and malaria vaccines, are areas of ongoing research. PMID:15159369

  5. Malaria

    MedlinePlus

    Malaria is a serious disease caused by a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of death worldwide, but ... at risk. There are four different types of malaria caused by four related parasites. The most deadly ...

  6. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  7. Macrophage migration inhibitory factor and placental malaria infection in an area characterized by unstable malaria transmission in central Sudan

    PubMed Central

    Eltayeb, Reem; Bilal, Naser; Abass, Awad-Elkareem; Elhassan, Elhassan M.; Mohammed, Ahmed; Adam, Ishag

    2015-01-01

    Background: The pathogenesis of malaria during pregnancy is not fully understood. A proinflammatory cytokine, macrophage migration inhibitory factor (MIF) is suggested as a factor involved in the pathogenesis of malaria during pregnancy. Methods: A cross-sectional study was conducted in Medani Hospital, Sudan to investigate MIF levels in placental malaria. Obstetrical and medical characteristics were gathered from each parturient woman using questionnaires. All women (151) were investigated for malaria using blood film and placental histology. MIF levels were measured using ELISA in paired maternal and cord blood samples. Results: There were no P. falciparum-positive blood films obtained from maternal peripheral blood, placenta or cord samples. Out of 151 placentae, four (2.6%), one (0.7%), 32 (21.2%) showed acute, chronic and past infection on histopathology examinations respectively, while the rest (114; 75.5%) of them showed no signs of infection.There was no significant difference in the median (interquartile) of maternal [5.0 (3.7─8.8) vs 6.2(3.5─12.0) ng/ml, P=0.643] and cord [8.1(3.3─16.9) vs 8.3(4.2─16.9), ng/ml, P= 0.601] MIF levels between women with a positive result for placental malaria infection (n=37) and women with a negative result for placental malaria infection (n=114). In regression models placental malaria was not associated with maternal MIF, hemoglobin or birth weight. MIF was not associated with hemoglobin or birth weight . Conclusion: There was no association between maternal and cord MIF levels, placental malaria, maternal hemoglobin and birth weight.

  8. 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

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

    PubMed

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

    2015-05-01

    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

  10. Effects of chronic avian malaria (Plasmodium relictum) infection on reproductive success of Hawaii Amakihi (Hemignathus virens)

    USGS Publications Warehouse

    Kilpatrick, A.M.; Lapointe, D.A.; Atkinson, C.T.; Woodworth, B.L.; Lease, J.K.; Reiter, M.E.; Gross, K.

    2006-01-01

    We studied the effects of chronic avian malaria (Plasmodium relictum) infections on the reproductive success of a native Hawaiian honeycreeper, Hawaii Amakihi (Hemignathus virens). Chronic malaria infections in male and female parents did not significantly reduce reproductive success as measured by clutch size, hatching success, fledging mass, number of nestlings fledged, nesting success (daily survival rate), and minimum fledgling survival. In fact, nesting success of pairs with chronically infected males was significantly higher than those with uninfected males (76% vs. 38%), and offspring that had at least one parent that had survived the acute phase of malaria infection had a significantly greater chance of being resighted the following year (25% vs. 10%). The reproduction and survival of infected birds were sufficient for a per-capita population growth rate >1, which suggests that chronically infected Hawaii Amakihi could support a growing population. ?? The American Ornithologists' Union, 2006.

  11. Dissecting the determinants of malaria chronicity: why within-host models struggle to reproduce infection dynamics.

    PubMed

    Childs, Lauren M; Buckee, Caroline O

    2015-03-01

    The duration of infection is fundamental to the epidemiological behaviour of any infectious disease, but remains one of the most poorly understood aspects of malaria. In endemic areas, the malaria parasite Plasmodium falciparum can cause both acute, severe infections and asymptomatic, chronic infections through its interaction with the host immune system. Frequent superinfection and massive parasite genetic diversity make it extremely difficult to accurately measure the distribution of infection lengths, complicating the estimation of basic epidemiological parameters and the prediction of the impact of interventions. Mathematical models have qualitatively reproduced parasite dynamics early during infection, but reproducing long-lived chronic infections remains much more challenging. Here, we construct a model of infection dynamics to examine the consequences of common biological assumptions for the generation of chronicity and the impact of co-infection. We find that although a combination of host and parasite heterogeneities are capable of generating chronic infections, they do so only under restricted parameter choices. Furthermore, under biologically plausible assumptions, co-infection of parasite genotypes can alter the course of infection of both the resident and co-infecting strain in complex non-intuitive ways. We outline the most important puzzles for within-host models of malaria arising from our analysis, and their implications for malaria epidemiology and control. PMID:25673299

  12. Malaria

    MedlinePlus

    ... a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of ... insect repellent with DEET Cover up Sleep under mosquito netting Centers for Disease Control and Prevention

  13. Parasite virulence, co-infections and cytokine balance in malaria

    PubMed Central

    Gonçalves, Raquel Müller; Lima, Nathália Ferreira; Ferreira, Marcelo Urbano

    2014-01-01

    Strong early inflammatory responses followed by a timely production of regulatory cytokines are required to control malaria parasite multiplication without inducing major host pathology. Here, we briefly examine the homeostasis of inflammatory responses to malaria parasite species with varying virulence levels and discuss how co-infections with bacteria, viruses, and helminths can modulate inflammation, either aggravating or alleviating malaria-related morbidity. PMID:24854175

  14. Anesthetic management of parturient with thoracic kyphoscoliosis, malaria and acute respiratory distress syndrome for urgent cesarean section

    PubMed Central

    Pandey, Ravindra Kr; Batra, Meenu M; Darlong, Vanlal; Garg, Rakesh; Punj, Jyotsna; Kumar, Sri

    2015-01-01

    The management of cesarean section in kyphoscoliotic patient is challenging. The respiratory changes and increased metabolic demands due to pregnancy may compromise the limited respiratory reserves in such patients. Presence of other comorbidities like malaria and respiratory tract infection will further compromise the effective oxygenation. We report a case of kyphoscoliosis along with malaria and acute respiratory distress syndrome for urgent cesarean section. PMID:26702219

  15. Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response

    PubMed Central

    Pathak, Vrushali A.

    2016-01-01

    Anemia is the primary clinical manifestation of malarial infections and is responsible for the substantial rate of morbidity. The pathophysiology discussed till now catalogued several causes for malarial anemia among which ineffective erythropoiesis being remarkable one occurs silently in the bone marrow. A systematic literature search was performed and summarized information on erythropoietic response upon malaria infection and the factors responsible for the same. This review summarizes the clinical and experimental studies on patients, mouse models, and in vitro cell cultures reporting erythropoietic changes upon malaria infection as well as factors accountable for the same. Inadequate erythropoietic response during malaria infection may be the collective effect of various mediators generated by host immune response as well as parasite metabolites. The interplay between various modulators causing the pathophysiology needs to be explored further. Globin gene expression profiling upon malaria infection should also be looked into as abnormal production of globin chains could be a possible contributor to ineffective erythropoiesis. PMID:27034825

  16. Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

    PubMed

    Choi, Iee Ho; Hwang, Pyoung Han; Choi, Sam Im; Lee, Dae Yeol; Kim, Min Sun

    2016-09-01

    Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas. PMID:27510397

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

    PubMed Central

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

    2013-01-01

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

  18. Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.

    PubMed

    Drabe, Camilla H; Vestergaard, Lasse S; Helleberg, Marie; Nyagonde, Nyagonde; Rose, Michala V; Francis, Filbert; Theilgaard, Ola P; Asbjørn, Jens; Amos, Ben; Bygbjerg, Ib Christian; Ruhwald, Morten; Ravn, Pernille

    2016-04-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment. PMID:26834199

  19. Malaria.

    PubMed

    White, Nicholas J; Pukrittayakamee, Sasithon; Hien, Tran Tinh; Faiz, M Abul; Mokuolu, Olugbenga A; Dondorp, Arjen M

    2014-02-22

    Although global morbidity and mortality have decreased substantially, malaria, a parasite infection of red blood cells, still kills roughly 2000 people per day, most of whom are children in Africa. Two factors largely account for these decreases; increased deployment of insecticide-treated bednets and increased availability of highly effective artemisinin combination treatments. In large trials, parenteral artesunate (an artemisinin derivative) reduced severe malaria mortality by 22·5% in Africa and 34·7% in Asia compared with quinine, whereas adjunctive interventions have been uniformly unsuccessful. Rapid tests have been an important addition to microscopy for malaria diagnosis. Chemopreventive strategies have been increasingly deployed in Africa, notably intermittent sulfadoxine-pyrimethamine treatment in pregnancy, and monthly amodiaquine-sulfadoxine-pyrimethamine during the rainy season months in children aged between 3 months and 5 years across the sub-Sahel. Enthusiasm for malaria elimination has resurfaced. This ambitious but laudable goal faces many challenges, including the worldwide economic downturn, difficulties in elimination of vivax malaria, development of pyrethroid resistance in some anopheline mosquitoes, and the emergence of artemisinin resistance in Plasmodium falciparum in southeast Asia. We review the epidemiology, clinical features, pathology, prevention, and treatment of malaria. PMID:23953767

  20. P. vivax Malaria and Dengue Fever Co-infection: A Cross-Sectional Study in the Brazilian Amazon

    PubMed Central

    Magalhães, Belisa M. L.; Siqueira, André M.; Alexandre, Márcia A. A.; Souza, Marcela S.; Gimaque, João B.; Bastos, Michele S.; Figueiredo, Regina M. P.; Melo, Gisely C.; Lacerda, Marcus V. G.; Mourão, Maria P. G.

    2014-01-01

    Background Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity. Methodology/Principal Findings A cross-sectional study was conducted (2009 to 2011) in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1%) presented P. vivax malaria mono-infection, 584 (37%) dengue fever mono-infection, and 44 (2.8%) were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected), deep bleeding (vs. P. vivax mono-infected), hepatomegaly, and jaundice (vs. dengue mono-infected). Conclusions/Significance In endemic areas for dengue and malaria, jaundice (in dengue patients) and spontaneous bleeding (in malaria patients) should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group. PMID:25340346

  1. Changes in serum lipid profile in the acute and convalescent Plasmodium vivax malaria: A cohort study.

    PubMed

    Mesquita, Teresinha C; Martin, Thamires G O; Alves, Eduardo R; Mello, Marcia B C; Nery, Andreia F; Gomes, Luciano T; Fontes, Cor Jesus F

    2016-11-01

    Although serum lipids are known to be altered in Plasmodium falciparum-induced malaria, little is known about such changes due to Plasmodium vivax infection. This cohort study assessed serum concentrations of triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in 164 patients in the acute phase of malaria caused by P. vivax and characterized these changes in the convalescent phase after treatment with chloroquine and primaquine. Compared to reference values, serum total cholesterol, LDL, and HDL levels were lower and triglyceride levels were higher in the acute phase. Moreover, the parasite density was negatively correlated with LDL (r=-0,189; p=0.027) and HDL (r=-0,256; p=0.001) serum levels. Eighty patients returned for clinical and laboratory revaluation 7-12days after treatment initiation. All patients showed parasite clearance and the absence of symptoms during the convalescent phase. Analysis of the serum lipids of these 80 patients showed significant increases in the serum levels of total cholesterol (p<0.0001), LDL (p<0.0001), and HDL (p<0.0001) as well as a significant reduction in triglycerides (p=0.004), indicating a trend towards a return to normal levels. This transient change in lipid profile between the acute and convalescent stages may be useful for the clinical monitoring of patients treated for vivax malaria. PMID:27461878

  2. Diagnosis of Malaria Infection with or without Disease

    PubMed Central

    Bisoffi, Zeno; Gobbi, Federico; Buonfrate, Dora; Van den Ende, Jef

    2012-01-01

    The revised W.H.O. guidelines for malaria management in endemic countries recommend that treatment should be reserved to laboratory confirmed cases, both for adults and children. Currently the most widely used tools are rapid diagnostic tests (RDTs), that are accurate and reliable in diagnosing malaria infection. However, an infection is not necessarily a clinical malaria, and RDTs may give positive results in febrile patients who have another cause of fever. Excessive reliance on RDTs may cause overlooking potentially severe non malarial febrile illnesses (NMFI) in these cases. In countries or areas where transmission intensity remains very high, fever management in children (especially in the rainy season) should probably remain presumptive, as a test-based management may not be safe, nor cost effective. In contrast, in countries with low transmission, including those targeted for malaria elimination, RDTs are a key resource to limit unnecessary antimalarial prescription and to identify pockets of infected individuals. Research should focus on very sensitive tools for infection on one side, and on improved tools for clinical management on the other, including biomarkers of clinical malaria and/or of alternative causes of fever. PMID:22708051

  3. Common Epidemiology of Rickettsia felis Infection and Malaria, Africa

    PubMed Central

    Mediannikov, Oleg; Socolovschi, Cristina; Edouard, Sophie; Fenollar, Florence; Mouffok, Nadjet; Bassene, Hubert; Diatta, Georges; Tall, Adama; Niangaly, Hamidou; Doumbo, Ogobara; Lekana-Douki, Jean Bernard; Znazen, Abir; Sarih, M’hammed; Ratmanov, Pavel; Richet, Herve; Ndiath, Mamadou O.; Sokhna, Cheikh; Parola, Philippe

    2013-01-01

    This study aimed to compare the epidemiology of Rickettsia felis infection and malaria in France, North Africa, and sub-Saharan Africa and to identify a common vector. Blood specimens from 3,122 febrile patients and from 500 nonfebrile persons were analyzed for R. felis and Plasmodium spp. We observed a significant linear trend (p<0.0001) of increasing risk for R. felis infection. The risks were lowest in France, Tunisia, and Algeria (1%), and highest in rural Senegal (15%). Co-infections with R. felis and Plasmodium spp. and occurrences of R. felis relapses or reinfections were identified. This study demonstrates a correlation between malaria and R. felis infection regarding geographic distribution, seasonality, asymptomatic infections, and a potential vector. R. felis infection should be suspected in these geographical areas where malaria is endemic. Doxycycline chemoprophylaxis against malaria in travelers to sub-Saharan Africa also protects against rickettsioses; thus, empirical treatment strategies for febrile illness for travelers and residents in sub-Saharan Africa may require reevaluation. PMID:24188709

  4. Backward elastic light scattering of malaria infected red blood cells

    NASA Astrophysics Data System (ADS)

    Lee, Seungjun; Lu, Wei

    2011-08-01

    We investigated the backward light scattering pattern of healthy and malaria (Plasmodium falciparum) parasitized red blood cells. The spectrum could clearly distinguish between predominant ring stage infected blood cells and healthy blood cells. Further, we found that infected samples mixed with different stages of P. falciparum showed different signals, suggesting that even variance in parasite stages could also be detected by the spectrum. These results together with the backward scattering technique suggest the potential of non-invasive diagnosis of malaria through light scattering of blood cells near the surface of human body, such as using eyes or skin surface.

  5. Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum

    PubMed Central

    Yamagishi, Junya; Natori, Anna; Tolba, Mohammed E.M.; Mongan, Arthur E.; Sugimoto, Chihiro; Katayama, Toshiaki; Kawashima, Shuichi; Makalowski, Wojciech; Maeda, Ryuichiro; Eshita, Yuki; Tuda, Josef

    2014-01-01

    To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasite Plasmodium falciparum (Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags. We were thus able to simultaneously analyze expression patterns in both humans and parasites. We identified human and parasite genes and pathways that correlated with various clinical data, which may serve as primary targets for drug developments. Of particular importance, we revealed characteristic expression changes in the human innate immune response pathway genes including TLR2 and TICAM2 that correlated with the severity of the malaria infection. We also found a group of transcription regulatory factors, JUND, for example, and signaling molecules, TNFAIP3, for example, that were strongly correlated in the expression patterns of humans and parasites. We also identified several genetic variations in important anti-malaria drug resistance-related genes. Furthermore, we identified the genetic variations which are potentially associated with severe malaria symptoms both in humans and parasites. The newly generated data should collectively lay a unique foundation for understanding variable behaviors of the field malaria parasites, which are far more complex than those observed under laboratory conditions. PMID:25091627

  6. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

    PubMed Central

    2013-01-01

    Background Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Methods Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient’s condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Results Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. Discussion In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Conclusion Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID:24180319

  7. Natural malaria infection reduces starvation resistance of nutritionally stressed mosquitoes.

    PubMed

    Lalubin, Fabrice; Delédevant, Aline; Glaizot, Olivier; Christe, Philippe

    2014-07-01

    In disease ecology, there is growing evidence that environmental quality interacts with parasite and host to determine host susceptibility to an infection. Most studies of malaria parasites have focused on the infection costs incurred by the hosts, and few have investigated the costs on mosquito vectors. The interplay between the environment, the vector and the parasite has therefore mostly been ignored and often relied on unnatural or allopatric Plasmodium/vector associations. Here, we investigated the effects of natural avian malaria infection on both fecundity and survival of field-caught female Culex pipiens mosquitoes, individually maintained in laboratory conditions. We manipulated environmental quality by providing mosquitoes with different concentrations of glucose-feeding solution prior to submitting them to a starvation challenge. We used molecular-based methods to assess mosquitoes' infection status. We found that mosquitoes infected with Plasmodium had lower starvation resistance than uninfected ones only under low nutritional conditions. The effect of nutritional stress varied with time, with the difference of starvation resistance between optimally and suboptimally fed mosquitoes increasing from spring to summer, as shown by a significant interaction between diet treatment and months of capture. Infected and uninfected mosquitoes had similar clutch size, indicating no effect of infection on fecundity. Overall, this study suggests that avian malaria vectors may suffer Plasmodium infection costs in their natural habitat, under certain environmental conditions. This may have major implications for disease transmission in the wild. PMID:24286465

  8. Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

    PubMed Central

    Lovegrove, Fiona E.; Gharib, Sina A.; Peña-Castillo, Lourdes; Patel, Samir N.; Ruzinski, John T.; Hughes, Timothy R.

    2008-01-01

    Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar–capillary membrane barrier—the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36−/− mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality. PMID:18483551

  9. Coagulation and Fibrinolysis Indicators and Placental Malaria Infection in an Area Characterized by Unstable Malaria Transmission in Central Sudan

    PubMed Central

    Mostafa, Amged G.; Bilal, Naser E.; Abass, Awad-Elkareem; Elhassan, Elhassan M.; Mohmmed, Ahmed A.; Adam, Ishag

    2015-01-01

    This study aimed to investigate coagulation, fibrinolysis indicators, and malaria during pregnancy. Methods. A cross-sectional study was conducted at Medani, Sudan. Sociodemographic characteristics were gathered from each parturient woman (163) and malaria was investigated by blood film and placental histology. Protein C, protein S, antithrombin-III, tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 levels (PAI-1) were measured using ELISA. Results. One (0.6%), three (1.8), and 19 (11.7%) of the placentae showed active, chronic, and past infection on a histopathological examination, respectively, while 140 (85.9%) of them showed no signs of malaria infection. While the mean [SD] of the protein C, antithrombin-III, and TFPI was significantly lower, there was no significant difference in protein S and PAI-1 levels in women with placental malaria infection (n = 23) compared to those without placental malaria infection (140). In linear regression, placental malaria infection was associated with antithrombin-III. There was no association between placental malaria infections and protein C, protein S, TFPI, and PAI-1 levels. There was no association between hemoglobin, birth weight, and the investigated coagulation and fibrinolysis indicators. Conclusion. This study showed significantly lower levels of protein C, antithrombin-III, and TFPI in women with placental malaria infections. PMID:26295004

  10. Single-cell genomics for dissection of complex malaria infections

    PubMed Central

    Nair, Shalini; Nkhoma, Standwell C.; Serre, David; Zimmerman, Peter A.; Gorena, Karla; Daniel, Benjamin J.; Nosten, François; Anderson, Timothy J.C.; Cheeseman, Ian H.

    2014-01-01

    Most malaria infections contain complex mixtures of distinct parasite lineages. These multiple-genotype infections (MGIs) impact virulence evolution, drug resistance, intra-host dynamics, and recombination, but are poorly understood. To address this we have developed a single-cell genomics approach to dissect MGIs. By combining cell sorting and whole-genome amplification (WGA), we are able to generate high-quality material from parasite-infected red blood cells (RBCs) for genotyping and next-generation sequencing. We optimized our approach through analysis of >260 single-cell assays. To quantify accuracy, we decomposed mixtures of known parasite genotypes and obtained highly accurate (>99%) single-cell genotypes. We applied this validated approach directly to infections of two major malaria species, Plasmodium falciparum, for which long term culture is possible, and Plasmodium vivax, for which no long-term culture is feasible. We demonstrate that our single-cell genomics approach can be used to generate parasite genome sequences directly from patient blood in order to unravel the complexity of P. vivax and P. falciparum infections. These methods open the door for large-scale analysis of within-host variation of malaria infections, and reveal information on relatedness and drug resistance haplotypes that is inaccessible through conventional sequencing of infections. PMID:24812326

  11. A Phenanthrene Methanol (WR 33063) for Treatment of Acute Malaria

    PubMed Central

    Arnold, J. D.; Martin, D. C.; Carson, P. E.; Rieckmann, K. H.; Willerson, D.; Clyde, D. F.; Miller, R. M.

    1973-01-01

    WR 33063, a phenanthrene methanol, was studied in human volunteers for tolerance and toxicity. In normal volunteers, it was possible to give 4.6 g in four divided doses without adverse effect for 10 days. At this dose level, there was neither evidence of photosensitivity nor adverse renal or cardiac effect. At a dose level of 1.6 g in four divided doses for 6 days, WR 33063 cured 18 of 23 nonimmune volunteers infected with the Smith strain of Plasmodium falciparum from Vietnam. In addition, infections due to the Marks and Braithwaite Vietnam strains were also treated because these strains represent a major therapeutic challenge to chloroquine; six of six and two of three volunteers, respectively, were cured. With the Malayan Camp strain, 1.6 g in four divided doses for 6 days cured all of five volunteers. The African Uganda I strain of chloroquine-responsive malaria was even more responsive to WR 33063; all of six men who received 1.6 g in four divided doses for 6 days were cured, and all of three men who received this same dosage for 3 days were cured. One subject infected with a Haitian strain of P. falciparum was treated and cured. Blood-induced infections with the Chesson strain of P. vivax also responded well to WR 33063 with four of five men cured. In all, 52 men received WR 33063 in tolerance trials, and 59 men with experimental malaria and one man with clinical malaria were treated with WR 33063. PMID:4597714

  12. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    ... by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact Urine Most people come into contact with ... with another person. You should avoid kissing and sexual contact with an infected person. The virus may ...

  13. Dendritic Cells and Their Multiple Roles during Malaria Infection

    PubMed Central

    Amorim, Kelly N. S.; Chagas, Daniele C. G.; Sulczewski, Fernando B.

    2016-01-01

    Dendritic cells (DCs) play a central role in the initiation of adaptive immune responses, efficiently presenting antigens to T cells. This ability relies on the presence of numerous surface and intracellular receptors capable of sensing microbial components as well as inflammation and on a very efficient machinery for antigen presentation. In this way, DCs sense the presence of a myriad of pathogens, including Plasmodium spp., the causative agent of malaria. Despite many efforts to control this infection, malaria is still responsible for high rates of morbidity and mortality. Different groups have shown that DCs act during Plasmodium infection, and data suggest that the phenotypically distinct DCs subsets are key factors in the regulation of immunity during infection. In this review, we will discuss the importance of DCs for the induction of immunity against the different stages of Plasmodium, the outcomes of DCs activation, and also what is currently known about Plasmodium components that trigger such activation. PMID:27110574

  14. Dendritic Cells and Their Multiple Roles during Malaria Infection.

    PubMed

    Amorim, Kelly N S; Chagas, Daniele C G; Sulczewski, Fernando B; Boscardin, Silvia B

    2016-01-01

    Dendritic cells (DCs) play a central role in the initiation of adaptive immune responses, efficiently presenting antigens to T cells. This ability relies on the presence of numerous surface and intracellular receptors capable of sensing microbial components as well as inflammation and on a very efficient machinery for antigen presentation. In this way, DCs sense the presence of a myriad of pathogens, including Plasmodium spp., the causative agent of malaria. Despite many efforts to control this infection, malaria is still responsible for high rates of morbidity and mortality. Different groups have shown that DCs act during Plasmodium infection, and data suggest that the phenotypically distinct DCs subsets are key factors in the regulation of immunity during infection. In this review, we will discuss the importance of DCs for the induction of immunity against the different stages of Plasmodium, the outcomes of DCs activation, and also what is currently known about Plasmodium components that trigger such activation. PMID:27110574

  15. Host immune response in returning travellers infected with malaria

    PubMed Central

    2012-01-01

    Background Clinical observations suggest that Canadian-born (CB) travellers are prone to more severe malaria, characterized by higher parasite density in the blood, and severe symptoms, such as cerebral malaria and renal failure, than foreign-born travellers (FB) from areas of malaria endemicity. It was hypothesized that host cytokine and chemokine responses differ significantly in CB versus FB patients returning with malaria, contributing to the courses of severity. A more detailed understanding of the profiles of cytokines, chemokines, and endothelial activation may be useful in developing biomarkers and novel therapeutic approaches for malaria. Materials and methods The patient population for the study (n = 186) was comprised of travellers returning to Toronto, Canada between 2007 and 2011. The patient blood samples’ cytokine, chemokine and angiopoietin concentrations were determined using cytokine multiplex assays, and ELISA assays. Results Significantly higher plasma cytokine levels of IL-12 (p40) were observed in CB compared to FB travellers, while epidermal growth factor (EGF) was observed to be higher in FB than CB travellers. Older travellers (55 years old or greater) with Plasmodium vivax infections had significantly higher mean cytokine levels for IL-6 and macrophage colony-stimulating factor (M-CSF) than other adults with P. vivax (ages 18–55). Patients with P. vivax infections had significantly higher mean cytokine levels for monocyte chemotactic protein-1 (MCP-1), and M-CSF than patients with Plasmodium falciparum. Angiopoietin 2 (Ang-2) was higher for patients infected with P. falciparum than P. vivax, especially when comparing just the FB groups. IL-12 (p40) was higher in FB patients with P. vivax compared to P. falciparum. Il-12 (p40) was also higher in patients infected with P. vivax than those infected with Plasmodium ovale. For patients travelling to West Africa, IFN-γ and IL-6 was lower than for patients who were in other regions of Africa

  16. Does avian malaria infection affect feather stable isotope signatures?

    PubMed

    Yohannes, Elizabeth; Palinauskas, Vaidas; Valkiūnas, Gediminas; Lee, Raymond W; Bolshakov, Casimir V; Bensch, Staffan

    2011-12-01

    It is widely accepted that stable isotope ratios in inert tissues such as feather keratin reflect the dietary isotopic signature at the time of the tissue synthesis. However, some elements such as stable nitrogen isotopes can be affected by individual physiological state and nutritional stress. Using malaria infection experiment protocols, we estimated the possible effect of malaria parasite infections on feather carbon (δ(13)C) and nitrogen (δ(15)N) isotope signatures in juvenile common crossbills Loxia curvirostra. The birds were experimentally infected with Plasmodium relictum (lineage SGS1) and P. ashfordi (GRW2), two widespread parasites of passerines. Experimental birds developed heavy parasitemia of both parasites and maintained high levels throughout the experiment (33 days). We found no significant difference between experimental and control birds in both δ(13)C and δ(15)N values of feathers re-grown. The study shows that even heavy primary infections of malaria parasites do not affect feather δ(13)C and δ(15)N isotopic signatures. The results of this experiment demonstrate that feather isotope values of wild-caught birds accurately reflect the dietary isotopic sources at the time of tissue synthesis even when the animal's immune system might be challenged due to parasitic infection. PMID:21671039

  17. Pathogenicity of avian malaria in experimentally-infected Hawaii Amakihi

    USGS Publications Warehouse

    Atkinson, Carter T.; Dusek, Robert J.; Woods, K.L.; Iko, W.M.

    2000-01-01

    The introduction of avian malaria (Plasmodium relictum) and mosquitoes (Culex quinquefasciatus) to the Hawaiian Islands (USA) is believed to have played a major role in the decline and extinction of native Hawaiian honeycreepers (Drepanidinae). This introduced disease is thought to be one of the primary factors limiting recovery of honeycreepers at elevations below 1,200 m where native forest habitats are still relatively intact. One of the few remaining species of honeycreepers with a wide elevational distribution is the Hawaii Amakihi (Hernignathus virens). We measured morbidity and mortality in experimentally-infected Hawaii Amakihi that were captured in a high elevation, xeric habitat that is above the current range of the mosquito vector. Mortality among amakihi exposed to a single infective mosquito bite was 65% (13/20). All infected birds had significant declines in food consumption and a corresponding loss in body weight over the 60 day course of the experiment. Gross and microscopic lesions in birds that succumbed to malaria included enlargement and discoloration of the spleen and liver and parasitemias as high as 50% of circulating erythrocytes. Mortality in experimentally-infected amakihi was similar to that observed in Apapane (Himnatione sanguinea) and lower than that observed in Iiwi (Vestiaria coccinea) infected under similar conditions with the same parasite isolate. We conclude that the current elevational and geographic distribution of Hawaiian honeycreepers is determined by relative susceptibility to avian malaria.

  18. Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

    PubMed Central

    Lokken, Kristen L.; Nanton, Minelva R.; Nuccio, Sean-Paul; McSorley, Stephen J.; Tsolis, Renée M.

    2015-01-01

    In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonlethal malaria parasite Plasmodium yoelii 17XNL exhibited a profound loss of protective immunity to NTS, but vaccine-mediated protection was restored after resolution of malaria. Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. Blockade of IL-10 restored protection against S. Typhimurium, without restoring CD4 T cell effector function. Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-γ production by vaccine-induced memory CD4 T cells but was not sufficient to restore protection. Together, these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms, and suggest that in the setting of acute malaria, protection against NTS mediated by live vaccines may be interrupted. PMID:26366739

  19. Concurrent Dengue and Malaria in Cayenne Hospital, French Guiana

    PubMed Central

    Matheus, Severine; Donutil, Gerd; Raulin, Olivia; Nacher, Mathieu; Morvan, Jacques

    2009-01-01

    Dengue–malaria co-infection reports are scarce. Of 1,723 consecutive febrile patients in Cayenne Hospital, 238 had dengue (174 early dengue fever cases) and 393 had malaria (371 acute malaria); 17 had both. Diagnosis of 1 of these 2 infections should not rule out testing for the other infection. PMID:19331769

  20. Malaria infections: what and how can mice teach us.

    PubMed

    Zuzarte-Luis, Vanessa; Mota, Maria M; Vigário, Ana M

    2014-08-01

    Malaria imposes a horrific public health burden - hundreds of millions of infections and millions of deaths - on large parts of the world. While this unacceptable health burden and its economic and social impact have made it a focal point of the international development agenda, it became consensual that malaria control or elimination will be difficult to attain prior to gain a better understanding of the complex interactions occurring between its main players: Plasmodium, the causative agent of disease, and its hosts. Practical and ethical limitations exist regarding the ability to carry out research with human subjects or with human samples. In this review, we highlight how rodent models of infection have contributed significantly during the past decades to a better understanding of the basic biology of the parasite, host response and pathogenesis. PMID:24837740

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

    PubMed Central

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

    2013-01-01

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

  2. Stretching and relaxation of malaria-infected red blood cells.

    PubMed

    Ye, Ting; Phan-Thien, Nhan; Khoo, Boo Cheong; Lim, Chwee Teck

    2013-09-01

    The invasion of red blood cells (RBCs) by malaria parasites is a complex dynamic process, in which the infected RBCs gradually lose their deformability and their ability to recover their original shape is greatly reduced with the maturation of the parasites. In this work, we developed two types of cell model, one with an included parasite, and the other without an included parasite. The former is a representation of real malaria-infected RBCs, in which the parasite is treated as a rigid body. In the latter, where the parasite is absent, the membrane modulus and viscosity are elevated so as to produce the same features present in the parasite model. In both cases, the cell membrane is modeled as a viscoelastic triangular network connected by wormlike chains. We studied the transient behaviors of stretching deformation and shape relaxation of malaria-infected RBCs based on these two models and found that both models can generate results in agreement with those of previously published studies. With the parasite maturation, the shape deformation becomes smaller and smaller due to increasing cell rigidity, whereas the shape relaxation time becomes longer and longer due to the cell's reduced ability to recover its original shape. PMID:24010653

  3. Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

    PubMed Central

    Obiero, Joshua M.; Shekalaghe, Seif; Hermsen, Cornelus C.; Mpina, Maxmillian; Bijker, Else M.; Roestenberg, Meta; Teelen, Karina; Billingsley, Peter F.; Sim, B. Kim Lee; James, Eric R.; Daubenberger, Claudia A.; Hoffman, Stephen L.; Abdulla, Salim

    2015-01-01

    To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreserved Plasmodium falciparum sporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection of P. falciparum sporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexual P. falciparum lysate and another that, based on P. falciparum serology, resembled the malaria-naive Dutch cohort. Positive P. falciparum serology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparum antibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increase P. falciparum-specific in vitro recall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower in P. falciparum lysate-seropositive individuals than in seronegative individuals. In conclusion, positive P. falciparum lysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is

  4. Immunoregulation in human malaria: the challenge of understanding asymptomatic infection

    PubMed Central

    de Mendonça, Vitor R; Barral-Netto, Manoel

    2015-01-01

    Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomaticPlasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reducedPlasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodiuminfection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-β) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c-Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection. PMID:26676319

  5. Vivax malaria in a blood donor in Spain, relapse or a new infection in a malaria non-endemic country?

    PubMed

    Rubio, J M; Jiménez Del Bianco, A I; Cervera-Alonso, Y; Fernandez-Garcia, M D; Lanza, M; Ta Tang, T H; Sevil Puras, F; Blanco, L

    2016-02-01

    Malaria is a vectorborne disease caused by protozoan of the genus Plasmodium, which can also be transmitted by the transfusion of infected red blood cells. One year after return from a travel to Honduras, a Spanish traveller developed vivax malaria. Prior to the onset of symptoms, the donor made a donation that tested non-reactive using an immunological test for malaria. Samples from the donor taken before donation and tested by serological and molecular methods were negative but positive at the time of hospital admission. The possible sources of the donors' infection, imported versus locally acquired, are discussed. PMID:26509738

  6. Helminths and malaria co-infections are associated with elevated serum IgE

    PubMed Central

    2014-01-01

    Background Both helminth and malaria infections result in a highly polarized immune response characterized by IgE production. This study aimed to investigate the total serum IgE profile in vivo as a measure of Th2 immune response in malaria patients with and without helminth co-infection. Methods A cross sectional observational study composed of microscopically confirmed malaria positive (N = 197) and malaria negative (N = 216) apparently healthy controls with and without helminth infection was conducted at Wondo Genet Health Center, Southern Ethiopia. A pre-designed structured format was utilized to collect socio-demographic and clinical data of the subjects. Detection and quantification of helminths, malaria parasites and determination of serum IgE levels were carried out following standard procedures. Results Irrespective of helminth infection, individuals infected by malaria showed significantly high levels of serum IgE compared with malaria free apparently healthy controls (with and without helminth infections). Moreover, malaria patients co-infected with intestinal helminths showed high level of serum IgE compared with those malaria patients without intestinal helminths (2198 IU/ml versus 1668 IU/ml). A strong statistically significant association was observed between malaria parasite density and elevated serum IgE levels (2047 IU/ml versus 1778 IU/ml; P = 0.001) with high and low parasitaemia (parasite density >50,000 parasite/μl of blood), respectively. Likewise, helminth egg loads were significantly associated with elevated serum IgE levels (P = 0.003). Conclusions The elevated serum IgE response in malaria patients irrespective of helminth infection and its correlation with malaria parasite density and helminth egg intensity support that malaria infection is also a strong driver of IgE production as compared to helminths. PMID:24886689

  7. Vivax malaria.

    PubMed

    Baker, P B; Dronen, S C

    1986-01-01

    Malaria occurs in the United States infrequently and is found exclusively among immigrants and travelers returning from areas where the disease is endemic. Cases of acute relapses of Plasmodium vivax infection can present to the emergency department. Patients are often immigrants from developing countries who were symptom-free in this country for weeks or months preceding their illness. The clinical presentation and current treatment of malaria are reviewed. Malarial infection may become apparent months after leaving endemic areas despite adherence to prophylactic regimens. The disease usually responds to appropriate drug therapy with rapid and often dramatic results, but it can be fatal if unrecognized. PMID:3511922

  8. Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax Infection

    PubMed Central

    Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose

    2016-01-01

    The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite’s enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the major histocompatibility complex (MHC) associated with host resistance or susceptibility to malaria have been identified and used as markers in host–pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance, or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases, and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with Plasmodium vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein, we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-α, LTA, BAT1, and CTL4) regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility, naturally

  9. Epidemiological and clinical correlates of malaria-helminth co-infections in southern Ethiopia

    PubMed Central

    2013-01-01

    Background In many areas of the world, including Ethiopia, malaria and helminths are co-endemic, therefore, co-infections are common. However, little is known how concurrent infections affect the epidemiology and/or pathogenesis of each other. Therefore, this study was conducted to assess the effects of intestinal helminth infections on the epidemiology and clinical patterns of malaria in southern Ethiopia where both infections are prevalent. Methods A cross-sectional study was conducted in 2006 at Wondo Genet Health Center and Bussa Clinic, southern Ethiopia. Consecutive blood film positive malaria patients (N=230) and malaria negative asymptomatic individuals (N=233) were recruited. Malaria parasite detection and quantification was diagnosed using Giemsa-stained thick and thin blood films, respectively. Helminths were detected using direct microscopy and formol-ether concentration techniques. Coarse quantification of helminths ova was made using Kato Katz method. Results The over all magnitude of intestinal parasitic infection was high irrespective of malaria infection (67% among malaria positive patients versus 53.1% among malaria non-infected asymptomatic individuals). Trichuris trichiura infection was associated with increased malaria prevalence while increased worm burden of helminths as expressed by egg intensity was associated with increased malaria parasitaemia which could be a potential factor for development of severe malarial infection with the course of the disease. Majority (77%) of the subjects had multiple helminths infection. T. trichiura, Ascaris lumbricoides, Schistosoma mansoni, and hookworm infestation accounted for 64.5, 57.7 %, 28.4%, and 12.2% of the infections, respectively. Conclusions Populations in malaria-endemic areas of southern Ethiopia are multi-parasitized with up to four helminths. Mass deworming may be a simple practical approach in endemic areas in reducing the risk of severe malarial attack particularly for those at high risk

  10. Investigating the Important Correlates of Maternal Education and Childhood Malaria Infections

    PubMed Central

    Njau, Joseph D.; Stephenson, Rob; Menon, Manoj P.; Kachur, S. Patrick; McFarland, Deborah A.

    2014-01-01

    The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection. PMID:25002302

  11. Investigating the important correlates of maternal education and childhood malaria infections.

    PubMed

    Njau, Joseph D; Stephenson, Rob; Menon, Manoj P; Kachur, S Patrick; McFarland, Deborah A

    2014-09-01

    The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection. PMID:25002302

  12. [THE CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF MALARIA CONCURRENT WITH OTHER INFECTIONS AND INVASIONS].

    PubMed

    Kondrashin, A V; Tokmalaev, A K; Morozov, E N; Morozova, L F

    2016-01-01

    The present review considers malaria infection concurrent with different species of helminths, bacterial and viral infections, as well as mixed malaria pathogens in the subtropical and tropical countries of the world, causing the clinical picture and epidemiological situation to be different. Malaria co-infections with different pathogenic micro-organisms, such as HIV, tuberculosis, viral hepatitides, and others, affect almost one third of the planet's population. It is known that people who are at risk for malaria may be also at risk for other parasitic and infectious diseases, most commonly helminthisms. PMID:27405219

  13. Associations Between Maternal Helminth and Malaria Infections in Pregnancy and Clinical Malaria in the Offspring: A Birth Cohort in Entebbe, Uganda

    PubMed Central

    Ndibazza, Juliet; Webb, Emily L.; Lule, Swaib; Mpairwe, Harriet; Akello, Miriam; Oduru, Gloria; Kizza, Moses; Akurut, Helen; Muhangi, Lawrence; Magnussen, Pascal; Vennervald, Birgitte; Elliott, Alison

    2013-01-01

    Background. Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood. Methods. In a birth cohort of 2345 mother–child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring. Results. Common maternal infections were hookworm (45%), Mansonella perstans (21%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10–1.41; aHR, 1.20, 95% CI, 1.05–1.38, respectively). S. mansoni infection had no consistent association with childhood malaria. Conclusions. This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity. PMID:23904293

  14. Plasmodium malariae Infection Associated with a High Burden of Anemia: A Hospital-Based Surveillance Study

    PubMed Central

    Lampah, Daniel A.; Simpson, Julie A.; Kenangalem, Enny; Sugiarto, Paulus; Anstey, Nicholas M.; Poespoprodjo, Jeanne Rini; Price, Ric N.

    2015-01-01

    Background Plasmodium malariae is a slow-growing parasite with a wide geographic distribution. Although generally regarded as a benign cause of malaria, it has been associated with nephrotic syndrome, particularly in young children, and can persist in the host for years. Morbidity associated with P. malariae infection has received relatively little attention, and the risk of P. malariae-associated nephrotic syndrome is unknown. Methodology/Principal Findings We used data from a very large hospital-based surveillance system incorporating information on clinical diagnoses, blood cell parameters and treatment to describe the demographic distribution, morbidity and mortality associated with P. malariae infection in southern Papua, Indonesia. Between April 2004 and December 2013 there were 1,054,674 patient presentations to Mitra Masyarakat Hospital of which 196,380 (18.6%) were associated with malaria and 5,097 were with P. malariae infection (constituting 2.6% of all malaria cases). The proportion of malaria cases attributable to P. malariae increased with age from 0.9% for patients under one year old to 3.1% for patients older than 15 years. Overall, 8.5% of patients with P. malariae infection required admission to hospital and the median length of stay for these patients was 2.5 days (Interquartile Range: 2.0–4.0 days). Patients with P. malariae infection had a lower mean hemoglobin concentration (9.0g/dL) than patients with P. falciparum (9.5g/dL), P. vivax (9.6g/dL) and mixed species infections (9.3g/dL). There were four cases of nephrotic syndrome recorded in patients with P. malariae infection, three of which were in children younger than 5 years old, giving a risk in this age group of 0.47% (95% Confidence Interval; 0.10% to 1.4%). Overall, 2.4% (n = 16) of patients hospitalized with P. malariae infection subsequently died in hospital, similar to the proportions for the other endemic Plasmodium species (range: 0% for P. ovale to 1.6% for P. falciparum

  15. Submicroscopic malaria infection during pregnancy and the impact of intermittent preventive treatment

    PubMed Central

    2014-01-01

    Background Malaria during pregnancy results in adverse outcomes for mothers and infants. Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) is the primary intervention aimed at reducing malaria infection during pregnancy. Although submicroscopic infection is common during pregnancy and at delivery, its impact throughout pregnancy on the development of placental malaria and adverse pregnancy outcomes has not been clearly established. Methods Quantitative PCR was used to detect submicroscopic infections in pregnant women enrolled in an observational study in Blantyre, Malawi to determine their effect on maternal, foetal and placental outcomes. The ability of SP to treat and prevent submicroscopic infections was also assessed. Results 2,681 samples from 448 women were analysed and 95 submicroscopic infections were detected in 68 women, a rate of 0.6 episodes per person-year of follow-up. Submicroscopic infections were most often detected at enrolment. The majority of women with submicroscopic infections did not have a microscopically detectable infection detected during pregnancy. Submicroscopic infection was associated with placental malaria even after controlling for microscopically detectable infection and was associated with decreased maternal haemoglobin at the time of detection. However, submicroscopic infection was not associated with adverse maternal or foetal outcomes at delivery. One-third of women with evidence of placental malaria did not have documented peripheral infection during pregnancy. SP was moderately effective in treating submicroscopic infections, but did not prevent the development of new submicroscopic infections in the month after administration. Conclusions Submicroscopic malaria infection is common and occurs early in pregnancy. SP-IPT can clear some submicroscopic infections but does not prevent new infections after administration. To effectively control pregnancy-associated malaria, new interventions are required

  16. Electrophysiological studies of malaria parasite-infected erythrocytes: Current status

    PubMed Central

    Staines, Henry M.; Alkhalil, Abdulnaser; Allen, Richard J.; De Jonge, Hugo R.; Derbyshire, Elvira; Egée, Stéphane; Ginsburg, Hagai; Hill, David A.; Huber, Stephan M.; Kirk, Kiaran; Lang, Florian; Lisk, Godfrey; Oteng, Eugene; Pillai, Ajay D.; Rayavara, Kempaiah; Rouhani, Sherin; Saliba, Kevin J.; Shen, Crystal; Solomon, Tsione; Thomas, Serge L. Y.; Verloo, Patrick; Desai, Sanjay A.

    2009-01-01

    The altered permeability characteristics of erythrocytes infected with malaria parasites have been a source of interest for over 30 years. Recent electrophysiological studies have provided strong evidence that these changes reflect transmembrane transport through ion channels in the host erythrocyte plasma membrane. However, conflicting results and differing interpretations of the data have led to confusion in this field. In an effort to unravel these issues, the groups involved recently came together for a week of discussion and experimentation. In this article, the various models for altered transport are reviewed, together with the areas of consensus in the field and those that require a better understanding. PMID:17292372

  17. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria

    PubMed Central

    Sharma, Ankur; Conteh, Solomon; Langhorne, Jean; Duffy, Patrick E.

    2016-01-01

    Pregnancy malaria (PM) is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6–7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis. PMID:27467392

  18. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria.

    PubMed

    Sharma, Ankur; Conteh, Solomon; Langhorne, Jean; Duffy, Patrick E

    2016-01-01

    Pregnancy malaria (PM) is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6-7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis. PMID:27467392

  19. Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

    PubMed Central

    2011-01-01

    Background Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative. Methods HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques. Results Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral P. falciparum malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental P. falciparum infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's X 2> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's X 2< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre

  20. Malaria (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Malaria KidsHealth > For Parents > Malaria Print A A A ... Prevention Diagnosis and Treatment en español Malaria About Malaria Malaria is a common infection in hot, tropical ...

  1. Loss of deformability of malaria-infected red blood cells

    NASA Astrophysics Data System (ADS)

    Hosseini, S. Majid; Feng, James

    2012-11-01

    The pathogenesis of malaria is largely due to stiffening of the infected red blood cells (RBCs). Contemporary understanding ascribes the loss of RBC deformability to a 10-fold increase in membrane stiffness caused by extra cross-linking in the spectrin network. Local measurements by micropipette aspiration, however, have reported only an increase of 3-fold in the shear modulus. We believe the discrepancy stems from the rigid parasite particles inside infected cells, and have carried out numerical simulations to demonstrate this mechanism. The cell membrane is represented by a set of discrete particles connected by linearly elastic springs. The cytosol is modeled as a homogeneous Newtonian fluid, and discretized by particles as in standard smoothed particle hydrodynamics. The malaria parasite is modeled as an aggregate of particles constrained to rigid-body motion. We simulate RBC stretching tests by optical tweezers in three dimensions. The results demonstrate that the presence of a sizeable parasite greatly reduces the ability of RBCs to deform under stretching. With the solid inclusion, the observed loss of deformability can be predicted quantitatively using the local membrane elasticity measured by micropipettes.

  2. On the effects of malaria treatment on parasite drug resistance--probability modelling of genotyped malaria infections.

    PubMed

    Kum, Cletus Kwa; Thorburn, Daniel; Ghilagaber, Gebrenegus; Gil, Pedro; Björkman, Anders

    2013-01-01

    We compare the frequency of resistant genes of malaria parasites before treatment and at first malaria incidence after treatment. The data come from a clinical trial at two health facilities in Tanzania and concerns single nucleotide polymorphisms (SNPs) at three positions believed to be related to resistance to malaria treatment. A problem is that mixed infections are common, which both obscures the underlying frequency of alleles at each locus as well as the associations between loci in samples where alleles are mixed. We use combinatorics and quite involved probability methods to handle multiple infections and multiple haplotypes. The infection with the different haplotypes seemed to be independent of each other. We showed that at two of the three studied SNPs, the proportion of resistant genes had increased after treatment with sulfadoxine-pyrimethamine alone but when treated in combination with artesunate, no effect was noticed. First recurrences of malaria associated more with sulfadoxine-pyrimethamine alone as treatment than when in combination with artesunate. We also found that the recruited children had two different ongoing malaria infections where the parasites had different gene types. PMID:24127546

  3. Malaria.

    ERIC Educational Resources Information Center

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  4. Altered Lipid Composition of Surfactant and Lung Tissue in Murine Experimental Malaria-Associated Acute Respiratory Distress Syndrome

    PubMed Central

    Scaccabarozzi, Diletta; Deroost, Katrien; Lays, Natacha; Taramelli, Donatella

    2015-01-01

    Malaria-associated acute lung injury (MA-ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) are common, often fatal complications of severe malaria infections. However, little is known about their pathogenesis. In this study, biochemical alterations of the lipid composition of the lungs were investigated as possible contributing factors to the severity of murine MA-ALI/ARDS. C57BL/6J mice were infected with Plasmodium berghei NK65 to induce lethal MA-ARDS, or with Plasmodium chabaudi AS, a parasite strain that does not induce lung pathology. The lipid profile of the lung tissue from mice infected with Plasmodium berghei NK65 developing MA-ALI/ARDS, but not that from mice without lung pathology or controls, was characterized by high levels of phospholipids -mainly phosphatidylcholine- and esterified cholesterol. The high levels of polyunsaturated fatty acids and the linoleic/oleic fatty acid ratio of the latter reflect the fatty acid composition of plasma cholesterol esters. In spite of the increased total polyunsaturated fatty acid pool, which augments the relative oxidability of the lung membranes, and the presence of hemozoin, a known pro-oxidant, no excess oxidative stress was detected in the lungs of Plasmodium berghei NK65 infected mice. The bronchoalveolar lavage (BAL) fluid of Plasmodium berghei NK65 infected mice was characterized by high levels of plasma proteins. The phospholipid profile of BAL large and small aggregate fractions was also different from uninfected controls, with a significant increase in the amounts of sphingomyelin and lysophosphatidylcholine and the decrease in phosphatidylglycerol. Both the increase of proteins and lysophosphatidylcholine are known to decrease the intrinsic surface activity of surfactant. Together, these data indicate that an altered lipid composition of lung tissue and BAL fluid, partially ascribed to oedema and lipoprotein infiltration, is a characteristic feature of murine

  5. Altered Lipid Composition of Surfactant and Lung Tissue in Murine Experimental Malaria-Associated Acute Respiratory Distress Syndrome.

    PubMed

    Scaccabarozzi, Diletta; Deroost, Katrien; Lays, Natacha; Omodeo Salè, Fausta; Van den Steen, Philippe E; Taramelli, Donatella

    2015-01-01

    Malaria-associated acute lung injury (MA-ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) are common, often fatal complications of severe malaria infections. However, little is known about their pathogenesis. In this study, biochemical alterations of the lipid composition of the lungs were investigated as possible contributing factors to the severity of murine MA-ALI/ARDS. C57BL/6J mice were infected with Plasmodium berghei NK65 to induce lethal MA-ARDS, or with Plasmodium chabaudi AS, a parasite strain that does not induce lung pathology. The lipid profile of the lung tissue from mice infected with Plasmodium berghei NK65 developing MA-ALI/ARDS, but not that from mice without lung pathology or controls, was characterized by high levels of phospholipids -mainly phosphatidylcholine- and esterified cholesterol. The high levels of polyunsaturated fatty acids and the linoleic/oleic fatty acid ratio of the latter reflect the fatty acid composition of plasma cholesterol esters. In spite of the increased total polyunsaturated fatty acid pool, which augments the relative oxidability of the lung membranes, and the presence of hemozoin, a known pro-oxidant, no excess oxidative stress was detected in the lungs of Plasmodium berghei NK65 infected mice. The bronchoalveolar lavage (BAL) fluid of Plasmodium berghei NK65 infected mice was characterized by high levels of plasma proteins. The phospholipid profile of BAL large and small aggregate fractions was also different from uninfected controls, with a significant increase in the amounts of sphingomyelin and lysophosphatidylcholine and the decrease in phosphatidylglycerol. Both the increase of proteins and lysophosphatidylcholine are known to decrease the intrinsic surface activity of surfactant. Together, these data indicate that an altered lipid composition of lung tissue and BAL fluid, partially ascribed to oedema and lipoprotein infiltration, is a characteristic feature of murine

  6. Optimal Population-Level Infection Detection Strategies for Malaria Control and Elimination in a Spatial Model of Malaria Transmission

    PubMed Central

    Gerardin, Jaline; Bever, Caitlin A.; Hamainza, Busiku; Miller, John M.; Eckhoff, Philip A.; Wenger, Edward A.

    2016-01-01

    Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies—mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic—were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Compared with untargeted approaches, selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics. Serological diagnosis is potentially an effective tool for

  7. Optimal Population-Level Infection Detection Strategies for Malaria Control and Elimination in a Spatial Model of Malaria Transmission.

    PubMed

    Gerardin, Jaline; Bever, Caitlin A; Hamainza, Busiku; Miller, John M; Eckhoff, Philip A; Wenger, Edward A

    2016-01-01

    Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies-mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic-were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Compared with untargeted approaches, selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics. Serological diagnosis is potentially an effective tool for

  8. Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi Infection in Countries Eliminating Malaria

    PubMed Central

    Shearer, Freya M.; Huang, Zhi; Weiss, Daniel J.; Wiebe, Antoinette; Gibson, Harry S.; Battle, Katherine E.; Pigott, David M.; Brady, Oliver J.; Putaporntip, Chaturong; Jongwutiwes, Somchai; Lau, Yee Ling; Manske, Magnus; Amato, Roberto; Elyazar, Iqbal R. F.; Vythilingam, Indra; Bhatt, Samir; Gething, Peter W.; Singh, Balbir; Golding, Nick; Hay, Simon I.

    2016-01-01

    Background Infection by the simian malaria parasite, Plasmodium knowlesi, can lead to severe and fatal disease in humans, and is the most common cause of malaria in parts of Malaysia. Despite being a serious public health concern, the geographical distribution of P. knowlesi malaria risk is poorly understood because the parasite is often misidentified as one of the human malarias. Human cases have been confirmed in at least nine Southeast Asian countries, many of which are making progress towards eliminating the human malarias. Understanding the geographical distribution of P. knowlesi is important for identifying areas where malaria transmission will continue after the human malarias have been eliminated. Methodology/Principal Findings A total of 439 records of P. knowlesi infections in humans, macaque reservoir and vector species were collated. To predict spatial variation in disease risk, a model was fitted using records from countries where the infection data coverage is high. Predictions were then made throughout Southeast Asia, including regions where infection data are sparse. The resulting map predicts areas of high risk for P. knowlesi infection in a number of countries that are forecast to be malaria-free by 2025 (Malaysia, Cambodia, Thailand and Vietnam) as well as countries projected to be eliminating malaria (Myanmar, Laos, Indonesia and the Philippines). Conclusions/Significance We have produced the first map of P. knowlesi malaria risk, at a fine-scale resolution, to identify priority areas for surveillance based on regions with sparse data and high estimated risk. Our map provides an initial evidence base to better understand the spatial distribution of this disease and its potential wider contribution to malaria incidence. Considering malaria elimination goals, areas for prioritised surveillance are identified. PMID:27494405

  9. Supplementation With Multivitamins and Vitamin A and Incidence of Malaria Among HIV-Infected Tanzanian Women

    PubMed Central

    Spiegelman, Donna; Aboud, Said; Duggan, Christopher; Danaei, Goodarz; Fawzi, Wafaie W.

    2014-01-01

    Introduction: HIV and malaria infections occur in the same individuals, particularly in sub-Saharan Africa. We examined whether daily multivitamin supplementation (vitamins B complex, C, and E) or vitamin A supplementation altered malaria incidence in HIV-infected women of reproductive age. Methods: HIV-infected pregnant Tanzanian women recruited into the study were randomly assigned to daily multivitamins (B complex, C, and E), vitamin A alone, both multivitamins and vitamin A, or placebo. Women received malaria prophylaxis during pregnancy and were followed monthly during the prenatal and postpartum periods. Malaria was defined in 2 ways: presumptive diagnosis based on a physician's or nurse's clinical judgment, which in many cases led to laboratory investigations, and periodic examination of blood smears for malaria parasites. Results: Multivitamin supplementation compared with no multivitamins significantly lowered women's risk of presumptively diagnosed clinical malaria (relative risk: 0.78, 95% confidence interval: 0.67 to 0.92), although multivitamins increased their risk of any malaria parasitemia (relative risk: 1.24, 95% confidence interval: 1.02 to 1.50). Vitamin A supplementation did not change malaria incidence during the study. Conclusions: Multivitamin supplements have been previously shown to reduce HIV disease progression among HIV-infected women, and consistent with that, these supplements protected against development of symptomatic malaria. The clinical significance of increased risk of malaria parasitemia among supplemented women deserves further research, however. Preventive measures for malaria are warranted as part of an integrated approach to the care of HIV-infected individuals exposed to malaria. PMID:25436815

  10. Impact of HIV infection on the haemostatic response during sepsis and malaria.

    PubMed

    Huson, Michaëla A M; Kalkman, Rachel; Hoogendijk, Arie J; Alabi, Abraham S; van 't Veer, Cornelis; Grobusch, Martin P; Meijers, Joost C M; van der Poll, Tom

    2016-06-01

    Patients positive for the human immunodeficiency virus (HIV) are more susceptible to sepsis and malaria, two conditions known to activate the coagulation system. As chronic HIV infection also influences haemostatic mechanisms, we determined the influence of HIV co-infection on coagulation, anticoagulation and the endothelium during sepsis or malaria. We performed a prospective observational study in 325 subjects with or without HIV infection (103 with sepsis, 127 with malaria and 95 asymptomatic controls) in an HIV endemic area in Central Africa. We measured plasma biomarkers indicative of activation of distinct haemostatic mechanisms. Sepsis and malaria had similar effects with elevated markers of coagulation, reduced anticoagulation markers and activation of endothelium. In particular, asymptomatic HIV infection reduced the plasma levels of the anticoagulant co-factor free protein S, and increased activation of the vascular endothelium, which were not normalized by combination antiretroviral therapy. HIV co-infection during sepsis and malaria caused more profound changes in free protein S and von Willebrand factor in sepsis and malaria, and ADAMTS13 in sepsis, while not influencing sepsis- or malaria-induced coagulation activation. These results show for the first time that HIV infection augments selective haemostatic changes during sepsis and malaria, which may contribute to the enhanced morbidity of these conditions in HIV patients. PMID:26970408

  11. Low Parasitemia in Submicroscopic Infections Significantly Impacts Malaria Diagnostic Sensitivity in the Highlands of Western Kenya

    PubMed Central

    Lo, Eugenia; Zhou, Guofa; Oo, Winny; Afrane, Yaw; Githeko, Andrew; Yan, Guiyun

    2015-01-01

    Asymptomatic malaria infections represent a major challenge in malaria control and elimination in Africa. They are reservoirs of malaria parasite that can contribute to disease transmission. Therefore, identification and control of asymptomatic infections are important to make malaria elimination feasible. In this study, we investigated the extent and distribution of asymptomatic malaria in Western Kenya and examined how varying parasitemia affects performance of diagnostic methods including microscopy, conventional PCR, and quantitative PCR. In addition, we compared parasite prevalence rates and parasitemia levels with respect to topography and age in order to explore factors that influence malaria infection. Over 11,000 asymptomatic blood samples from children and adolescents up to 18 years old representing broad areas of Western Kenya were included. Quantitative PCR revealed the highest parasite positive rate among all methods and malaria prevalence in western Kenya varied widely from less than 1% to over 50%. A significantly lower parasitemia was detected in highland than in lowland samples and this contrast was also observed primarily among submicroscopic samples. Although we found no correlation between parasitemia level and age, individuals of younger age group (aged <14) showed significantly higher parasite prevalence. In the lowlands, individuals of aged 5–14 showed significantly higher prevalence than those under age 5. Our findings highlight the need for a more sensitive and time-efficient assay for asymptomatic malaria detection particularly in areas of low-transmission. Combining QPCR with microscopy can enhance the capacity of detecting submicroscopic asymptomatic malaria infections. PMID:25816298

  12. Blood Smear Image Based Malaria Parasite and Infected-Erythrocyte Detection and Segmentation.

    PubMed

    Tsai, Meng-Hsiun; Yu, Shyr-Shen; Chan, Yung-Kuan; Jen, Chun-Chu

    2015-10-01

    In this study, an automatic malaria parasite detector is proposed to perceive the malaria-infected erythrocytes in a blood smear image and to separate parasites from the infected erythrocytes. The detector hence can verify whether a patient is infected with malaria. It could more objectively and efficiently help a doctor in diagnosing malaria. The experimental results show that the proposed method can provide impressive performance in segmenting the malaria-infected erythrocytes and the parasites from a blood smear image taken under a microscope. This paper also presents a weighted Sobel operation to compute the image gradient. The experimental results demonstrates that the weighted Sobel operation can provide more clear-cut and thinner object contours in object segmentation. PMID:26289625

  13. Post-Plasmodium vivax malaria cerebellar ataxia and optic neuritis: A new form of delayed cerebellar ataxia or cerebellar variant of acute disseminated encephalomyelitis?

    PubMed Central

    Kasundra, Gaurav M.; Bhargava, Amita Narendra; Bhushan, Bharat; Shubhakaran, Khichar; Sood, Isha

    2015-01-01

    Acute disseminated encephalomyelitis (ADEM) is commonly seen after viral and bacterial infections, immunization, and Plasmodium falciparum (PF) malaria. Plasmodium vivax (PV) rarely causes ADEM. We report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from PV. Magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of ADEM. No specific viral etiology was found on cerebrospinal fluid examination. Patient responded well to treatment without any sequelae. Thus, PV too is an important cause of ADEM along with PF. Two of the previously reported cases had co-infection with falciparum malaria. The only other two reported cases, as also this patient, are from Asia. A geographical or racial predisposition needs to be evaluated. Also, a possibility of post-PV delayed cerebellar ataxia, which is classically described post-PF infection, may be considered as it may be clinically, radiologically, and prognostically indistinguishable from a milder presentation of ADEM. PMID:25878748

  14. Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience

    PubMed Central

    Kute, V. B.; Shah, P. R.; Munjappa, B. C.; Gumber, M. R.; Patel, H. V.; Jain, S. H.; Engineer, D. P.; Naresh, V. V. Sai; Vanikar, A. V.; Trivedi, H. L.

    2012-01-01

    Acute kidney injury (AKI) is one of the most dreaded complications of severe malaria. We carried out prospective study in 2010, to describe clinical characteristics, laboratory parameters, prognostic factors, and outcome in 59 (44 males, 15 females) smear-positive malaria patients with AKI. The severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA) score, Multiple Organ Dysfunction Score (MODS), and Glasgow Coma Scale (GCS) scores. All patients received artesunate and hemodialysis (HD). Mean age of patients was 33.63 ± 14 years. Plasmodium falciparum malaria was seen in 76.3% (n = 45), Plasmodium vivax in 16.9% (n = 10), and mixed infection in 6.8% (n = 4) patients. Presenting clinical features were fever (100%), nausea-vomiting (85%), oliguria (61%), abdominal pain/tenderness (50.8%), and jaundice (74.5%). Mean APACHE II, SOFA, MODS, and GCS scores were 18.1 ± 3, 10.16 ± 3.09, 9.71 ± 2.69, and 14.15 ± 1.67, respectively, all were higher among patients who died than among those who survived. APACHE II ≥20, SOFA and MODS scores ≥12 were associated with higher mortality (P < 0.05). 34% patients received blood component transfusion and exchange transfusion was done in 15%. Mean number of HD sessions required was 4.59 ± 3.03. Renal biopsies were performed in five patients (three with patchy cortical necrosis and two with acute tubular necrosis). 81.3% of patients had complete renal recovery and 11.8% succumbed to malaria. Prompt diagnosis, timely HD, and supportive therapy were associated with improved survival and recovery of kidney functions in malarial with AKI. Mortality was associated with higher APACHE II, SOFA, MODS, GCS scores, requirement of inotrope, and ventilator support. PMID:22279340

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

    PubMed

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

    2014-01-01

    The association between severe malaria and Plasmodium vivax species is contentious. On the Thai-Myanmar border, all pregnant women are followed systematically with active weekly malaria screening. Over a 27-year period of providing antenatal care, 48,983 have been prospectively followed until pregnancy outcome (miscarriage or delivery) and 4,298 women have had P. vivax detected at least once. Reported here is the first known P. vivax-associated death amongst these women. The initial patient presentation was of uncomplicated P. vivax (0.5% parasitaemia) in a term, multigravida woman who responded rapidly to oral artesunate and mefloquine treatment, clearing her blood stage parasites within 48 hours. The patient appeared well, was ambulatory and due to be discharged but became unwell with acute respiratory distress syndrome (ARDS) requiring ventilation three days (67 hours) into treatment. Despite induction and delivery of a stillborn foetus, ventilatory requirements increased and the patient died on day 7. The patient had a low body mass index. Sensitive detection with nested PCR confirmed only the presence of P. vivax species and concomitant infections such as tuberculosis and human immunodeficiency virus (HIV) were also ruled out. The contemporaneous treatment of acute uncomplicated P. vivax and the onset of ARDS on day 3 in this patient implies a possible but unconfirmed association with death in this patient. Assuming this death was caused by P. vivax, the risk of ARDS-related maternal mortality in this setting did not differ significantly between Plasmodium falciparum and P. vivax (0.24 per 1,000 (1/4,158) versus 0.23 per 1,000 (1/4,298), contrary to the increased risk of maternal mortality from P. falciparum compared to P. vivax, 2.89 per 1,000 (12/4,158) versus 0.23 per 1,000 (1/4,298), P = 0.003. PMID:24886559

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

    PubMed Central

    2014-01-01

    The association between severe malaria and Plasmodium vivax species is contentious. On the Thai-Myanmar border, all pregnant women are followed systematically with active weekly malaria screening. Over a 27-year period of providing antenatal care, 48,983 have been prospectively followed until pregnancy outcome (miscarriage or delivery) and 4,298 women have had P. vivax detected at least once. Reported here is the first known P. vivax-associated death amongst these women. The initial patient presentation was of uncomplicated P. vivax (0.5% parasitaemia) in a term, multigravida woman who responded rapidly to oral artesunate and mefloquine treatment, clearing her blood stage parasites within 48 hours. The patient appeared well, was ambulatory and due to be discharged but became unwell with acute respiratory distress syndrome (ARDS) requiring ventilation three days (67 hours) into treatment. Despite induction and delivery of a stillborn foetus, ventilatory requirements increased and the patient died on day 7. The patient had a low body mass index. Sensitive detection with nested PCR confirmed only the presence of P. vivax species and concomitant infections such as tuberculosis and human immunodeficiency virus (HIV) were also ruled out. The contemporaneous treatment of acute uncomplicated P. vivax and the onset of ARDS on day 3 in this patient implies a possible but unconfirmed association with death in this patient. Assuming this death was caused by P. vivax, the risk of ARDS-related maternal mortality in this setting did not differ significantly between Plasmodium falciparum and P. vivax (0.24 per 1,000 (1/4,158) versus 0.23 per 1,000 (1/4,298), contrary to the increased risk of maternal mortality from P. falciparum compared to P. vivax, 2.89 per 1,000 (12/4,158) versus 0.23 per 1,000 (1/4,298), P = 0.003. PMID:24886559

  17. Malaria and Vascular Endothelium

    PubMed Central

    de Alencar, Aristóteles Comte; de Lacerda, Marcus Vinícius Guimarães; Okoshi, Katashi; Okoshi, Marina Politi

    2014-01-01

    Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease. PMID:25014058

  18. Malaria and vascular endothelium.

    PubMed

    Alencar Filho, Aristóteles Comte de; Lacerda, Marcus Vinícius Guimarães de; Okoshi, Katashi; Okoshi, Marina Politi

    2014-08-01

    Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease. PMID:25014058

  19. Fungal infection counters insecticide resistance in African malaria mosquitoes

    PubMed Central

    Farenhorst, Marit; Mouatcho, Joel C.; Kikankie, Christophe K.; Brooke, Basil D.; Hunt, Richard H.; Thomas, Matthew B.; Koekemoer, Lizette L.; Knols, Bart G. J.; Coetzee, Maureen

    2009-01-01

    The evolution of insecticide resistance in mosquitoes is threatening the effectiveness and sustainability of malaria control programs in various parts of the world. Through their unique mode of action, entomopathogenic fungi provide promising alternatives to chemical control. However, potential interactions between fungal infection and insecticide resistance, such as cross-resistance, have not been investigated. We show that insecticide-resistant Anopheles mosquitoes remain susceptible to infection with the fungus Beauveria bassiana. Four different mosquito strains with high resistance levels against pyrethroids, organochlorines, or carbamates were equally susceptible to B. bassiana infection as their baseline counterparts, showing significantly reduced mosquito survival. Moreover, fungal infection reduced the expression of resistance to the key public health insecticides permethrin and dichlorodiphenyltrichloroethane. Mosquitoes preinfected with B. bassiana or Metarhizium anisopliae showed a significant increase in mortality after insecticide exposure compared with uninfected control mosquitoes. Our results show a high potential utility of fungal biopesticides for complementing existing vector control measures and provide products for use in resistance management strategies. PMID:19805146

  20. Malaria-Cutaneous Leishmaniasis Co-infection: Influence on Disease Outcomes and Immune Response

    PubMed Central

    Pinna, Raquel A.; Silva-dos-Santos, Danielle; Perce-da-Silva, Daiana S.; Oliveira-Ferreira, Joseli; Villa-Verde, Dea M. S.; De Luca, Paula M.; Banic, Dalma M.

    2016-01-01

    Malaria and Cutaneous Leishmaniasis (CL) are co-endemic throughout large regions in tropical countries and co-infection may impact the evolution of host-parasite interactions. In the present study, we evaluate Malaria/Leishmaniasis disease outcome, Th1/Th2 cytokine levels and the CD4 and CD8 T-cell profiles in a co-infection murine model (BALB/c) of Plasmodium yoelii 17XNL (Py) and Leishmania amazonensis (La) or L. braziliensis (Lb). Malaria parasitaemia was assessed through blood strains stained with Giemsa. Leishmania lesions were monitored with a digital caliper and parasite loads determined by limiting-dilution assay. Serum levels of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17 were determined using multiplexed bead assay and expression of CD3, CD4, and CD8 T-cells markers were determined by Flow Cytometry in the thymus, spleens and lymph nodes. Parasitaemia in Lb+Py co-infected group was lower than in Py single-infected group, suggesting a protective effect of Lb co-infection in Malaria progression. In contrast, La+Py co-infection increased parasitaemia, patent infection and induced mortality in non-lethal Malaria infection. Regarding Leishmaniasis, Lb+Py co-infected group presented smaller lesions and less ulceration than Lb single-infected animals. In contrast, La+Py co-infected group presented only a transitory delay on the development of lesions when compared to La single-infected mice. Decreased levels of IFN-γ, TNF, IL-6, and IL-10 were observed in the serum of co-infected groups, demonstrating a modulation of Malaria immune response by Leishmania co-infections. We observed an intense thymic atrophy in Py single-infected and co-infected groups, which recovered earlier in co-infected animals. The CD4 and CD8 T cell profiles in thymus, spleens and lymph nodes did not differ between Py single and co-infected groups, except for a decrease in CD4+CD8+ T cells which also increased faster in co-infected mice. Our results suggest that Py and Leishmania co-infection

  1. Asymptomatic Plasmodium Infections in Children in Low Malaria Transmission Setting, Southwestern Uganda1

    PubMed Central

    Roh, Michelle E.; Oyet, Caesar; Orikiriza, Patrick; Wade, Martina; Kiwanuka, Gertrude N.; Mwanga-Amumpaire, Juliet; Boum, Yap

    2016-01-01

    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. PMID:27434741

  2. 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. PMID:27434741

  3. How malaria merozoites reduce the deformability of infected RBC

    NASA Astrophysics Data System (ADS)

    Hosseini, Majid; Feng, James

    2011-11-01

    This talk presents a three-dimensional particle-based model for the red blood cell (RBC), and uses it to explore the changes in the deformability of RBC due to presence of malaria parasite. The cell membrane is represented by a set of discrete particles connected by nonlinear springs that represent shear and bending elasticity. The cytoplasm and the external liquid are modeled as homogeneous Newtonian fluids, and discretized by particles as in standard smoothed-particle-hydrodynamics models. The merozoite is modeled as an aggregate of particles constrained to rigid-body motion. The fluid flow and membrane deformation are computed, via the particle motion, by a two-step explicit scheme, with model parameters determined from experiments. The stretching of healthy and infected RBC by optical tweezers has been simulated to investigate the contribution of rigid merozoites to the decrease in deformability. Department of Mathematics, University of British Columbia, Vancouver, BC V6T 1Z2, Canada.

  4. IL-27 promotes IL-10 production by effector Th1 CD4+ T cells; a critical mechanism for protection from severe immunopathology during malaria infection1

    PubMed Central

    Freitas do Rosário, Ana Paula; Lamb, Tracey; Spence, Philip; Stephens, Robin; Lang, Agathe; Roers, Axel; Muller, Werner; O’Garra, Anne; Langhorne, Jean

    2012-01-01

    Infection with the malaria parasite, Plasmodium, is characterized by excessive inflammation. The establishment of a precise balance between the pro- and anti-inflammatory responses is critical to guarantee control of the parasite and survival of the host. Interleukin (IL)-10, a key regulatory cytokine produced by many cells of the immune system, has been shown to protect mice against pathology during acute Plasmodium chabaudi chabaudi AS model of malaria. However, the critical cellular source of IL-10 is still unknown. Here, we demonstrate that T cell-derived IL-10 is necessary for the control of pathology during acute malaria, as mice bearing specific deletion of Il10 in T cells fully reproduce the phenotype observed in Il10−/− mice, with significant weight loss, drop in temperature and increased mortality. Furthermore, we show that IFN-γ+ Th1 cells are the main producers of IL-10 throughout acute infection, expressing high levels of CD44 and ICOS and low levels of CD127. Although Foxp3+ regulatory CD4+ T cells produce IL-10 during infection, highly activated IFN-γ+ Th1 cells were shown to be the essential and sufficient source of IL-10 to guarantee protection against severe immune-mediated pathology. Finally, in this model of malaria we demonstrate that the generation of protective IL10+IFN-γ+ Th1 cells is dependent on IL-27 signaling, and independent of IL-21. PMID:22205023

  5. Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

    PubMed Central

    JABBARZARE, Marzieh; CHIN, Voon Kin; TALIB, Herni; YAM, Mun Fei; ADAM, Siti Khadijah; HASSAN, Haniza; ABDUL MAJID, Roslaini; MAT TAIB, Che Norma; MOHD MOKLAS, Mohamad Aris; TAUFIK HIDAYAT, Mohamad; MOHD SIDEK, Hasidah; BASIR, Rusliza

    2015-01-01

    Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host. PMID:26622294

  6. Lack of association between falciparum malaria parasitemia and acute diarrhea in Nigerian children.

    PubMed

    Sodeinde, O; Gbadegesin, R A; Ademowo, O G; Adeyemo, A A

    1997-12-01

    It is widely believed that malaria causes diarrhea. Yet, national and international diarrheal diseases control programs are silent about the overlap between these two major public health problems that coexist in most tropical countries. To test the hypothesis that malaria is associated with diarrhea and to define the role of malaria in morbidity due to diarrhea, 522 children 6-60 months of age presenting with acute diarrhea to the Children's Emergency Ward of the University College Hospital in Ibadan, Nigeria were routinely screened by means of thin and thick blood films for malaria parasitemia. Controls, without diarrhea, were studied in parallel. Detailed clinical features were recorded for every patient. Sixty-eight (13%) of the 522 diarrhea patients screened had malaria parasitemia. Among the controls (who had similar distributions of admission temperature, hemoglobin types, glucose-6-phosphate dehydrogenase deficiency, and prior treatment with antimalarial drugs), parasitemia was not significantly different, occurring in 56 (17.9%) of 313. In the dry season, however, a significantly higher prevalence of parasitemia was observed among the control group (15.5%) than in the diarrhea group (7.0%) (P = 0.004). Parasitemia was significantly more common in the dehydrated diarrhea patients than their well-hydrated counterparts (25% of 56 versus 11% of 466; P < 0.005). There were no significant differences in admission temperature, the presence of vomiting, or the home use of oral rehydration fluids between the dehydrated and the well-hydrated subsets of diarrhea patients. Consideration of parasite densities did not alter any of the foregoing relationships. These data contradict the widely held view that diarrhea is a symptom of malaria or that malaria causes diarrhea. They do, however, provide support for examining blood smears at least in dehydrated children with diarrhea in malaria-endemic areas and giving immediate antimalarial therapy to those who have malaria

  7. Artesunate-amodiaquine efficacy in Congolese children with acute uncomplicated falciparum malaria in Brazzaville

    PubMed Central

    2013-01-01

    Background Congo-Brazzaville adopted artemisinin-based combination therapy (ACT) in 2006. Artesunate-amodiaquine (AS + AQ) and artemether-lumefantrine are the first-line and second-line anti-malarial drugs to treat uncomplicated Plasmodium falciparum malaria, respectively. The baseline efficacy of AS + AQ was evaluated from February to August 2005 in patients living in Brazzaville, the capital city of the Republic of Congo. Methods One hundred and ninety-seven patients (96 ≤5 years old and 101 >5 years old, including adults) were recruited in a non-randomized study, treated under supervision with AS + AQ, and were followed up for 28 days in accordance with the 2003 World Health Organization protocol. Plasmodium falciparum recrudescent isolates from day 7 to day 28 were compared to pretreatment isolates by polymerase chain reaction (PCR) to distinguish between re-infection and recrudescence. Results The overall efficacy of AS + AQ after PCR correction on day 28 was 94.4%. An adequate clinical and parasitological response was observed in 94.3% and 94.4% of children aged ≤5 years old and those aged >5 years old (including adults), respectively. The main reported adverse events were dizziness, vomiting, diarrhoea, pruritus, headache, anorexia, and abdominal pain. Conclusion This study has shown the high efficacy of AS + AQ in Congolese patients of all ages with acute uncomplicated falciparum malaria and serves as the baseline efficacy and tolerance of this ACT in Brazzaville. PMID:23384005

  8. The Anopheles innate immune system in the defense against malaria infection

    PubMed Central

    Clayton, April M.; Dong, Yuemei; Dimopoulos, George

    2014-01-01

    The multifaceted innate immune system of insects is capable of fighting infection by a variety of pathogens including those causing human malaria. Malaria transmission by the Anopheles mosquito depends on the Plasmodium parasite’s successful completion of its lifecycle in the insect vector, a process that involves interactions with several tissues and cell types as well as with the mosquito’s innate immune system. This review will discuss our current understanding of the Anopheles mosquito’s innate immune responses against the malaria parasite Plasmodium and the influence of the insect’s intestinal microbiota on parasite infection. PMID:23988482

  9. 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. PMID:26626201

  10. Epidemiological Study of the Association Between Malaria and Helminth Infections in Nigeria

    PubMed Central

    Efunshile, Akinwale Michael; Olawale, Temitope; Stensvold, Christen Rune; Kurtzhals, Jørgen A. L.; König, Brigitte

    2015-01-01

    The relationship between intestinal helminth infection and susceptibility to malaria remains unclear. We studied the relationship between these infections. Seven schools in Ilero, Nigeria referred all pupils with febrile illness to our study center for free malaria treatment during a 3-month study period. At the end, all pupils submitted a stool sample for microscopic investigation for helminth eggs. We used an unmatched case-control design to calculate the odds ratios for helminth infection in children with at least one attack of malaria (cases) and children with no malaria episodes during the study (controls). We recorded 115 malaria cases in 82 of 354 (23.2%), 16 of 736 (2.2%), and 17 of 348 (4.7%) children ages ≤ 5, 6–10, and 11–15 years old, respectively (P = 0.001). Helminth infection rate in cases was 21 of 115 (18.3%) compared with 456 of 1,327 (34.4%) in controls. Weighted odds ratio stratified by age group for helminth infection in cases versus controls was 0.50 (95% confidence interval = 0.2–0.84, P < 0.01). Ascaris and hookworm were the most common helminths detected, with prevalence rates of 14 (12.2%) and 6 (5.2%) among cases compared with 333 (25.1%) and 132 (10.0%) in controls, respectively (P = 0.001). The negative association between helminth infection and malaria may be of importance in the design of deworming programs. PMID:25624401

  11. Effect of Transmission Setting and Mixed Species Infections on Clinical Measures of Malaria in Malawi

    PubMed Central

    Bruce, Marian C.; Macheso, Allan; Kelly-Hope, Louise A.; Nkhoma, Standwell; McConnachie, Alex; Molyneux, Malcolm E.

    2008-01-01

    Background In malaria endemic regions people are commonly infected with multiple species of malaria parasites but the clinical impact of these Plasmodium co-infections is unclear. Differences in transmission seasonality and transmission intensity between endemic regions have been suggested as important factors in determining the effect of multiple species co-infections. Principal Findings In order to investigate the impact of multiple-species infections on clinical measures of malaria we carried out a cross-sectional community survey in Malawi, in 2002. We collected clinical and parasitological data from 2918 participants aged >6 months, and applied a questionnaire to measure malaria morbidity. We examined the effect of transmission seasonality and intensity on fever, history of fever, haemoglobin concentration ([Hb]) and parasite density, by comparing three regions: perennial transmission (PT), high intensity seasonal transmission (HIST) and low intensity seasonal transmission (LIST). These regions were defined using multi-level modelling of PCR prevalence data and spatial and geo-climatic measures. The three Plasmodium species (P. falciparum, P. malariae and P. ovale) were randomly distributed amongst all children but not adults in the LIST and PT regions. Mean parasite density in children was lower in the HIST compared with the other two regions. Mixed species infections had lower mean parasite density compared with single species infections in the PT region. Fever rates were similar between transmission regions and were unaffected by mixed species infections. A history of fever was associated with single species infections but only in the HIST region. Reduced mean [Hb] and increased anaemia was associated with perennial transmission compared to seasonal transmission. Children with mixed species infections had higher [Hb] in the HIST region. Conclusions Our study suggests that the interaction of Plasmodium co-infecting species can have protective effects against

  12. Human Plasmodium knowlesi Infection Detected by Rapid Diagnostic Tests for Malaria

    PubMed Central

    van Hellemond, Jaap J.; Rutten, Marijke; Koelewijn, Rob; Zeeman, Anne-Marie; Verweij, Jaco J.; Wismans, Pieter J.; Kocken, Clemens H.

    2009-01-01

    We describe a PCR-confirmed case of Plasmodium knowlesi infection with a high parasitemia level and clinical signs of severe malaria in a migrant worker from Malaysian Borneo in the Netherlands. Investigations showed that commercially available rapid antigen tests for detection of human Plasmodium infections can detect P. knowlesi infections in humans. PMID:19788819

  13. Dengue infection presenting as acute hypokalemic quadriparesis.

    PubMed

    Gupta, N; Garg, A; Chhabra, P

    2014-01-01

    Dengue infection is one of the most common viral hemorrhagic fevers seen in the tropical countries, including India. Its presentation varies from an acute self-resolving febrile illness to life-threatening hemorrhagic shock and multiorgan dysfunction leading to death. Neurological presentations are uncommon and limited to case reports only. Most common neurological manifestations being encephalitis, acute inflammatory demyelinating polyradiculoneuropathy, transverse myelitis, and acute disseminated encephalomyelitis.Hypokalemic quadriparesis as a presenting feature of dengue is extremely rare. Here, we report this case of a 33-year-old female, who presented with hypokalemic quadriparesis and was subsequently diagnosed as dengue infection. PMID:25121379

  14. Malaria

    MedlinePlus

    ... Malaria can be carried by mosquitoes in temperate climates, but the parasite disappears over the winter. The ... a major disease hazard for travelers to warm climates. In some areas of the world, mosquitoes that ...

  15. Chemokines responses to Plasmodium falciparum malaria and co-infections among rural Cameroonians.

    PubMed

    Che, Jane Nchangnwi; Nmorsi, Onyebiguwa Patrick Goddey; Nkot, Baleguel Pierre; Isaac, Clement; Okonkwo, Browne Chukwudi

    2015-04-01

    Malaria remains the major cause of disease morbidity and mortality in sub-Saharan Africa with complex immune responses associated with disease outcomes. Symptoms associated with severe malaria have generally shown chemokine upregulation but little is known of responses to uncomplicated malaria. Eight villages in central Cameroon of 1045 volunteers were screened. Among these, malaria-positive individuals with some healthy controls were selected for chemokine analysis using Enzyme-Linked Immunosorbent Assay (ELISA) kits. Depressed serum levels of CXCL5 and raised CCL28 were observed in malarial positives when compared with healthy controls. The mean concentration of CXCL11 was higher in symptomatic than asymptomatic group, while CCL28 was lower in symptomatic individuals. Lower chemokine levels were associated with symptoms of uncomplicated malaria except for CXCL11 which was upregulated among fever-positive group. The mean CXCL5 level was higher in malaria sole infection than co-infections with HIV and Loa loa. Also, there was a raised mean level of malaria+HIV co-infection for CXCL9. This study hypothesises a situation where depressed chemokines in the face of clinical presentations could indicate an attempt by the immune system in preventing a progression process from uncomplicated to complicated outcomes with CXCL11 being identified as possible biomarker for malarial fever. PMID:25462711

  16. Testing in Mice the Hypothesis That Melanin Is Protective in Malaria Infections

    PubMed Central

    Waisberg, Michael; Vickers, Brandi K.; Yager, Stephanie B.; Lin, Christina K.; Pierce, Susan K.

    2012-01-01

    Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria. PMID:22242171

  17. Optical diagnosis of malaria infection in human plasma using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Bilal, Muhammad; Saleem, Muhammad; Amanat, Samina Tufail; Shakoor, Huma Abdul; Rashid, Rashad; Mahmood, Arshad; Ahmed, Mushtaq

    2015-01-01

    We present the prediction of malaria infection in human plasma using Raman spectroscopy. Raman spectra of malaria-infected samples are compared with those of healthy and dengue virus infected ones for disease recognition. Raman spectra were acquired using a laser at 532 nm as an excitation source and 10 distinct spectral signatures that statistically differentiated malaria from healthy and dengue-infected cases were found. A multivariate regression model has been developed that utilized Raman spectra of 20 malaria-infected, 10 non-malarial with fever, 10 healthy, and 6 dengue-infected samples to optically predict the malaria infection. The model yields the correlation coefficient r2 value of 0.981 between the predicted values and clinically known results of trainee samples, and the root mean square error in cross validation was found to be 0.09; both these parameters validated the model. The model was further blindly tested for 30 unknown suspected samples and found to be 86% accurate compared with the clinical results, with the inaccuracy due to three samples which were predicted in the gray region. Standard deviation and root mean square error in prediction for unknown samples were found to be 0.150 and 0.149, which are accepted for the clinical validation of the model.

  18. Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine.

    PubMed

    Corpolongo, Angela; De Nardo, Pasquale; Ghirga, Piero; Gentilotti, Elisa; Bellagamba, Rita; Tommasi, Chiara; Paglia, Maria Grazia; Nicastri, Emanuele; Narciso, Pasquale

    2012-01-01

    Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine.The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet(®)) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence.This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives. PMID:22453057

  19. Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine

    PubMed Central

    2012-01-01

    Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine. The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet®) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence. This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives. PMID:22453057

  20. Acute disseminated encephalomyelitis (ADEM)--a rare complication of falciparum malaria.

    PubMed

    Rachita, Sarangi; Satyasundar, Mahapatra; Mrutunjaya, Dash; Birakishore, Rath

    2013-06-01

    A 4-y-old girl was admitted with fever and altered sensorium. Peripheral blood smear and quantified buffy coat test showed Plasmodium falciparum infection. She received antimalarial therapy and got discharged on seventh day without any neurological deficit. Seven days later she was readmitted with fever and disorientation. Neurological examination revealed coma and decerebration. The deep tendon reflexes were exaggerated and babiniski response was positive in the right lower limb. MRI of brain revealed multifocal asymmetrical T2W/FLAIR hyperintensities in cerebral hemispheres, sub cortical white matter and midbrain. There was minimal patchy enhancement on contrast study. Any feature of grey matter involvement was not observed. The child improved remarkably after the treatment with methyl prednisolone. A follow up MRI after one year showed a complete resolution of demyelinating lesions. Diagnosis of acute disseminated encephalomyelitis (ADEM) as a complication of falciparum malaria was made based on sudden onset of neurological events, MRI findings and prompt response to corticosteroid therapy. PMID:22700387

  1. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  2. Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.

    PubMed

    Yamamoto, Daisuke S; Sumitani, Megumi; Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

    2016-09-01

    Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control. PMID:27598328

  3. Increase of malaria attacks among children presenting concomitant infection by Schistosoma mansoni in Senegal

    PubMed Central

    Sokhna, Cheikh; Le Hesran, Jean-Yves; Mbaye, Pape A; Akiana, Jean; Camara, Pape; Diop, Mamadou; Ly, Abdoulaye; Druilhe, Pierre

    2004-01-01

    Helminthic infections concomitant with malaria are common in inter-tropical areas. A recent study showed that mice co-infected with Schistosoma mansoni and Plasmodium chabaudi develop higher P. chabaudi parasitaemia and had a higher mortality rate. This important observation deserved to be further investigated among human populations. Malaria attacks were recorded in 512 children aged 6–15 years living in Richard Toll (Northern Senegal) among whom 336 were infected by S. mansoni, and 175 were not. The incidence rate of malaria attacks was significantly higher among S. mansoni-infected individuals, particularly those carrying the highest worm loads, as compared to uninfected subjects (26.6% versus 16,4 %). In contrast, the rate of malaria attacks was lower, without reaching significance, in medium grade S. mansoni infections. Thus, infection by S. mansoni affects susceptibility to malaria, but this can vary according to the intensity of parasite load. The immunological mechanisms underlying this dual effect need to be further explored. PMID:15544703

  4. [Associated infections in acute bronchopulmonary infections in children].

    PubMed

    Lykova, E A; Vorob'ev, A A; Bokovoĭ, A G; Karazhas, N V; Evseeva, L F

    2003-01-01

    A total of 189 children with bacterial complications of the acute respiratory viral infection (ARVI)--primarily with pneumonia and bronchitis--were dynamically examined for typical and atypical pneumotropic causative agents of the infection process (Mycoplasma pneumoniae, Chlamydia spp., Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis carini, and Citomegalovirus). A high frequency rate of the associative infection involving mycoplasmas and pneumocysts was registered (45-50%); it was lower in the cases involving Chlamydias, hemophilic bacteria, pneumococcus, and cytomegalovirus--up to 25-30%. No sharp difference was found between the indices of an infection degree and those of an active clinical infectious process involving the same pneumotropic agent: the biggest difference was observed in Chlamydia infections (9.4%) and the lowest one--in mycoplasma infections (3%). A dynamic comparison of different classes of immunoglobulins revealed that, in acute bronchitis and pneumonias, the Chlamydia and cytomegalovirus infections are, primarily, of the persistent nature; the hemophilic and pneumocystic infections are of a mixed nature; and the pneumococcus one is of the acute nature. The Mycoplasma infection, which is more often encountered in pre-school children, is of the primary type with a trend towards a prolonged clinical course. All pneumonias had a typical clinical course; the clinical picture was compared in 128 patients with the etiological factor (including a description of characteristic symptoms). PMID:12861708

  5. Occlusion of Small Vessels by Malaria-Infected Red Blood Cells

    NASA Astrophysics Data System (ADS)

    Lei, Huan; Fedosov, Dmitry; Caswell, Bruce; Karniadakis, George

    2010-11-01

    We use dissipative particle dynamics (DPD) method to study malaria-infected red blood cells (i-RBC). We have developed a multi-scale model to describe both static and dynamic properties of RBCs. With this model, we study the adhesive interaction between RBCs as well as the interaction between the Plasmodium falciparum (Pf)-parasitized cells and a vessel wall coated with purified ICAM-1. In this talk, we will discuss the effect of the Pf-parasitized malaria cell on the flow resistance of the blood flow at different parasetimia levels. The blood flow in malaria disease shows high flow resistance as compared with the healthy case due to both the stiffening of the i-RBCs (up to ten times) as well as the adhesion dynamics. For certain sizes of of small vessels, the malaria-infected cells can even lead to occlusion of the blood flow, in agreement with recent experiments.

  6. Co-infection of Plasmodium vivax Malaria and Cytomegalovirus in an Immunocompetent Neonate.

    PubMed

    Chandelia, Sudha; Jain, Sarika

    2014-12-01

    Co-infections when occur can pose substantial diagnostic and treatment challenges for clinicians. In this case report we describe a neonate with co infection of plasmodium vivax malaria with Cytomegalovirus and discuss whether it can be the result of reactivation of one by the other infection postnatally or if these infections can affect and facilitate the transplacental transmission of each other from the mother. PMID:25653999

  7. Parasite Specific Antibody Increase Induced by an Episode of Acute P. falciparum Uncomplicated Malaria

    PubMed Central

    Kaddumukasa, Mark; Lwanira, Catherine; Lugaajju, Allan; Katabira, Elly; Persson, Kristina E. M.; Wahlgren, Mats; Kironde, Fred

    2015-01-01

    Introduction There is no approved vaccine for malaria, and precisely how human antibody responses to malaria parasite components and potential vaccine molecules are developed and maintained remains poorly defined. In this study, antibody anamnestic or memory response elicited by a single episode of P. falciparum infection was investigated. Methods This study involved 362 malaria patients aged between 6 months to 60 years, of whom 19% were early-diagnosed people living with HIV/AIDS (PLWHA). On the day malaria was diagnosed and 42 days later, blood specimens were collected. Parasite density, CD4+ cells, and antibodies specific to synthetic peptides representing antigenic regions of the P. falciparum proteins GLURP, MSP3 and HRPII were measured. Results On the day of malaria diagnosis, Immunoglobulin (IgG) antibodies against GLURP, MSP3 and HRP II peptides were present in the blood of 75%, 41% and 60% of patients, respectively. 42 days later, the majority of patients had boosted their serum IgG antibody more than 1.2 fold. The increase in level of IgG antibody against the peptides was not affected by parasite density at diagnosis. The median CD4+ cell counts of PLWHAs and HIV negative individuals were not statistically different, and median post-infection increases in anti-peptide IgG were similar in both groups of patients. Conclusion In the majority (70%) of individuals, an infection of P. falciparum elicits at least 20% increase in level of anti-parasite IgG. This boost in anti-P. falciparum IgG is not affected by parasite density on the day of malaria diagnosis, or by HIV status. PMID:25906165

  8. Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

    PubMed Central

    Abeles, Shira R.; Chuquiyauri, Raul; Tong, Carlos; Vinetz, Joseph M.

    2013-01-01

    Infection of mosquitoes by humans is not always successful in the setting of patent gametocytemia. This study tested the hypothesis that pro- or anti-inflammatory cytokines are associated with transmission of Plasmodium vivax to Anopheles darlingi mosquitoes in experimental infection. Blood from adults with acute, non-severe P. vivax malaria was fed to laboratory-reared F1 An. darlingi mosquitoes. A panel of cytokines at the time of mosquito infection was assessed in patient sera and levels compared among subjects who did and did not infect mosquitoes. Overall, blood from 43 of 99 (43%) subjects led to mosquito infection as shown by oocyst counts. Levels of IL-10, IL-6, TNF-α, and IFN-γ were significantly elevated in vivax infection and normalized 3 weeks later. The anti-inflammatory cytokine IL-10 was significantly higher in nontransmitters compared with top transmitters but was not in TNF-α and IFN-γ. The IL-10 elevation during acute malaria was associated with P. vivax transmission blocking. PMID:23478585

  9. Managing malaria in the intensive care unit

    PubMed Central

    Marks, M.; Gupta-Wright, A.; Doherty, J. F.; Singer, M.; Walker, D.

    2014-01-01

    The number of people travelling to malaria-endemic countries continues to increase, and malaria remains the commonest cause of serious imported infection in non-endemic areas. Severe malaria, mostly caused by Plasmodium falciparum, often requires intensive care unit (ICU) admission and can be complicated by cerebral malaria, respiratory distress, acute kidney injury, bleeding complications, and co-infection. The mortality from imported malaria remains significant. This article reviews the manifestations, complications and principles of management of severe malaria as relevant to critical care clinicians, incorporating recent studies of anti-malarial and adjunctive treatment. Effective management of severe malaria includes prompt diagnosis and early institution of effective anti-malarial therapy, recognition of complications, and appropriate supportive management in an ICU. All cases should be discussed with a specialist unit and transfer of the patient considered. PMID:24946778

  10. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam.

    PubMed

    Phuong, Hoang Lan; Nga, Tran T T; van Doornum, Gerard J; Groen, Jan; Binh, Tran Q; Giao, Phan T; Hung, Le Q; Nams, Nguyen V; Kager, P A; de Vries, Peter J

    2010-09-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control program. Serum was collected on first presentation (t0) and after 3 weeks (t3) for serology. After exclusion of acute dengue infection, acute and convalescent serum samples from 606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM and IgG antibodies against common respiratory viruses. Paired sera showed the following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial virus (HRSV, 0.6%). There was no association between type of infection and age, sex or seasonality; some inter-annual differences were observed for influenza. Antibody prevalence, indicative of previous infections, was relatively low: HPV, 56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%. PMID:21073032

  11. Kocuria kristinae infection associated with acute cholecystitis

    PubMed Central

    Ma, Edmond SK; Wong, Chris LP; Lai, Kristi TW; Chan, Edmond CH; Yam, WC; Chan, Angus CW

    2005-01-01

    Background Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. Case presentation We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. Conclusion Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases. PMID:16029488

  12. Thermal behaviour of Anopheles stephensi in response to infection with malaria and fungal entomopathogens

    PubMed Central

    Blanford, Simon; Read, Andrew F; Thomas, Matthew B

    2009-01-01

    Background Temperature is a critical determinant of the development of malaria parasites in mosquitoes, and hence the geographic distribution of malaria risk, but little is known about the thermal preferences of Anopheles. A number of other insects modify their thermal behaviour in response to infection. These alterations can be beneficial for the insect or for the infectious agent. Given current interest in developing fungal biopesticides for control of mosquitoes, Anopheles stephensi were examined to test whether mosquitoes showed thermally-mediated behaviour in response to infection with fungal entomopathogens and the rodent malaria, Plasmodium yoelii. Methods Over two experiments, groups of An. stephensi were infected with one of three entomopathogenic fungi, and/or P. yoelii. Infected and uninfected mosquitoes were released on to a thermal gradient (14 – 38°C) for "snapshot" assessments of thermal preference during the first five days post-infection. Mosquito survival was monitored for eight days and, where appropriate, oocyst prevalence and intensity was assessed. Results and conclusion Both infected and uninfected An. stephensi showed a non-random distribution on the gradient, indicating some capacity to behaviourally thermoregulate. However, chosen resting temperatures were not altered by any of the infections. There is thus no evidence that thermally-mediated behaviours play a role in determining malaria prevalence or that they will influence the performance of fungal biopesticides against adult Anopheles. PMID:19379519

  13. The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections

    PubMed Central

    Williams, John E.; Cairns, Matthew; Njie, Fanta; Laryea Quaye, Stephen; Awine, Timothy; Oduro, Abraham; Tagbor, Harry; Bojang, Kalifa; Magnussen, Pascal; ter Kuile, Feiko O.; Woukeu, Arouna; Milligan, Paul; Chandramohan, Daniel; Greenwood, Brian

    2016-01-01

    Background. Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern. Methods. Primigravidae and secundigravidae who participated in the ISTp arm of a noninferiority trial in 4 West African countries were screened with an HRP2/pLDH RDT on enrollment and, in Ghana, at subsequent antenatal clinic (ANC) visits. Blood samples were examined subsequently by microscopy and by a polymerase chain reaction (PCR) assay. Results. The sensitivity of the RDT to detect peripheral blood infections confirmed by microscopy and/or PCR at enrollment ranged from 91% (95% confidence interval [CI], 88%, 94%) in Burkina Faso to 59% (95% CI, 48%, 70% in The Gambia. In Ghana, RDT sensitivity was 89% (95% CI, 85%, 92%), 83% (95% CI, 76%, 90%) and 77% (95% CI, 67%, 86%) at enrollment, second and third ANC visits respectively but only 49% (95% CI, 31%, 66%) at delivery. Screening at enrollment detected 56% of all infections detected throughout pregnancy. Seventy-five RDT negative PCR or microscopy positive infections were detected in 540 women; these were not associated with maternal anemia, placental malaria, or low birth weight. Conclusions. The sensitivity of an RDT to detect malaria in primigravidae and secundigravidae was high at enrollment in 3 of 4 countries and, in Ghana, at subsequent ANC visits. In Ghana, RDT negative malaria infections were not associated with adverse birth outcomes but missed infections were uncommon. PMID:26721833

  14. Mathematical Analysis of the Effects of HIV-Malaria Co-infection on Workplace Productivity.

    PubMed

    Seidu, Baba; Makinde, Oluwole D; Seini, Ibrahim Y

    2015-06-01

    In this paper, a nonlinear dynamical system is proposed and qualitatively analyzed to study the dynamics and effects of HIV-malaria co-infection in the workplace. Basic reproduction numbers of sub-models are derived and are shown to have LAS disease-free equilibria when their respective basic reproduction numbers are less than unity. Conditions for existence of endemic equilibria of sub-models are also derived. Unlike the HIV-only model, the malaria-only model is shown to exhibit a backward bifurcation under certain conditions. Conditions for optimal control of the co-infection are derived using the Pontryagin's maximum principle. Numerical experimentation on the resulting optimality system is performed. Using the incremental cost-effectiveness ratio, it is observed that combining preventative measures for both diseases is the best strategy for optimal control of HIV-malaria co-infection at the workplace. PMID:25980477

  15. Association between Subclinical Malaria Infection and Inflammatory Host Response in a Pre-Elimination Setting

    PubMed Central

    Peto, Thomas J.; Tripura, Rupam; Lee, Sue J.; Althaus, Thomas; Dunachie, Susanna; Nguon, Chea; Dhorda, Mehul; Promnarate, Cholrawee; Chalk, Jeremy; Imwong, Mallika; von Seidlein, Lorenz; Day, Nicholas P.; Dondorp, Arjen M.; White, Nicholas J.; Lubell, Yoel

    2016-01-01

    Background Subclinical infections in endemic areas of Southeast Asia sustain malaria transmission. These asymptomatic infections might sustain immunity against clinical malaria and have been considered benign for the host, but if they are associated with chronic low-grade inflammation this could be harmful. We conducted a case-control study to explore the association between subclinical malaria and C-reactive protein (CRP), an established biomarker of inflammation. Methods Blood samples from asymptomatic villagers in Pailin, Western Cambodia were tested for malaria by high-volume ultra-sensitive polymerase chain reaction (uPCR) to determine the Plasmodium species. Plasma CRP concentration was measured in 328 individuals with parasitaemia (cases) and compared with: i) the same individual’s value at the first time point when they had no detectable parasites (n = 282); and ii) age- sex- and village-matched controls (n = 328) free of Plasmodium infection. Plasma CRP concentrations were compared against thresholds of 3mg/L and 10mg/L. Subgroup analysis was carried out for cases with P vivax and P falciparum mono-infections. Results Median plasma CRP level for all samples was 0.59mg/L (interquartile range: 0.24–1.64mg/L). CRP concentrations were higher in parasitaemic individuals compared with same-person-controls (p = 0.050); and matched-controls (p = 0.025). 4.9% of samples had CRP concentrations above 10mg/L and 14.6% were above 3mg/L. Cases were more likely to have plasma CRP concentrations above these thresholds than age/sex matched controls, odds ratio 3.5 (95%CI 1.5–9.8) and 1.8 (95%CI 1.1–2.9), respectively. Amongst cases, parasite density and CRP were positively correlated (p<0.001), an association that remained significant when controlling for age and fever. Individuals with P.vivax mono-infections had the highest plasma CRP concentrations with the greatest association with parasitaemia. Discussion In this setting persistent malaria infections in

  16. A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys.

    PubMed

    Aikawa, M; Brown, A; Smith, C D; Tegoshi, T; Howard, R J; Hasler, T H; Ito, Y; Perry, G; Collins, W E; Webster, K

    1992-04-01

    A major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels is mediated by the attachment of knobs on PRBC to receptors on the endothelial cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because fresh human brain tissues from cerebral malarial autopsy cases are not easy to obtain. Although several animal models for human cerebral malaria have been proposed, none have shown pathologic findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied brains of rhesus monkeys infected with the primate malaria parasite, Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence of knobs on PRBC to endothelial cells in the cerebral microvessels of these monkeys. Cerebral microvessels with sequestered PRBC were shown by immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins were not evident in the cerebral microvessels of uninfected control monkeys. Thus, our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria. By using this animal model, we may be able to evaluate strategies for the development of vaccines to prevent human cerebral malaria. PMID:1374220

  17. [The Most Common Acute Gastrointestinal Infections].

    PubMed

    Greuter, Thomas; Magdeburg, Bernhard

    2015-10-14

    Acute gastrointestinal infections and diarrhea with vomiting as its main presentation are a frequently encountered entity in an outpatient setting. Due to a mostly self-limiting disease course a diagnostic work-up is often futile. Viral infections caused by Noro- or Rotavirus are most frequent, while bacterial infections are second line due to high hygienic standards in developed countries. In an inpatient setting and after a precedent antibiotic treatment one should think of clostridium difficile. Traveler’s diarrhea represents a special case, with most of the cases caused by enterovirulent E. coli. In this mini review we describe the most important pathogens in detail. PMID:26463905

  18. Avian malaria in Hawaiian forest birds: Infection and population impacts across species and elevations

    USGS Publications Warehouse

    Samuel, Michael D.; Woodworth, Bethany L.; Atkinson, Carter T.; Hart, P. J.; LaPointe, Dennis

    2015-01-01

    Wildlife diseases can present significant threats to ecological systems and biological diversity, as well as domestic animal and human health. However, determining the dynamics of wildlife diseases and understanding the impact on host populations is a significant challenge. In Hawai‘i, there is ample circumstantial evidence that introduced avian malaria (Plasmodium relictum) has played an important role in the decline and extinction of many native forest birds. However, few studies have attempted to estimate disease transmission and mortality, survival, and individual species impacts in this distinctive ecosystem. We combined multi-state capture-recapture (longitudinal) models with cumulative age-prevalence (cross-sectional) models to evaluate these patterns in Apapane, Hawai‘i Amakihi, and Iiwi in low-, mid-, and high-elevation forests on the island of Hawai‘i based on four longitudinal studies of 3–7 years in length. We found species-specific patterns of malaria prevalence, transmission, and mortality rates that varied among elevations, likely in response to ecological factors that drive mosquito abundance. Malaria infection was highest at low elevations, moderate at mid elevations, and limited in high-elevation forests. Infection rates were highest for Iiwi and Apapane, likely contributing to the absence of these species in low-elevation forests. Adult malaria fatality rates were highest for Iiwi, intermediate for Amakihi at mid and high elevations, and lower for Apapane; low-elevation Amakihi had the lowest malaria fatality, providing strong evidence of malaria tolerance in this low-elevation population. Our study indicates that hatch-year birds may have greater malaria infection and/or fatality rates than adults. Our study also found that mosquitoes prefer feeding on Amakihi rather than Apapane, but Apapane are likely a more important reservoir for malaria transmission to mosquitoes. Our approach, based on host abundance and infection rates, may be an

  19. Evidence and Implications of Mortality Associated with Acute Plasmodium vivax Malaria

    PubMed Central

    2013-01-01

    Vivax malaria threatens patients despite relatively low-grade parasitemias in peripheral blood. The tenet of death as a rare outcome, derived from antiquated and flawed clinical classifications, disregarded key clinical evidence, including (i) high rates of mortality in neurosyphilis patients treated with vivax malaria; (ii) significant mortality from zones of endemicity; and (iii) the physiological threat inherent in repeated, very severe paroxysms in any patient, healthy or otherwise. The very well-documented course of this infection, with the exception of parasitemia, carries all of the attributes of “perniciousness” historically linked to falciparum malaria, including severe disease and fatal outcomes. A systematic analysis of the parasite biomass in severely ill patients that includes blood, marrow, and spleen may ultimately explain this historic misunderstanding. Regardless of how this parasite is pernicious, recent data demonstrate that the infection comes with a significant burden of morbidity and associated mortality. The extraordinary burden of malaria is not heavily weighted upon any single continent by a single species of parasite—it is a complex problem for the entire endemic world, and both species are of fundamental importance. Humanity must rally substantial resources, intellect, and energy to counter this daunting but profound threat. PMID:23297258

  20. Infectivity of pestivirus following persistence of acute infection.

    PubMed

    Collins, Margaret E; Heaney, Judith; Thomas, Carole J; Brownlie, Joe

    2009-09-18

    Bovine viral diarrhoea virus (BVDV) is an endemic pathogen worldwide and eradication strategies focus on the identification and removal of persistently infected (PI) animals arising after in utero infection. Despite this, acute infections with BVDV can persist for months or years after the removal of the PI source despite repeated screening for PIs and tight biosecurity measures. Recent evidence for a prolonged duration of viraemia in the testicles of bulls following acute BVDV infection suggests the possibility of a form of chronic persistence that may more closely resemble the persistence strategies of hepatitis C virus (HCV). To investigate the potential for virus transmission from infected and recovered cattle to virus naïve hosts we established an acute infection of 5 BVDV-naïve calves and monitored animals over 129 days. Infectious BVDV was detected in white blood cells between days 3 and 7 post-challenge. The animals seroconverted by day 21 post-infection and subsequently were apparently immune and free from infectious virus and viral antigen. Animals were further monitored and purified white blood cells were stimulated in vitro with phytohaemagglutinin A (PHA) during which time BVDV RNA was detected intermittently. Ninety-eight days following challenge, blood was transferred from these apparently virus-free and actively immune animals to a further group of 5 BVDV-naïve calves and transmission of infection was achieved. This indicates that BVDV-infected, recovered and immune animals have the potential to remain infectious for BVDV-naïve cohorts for longer than previously demonstrated. PMID:19443139

  1. Intestinal Parasites Coinfection Does Not Alter Plasma Cytokines Profile Elicited in Acute Malaria in Subjects from Endemic Area of Brazil

    PubMed Central

    Perce-da-Silva, Daiana de Souza; Lima-Junior, Josué da Costa

    2014-01-01

    In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO) concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan) does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax. PMID:25309052

  2. Pulmonary embolism and acute cytomegalovirus infection in an immunocompetent patient.

    PubMed

    Del Borgo, Cosmo; Gianfreda, Romina; Belvisi, Valeria; Citton, Rita; Soscia, Fabrizio; Notarianni, Ermanno; Tieghi, Tiziana; Mastroianni, Claudio Maria

    2010-12-01

    A case of an immunocompetent man with acute CMV infection associated with a pulmonary embolism is described. Acute CMV infection could be a risk factor for developing thromboembolism. Pulmonary embolism should be included in differential diagnosis in patients with acute CMV infections and pulmonary opacities. PMID:21196823

  3. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

  4. Malaria endemicity and co-infection with tissue-dwelling parasites in Sub-Saharan Africa: a review.

    PubMed

    Onkoba, Nyamongo W; Chimbari, Moses J; Mukaratirwa, Samson

    2015-01-01

    Mechanisms and outcomes of host-parasite interactions during malaria co-infections with gastrointestinal helminths are reasonably understood. In contrast, very little is known about such mechanisms in cases of malaria co-infections with tissue-dwelling parasites. This is lack of knowledge is exacerbated by misdiagnosis, lack of pathognomonic clinical signs and the chronic nature of tissue-dwelling helminthic infections. A good understanding of the implications of tissue-dwelling parasitic co-infections with malaria will contribute towards the improvement of the control and management of such co-infections in endemic areas. This review summarises and discusses current information available and gaps in research on malaria co-infection with gastro-intestinal helminths and tissue-dwelling parasites with emphasis on helminthic infections, in terms of the effects of migrating larval stages and intra and extracellular localisations of protozoan parasites and helminths in organs, tissues, and vascular and lymphatic circulations. PMID:26377900

  5. Variation in infection length and superinfection enhance selection efficiency in the human malaria parasite.

    PubMed

    Chang, Hsiao-Han; Childs, Lauren M; Buckee, Caroline O

    2016-01-01

    The capacity for adaptation is central to the evolutionary success of the human malaria parasite Plasmodium falciparum. Malaria epidemiology is characterized by the circulation of multiple, genetically diverse parasite clones, frequent superinfection, and highly variable infection lengths, a large number of which are chronic and asymptomatic. The impact of these characteristics on the evolution of the parasite is largely unknown, however, hampering our understanding of the impact of interventions and the emergence of drug resistance. In particular, standard population genetic frameworks do not accommodate variation in infection length or superinfection. Here, we develop a population genetic model of malaria including these variations, and show that these aspects of malaria infection dynamics enhance both the probability and speed of fixation for beneficial alleles in complex and non-intuitive ways. We find that populations containing a mixture of short- and long-lived infections promote selection efficiency. Interestingly, this increase in selection efficiency occurs even when only a small fraction of the infections are chronic, suggesting that selection can occur efficiently in areas of low transmission intensity, providing a hypothesis for the repeated emergence of drug resistance in the low transmission setting of Southeast Asia. PMID:27193195

  6. Photoacoustic detection of hemozoin in human mononuclear cells as an early indicator of malaria infection

    NASA Astrophysics Data System (ADS)

    Custer, Jonathan R.; Kariuki, Michael; Beerntsen, Brenda T.; Viator, John A.

    2010-02-01

    Malaria is a blood borne infection affecting hundreds of millions of people worldwide2. The parasites reproduce within the blood cells, eventually causing their death and lysis. This process releases the parasites into the blood, continuing the cycle of infection. Usually, malaria is diagnosed only after a patient presents symptoms, including high fever, nausea, and, in advanced cases, coma and death. While invading the bloodstream of a host, malaria parasites convert hemoglobin into an insoluble crystal, known as hemozoin. These crystals, approximately several hundred nanometers in size, are contained within red blood cells and white blood cells that ingest free hemozoin in the blood. Thus, infected red blood cells and white blood cells contain a unique optical absorber that can be detected in blood samples using static photoacoustic detection methods. We separated the white blood cells from malaria infected blood and tested it in a photoacoustic set up using a tunable laser system consisting of an optical parametric oscillator pumped by an Nd:YAG laser with pulse duration of 5 ns. Our threshold of detection was 10 infected white blood cells per microliter, which is more sensitive than current diagnosis methods using microscopic analysis of blood.

  7. Variation in infection length and superinfection enhance selection efficiency in the human malaria parasite

    PubMed Central

    Chang, Hsiao-Han; Childs, Lauren M.; Buckee, Caroline O.

    2016-01-01

    The capacity for adaptation is central to the evolutionary success of the human malaria parasite Plasmodium falciparum. Malaria epidemiology is characterized by the circulation of multiple, genetically diverse parasite clones, frequent superinfection, and highly variable infection lengths, a large number of which are chronic and asymptomatic. The impact of these characteristics on the evolution of the parasite is largely unknown, however, hampering our understanding of the impact of interventions and the emergence of drug resistance. In particular, standard population genetic frameworks do not accommodate variation in infection length or superinfection. Here, we develop a population genetic model of malaria including these variations, and show that these aspects of malaria infection dynamics enhance both the probability and speed of fixation for beneficial alleles in complex and non-intuitive ways. We find that populations containing a mixture of short- and long-lived infections promote selection efficiency. Interestingly, this increase in selection efficiency occurs even when only a small fraction of the infections are chronic, suggesting that selection can occur efficiently in areas of low transmission intensity, providing a hypothesis for the repeated emergence of drug resistance in the low transmission setting of Southeast Asia. PMID:27193195

  8. 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.

  9. Swaddling and acute respiratory infections.

    PubMed

    Yurdakok, K; Yavuz, T; Taylor, C E

    1990-07-01

    In Turkey and China the ancient practice of swaddling is still commonly practiced. Both countries have extremely high rates of pneumonia, especially during the neonatal period. Preliminary evidence on the possibility that swaddling may interfere with normal respiratory function and thereby predispose to pneumonia was gathered in a teaching health center in Ankara. Babies who had been swaddled for at least three months were four times more likely to have developed pneumonia (confirmed radiologically) and upper respiratory infections than babies who were unswaddled. These preliminary findings were highly significant and are being followed up by further studies. PMID:2356917

  10. An 11-year-old boy with Plasmodium falciparum malaria and dengue co-infection.

    PubMed

    Issaranggoon na ayuthaya, Satja; Wangjirapan, Anchalee; Oberdorfer, Peninnah

    2014-01-01

    Malaria and dengue fever are major mosquito-borne public health problems in tropical countries. The authors report a malaria and dengue co-infection in an 11-year-old boy who presented with sustained fever for 10 days. The physical examination revealed a flushed face, injected conjunctivae and left submandibular lymphadenopathy. His peripheral blood smear showed few ring-form trophozoites of Plasmodium falciparum. His blood tests were positive for dengue NS-1 antigen and IgM antibody, and negative for IgG antibody. After the initiation of antimalarial treatment with artesunate and mefloquine, his clinical condition gradually improved. However, he still had low-grade fever that persisted for 6 days. Finally, he recovered well without fluid leakage, shock or severe bleeding. This case report emphasises that early recognition and concomitant treatment of malaria and dengue co-infection in endemic areas can improve clinical outcome and prevent serious complications. PMID:24692379

  11. Probucol-Induced α-Tocopherol Deficiency Protects Mice against Malaria Infection

    PubMed Central

    Ishida, Noriko; Kume, Aiko; Hagihara, Yoshihisa; Yoshida, Yasukazu; Suzuki, Hiroshi

    2015-01-01

    The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma α-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by α-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing α-tocopherol deficiency without dietary α-tocopherol restriction. PMID:26296197

  12. Probucol-Induced α-Tocopherol Deficiency Protects Mice against Malaria Infection.

    PubMed

    Herbas, Maria Shirely; Shichiri, Mototada; Ishida, Noriko; Kume, Aiko; Hagihara, Yoshihisa; Yoshida, Yasukazu; Suzuki, Hiroshi

    2015-01-01

    The emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. Recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. However, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. Here, we report on a new strategy to potentially treat malaria by using probucol, a drug that can reduce the plasma α-tocopherol concentration. Probucol pre-treatment for 2 weeks and treatment throughout the infection rescued from death of mice infected with Plasmodium yoelii XL-17 or P. berghei ANKA. In addition, survival was extended when the treatment started immediately after parasite inoculation. The ratio of lipid peroxidation products to parent lipids increased in plasma after 2 weeks treatment of probucol. This indicates that the protective effect of probucol might be mediated by the oxidative stressful environment induced by α-tocopherol deficiency. Probucol in combination with dihydroartemisin suppressed the proliferation of P. yoelii XL-17. These results indicated that probucol might be a candidate for a drug against malaria infection by inducing α-tocopherol deficiency without dietary α-tocopherol restriction. PMID:26296197

  13. The cell biology of malaria infection of mosquito: advances and opportunities

    PubMed Central

    Sinden, R E

    2015-01-01

    Recent reviews (Feachem et al.; Alonso et al.) have concluded that in order to have a sustainable impact on the global burden of malaria, it is essential that we knowingly reduce the global incidence of infected persons. To achieve this we must reduce the basic reproductive rate of the parasites to < 1 in diverse epidemiological settings. This can be achieved by impacting combinations of the following parameters: the number of mosquitoes relative to the number of persons, the mosquito/human biting rate, the proportion of mosquitoes carrying infectious sporozoites, the daily survival rate of the infectious mosquito and the ability of malaria-infected persons to infect mosquito vectors. This paper focuses on our understanding of parasite biology underpinning the last of these terms: infection of the mosquito. The article attempts to highlight central issues that require further study to assist in the discovery of useful transmission-blocking measures. PMID:25557077

  14. Parallel telomere shortening in multiple body tissues owing to malaria infection.

    PubMed

    Asghar, Muhammad; Palinauskas, Vaidas; Zaghdoudi-Allan, Nadège; Valkiūnas, Gediminas; Mukhin, Andrey; Platonova, Elena; Färnert, Anna; Bensch, Staffan; Hasselquist, Dennis

    2016-08-17

    Several studies have shown associations between shorter telomere length in blood and weakened immune function, susceptibility to infections, and increased risk of morbidity and mortality. Recently, we have shown that malaria accelerates telomere attrition in blood cells and shortens lifespan in birds. However, the impact of infections on telomere attrition in different body tissues within an individual is unknown. Here, we tested whether malarial infection leads to parallel telomere shortening in blood and tissue samples from different organs. We experimentally infected siskins (Spinus spinus) with the avian malaria parasite Plasmodium ashfordi, and used real-time quantitative polymerase chain reaction (PCR) to measure telomere length in control and experimentally infected siskins. We found that experimentally infected birds showed faster telomere attrition in blood over the course of infection compared with control individuals (repeatedly measured over 105 days post-infection (DPI)). Shorter telomeres were also found in the tissue of all six major organs investigated (liver, lungs, spleen, heart, kidney, and brain) in infected birds compared with controls at 105 DPI. To the best of our knowledge, this is the first study showing that an infectious disease results in synchronous telomere shortening in the blood and tissue cells of internal organs within individuals, implying that the infection induces systemic stress. Our results have far-reaching implications for understanding how the short-term effects of an infection can translate into long-term costs, such as organ dysfunction, degenerative diseases, and ageing. PMID:27488651

  15. Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies

    PubMed Central

    2014-01-01

    Background When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed. Methods Several species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the effect of number of infectious bites on monkey parasitaemia was documented. Results Anopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross between the two species) produced large numbers of P. knowlesi sporozoites. Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged only 32% when donor monkeys had a parasitaemia above 2%. However, when donor monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained ample sporozoites in their salivary glands. Adding methylparaben to sugar solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi was very infectious, with all monkeys developing blood stage infections if one or more infected mosquitoes successfully fed. There was also a dose-response, with monkeys that received higher numbers of infected mosquito bites developing malaria sooner. Conclusions Anopheles dirus, An. crascens and a

  16. Prevalence of malaria infection in Sarbaz, Sistan and Bluchistan province

    PubMed Central

    Reza, Youssefi Mohammad; Taghi, Rahimi Mohammad

    2011-01-01

    Objective To survey malaria prevalence in Sarbaz from April 2009 to October 2010. Methods Epidemiological data of 1 464 confirmed malarial patients were analyzed according to demographic status, sex, age, nationality, isolated species and residence place. Results The majority of patients were male 950 (64.8%) but 514 (35.2%) were female. 82.5% of patients were Iranian, 14% Pakistani immigrants, and 3.5% Afghan immigrants. Data collected showed that 90% of isolated species were Plasmodium vivax, 7.8% Plasmodium falciparum, and 2.2% Plasmodium malariae and mixed species. Conclusions Therefore, it is crystal clear that refugees should be prohibited by government and controlled by experts in health centers in order to campaign effectively with this life threating disease. PMID:23569820

  17. Co-infection of human parvovirus B19 with Plasmodium falciparum contributes to malaria disease severity in Gabonese patients

    PubMed Central

    2013-01-01

    Background High seroprevalence of parvovirus B19 (B19V) coinfection with Plasmodium falciparum has been previously reported. However, the impact of B19V-infection on the clinical course of malaria is still elusive. In this study, we investigated the prevalence and clinical significance of B19V co-infection in Gabonese children with malaria. Methods B19V prevalence was analyzed in serum samples of 197 Gabonese children with P. falciparum malaria and 85 healthy controls using polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct DNA-sequencing. Results B19V was detected in 29/282 (10.28%) of Gabonese children. B19V was observed more frequently in P. falciparum malaria patients (14.21%) in comparison to healthy individuals (1.17%) (P<0.001). Notably, the mild-malaria group revealed significantly lower hematocrit levels in B19V/P. falciparum co-infection than in P. falciparum mono-infection (P<0.05). Genetic analysis revealed a predominance of B19V genotype-1 (71.43%) in the studied population. However, B19V-genotype 2 was observed significantly more often in children with severe-malaria than in mild-malaria (P=0.04). Conclusion Our findings reveal that B19V-infection is frequent in Gabonese children with P. falciparum malaria and signifies a possible contribution of B19V on the clinical course of malaria in a genotype-dependent manner. B19V co-infection should be considered as a additional diagnostic measure in malaria patients with life threatening anemia. PMID:23945350

  18. Consistent Safety and Infectivity in Sporozoite Challenge Model of Plasmodium vivax in Malaria-Naive Human Volunteers

    PubMed Central

    Herrera, Sócrates; Solarte, Yezid; Jordán-Villegas, Alejandro; Echavarría, Juan Fernando; Rocha, Leonardo; Palacios, Ricardo; Ramírez, Óscar; Vélez, Juan D.; Epstein, Judith E.; Richie, Thomas L.; Arévalo-Herrera, Myriam

    2011-01-01

    A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (−) subjects were randomly allocated into three (A–C) groups and were exposed to the bites of 2–4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (−) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax-infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials. PMID:21292872

  19. Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers.

    PubMed

    Herrera, Sócrates; Solarte, Yezid; Jordán-Villegas, Alejandro; Echavarría, Juan Fernando; Rocha, Leonardo; Palacios, Ricardo; Ramírez, Oscar; Vélez, Juan D; Epstein, Judith E; Richie, Thomas L; Arévalo-Herrera, Myriam

    2011-02-01

    A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (-) subjects were randomly allocated into three (A-C) groups and were exposed to the bites of 2-4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (-) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax-infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials. PMID:21292872

  20. Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

    PubMed Central

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

  1. Neurological manifestations of malaria.

    PubMed

    Román, G C; Senanayake, N

    1992-03-01

    The involvement of the nervous system in malaria is reviewed in this paper. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red cells causing sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes nonspecific, immune-mediated, inflammatory responses with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations remains unexplored, but offers excellent perspectives for research at a clinical as well as experimental level. PMID:1307475

  2. Review: HIV-Plasmodium Co-infection: Malaria in AIDS patients.

    PubMed

    Qadir, Muhammad Imran; Maqbool, Faheem; Maqbool, Ayesha; Ali, Muhammad

    2015-09-01

    Malaria and HIV are amongst the two main diseases worldwide and creating troubles of our time. Together, they grounds extra than four million deaths a year. Malaria causes around about for more than a million deaths each year, of which over 80-90 % come about in tropical Africa, somewhere malaria is the primary source of mortality in children below six years of age. Sideways as of adolescent, children, pregnant women are surrounded by the largest part exaggerated by the disease. In the wide geographical extend beyond in event and the follow-on co-infection, the interface flanked as a result of the two diseases visibly has foremost communal strength results. Thus both are dangerous for health at the same time. PMID:26408902

  3. A case of quadruple malaria infection imported from Mozambique to Japan.

    PubMed

    Oki, Masayuki; Asai, Satomi; Saito-Nakano, Yumiko; Nakayama, Taira; Tanaka, Yumiko; Tachibana, Hiroshi; Ohmae, Hiroshi; Nozaki, Tomoyoshi; Miyachi, Hayato

    2014-06-01

    A 35-year-old Japanese man had an intermittent fever and mild headache for eight weeks after he returned to Japan from working in Mozambique. He had taken antimalarial prophylaxis (doxycycline) for 25 weeks, and stopped taking this drug two weeks after his return. Microscopic examination of a peripheral blood smear showed a mixed infection with Plasmodium vivax, P. falciparum, and P. ovale. In addition, a nested polymerase chain reaction and subsequent sequencing detected specific DNA sequences of four species of Plasmodium, including P. malariae. The patient was successfully treated with artemether-lumefantrine and primaquine phosphate. The present case is a rare instance of a mixed infection with four species of Plasmodium. Nonimmune persons in malaria-endemic areas may have a risk of mixed infection. All four species must be identified by using sensitive and specific tests, such as a nested polymerase chain reaction, in addition to conventional morphologic identification. PMID:24732464

  4. CD68 acts as a major gateway for malaria sporozoite liver infection

    PubMed Central

    Cha, Sung-Jae; Park, Kiwon; Srinivasan, Prakash; Schindler, Christian W.; van Rooijen, Nico; Stins, Monique

    2015-01-01

    After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite–Kupffer cell interactions are unknown. Understanding the molecular basis for this specific recognition may lead to novel therapeutic strategies to control malaria. Using a phage display library screen, we identified a peptide, P39, that strongly binds to the Kupffer cell surface and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we determined that P39 binds to CD68, a putative receptor for sporozoite invasion of Kupffer cells that acts as a gateway for malaria infection of the liver. PMID:26216124

  5. Genistein-Supplemented Diet Decreases Malaria Liver Infection in Mice and Constitutes a Potential Prophylactic Strategy

    PubMed Central

    Prudêncio, Miguel; Gonçalves, Lígia A.; Casalou, Cristina; Buger, Dominik; Sauerwein, Robert; Haas, Werner; Mota, Maria M.

    2008-01-01

    In tropical regions millions of people still live at risk of malaria infection. Indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. Genistein is a naturally occurring compound that is widely used as a food supplment and is thought to be effective in countering several pathologies. Results presented here show that genistein inhibits liver infection by the Plasmodium parasite, the causative agent of malaria. In vitro, genistein decreased the infection rates of both mouse and human hepatoma cells by inhibiting the early stages of the parasite's intracellular development. Oral or intraperitoneal administration of genistein decreased the liver parasite load of P. berghei-infected mice. Moreover, mice fed on a genistein-supplemented diet showed a significant reduction in Plasmodium liver infection as well as a reduced blood parasitemia and partial protection from severe disease. Since genistein is a safe, low-cost, natural compound that can be used permanently in a diet, we propose its use as a prophylactic agent against malaria for endemic populations and long-time travelers. PMID:18628947

  6. The genetic risk of acute seizures in African children with falciparum malaria

    PubMed Central

    Kariuki, Symon M; Rockett, Kirk; Clark, Taane G; Reyburn, Hugh; Agbenyega, Tsiri; Taylor, Terrie E; Birbeck, Gretchen L; Williams, Thomas N; Newton, Charles R J C

    2013-01-01

    Purpose It is unclear why some children with falciparum malaria develop acute seizures and what determines the phenotype of seizures. We sought to determine if polymorphisms of malaria candidate genes are associated with acute seizures. Methods Logistic regression was used to investigate genetic associations with malaria-associated seizures (MAS) and complex MAS (repetitive, prolonged, or focal seizures) in four MalariaGEN African sites, namely: Blantyre, Malawi; Kilifi, Kenya; Kumasi, Ghana; and Muheza, Tanzania. The analysis was repeated for five inheritance models (dominant, heterozygous, recessive, additive, and general) and adjusted for potential confounders and multiple testing. Key Findings Complex phenotypes of seizures constituted 71% of all admissions with MAS across the sites. MAS were strongly associated with cluster of differentiation-ligand-rs3092945 in females in Kilifi (p = 0.00068) and interleukin (IL)-17 receptor E-rs708567 in the pooled analysis across the sites (p = 0.00709). Complex MAS were strongly associated with epidermal growth factor module-containing mucin-like hormone receptor (EMR)1-rs373533 in Kumasi (p = 0.00033), but none in the pooled analysis. Focal MAS were strongly associated with IL-20 receptor A-rs1555498 in Muheza (p = 0.00016), but none in the pooled analysis. Prolonged MAS were strongly associated with complement receptor 1-rs17047660 in Kilifi (p = 0.00121) and glucose-6-phosphate dehydrogenase-rs1050828 in females in the pooled analysis (p = 0.00155). Repetitive MAS were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00003) and cystic fibrosis transmembrane conductance receptor-rs17140229 in the pooled analysis (p = 0.00543). MAS with coma/cerebral malaria were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00019) and IL10-rs3024500 in the pooled analysis across the sites (p = 0.00064). Significance We have identified a number of genetic associations that may explain the risk of seizures in >2,000 cases

  7. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon

    PubMed Central

    Lalremruata, Albert; Magris, Magda; Vivas-Martínez, Sarai; Koehler, Maike; Esen, Meral; Kempaiah, Prakasha; Jeyaraj, Sankarganesh; Perkins, Douglas Jay; Mordmüller, Benjamin; Metzger, Wolfram G.

    2015-01-01

    Background The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. Methods We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. Findings Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. Interpretation This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts. PMID:26501116

  8. Parasitic Central Nervous System Infections in Immunocompromised Hosts: Malaria, Microsporidiosis, Leishmaniasis, and African Trypanosomiasis

    PubMed Central

    Walker, Melanie; Kublin, James G.; Zunt, Joseph R.

    2009-01-01

    Immunosuppression associated with HIV infection or following transplantation increases susceptibility to central nervous system (CNS) infections. Because of increasing international travel, parasites that were previously limited to tropical regions pose an increasing infectious threat to populations at risk for acquiring opportunistic infection, especially people with HIV infection or individuals who have received a solid organ or bone marrow transplant. Although long-term immunosuppression caused by medications such as prednisone likely also increases the risk for acquiring infection and for developing CNS manifestations, little published information is available to support this hypothesis. In an earlier article published in Clinical Infectious Diseases, we described the neurologic manifestations of some of the more common parasitic CNS infections. This review will discuss the presentation, diagnosis, and treatment of the following additional parasitic CNS infections: malaria, microsporidiosis, leishmaniasis, and African trypanosomiasis. PMID:16323101

  9. Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function

    PubMed Central

    Butler, Brian P.; Xavier, Mariana N.; Chau, Jennifer Y.; Schaltenberg, Nicola; Begum, Ramie H.; Müller, Werner; Luckhart, Shirley; Tsolis, Renée M.

    2014-01-01

    Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection. PMID:24787713

  10. Malaria parasite infection compromises control of concurrent systemic non-typhoidal Salmonella infection via IL-10-mediated alteration of myeloid cell function.

    PubMed

    Lokken, Kristen L; Mooney, Jason P; Butler, Brian P; Xavier, Mariana N; Chau, Jennifer Y; Schaltenberg, Nicola; Begum, Ramie H; Müller, Werner; Luckhart, Shirley; Tsolis, Renée M

    2014-05-01

    Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood. Here, we report that in a mouse co-infection model, malaria parasite infection blunts inflammatory responses to NTS, leading to decreased inflammatory pathology and increased systemic bacterial colonization. Blunting of NTS-induced inflammatory responses required induction of IL-10 by the parasites. In the absence of malaria parasite infection, administration of recombinant IL-10 together with induction of anemia had an additive effect on systemic bacterial colonization. Mice that were conditionally deficient for either myeloid cell IL-10 production or myeloid cell expression of IL-10 receptor were better able to control systemic Salmonella infection, suggesting that phagocytic cells are both producers and targets of malaria parasite-induced IL-10. Thus, IL-10 produced during the immune response to malaria increases susceptibility to disseminated NTS infection by suppressing the ability of myeloid cells, most likely macrophages, to control bacterial infection. PMID:24787713

  11. Management of infection in acute pancreatitis.

    PubMed

    Hartwig, Werner; Werner, Jens; Uhl, Waldemar; Büchler, Markus W

    2002-01-01

    The clinical course of acute pancreatitis varies from a mild, transitory illness to a severe, rapidly fatal disease. In about 80% to 90% of cases pancreatitis presents as a mild, self-limiting disease with low morbidity and mortality. Unlike mild pancreatitis, necrotizing pancreatitis develops in about 15% of patients, with infection of pancreatic and peripancreatic necrosis representing the single most important risk factor for a fatal outcome. Infection of pancreatic necrosis in the natural course develops in the second and third week after onset of the disease and is reported in 40% to 70% of patients with necrotizing pancreatitis. Just recently, prevention of infection by prophylactic antibiotic treatment and assessment of the infection status of pancreatic necrosis by fine-needle aspiration have been established in the management of severe pancreatitis. Because medical treatment alone will result in a mortality rate of almost 100% in patients with signs of local and systemic septic complications, patients with infected necrosis must undergo surgical intervention, which consists of an organ-preserving necrosectomy combined with a postoperative closed lavage concept that maximizes further evacuation of infected debris and exudate. However, intensive care treatment, including prophylactic antibiotics, reduces the infection rate and delays the need for surgery in most patients until the third or fourth week after the onset of symptoms. At that time, debridement of necrosis is technically easier to perform, due to better demarcation between viable and necrotic tissue compared with necrosectomy earlier in the disease. In contrast, surgery is rarely needed in the presence of sterile pancreatic necrosis. In those patients the conservative approach is supported by the present data. PMID:12483263

  12. The Effect of Malaria and HIV Co-Infection on Anemia: A Meta-Analysis.

    PubMed

    Naing, Cho; Sandhu, Nisha Kaur; Wai, Victor Nyunt

    2016-04-01

    Malaria and human immunodeficiency virus (HIV) infections are globally important public health concerns. The objectives of this study were (i) to determine the prevalence of malaria and HIV co-infections in people living in endemic countries, and (ii) to assess the effect of co-infection on anemia.Studies were searched on electronic databases including PubMed, Embase, Medline, Google Scholar, and African Journals Online. Observational studies, assessing the prevalence of co-infection and reporting its association with anemia, were included. The methodological quality of included studies was assessed using a tool called the risk of bias assessment for non-randomized studies. Heterogeneity among studies was investigated with the I-square test. Pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effect model, reflected on heterogeneity among studies. Summary odds ratio (OR), summary standardized mean difference (SMD), and their corresponding 95% CIs were estimated, as appropriate. Subgroup analysis and meta-regression were performed for robustness of results. Publication bias was assessed by visualization of a funnel plot.Twenty-three studies were included in the present study. Overall, the pooled prevalence of co-infection was 19% (95% CI: 15-23%, I: 98.1%), showing 26% (95% CI: 20-32%, I: 98.7%) in adults, 12% (95% CI: 7-17%, I: 95.0) in pregnant women, and 9% (95% CI: 6-11%, I: 68.6%) in children. Anemia was comparable between the monoinfected and co-infected adults (summary OR: 1.49, 95% CI: 0.93-2.37) and increased by 49% in co-infected pregnant women (summary OR: 1.49, 95% CI: 1.14-1.94). The mean hemoglobin concentration was significantly lower in the co-infected group than the monoinfected group (summary SMD: -0.47, 95% CI: -0.61 to -0.33). The results of meta-regression on the prevalence of co-infection using the publication year and total population as covariates showed the I value remained high implying

  13. Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia.

    PubMed

    Punjabi, Narain H; Taylor, Walter R J; Murphy, Gerald S; Purwaningsih, Sri; Picarima, Helena; Sisson, John; Olson, James G; Baso, Samuel; Wangsasaputra, Ferry; Lesmana, Murad; Oyofo, Buhari A; Simanjuntak, Cyrus H; Subekti, Decy; Corwin, Andrew L; Richie, Thomas L

    2012-01-01

    We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics. PMID:22232450

  14. Acute encephalitis as initial presentation of primary HIV infection.

    PubMed

    Nzwalo, Hipólito; Añón, Rosário Pazos; Àguas, Maria João

    2012-01-01

    Acute encephalitis is a life-threatening condition. A wide variety of infectious agents are implicated and in many patients no cause is found. HIV acute seroconversion illness can rarely present as acute encephalitis. Although most experts agree in starting antiretroviral treatment in severe acute HIV infection, the evidence of the benefits are still lacking. The authors report a case of severe acute encephalitis as a primary presentation of HIV infection in which introduction of highly active antiretroviral treatment resulted in clinical recovery. This case highlights the need to consider HIV infection in the differential diagnosis of treatable viral encephalitis. PMID:22761210

  15. Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon

    PubMed Central

    Siqueira, Andre M; Cavalcante, Janieldo A; Vítor-Silva, Shelia; Reyes-Lecca, Roberto C; Alencar, Aline C; Monteiro, Wuelton M; Alexandre, Márcia AA; Maria Paula G, Mourão; Guinovart, Caterina; Bassat, Quique; Alecrim, Maria das Graças C; Lacerda, Marcus VG

    2014-01-01

    Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria-negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range. PMID:25141283

  16. Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon.

    PubMed

    Siqueira, Andre M; Cavalcante, Janieldo A; Vítor-Silva, Shelia; Reyes-Lecca, Roberto C; Alencar, Aline C; Monteiro, Wuelton M; Alexandre, Márcia A A; Mourão, Maria Paula G; Guinovart, Caterina; Bassat, Quique; Alecrim, Maria das Graças C; Lacerda, Marcus V G

    2014-08-01

    Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria-negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range. PMID:25141283

  17. The Strategy to Survive Primary Malaria Infection: An Experimental Study on Behavioural Changes in Parasitized Birds

    PubMed Central

    Mukhin, Andrey; Palinauskas, Vaidas; Platonova, Elena; Kobylkov, Dmitry; Vakoliuk, Irina; Valkiūnas, Gediminas

    2016-01-01

    Avian malaria parasites (Haemosporida, Plasmodium) are of cosmopolitan distribution, and they have a significant impact on vertebrate host fitness. Experimental studies show that high parasitemia often develops during primary malaria infections. However, field studies only occasionally reveal high parasitemia in free-living birds sampled using the traditional methods of mist-netting or trapping, and light chronic infections predominate. The reason for this discrepancy between field observation and experimental data remains insufficiently understood. Since mist-netting is a passive capture method, two main parameters determine its success in sampling infected birds in wildlife, i. e. the presence of parasitized birds at a study site and their mobility. In other words, the trapping probability depends on the survival rate of birds and their locomotor activity during infection. Here we test (1) the mortality rate of wild birds infected with Plasmodium relictum (the lineage pSGS1), (2) the changes in their behaviour during presence of an aerial predator, and (3) the changes in their locomotor activity at the stage of high primary parasitemia.We show that some behavioural features which might affect a bird's survival during a predator attack (time of reaction, speed of flush flight and take off angle) did not change significantly during primary infection. However, the locomotor activity of infected birds was almost halved compared to control (non-infected) birds during the peak of parasitemia. We report (1) the markedly reduced mobility and (2) the 20% mortality rate caused by P. relictum and conclude that these factors are responsible for the underrepresentation of birds in mist nets and traps during the stage of high primary parasitemia in wildlife. This study indicates that the widespread parasite, P. relictum (pSGS1) influences the behaviour of birds during primary parasitemia. Experimental studies combined with field observations are needed to better understand the

  18. The Strategy to Survive Primary Malaria Infection: An Experimental Study on Behavioural Changes in Parasitized Birds.

    PubMed

    Mukhin, Andrey; Palinauskas, Vaidas; Platonova, Elena; Kobylkov, Dmitry; Vakoliuk, Irina; Valkiūnas, Gediminas

    2016-01-01

    Avian malaria parasites (Haemosporida, Plasmodium) are of cosmopolitan distribution, and they have a significant impact on vertebrate host fitness. Experimental studies show that high parasitemia often develops during primary malaria infections. However, field studies only occasionally reveal high parasitemia in free-living birds sampled using the traditional methods of mist-netting or trapping, and light chronic infections predominate. The reason for this discrepancy between field observation and experimental data remains insufficiently understood. Since mist-netting is a passive capture method, two main parameters determine its success in sampling infected birds in wildlife, i. e. the presence of parasitized birds at a study site and their mobility. In other words, the trapping probability depends on the survival rate of birds and their locomotor activity during infection. Here we test (1) the mortality rate of wild birds infected with Plasmodium relictum (the lineage pSGS1), (2) the changes in their behaviour during presence of an aerial predator, and (3) the changes in their locomotor activity at the stage of high primary parasitemia.We show that some behavioural features which might affect a bird's survival during a predator attack (time of reaction, speed of flush flight and take off angle) did not change significantly during primary infection. However, the locomotor activity of infected birds was almost halved compared to control (non-infected) birds during the peak of parasitemia. We report (1) the markedly reduced mobility and (2) the 20% mortality rate caused by P. relictum and conclude that these factors are responsible for the underrepresentation of birds in mist nets and traps during the stage of high primary parasitemia in wildlife. This study indicates that the widespread parasite, P. relictum (pSGS1) influences the behaviour of birds during primary parasitemia. Experimental studies combined with field observations are needed to better understand the

  19. An Analysis of Hematological Parameters as a Diagnostic test for Malaria in Patients with Acute Febrile Illness: An Institutional Experience

    PubMed Central

    Jairajpuri, Zeeba Shamim; Rana, Safia; Hassan, Mohd Jaseem; Nabi, Farhat; Jetley, Sujata

    2014-01-01

    Objectives Hematological changes are among the most common complications encountered in malaria. This study analyzes and statistically evaluates the hematological changes as a diagnostic test for malaria in patients with acute febrile illness and whether these could guide the physician to institute specific antimalarial treatment. Methods The present study was an observational study, conducted from January to December 2012. A total of 723 patients presenting with acute febrile illness at our hospital were evaluated. A complete blood count and malarial parasite microscopy were performed for each patient. Results The findings showed that 172 out of 723 patients (24%) were diagnosed to have malaria by positive smear report. There were 121 males and 51 females with a male to female ratio of 2.3:1. Maximum number of cases were seen in the 20-30 years age group. There was a statistically significant reduction in hemoglobin (p<0.005), platelet count (p<0.001) and total leukocyte count (p<0.001) levels in patients with malaria compared to those without the disease. Likelihood ratios for a positive result of platelets (6.2) and total leukocyte count (3.4) was relevant as compared to hemoglobin (1.61) and Red cell distribution width (1.79). The negative predictive values for hemoglobin (79%), total leukocyte count (86%), platelets (94%) and Red cell distribution width (93%) were significant. Red cell distribution width values were found to be higher in patients with malaria than in patients without malaria (p<0.001). Conclusion This study revealed that routinely used laboratory findings such as hemoglobin, leukocytes, platelet counts and even red cell distribution width values can provide a diagnostic clue in a patient with acute febrile illness in endemic areas, thus increasing the probability of malaria and enhancing prompt initiation of treatment. PMID:24498476

  20. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  1. Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections.

    PubMed

    Nagaraj, Viswanathan A; Mukhi, Dhanunjay; Sathishkumar, Vinayagam; Subramani, Pradeep A; Ghosh, Susanta K; Pandey, Rajeev R; Shetty, Manjunatha C; Padmanaban, Govindarajan

    2015-01-01

    The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual- and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections. PMID:26531182

  2. Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections

    PubMed Central

    Nagaraj, Viswanathan A.; Mukhi, Dhanunjay; Sathishkumar, Vinayagam; Subramani, Pradeep A.; Ghosh, Susanta K.; Pandey, Rajeev R.; Shetty, Manjunatha C.; Padmanaban, Govindarajan

    2015-01-01

    The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual- and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections. PMID:26531182

  3. Rapid and Highly Sensitive Detection of Malaria-Infected Erythrocytes Using a Cell Microarray Chip

    PubMed Central

    Yamaguchi, Yuka; Shinohara, Yasuo; Tamiya, Eiichi; Horii, Toshihiro; Baba, Yoshinobu; Kataoka, Masatoshi

    2010-01-01

    Background Malaria is one of the major human infectious diseases in many endemic countries. For prevention of the spread of malaria, it is necessary to develop an early, sensitive, accurate and conventional diagnosis system. Methods and Findings A cell microarray chip was used to detect for malaria-infected erythrocytes. The chip, with 20,944 microchambers (105 µm width and 50 µm depth), was made from polystyrene, and the formation of monolayers of erythrocytes in the microchambers was observed. Cultured Plasmodium falciparum strain 3D7 was used to examine the potential of the cell microarray chip for malaria diagnosis. An erythrocyte suspension in a nuclear staining dye, SYTO 59, was dispersed on the chip surface, followed by 10 min standing to allow the erythrocytes to settle down into the microchambers. About 130 erythrocytes were accommodated in each microchamber, there being over 2,700,000 erythrocytes in total on a chip. A microarray scanner was employed to detect any fluorescence-positive erythrocytes within 5 min, and 0.0001% parasitemia could be detected. To examine the contamination by leukocytes of purified erythrocytes from human blood, 20 µl of whole blood was mixed with 10 ml of RPMI 1640, and the mixture was passed through a leukocyte isolation filter. The eluted portion was centrifuged at 1,000×g for 2 min, and the pellet was dispersed in 1.0 ml of medium. SYTO 59 was added to the erythrocyte suspension, followed by analysis on a cell microarray chip. Similar accommodation of cells in the microchambers was observed. The number of contaminating leukocytes was less than 1 on a cell microarray chip. Conclusion The potential of the cell microarray chip for the detection of malaria-infected erythrocytes was shown, it offering 10–100 times higher sensitivity than that of conventional light microscopy and easy operation in 15 min with purified erythrocytes. PMID:20967248

  4. Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection

    PubMed Central

    Lyke, Kirsten E.; Laurens, Matthew B.; Strauss, Kathy; Adams, Matthew; Billingsley, Peter F.; James, Eric; Manoj, Anita; Chakravarty, Sumana; Plowe, Christopher V.; Li, Ming Lin; Ruben, Adam; Edelman, Robert; Green, Michael; Dube, Tina J.; Kim Lee Sim, B.; Hoffman, Stephen L.

    2015-01-01

    Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18–45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 104 versus 5 × 104 PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 μL versus 50 μL) were studied. Three groups attained 100% infection: 1 × 104 PfSPZ in 50 μL/2 doses, 1 × 104 PfSPZ in 10 μL/2 doses, and 5 × 104 PfSPZ in 10 μL/8 doses. The group that received 5 × 104 PfSPZ total dose in eight 10 μL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes. PMID:26416102

  5. Absence of dry season Plasmodium parasitaemia, but high rates of reported acute respiratory infection and diarrhoea in preschool-aged children in Kaédi, southern Mauritania

    PubMed Central

    2012-01-01

    Background The epidemiology of malaria in the Senegal River Gorgol valley, southern Mauritania, requires particular attention in the face of ongoing and predicted environmental and climate changes. While “malaria cases” are reported in health facilities throughout the year, past and current climatic and ecological conditions do not favour transmission in the dry season (lack of rainfall and very high temperatures). Moreover, entomological investigations in neighbouring regions point to an absence of malaria transmission in mosquito vectors in the dry season. Because the clinical signs of malaria are non-specific and overlap with those of other diseases (e.g. acute respiratory infections and diarrhoea), new research is needed to better understand malaria transmission patterns in this region to improve adaptive, preventive and curative measures. Methods We conducted a multipurpose cross-sectional survey in the city of Kaédi in April 2011 (dry season), assessing three major disease patterns, including malaria. Plasmodium spp. parasite rates were tested among children aged 6–59 months who were recruited from a random selection of households using a rapid diagnostic test and microscopic examination of Giemsa-stained thick and thin blood films. Acute respiratory infection and diarrhoea were the two other diseases investigated, administering a parental questionnaire to determine the reported prevalence among participating children. Findings No Plasmodium infection was found in any of the 371 surveyed preschool-aged children using two different diagnostic methods. Acute respiratory infections and diarrhoea were reported in 43.4% and 35.0% of the participants, respectively. About two thirds of the children with acute respiratory infections and diarrhoea required medical follow-up by a health worker. Conclusions Malaria was absent in the present dry season survey in the capital of the Gorgol valley of Mauritania, while acute respiratory infections and diarrhea were

  6. Comparison of mathematical frameworks for modeling erythropoiesis in the context of malaria infection.

    PubMed

    Fonseca, Luis L; Voit, Eberhard O

    2015-12-01

    Malaria is an infectious disease present all around the globe and responsible for half a million deaths per year. A within-host model of this infection requires a framework capable of properly approximating not only the blood stage of the infection but also the erythropoietic process that is in charge of overcoming the malaria induced anemia. Within this context, we compare ordinary differential equations (ODEs) with and without age classes, delayed differential equations (DDEs), and discrete recursive equations (DREs) with age classes. Results show that ODEs without age classes are fair approximations that do not provide a crisp temporal representation of the processes involved, and inclusion of age classes only mitigates the problem to some degree. DDEs perform well with respect to generating the essentially fixed delay between cell production and cell removal due to age, but the inclusion of any other processes, such as sudden blood loss, becomes cumbersome. The framework that was found to perform best in representing the dynamics of red blood cells during malaria infection is a DRE with age classes. In this model structure, the amount of time a cell remains alive is easily controlled, and the addition of age dependent or independent processes is straightforward. All events that populations of cells face during their lifespan, like growth or adaptation in differentiation or maturation rate, are properly represented in this framework. PMID:26362230

  7. Removal of malaria-infected red blood cells using magnetic cell separators: A computational study.

    PubMed

    Kim, Jeongho; Massoudi, Mehrdad; Antaki, James F; Gandini, Alberto

    2012-02-15

    High gradient magnetic field separators have been widely used in a variety of biological applications. Recently, the use of magnetic separators to remove malaria-infected red blood cells (pRBCs) from blood circulation in patients with severe malaria has been proposed in a dialysis-like treatment. The capture efficiency of this process depends on many interrelated design variables and constraints such as magnetic pole array pitch, chamber height, and flow rate. In this paper, we model the malaria-infected RBCs (pRBCs) as paramagnetic particles suspended in a Newtonian fluid. Trajectories of the infected cells are numerically calculated inside a micro-channel exposed to a periodic magnetic field gradient. First-order stiff ordinary differential equations (ODEs) governing the trajectory of particles under periodic magnetic fields due to an array of wires are solved numerically using the 1(st) -5(th) order adaptive step Runge-Kutta solver. The numerical experiments show that in order to achieve a capture efficiency of 99% for the pRBCs it is required to have a longer length than 80 mm; this implies that in principle, using optimization techniques the length could be adjusted, i.e., shortened to achieve 99% capture efficiency of the pRBCs. PMID:22345827

  8. UK malaria treatment guidelines 2016.

    PubMed

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

    2016-06-01

    . Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet(®)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone-proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram-negative bacteraemia/septicaemia. 14. Children with

  9. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality.

    PubMed

    Conroy, Andrea L; Hawkes, Michael; Elphinstone, Robyn E; Morgan, Catherine; Hermann, Laura; Barker, Kevin R; Namasopo, Sophie; Opoka, Robert O; John, Chandy C; Liles, W Conrad; Kain, Kevin C

    2016-03-01

    Background.  Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods.  One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results.  Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-.95; P = .006) and 0.72 (95% CI, .57-.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions.  Acute kidney injury is an underrecognized complication in young children with SM

  10. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality

    PubMed Central

    Conroy, Andrea L.; Hawkes, Michael; Elphinstone, Robyn E.; Morgan, Catherine; Hermann, Laura; Barker, Kevin R.; Namasopo, Sophie; Opoka, Robert O.; John, Chandy C.; Liles, W. Conrad; Kain, Kevin C.

    2016-01-01

    Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03–1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65–.95; P = .006) and 0.72 (95% CI, .57–.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions. Acute kidney injury is an underrecognized complication in young children with SM

  11. In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

    PubMed Central

    Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M.; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D’Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

    2015-01-01

    Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection. PMID:25658925

  12. Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.

    PubMed

    Ng, Shengyong; March, Sandra; Galstian, Ani; Hanson, Kirsten; Carvalho, Tânia; Mota, Maria M; Bhatia, Sangeeta N

    2014-02-01

    Homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. In vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. Existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possibly due to missing microenvironmental support signals. One cue that could influence the infection capacity of cultured human hepatocytes is the dissolved oxygen concentration. We developed a microscale human liver platform comprised of precisely patterned primary human hepatocytes and nonparenchymal cells to model liver-stage malaria, but the oxygen concentrations are typically higher in the in vitro liver platform than anywhere along the hepatic sinusoid. Indeed, we observed that liver-stage Plasmodium parasite development in vivo correlates with hepatic sinusoidal oxygen gradients. Therefore, we hypothesized that in vitro liver-stage malaria infection efficiencies might improve under hypoxia. Using the infection of micropatterned co-cultures with Plasmodium berghei, Plasmodium yoelii or Plasmodium falciparum as a model, we observed that ambient hypoxia resulted in increased survival of exo-erythrocytic forms (EEFs) in hepatocytes and improved parasite development in a subset of surviving EEFs, based on EEF size. Further, the effective cell surface oxygen tensions (pO2) experienced by the hepatocytes, as predicted by a mathematical model, were systematically perturbed by varying culture parameters such as hepatocyte density and height of the medium, uncovering an optimal cell surface pO2 to maximize the number of mature EEFs. Initial mechanistic experiments revealed that treatment of primary human hepatocytes with the hypoxia mimetic, cobalt(II) chloride, as well as a HIF-1

  13. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection. PMID:26310309

  14. Helicobacter pylori infection and acute myocardial infarction.

    PubMed

    Nakić, Dario; Vcev, Aleksandar; Jović, Albino; Patrk, Jogen; Zekanović, Drazen; Klarin, Ivo; Ivanac, Kresimir; Mrden, Anamarija; Balen, Sanja

    2011-09-01

    The aim of this investigation was to determine whether H. pylori infection is an independent risk factor for acute myocardial infarction (AMI), determine is there a link between H. pylori infection and severity of disease. In this prospective, single centre study, were enrolled 100 patients with AMI and control group was consisted 93 healthy individuals. The results of this study showed no difference between H. pylori seropositivity distribution in the investigate and control group (29 vs. 26 %) and there was no significant difference on the severity of the disease. There was significant association in the patients with three and more risk factors, where the patients with lower blood pressure (124.4/77.4 vs. 145.9/87.7 mmHg) and better controlled diabetes (HbA1c 6.1% vs. 6.9%) had greater risk for AMI if they are H. pylori seropositive. The large multicentric trials would be needed to define a precise role of H. pylori infection on the developement of AMI. PMID:22053556

  15. Prevalence of malaria among acute febrile patients clinically suspected of having malaria in the Zeway Health Center, Ethiopia.

    PubMed

    Feleke, Sendeaw M; Animut, Abebe; Belay, Mulugeta

    2015-01-01

    Malaria diagnosis is a common challenge in developing countries with limited diagnostic services. Common febrile illnesses were assessed in 280 malaria-suspected patients, and each case was subjected to clinical and laboratory examinations for malaria, relapsing fever, typhoid fever, typhus, and brucellosis. Data were entered and analyzed using Epi Info version 3.1 software. Malaria accounted for 17% (CI, 12.6-21.4%) of febrile illnesses. The remaining cases were associated with typhoid fever (18.5%; CI, 13.95-23.05%), typhus (17.8%; CI, 13.32-22.28%), brucellosis (1%; CI, -0.17-2.17%), relapsing fever (2%; CI, 0.36-3.64%), and unknown causes (44%). Approximately 7% of patients had coinfections, and 2% of patients treated as monoinfections. Approximately 1.4% of the nonmalarial patients received antimalarial treatment. The sensitivity and specificity of the CareStart Pf/pan rapid diagnostic tests in comparison with those of microscopy were 100% and 91%, respectively, with positive- and negative-predictive values of 94% and 100%, respectively. Compared with microscopy, the positive-predictive value of each malaria symptom was much lower than that of the symptoms combined: fever, 17%; sweating, 30%; headache, 18%; general body ache, 22%; loss of appetite, 21%. The study findings revealed a high proportion of nonmalarial illnesses were clinically categorized as malaria. Parasite-based diagnosis is recommended for the management of malarial and nonmalarial cases. PMID:25420658

  16. Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies☆

    PubMed Central

    Lillie, Patrick J.; Duncan, Christopher J.A.; Sheehy, Susanne H.; Meyer, Joel; O'Hara, Geraldine A.; Gilbert, Sarah C.; Hill, Adrian V.S.

    2012-01-01

    Summary During the H1N1 influenza pandemic (pH1N1/09) diagnostic algorithms were developed to guide antiviral provision. However febrile illnesses are notoriously difficult to distinguish clinically. Recent evidence highlights the importance of incorporating travel history into diagnostic algorithms to prevent the catastrophic misdiagnosis of life-threatening infections such as malaria. We applied retrospectively the UK pH1N1/09 case definition to a unique cohort of healthy adult volunteers exposed to Plasmodium falciparum malaria or influenza to assess the predictive value of this case definition, and to explore the distinguishing clinical features of early phase infection with these pathogens under experimental conditions. For influenza exposure the positive predictive value of the pH1N1/09 case definition was only 0.38 (95% CI: 0.06–0.60), with a negative predictive value of 0.27 (95% CI: 0.02–0.51). Interestingly, 8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenza-exposed volunteers would have been classified without influenza (P = 0.18 Fisher's exact). Cough (P = 0.005) and nasal symptoms (P = 0.001) were the only clinical features that distinguished influenza-exposed from malaria-exposed volunteers. An open mind regarding the clinical cause of undifferentiated febrile illness, particularly in the absence of upper respiratory tract symptoms, remains important even during influenza pandemic settings. These data support incorporating travel history into pandemic algorithms. PMID:22531678

  17. Studying fitness cost of Plasmodium falciparum infection in malaria vectors: validation of an appropriate negative control

    PubMed Central

    2013-01-01

    Background The question whether Plasmodium falciparum infection affects the fitness of mosquito vectors remains open. A hurdle for resolving this question is the lack of appropriate control, non-infected mosquitoes that can be compared to the infected ones. It was shown recently that heating P. falciparum gametocyte-infected blood before feeding by malaria vectors inhibits the infection. Therefore, the same source of gametocyte-infected blood could be divided in two parts, one heated, serving as the control, the other unheated, allowing the comparison of infected and uninfected mosquitoes which fed on exactly the same blood otherwise. However, before using this method for characterizing the cost of infection to mosquitoes, it is necessary to establish whether feeding on previously heated blood affects the survival and fecundity of mosquito females. Methods Anopheles gambiae M molecular form females were exposed to heated versus non-heated, parasite-free human blood to mimic blood meal on non-infectious versus infectious gametocyte-containing blood. Life history traits of mosquito females fed on blood that was heat-treated or not were then compared. Results The results reveal that heat treatment of the blood did not affect the survival and fecundity of mosquito females. Consistently, blood heat treatment did not affect the quantity of blood ingested. Conclusions The study indicates that heat inactivation of gametocyte-infected blood will only inhibit mosquito infection and that this method is suitable for quantifying the fitness cost incurred by mosquitoes upon infection by P. falciparum. PMID:23282172

  18. Acute HIV infection - New York City, 2008.

    PubMed

    2009-11-27

    Acute human immunodeficiency virus (HIV) infection (AHI) is a highly infectious phase of disease that lasts approximately 2 months and is characterized by nonspecific clinical symptoms. AHI contributes disproportionately to HIV transmission because it is associated with a high level of viremia, despite negative or indeterminate antibody (Ab) tests. Diagnosis of AHI with individual or pooled nucleic acid amplification tests (p-NAAT) can enable infected persons to adopt behaviors that reduce HIV transmission, facilitate partner referral for counseling and testing, and identify social networks of persons with elevated rates of HIV transmission. The national HIV surveillance case definition does not distinguish AHI from other stages of HIV infection, and the frequency of AHI among reported HIV cases is unknown. In 2008, to increase detection of AHI and demonstrate the feasibility of AHI surveillance, the New York City Department of Health and Mental Hygiene (NYC DOHMH) initiated p-NAAT screening at four sexually transmitted disease (STD) clinics and enhanced citywide HIV surveillance (using a standard case definition) to differentiate AHI among newly reported cases. Seventy cases of AHI (representing 1.9% of all 3,635 HIV diagnoses reported in New York City) were identified: 53 cases from enhanced surveillance and 17 cases from p-NAAT screening (representing 9% of 198 HIV diagnoses at the four clinics). Men who have sex with men (MSM) constituted 81% of AHI cases. Screening STD clinic patients, especially MSM, with p-NAAT can identify additional cases of HIV infection. Surveillance for AHI is feasible and can identify circumstances in which HIV prevention efforts should be intensified. PMID:19940835

  19. Existing Infection Facilitates Establishment and Density of Malaria Parasites in Their Mosquito Vector.

    PubMed

    Pollitt, Laura C; Bram, Joshua T; Blanford, Simon; Jones, Matthew J; Read, Andrew F

    2015-07-01

    Very little is known about how vector-borne pathogens interact within their vector and how this impacts transmission. Here we show that mosquitoes can accumulate mixed strain malaria infections after feeding on multiple hosts. We found that parasites have a greater chance of establishing and reach higher densities if another strain is already present in a mosquito. Mixed infections contained more parasites but these larger populations did not have a detectable impact on vector survival. Together these results suggest that mosquitoes taking multiple infective bites may disproportionally contribute to malaria transmission. This will increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains. Moreover, control measures that reduce parasite prevalence in vertebrate hosts will reduce the likelihood of mosquitoes taking multiple infective feeds, and thus disproportionally reduce transmission. More generally, our study shows that the types of strain interactions detected in vertebrate hosts cannot necessarily be extrapolated to vectors. PMID:26181518

  20. Existing Infection Facilitates Establishment and Density of Malaria Parasites in Their Mosquito Vector

    PubMed Central

    Pollitt, Laura C.; Bram, Joshua T.; Blanford, Simon; Jones, Matthew J.; Read, Andrew F.

    2015-01-01

    Very little is known about how vector-borne pathogens interact within their vector and how this impacts transmission. Here we show that mosquitoes can accumulate mixed strain malaria infections after feeding on multiple hosts. We found that parasites have a greater chance of establishing and reach higher densities if another strain is already present in a mosquito. Mixed infections contained more parasites but these larger populations did not have a detectable impact on vector survival. Together these results suggest that mosquitoes taking multiple infective bites may disproportionally contribute to malaria transmission. This will increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains. Moreover, control measures that reduce parasite prevalence in vertebrate hosts will reduce the likelihood of mosquitoes taking multiple infective feeds, and thus disproportionally reduce transmission. More generally, our study shows that the types of strain interactions detected in vertebrate hosts cannot necessarily be extrapolated to vectors. PMID:26181518

  1. Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

    PubMed Central

    Shekalaghe, Seif; Rutaihwa, Mastidia; Billingsley, Peter F.; Chemba, Mwajuma; Daubenberger, Claudia A.; James, Eric R.; Mpina, Maximillian; Ali Juma, Omar; Schindler, Tobias; Huber, Eric; Gunasekera, Anusha; Manoj, Anita; Simon, Beatus; Saverino, Elizabeth; Church, L. W. Preston; Hermsen, Cornelus C.; Sauerwein, Robert W.; Plowe, Christopher; Venkatesan, Meera; Sasi, Philip; Lweno, Omar; Mutani, Paul; Hamad, Ali; Mohammed, Ali; Urassa, Alwisa; Mzee, Tutu; Padilla, Debbie; Ruben, Adam; Lee Sim, B. Kim; Tanner, Marcel; Abdulla, Salim; Hoffman, Stephen L.

    2014-01-01

    Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious. PMID:25070995

  2. Effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection.

    PubMed

    Kume, Aiko; Herbas, Maria Shirley; Shichiri, Mototada; Ishida, Noriko; Suzuki, Hiroshi

    2016-01-01

    The current preventions of malaria are protection against mosquito bites and taking chemoprophylactic anti-malarial drugs. However, drug therapies are usually associated with adverse events and emergency of drug-resistant malaria parasites. Previous study showed that host plasma alpha-tocopherol deficiency enhanced resistance against malaria infection in mice. Here, we report a new prevention strategy against malaria by using anti-hyperlipidemia drugs, ezetimibe, berberine, cholestyramine, and probucol to modify the host plasma alpha-tocopherol concentration. The drugs were mixed with diet and fed to C57BL/6J mice for 2 weeks. Although all drugs reduced plasma alpha-tocopherol concentration after 2 weeks of feeding, probucol-treated mice showed 90 % reduction and it was the lowest alpha-tocopherol concentration among the four drugs. Ezetimibe, berberine, and combination of ezetimibe and berberine pretreatment for 2 weeks were not effective against infection of Plasmodium yoelii XL17, a lethal strain, for survival and parasitemia in mice. Two-week pretreatment and 1-week treatment after infection of cholestyramine had also no effect on malaria infection. Survival rates of cholestyramine, ezetimibe, and/or berberine treated mice were 0-22 %. However, probucol caused significant decrease in parasitemia and increased in mice survival following 2-week pretreatment and 1-week treatment after infection. All control mice died while all probucol treated mice survived during the course of infection. Thus, probucol which reduced plasma alpha-tocopherol concentration was effective in enhancing the host to resist malaria infection in mice. Our finding indicates that plasma alpha-tocopherol reducing drugs like probucol might be a candidate for beneficial prevention strategy for travelers from malaria-free area. PMID:26358099

  3. NOS2 Variants Reveal a Dual Genetic Control of Nitric Oxide Levels, Susceptibility to Plasmodium Infection, and Cerebral Malaria

    PubMed Central

    Trovoada, Maria de Jesus; Martins, Madalena; Ben Mansour, Riadh; Sambo, Maria do Rosário; Fernandes, Ana B.; Antunes Gonçalves, Lígia; Borja, Artur; Moya, Roni; Almeida, Paulo; Costa, João; Marques, Isabel; Macedo, M. Paula; Coutinho, António; Narum, David L.

    2014-01-01

    Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E–04 < P < 7.57E–04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E–05 < P < 7.90E–04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E–4 < P < 4.33E–02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes. PMID:24379293

  4. Dynamics of Plasmodium falciparum Parasitemia Regarding Combined Treatment Regimens for Acute Uncomplicated Malaria, Antioquia, Colombia

    PubMed Central

    Álvarez, Gonzalo; Tobón, Alberto; Piñeros, Juan-Gabriel; Ríos, Alexandra; Blair, Silvia

    2010-01-01

    Selecting suitable anti-malarial treatment represents one of the best tools for reducing morbidity and mortality caused by this disease. Sexual and asexual parasite dynamics were thus evaluated in patients involved in antimalarial drug efficacy studies by using combined treatment with and without artemisinin derivatives for treating uncomplicated acute Plasmodium falciparum malaria in Antioquia, Colombia. All treatment doses were supervised and administered according to patients' weight; sexual and asexual parasitemia were evaluated during 28- or 42-days follow-up in 468 patients. Artemisinin-based combination therapy showed greater parasiticidal ability, showing a mean asexual parasitemia survival rate of one day and mean gametocyte survival rate of 1–2 days. Sexual and asexual parasitemias were eliminated more quickly and effectively in the group receiving artemisinin-based combination therapy. Adding 45 mg of primaquine to treatment with artesunate and mefloquine reduced gametocyte and asexual parasite survival by one day. PMID:20595483

  5. The Cinderella syndrome: why do malaria-infected cells burst at midnight?

    PubMed

    Mideo, Nicole; Reece, Sarah E; Smith, Adrian L; Metcalf, C Jessica E

    2013-01-01

    An interesting quirk of many malaria infections is that all parasites within a host - millions of them - progress through their cell cycle synchronously. This surprising coordination has long been recognized, yet there is little understanding of what controls it or why it has evolved. Interestingly, the conventional explanation for coordinated development in other parasite species does not seem to apply here. We argue that for malaria parasites, a critical question has yet to be answered: is the coordination due to parasites bursting at the same time or at a particular time? We explicitly delineate these fundamentally different scenarios, possible underlying mechanistic explanations and evolutionary drivers, and discuss the existing corroborating data and key evidence needed to solve this evolutionary mystery. PMID:23253515

  6. The Cinderella syndrome: why do malaria-infected cells burst at midnight?

    PubMed Central

    Mideo, Nicole; Reece, Sarah E.; Smith, Adrian L.; Metcalf, C. Jessica E.

    2013-01-01

    An interesting quirk of many malaria infections is that all parasites within a host – millions of them – progress through their cell cycle synchronously. This surprising coordination has long been recognized, yet there is little understanding of what controls it or why it has evolved. Interestingly, the conventional explanation for coordinated development in other parasite species does not seem to apply here. We argue that for malaria parasites, a critical question has yet to be answered: is the coordination due to parasites bursting at the same time or at a particular time? We explicitly delineate these fundamentally different scenarios, possible underlying mechanistic explanations and evolutionary drivers, and discuss the existing corroborating data and key evidence needed to solve this evolutionary mystery. PMID:23253515

  7. Holographic analysis on deformation and restoration of malaria-infected red blood cells by antimalarial drug

    NASA Astrophysics Data System (ADS)

    Byeon, Hyeokjun; Ha, Young-Ran; Lee, Sang Joon

    2015-11-01

    Malaria parasites induce morphological, biochemical, and mechanical changes in red blood cells (RBCs). Mechanical variations are closely related to the deformability of individual RBCs. The deformation of various RBCs, including healthy and malaria-infected RBCs (iRBCs), can be directly observed through quantitative phase imaging (QPI). The effects of chloroquine treatment on the mechanical property variation of iRBCs were investigated using time-resolved holographic QPI of single live cells on a millisecond time scale. The deformabilities of healthy RBCs, iRBCs, and drug-treated iRBCs were compared, and the effect of chloroquine on iRBC restoration was experimentally examined. The present results are beneficial to elucidate the dynamic characteristics of iRBCs and the effect of the antimalarial drug on iRBCs.

  8. Dispersal in a patchy landscape reveals contrasting determinants of infection in a wild avian malaria system.

    PubMed

    Knowles, Sarah C L; Wood, Matthew J; Alves, Ricardo; Sheldon, Ben C

    2014-03-01

    Understanding exactly when, where and how hosts become infected with parasites is critical to understanding host-parasite co-evolution in natural populations. However, for host-parasite systems in which hosts or parasites are mobile, for example in vector-borne diseases, the spatial location of infection and the relative importance of parasite exposure at successive host life-history stages are often uncertain. Here, using a 6-year longitudinal data set from a spatially referenced population of blue tits, we test the extent to which infection by avian malaria parasites is determined by conditions experienced at natal or breeding sites, as well as by postnatal dispersal between the two. We show that the location and timing of infection differs markedly between two sympatric malaria parasite species. For one species (Plasmodium circumflexum), our analyses indicate that infection occurs after birds have settled on breeding territories, and because the distribution of this parasite is temporally stable across years, hosts born in malarious areas could in principle alter their exposure and potentially avoid infection through postnatal dispersal. Conversely, the spatial distribution of another parasite species (Plasmodium relictum) is unpredictable and infection probability is positively associated with postnatal dispersal distance, potentially indicating that infection occurs during this major dispersal event. These findings suggest that hosts in this population may be subject to divergent selection pressures from these two parasites, potentially acting at different life-history stages. Because this implies parasite species-specific predictions for many coevolutionary processes, they also illustrate the complexity of predicting such processes in multi-parasite systems. PMID:24117384

  9. The treatment of malaria.

    PubMed

    White, N J

    1996-09-12

    Increasing drug resistance in Plasmodium falciparum and a resurgence of malaria in tropical areas have effected a change in treatment of malaria in the last two decades. Symptoms of malaria are fever, chills, headache, and malaise. The prognosis worsens as the parasite counts, counts of mature parasites, and counts of neutrophils containing pigment increase. Treatment depends on severity, age of patient, degree of background immunity, likely pattern of susceptibility to antimalarial drugs, and the cost and availability of drugs. Chloroquine should be used for P. vivax, P. malariae, and P. ovale. P. vivax has shown high resistance to chloroquine in Oceania, however. Primaquine may be needed to treat P. vivax and P. ovale to rid the body of hypnozoites that survive in the liver. Chloroquine can treat P. falciparum infections acquired in North Africa, Central America north of the Panama Canal, Haiti, or the Middle East but not in most of Africa and some parts of Asia and South America. In areas of low grade resistance to chloroquine, amodiaquine can be used to effectively treat falciparum malaria. A combination of sulfadoxine-pyrimethamine is responsive to falciparum infections with high grade resistance to chloroquine. Mefloquine, halofantrine, or quinine with tetracycline can be used to treat multidrug-resistant P. falciparum. Derivatives of artemisinin obtained from qinghao or sweet wormwood developed as pharmaceuticals in China are the most rapidly acting of all antimalarial drugs. Children tend to tolerate antimalarial drugs well. Children who weigh less than 15 kg should not be given mefloquine. Health workers should not prescribe primaquine to pregnant women or newborns due to the risk of hemolysis. Chloroquine, sulfadoxine-pyrimethamine, quinine, and quinidine can be safely given in therapeutic doses throughout pregnancy. Clinical manifestations of severe malaria are hypoglycemia, convulsions, severe anemia, acute renal failure, jaundice, pulmonary edema

  10. Simulation of malaria-infected red blood cells in microfluidic channels: Passage and blockage

    PubMed Central

    Wu, Tenghu; Feng, James J.

    2013-01-01

    Malaria-infected red blood cells (iRBCs) become less deformable with the progression of infection and tend to occlude microcapillaries. This process has been investigated in vitro using microfluidic channels. The objective of this paper is to provide a quantitative basis for interpreting the experimental observations of iRBC occlusion of microfluidic channels. Using a particle-based model for the iRBC, we simulate the traverse of iRBCs through a converging microfluidic channel and explore the progressive loss of cell deformability due to three factors: the stiffening of the membrane, the reduction of the cell's surface-volume ratio, and the growing solid parasites inside the cell. When examined individually, each factor tends to hinder the passage of the iRBC and lengthen the transit time. Moreover, at sufficient magnitude, each may lead to obstruction of narrow microfluidic channels. We then integrate the three factors into a series of simulations that mimic the development of malaria infection through the ring, trophozoite, and schizont stages. These simulations successfully reproduce the experimental observation that with progression of infection, the iRBC transitions from passage to blockage in larger and larger channels. The numerical results suggest a scheme for quantifying iRBC rigidification through microfluidic measurements of the critical pressure required for passage. PMID:24404048

  11. Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow

    PubMed Central

    Xu, Xiaofeng; Efremov, Artem K.; Li, Ang; Lai, Lipeng; Dao, Ming; Lim, Chwee Teck; Cao, Jianshu

    2013-01-01

    Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P.) species with the P.falciparum being the most deadly. The parasites are capable of invading red blood cells (RBCs) during infection. At the late stage of parasites’ development, the parasites export proteins to the infected RBCs (iRBC) membrane and bind to receptors of surface proteins on the endothelial cells that line microvasculature walls. Resulting adhesion of iRBCs to microvasculature is one of the main sources of most complications during malaria infection. Therefore, it is important to develop a versatile and simple experimental method to quantitatively investigate iRBCs cytoadhesion and binding kinetics. Here, we developed an advanced flow based adhesion assay to demonstrate that iRBC’s adhesion to endothelial CD36 receptor protein coated channels is a bistable process possessing a hysteresis loop. This finding confirms a recently developed model of cell adhesion which we used to fit our experimental data. We measured the contact area of iRBC under shear flow at different stages of infection using Total Internal Reflection Fluorescence (TIRF), and also adhesion receptor and ligand binding kinetics using Atomic Force Microscopy (AFM). With these parameters, we reproduced in our model the experimentally observed changes in adhesion properties of iRBCs accompanying parasite maturation and investigated the main mechanisms responsible for these changes, which are the contact area during the shear flow as well as the rupture area size. PMID:23724092

  12. Treatment of Acute HIV Infection and the Potential Role of Acutely HIV-Infected Persons in Cure Studies.

    PubMed

    Little, Susan J

    Diagnosis of acute HIV infection is important for accurate estimation of HIV incidence, identifying persons who are unaware of their HIV infection, and offering immediate treatment and risk-reduction strategies. The higher viral loads associated with acute HIV infection are associated with an increased risk of transmission. Current treatment recommendations are the same for acute and established infections. Studies of acute HIV infection indicate that initiation of antiretroviral therapy during this period may allow greater recovery of CD4+ T-cell count and function and may result in a smaller latent viral reservoir and a skewing of infection away from central memory CD4+ T cells toward shorter-lived transitional memory CD4+ T cells. This article summarizes a presentation by Susan J. Little, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Los Angeles, California, in April 2015. PMID:27398768

  13. Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association.

    PubMed

    Theochari, Evangelia; Vincent-Smith, Lisa; Ellis, Cathy

    2015-01-01

    Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis. PMID:25739795

  14. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe

    PubMed Central

    Sheehy, Susanne H.; Spencer, Alexandra J.; Douglas, Alexander D.; Sim, B. Kim Lee; Longley, Rhea J.; Edwards, Nick J.; Poulton, Ian D.; Kimani, Domtila; Williams, Andrew R.; Anagnostou, Nicholas A.; Roberts, Rachel; Kerridge, Simon; Voysey, Merryn; James, Eric R.; Billingsley, Peter F.; Gunasekera, Anusha; Lawrie, Alison M.; Hoffman, Stephen L.; Hill, Adrian V. S.

    2013-01-01

    Background Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection. Methodology We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM. Findings Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test). Conclusions 2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants. Trial Registration ClinicalTrials.gov NCT01465048 PMID:23823332

  15. Prevalence, Features and Risk Factors for Malaria Co-Infections amongst Visceral Leishmaniasis Patients from Amudat Hospital, Uganda

    PubMed Central

    Adams, Emily R.; Mens, Pètra F.; Sentongo, Elizabeth; Mbulamberi, Dawson B.; Straetemans, Masja; Schallig, Henk D. F. H.; Chappuis, Francois

    2012-01-01

    Background and methodology Due to geographic overlap of malaria and visceral leishmaniasis (VL), co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000–2006) by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients' characteristics and the occurrence of the co-infection. Results Of 2414 patients with confirmed VL, 450 (19%) were positively diagnosed with concomitant malaria. Most co-infected patients were males, residing in Kenya (69%). While young age was identified by multivariate analysis as a risk factor for concurrent VL and malaria, particularly the age groups 0–4 (odds ratio (OR): 2.44; 95% confidence interval (CI): 1.52–3.92) and 5–9 years (OR: 2.23, 95% CI: 1.45-3-45), mild (OR: 0.53; 95% CI: 0.32–0.88) and moderate (OR: 0.45; 95% CI: 0.27–0.77) anemia negatively correlated with the co-morbidity. VL patients harboring skin infections were nearly three times less likely to have the co-infection (OR: 0.35; 95% CI: 0.17–0.72), as highlighted by the multivariate model. Anorexia was slightly more frequent among co-infected patients (OR: 1.71; 95% CI: 0.96–3.03). The in-hospital case-fatality rate did not significantly differ between cases and controls, being 2.7% and 3.1% respectively (OR: 0.87; 95% CI: 0.46–1.63). Conclusions Concurrent malaria represents a common condition among young VL patients living in the Pokot region of Kenya and Uganda. Although these co-morbidities did not result in a poorer prognosis, possibly due to early detection of malaria, a positive trend towards more severe symptoms was identified, indicating that

  16. The recent malaria situation in Chittagong, Bangladesh.

    PubMed

    Hussain, S M B; Rahman, M M; Ahmed, Z; Siddique, M M

    2003-01-01

    This is a retrospective study on 7,005 cases of malaria treated in a base hospital during the period 1998 to 2001. The aim of the study is to analyze the patterns, complications and mortality rates of malaria and its response to standard anti-malarial drugs. Diagnosis of malaria was made from identification of parasites on Giemsa stained thick and thin blood slides among the febrile cases and the clinical (unspecified) malaria was diagnosed as per WHO criteria. Malaria cases accounted for 136.17 per thousand-hospital admissions. Out of 7,005 malaria cases, 54.22% were falciparum, 26.18% were vivax and 12.02% were mixed infections. The most common complications of falciparum malaria were cerebral malaria (2.80%), malarial hepatitis (1.55%), acute pneumonia and/or pulmonary edema (0.22%), acute renal failure (0.13%), algid malaria (0.13%) and black water fever (0.06%). Most of the cases (66.98%) responded (S-response) well to chloroquine. Among the rest, 11.99% required quinine, 9.79% required artemether and 0.08% required both mefloquine and artemether. The total mortality rate was 0.30% but it was 9.25% and 6.17% among complicated malaria and cerebral malaria cases, respectively. Prognosis appeared better on early recognition of complications and initiation of prompt, effective treatment and adequate nursing care. Most mortality was due to complicated falciparum malaria and the emergence of drug resistance. PMID:19238662

  17. UK malaria treatment guidelines.

    PubMed

    Lalloo, David G; Shingadia, Delane; Pasvol, Geoffrey; Chiodini, Peter L; Whitty, Christopher J; Beeching, Nicholas J; Hill, David R; Warrell, David A; Bannister, Barbara A

    2007-02-01

    ); quinine is highly effective but poorly tolerated in prolonged dosage and is always supplemented by additional treatment, usually with oral doxycycline. ALL patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h, since patients can deteriorate suddenly, especially early in the course of treatment. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized), should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. In the UK, the treatment of choice for severe or complicated malaria is currently an infusion of intravenous quinine. This may exacerbate hypoglycaemia that can occur in malaria; patients treated with intravenous quinine therefore require careful monitoring. Intravenous artesunate reduces high parasite loads more rapidly than quinine and is more effective in treating severe malaria in selected situations. It can also be used in patients with contra-indications to quinine. Intravenous artesunate is unlicensed in the EU. Assistance in obtaining artesunate may be sought from specialist tropical medicine centres, on consultation, for named patients. Patients with severe or complicated malaria should be managed in a high dependency or intensive care environment. They may require haemodynamic support and management of acute respiratory distress syndrome, disseminated intravascular coagulation, renal impairment/failure, seizures, and severe intercurrent infections including gram-negative bacteraemia/septicaemia. Falciparum malaria in pregnancy is more likely to be severe and complicated: the placenta contains high levels of parasites. Stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. The treatment of choice for falciparum malaria in pregnancy is quinine; doxycycline is contraindicated in pregnancy but clindamycin can be

  18. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  19. Resistance and Susceptibility to Malarial Infection: A Host Defense Strategy against Malaria

    PubMed Central

    BAKIR, Hanaa; YONES, Doaa; GALAL, Lamia; HUSEEIN, Enas

    2015-01-01

    Background: In an effort to understand what limits the virulence of malaria parasites in relation to the host genetic and immunogenic background, we investigated the possibility that the parasite and host genotype crossover interactions constrain virulence. Methods: Two groups of mice from different genotypes were used (C57BL/6 (B6) and DBA/2 mice). The mice were infected with a virulent parasite line Plasmodium yoelii 17XL (P. yoelii 17XL). Parasitemia, hematocrit value and lymphocytes yielded by livers and spleens were evaluated. Fluorescence Activated Cell Sorting (FACS) analysis illustrated phenotypic characterization of lymphocytes. Results: Infection with P. yoelii 17XL did not result in the death of DBA/2 mice. In contrast, B6 mice developed significantly high parasitemia and succumbed to death. Using (FACS) analysis, DBA/2 mice were found to experience a marked expansion of interleukin (IL)-2Rβ+ CD3int cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 mice. Conclusion: The outcome of murine malaria infections depends on the dynamic interplay between the immune-mediator and the genotype of the host. PMID:26811732

  20. Spontaneous Subdural Empyema Following a High-Parasitemia Falciparum Infection in a 58-Year-Old Female From a Malaria-Endemic Region

    PubMed Central

    Pallangyo, Pedro; Lyimo, Frederick; Nicholaus, Paulina; Kain, Ulimbakisya; Janabi, Mohamed

    2016-01-01

    Malaria remains a significant public health problem of the tropical world. Falciparum malaria is most prevalent in the sub-Saharan African region, which harbors about 90% of all malaria cases and fatalities globally. Infection by the falciparum species often manifests with a spectrum of multi-organ complications (eg, cerebral malaria), some of which are life-threatening. Spontaneous subdural empyema is a very rare complication of cerebral malaria that portends a very poor prognosis unless diagnosed and treated promptly. We report a case of spontaneous subdural empyema in a 58-year-old woman from Tanzania who presented with high-grade fever, decreased urine output, and altered sensorium.

  1. Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships

    PubMed Central

    Walker, Karen M; Okitsu, Shinji; Porter, David W; Duncan, Christopher; Amacker, Mario; Pluschke, Gerd; Cavanagh, David R; Hill, Adrian V S; Todryk, Stephen M

    2015-01-01

    This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11–12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119, correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related. PMID:25471322

  2. Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.

    PubMed

    Walker, Karen M; Okitsu, Shinji; Porter, David W; Duncan, Christopher; Amacker, Mario; Pluschke, Gerd; Cavanagh, David R; Hill, Adrian V S; Todryk, Stephen M

    2015-05-01

    This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related. PMID:25471322

  3. Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA.

    PubMed

    Ding, Yan; Xu, Wenyue; Zhou, Taoli; Liu, Taiping; Zheng, Hong; Fu, Yong

    2016-10-01

    Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood-brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM. PMID:27574013

  4. Assessment of Humoral Immune Responses to Blood-Stage Malaria Antigens following ChAd63-MVA Immunization, Controlled Human Malaria Infection and Natural Exposure

    PubMed Central

    Elias, Sean C.; Miura, Kazutoyo; Milne, Kathryn H.; de Cassan, Simone C.; Collins, Katharine A.; Halstead, Fenella D.; Bliss, Carly M.; Ewer, Katie J.; Osier, Faith H.; Hodgson, Susanne H.; Duncan, Christopher J. A.; O’Hara, Geraldine A.; Long, Carole A.; Hill, Adrian V. S.; Draper, Simon J.

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite – MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors – ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

  5. Anaemia of Plasmodium falciparum malaria.

    PubMed

    Phillips, R E; Pasvol, G

    1992-04-01

    The pathophysiology of the anaemia of falciparum malaria is both complex and multifactorial, and results in a condition which is a major cause of mortality and morbidity in patients, especially children and pregnant women, living in malarial endemic areas. The importance of anaemia as a cause of death in malaria may well be underestimated because of difficulty in diagnosis, especially where parasitaemia may be low and the clinical picture may be confused with other causes of anaemia. Two clinical presentations predominate: severe acute malaria in which anaemia supervenes, and severe anaemia in patients in whom there have been repeated attacks of malaria. The major mechanisms are those of red cell destruction and decreased red cell production. Potential causes of haemolysis include loss of infected cells by rupture or phagocytosis, removal of uninfected cells due to antibody sensitization or other physicochemical membrane changes, and increased reticuloendothelial activity, particularly in organs such as the spleen. Decreased production results from marrow hypoplasia seen in acute infections, and dyserythropoiesis, a morphological appearance, which in functional terms results in ineffective erythropoiesis. The role of parvovirus B19 as a possible cause of bone marrow aplasia in a few cases is postulated. Finally, there is now evidence which points to genetic factors, HLA associated, which may protect against the development of malarial anaemia and which has become common in areas endemic for malaria. PMID:1511178

  6. Meditation or Exercise May Help Acute Respiratory Infections

    MedlinePlus

    ... U V W X Y Z Meditation or Exercise May Help Acute Respiratory Infections, Study Finds Share: © ... of three groups: a mindfulness meditation group, an exercise group, or a wait-list control group. Participants ...

  7. Malaria Transmission, Infection, and Disease at Three Sites with Varied Transmission Intensity in Uganda: Implications for Malaria Control

    PubMed Central

    Kamya, Moses R.; Arinaitwe, Emmanuel; Wanzira, Humphrey; Katureebe, Agaba; Barusya, Chris; Kigozi, Simon P.; Kilama, Maxwell; Tatem, Andrew J.; Rosenthal, Philip J.; Drakeley, Chris; Lindsay, Steve W.; Staedke, Sarah G.; Smith, David L.; Greenhouse, Bryan; Dorsey, Grant

    2015-01-01

    The intensification of control interventions has led to marked reductions in malaria burden in some settings, but not others. To provide a comprehensive description of malaria epidemiology in Uganda, we conducted surveillance studies over 24 months in 100 houses randomly selected from each of three subcounties: Walukuba (peri-urban), Kihihi (rural), and Nagongera (rural). Annual entomological inoculation rate (aEIR) was estimated from monthly Centers for Disease Control and Prevention (CDC) light trap mosquito collections. Children aged 0.5–10 years were provided long-lasting insecticidal nets (LLINs) and followed for measures of parasite prevalence, anemia and malaria incidence. Estimates of aEIR were 2.8, 32.0, and 310 infectious bites per year, and estimates of parasite prevalence 7.4%, 9.3%, and 28.7% for Walukuba, Kihihi, and Nagongera, respectively. Over the 2-year study, malaria incidence per person-years decreased in Walukuba (0.51 versus 0.31, P = 0.001) and increased in Kihihi (0.97 versus 1.93, P < 0.001) and Nagongera (2.33 versus 3.30, P < 0.001). Of 2,582 episodes of malaria, only 8 (0.3%) met criteria for severe disease. The prevalence of anemia was low and not associated with transmission intensity. In our cohorts, where LLINs and prompt effective treatment were provided, the risk of complicated malaria and anemia was extremely low. However, malaria incidence was high and increased over time at the two rural sites, suggesting improved community-wide coverage of LLIN and additional malaria control interventions are needed in Uganda. PMID:25778501

  8. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control.

    PubMed

    Kamya, Moses R; Arinaitwe, Emmanuel; Wanzira, Humphrey; Katureebe, Agaba; Barusya, Chris; Kigozi, Simon P; Kilama, Maxwell; Tatem, Andrew J; Rosenthal, Philip J; Drakeley, Chris; Lindsay, Steve W; Staedke, Sarah G; Smith, David L; Greenhouse, Bryan; Dorsey, Grant

    2015-05-01

    The intensification of control interventions has led to marked reductions in malaria burden in some settings, but not others. To provide a comprehensive description of malaria epidemiology in Uganda, we conducted surveillance studies over 24 months in 100 houses randomly selected from each of three subcounties: Walukuba (peri-urban), Kihihi (rural), and Nagongera (rural). Annual entomological inoculation rate (aEIR) was estimated from monthly Centers for Disease Control and Prevention (CDC) light trap mosquito collections. Children aged 0.5-10 years were provided long-lasting insecticidal nets (LLINs) and followed for measures of parasite prevalence, anemia and malaria incidence. Estimates of aEIR were 2.8, 32.0, and 310 infectious bites per year, and estimates of parasite prevalence 7.4%, 9.3%, and 28.7% for Walukuba, Kihihi, and Nagongera, respectively. Over the 2-year study, malaria incidence per person-years decreased in Walukuba (0.51 versus 0.31, P = 0.001) and increased in Kihihi (0.97 versus 1.93, P < 0.001) and Nagongera (2.33 versus 3.30, P < 0.001). Of 2,582 episodes of malaria, only 8 (0.3%) met criteria for severe disease. The prevalence of anemia was low and not associated with transmission intensity. In our cohorts, where LLINs and prompt effective treatment were provided, the risk of complicated malaria and anemia was extremely low. However, malaria incidence was high and increased over time at the two rural sites, suggesting improved community-wide coverage of LLIN and additional malaria control interventions are needed in Uganda. PMID:25778501

  9. Individual genetic diversity and probability of infection by avian malaria parasites in blue tits (Cyanistes caeruleus).

    PubMed

    Ferrer, E S; García-Navas, V; Sanz, J J; Ortego, J

    2014-11-01

    Understanding the importance of host genetic diversity for coping with parasites and infectious diseases is a long-standing goal in evolutionary biology. Here, we study the association between probability of infection by avian malaria (Plasmodium relictum) and individual genetic diversity in three blue tit (Cyanistes caeruleus) populations that strongly differ in prevalence of this parasite. For this purpose, we screened avian malaria infections and genotyped 789 blue tits across 26 microsatellite markers. We used two different arrays of markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found a significant relationship between probability of infection and host genetic diversity estimated at the subset of neutral markers that was not explained by strong local effects and did not differ among the studied populations. This relationship was not linear, and probability of infection increased up to values of homozygosity by locus (HL) around 0.15, reached a plateau at values of HL from 0.15 to 0.40 and finally declined among a small proportion of highly homozygous individuals (HL > 0.4). We did not find evidence for significant identity disequilibrium, which may have resulted from a low variance of inbreeding in the study populations and/or the small power of our set of markers to detect it. A combination of subtle positive and negative local effects and/or a saturation threshold in the association between probability of infection and host genetic diversity in combination with increased resistance to parasites in highly homozygous individuals may explain the observed negative quadratic relationship. Overall, our study highlights that parasites play an important role in shaping host genetic variation and suggests that the use of large sets of neutral markers may be more appropriate for the study of heterozygosity-fitness correlations. PMID:25264126

  10. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion. PMID:25745498

  11. Evidence for additive and interaction effects of host genotype and infection in malaria

    PubMed Central

    Idaghdour, Youssef; Quinlan, Jacklyn; Goulet, Jean-Philippe; Berghout, Joanne; Gbeha, Elias; Bruat, Vanessa; de Malliard, Thibault; Grenier, Jean-Christophe; Gomez, Selma; Gros, Philippe; Rahimy, Mohamed Chérif; Sanni, Ambaliou; Awadalla, Philip

    2012-01-01

    The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children’s ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility. PMID:22949651

  12. Ecology of malaria infections in western lowland gorillas inhabiting Dzanga Sangha Protected Areas, Central African Republic.

    PubMed

    Mapua, Mwanahamisi I; Qablan, Moneeb A; Pomajbíková, Kateřina; Petrželková, Klára J; Hůzová, Zuzana; Rádrová, Jana; Votýpka, Jan; Todd, Angelique; Jirků, Milan; Leendertz, Fabian H; Lukeš, Julius; Neel, Cecile; Modrý, David

    2015-06-01

    African great apes are susceptible to infections with several species of Plasmodium, including the predecessor of Plasmodium falciparum. Little is known about the ecology of these pathogens in gorillas. A total of 131 gorilla fecal samples were collected from Dzanga-Sangha Protected Areas to study the diversity and prevalence of Plasmodium species. The effects of sex and age as factors influencing levels of infection with Plasmodium in habituated gorilla groups were assessed. Ninety-five human blood samples from the same locality were also analysed to test for cross-transmission between humans and gorillas. According to a cytB PCR assay 32% of gorilla's fecal samples and 43·1% human individuals were infected with Plasmodium spp. All Laverania species, Plasmodium vivax, and for the first time Plasmodium ovale were identified from gorilla samples. Plasmodium praefalciparum was present only from habituated individuals and P. falciparum was detected from human samples. Although few P. vivax and P. ovale sequences were obtained from gorillas, the evidence for cross-species transmission between humans and gorillas requires more in depth analysis. No association was found between malaria infection and sex, however, younger individuals aged ≤6 years were more susceptible. Switching between two different Plasmodium spp. was observed in three individuals. Prolonged monitoring of Plasmodium infection during various seasons and recording behavioural data is necessary to draw a precise picture about the infection dynamics. PMID:25736484

  13. Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy.

    PubMed

    Ogolla, Sidney; Daud, Ibrahim I; Asito, Amolo S; Sumba, Odada P; Ouma, Collins; Vulule, John; Middeldorp, Jaap M; Dent, Arlene E; Mehta, Saurabh; Rochford, Rosemary

    2015-11-01

    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV- and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P = 0.0234 and P = 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection. PMID:26376931

  14. Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy

    PubMed Central

    Ogolla, Sidney; Daud, Ibrahim I.; Asito, Amolo S.; Sumba, Odada P.; Ouma, Collins; Vulule, John; Middeldorp, Jaap M.; Dent, Arlene E.; Mehta, Saurabh

    2015-01-01

    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV- and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P = 0.0234 and P = 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection. PMID:26376931

  15. Direct detection of malaria infected red blood cells by surface enhanced Raman spectroscopy.

    PubMed

    Chen, Funing; Flaherty, Briana R; Cohen, Charli E; Peterson, David S; Zhao, Yiping

    2016-08-01

    Surface enhanced Raman spectra (SERS) of normal red blood cells (RBCs) and Plasmodium falciparum infected RBCs (iRBCs) at different post invasion time were obtained based on silver nanorod array substrates. Distinct spectral differences were observed due to the cell membrane modification of RBCs during malaria infection. The SERS spectra of ring stage iRBCs had a characteristic Raman peak at Δv=1599cm(-1) as compared to those of normal RBCs, while the trophozoite and schizoid stages had identical SERS spectra with a characteristic peak at Δv=723cm(-1), which is significantly different from ring stage iRBCs, consistent with ongoing modification of the iRBC membrane. Since ring stage iRBCs of P. falciparum are found circulating in blood, such a difference provides a new strategy for rapid malaria detection. The limit of detection as well as the ability to detect a mixed iRBC and RBC solution was also investigated. PMID:27015769

  16. Genetic diversity and multiple infections of Plasmodium vivax malaria in Western Thailand.

    PubMed

    Cui, Liwang; Mascorro, Carlye N; Fan, Ql; Rzomp, Kimberly A; Khuntirat, Benjawan; Zhou, Guofa; Chen, Hong; Yan, Guiyun; Sattabongkot, Jetsumon

    2003-05-01

    Using two polymorphic genetic markers, the merozoite surface protein-3alpha (MSP-3alpha) and the circumsporozoite protein (CSP), we investigated the population diversity of Plasmodium vivax in Mae Sod, Thailand from April 2000 through June 2001. Genotyping the parasites isolated from 90 malaria patients attending two local clinics for the dimorphic CSP gene revealed that the majority of the parasites (77%) were the VK210 type. Genotyping the MSP3-alpha gene indicated that P. vivax populations exhibited an equally high level of polymorphism as those from Papua New Guinea, a hyperendemic region. Based on the length of polymerase chain reaction products, three major types of the MSP-3alpha locus were distinguished, with frequencies of 74.8%, 18.7%, and 6.5%, respectively. The 13 alleles distinguished by restriction fragment length polymorphism analysis did not show a significant seasonal variation in frequency. Genotyping the MSP-3alpha and CSP genes showed that 19.3% and 25.6% of the patients had multiple infections, respectively, and the combined rate was 35.6%. Comparisons of MSP-3alpha sequences from nine clones further confirmed the high level of genetic diversity of the parasite and also suggested that geographic isolation may exist. These results strongly indicate that P. vivax populations are highly diverse and multiple clonal infections are common in this malaria-hypoendemic region of Thailand. PMID:12812356

  17. Malaria infection potential of anopheline mosquitoes sampled by light trapping indoors in coastal Tanzanian villages.

    PubMed

    Shiff, C J; Minjas, J N; Hall, T; Hunt, R H; Lyimo, S; Davis, J R

    1995-07-01

    Anopheline mosquito populations were studied during 1992 in seven villages south of Bagamoyo, coastal Tanzania, prior to malaria control intervention using insecticide treated bednets. To collect mosquitoes, CDC light traps were used in ten houses per village fortnightly for 12 months. Anopheles females were identified and checked by ELISA for the presence of malaria sporozoite antigen and source of bloodmeal. An.funestus peaked in June-July after the long rains. Three members of the An.gambiae complex had different seasonality: An.arabiensis, An.gambiae and small numbers of An.merus were collected. In most villages transmission was extremely high and perennial with the entomological inoculation rate reaching three to eleven infective bites per person per night in July and persisting at around 0.1 and 1 for most of the remainder of the year. Sporozoite infection rates within the An.gambiae complex ranged from 2% to 25%, with the peaks in January and July following the two rainy periods. An.funestus showed a similar pattern. The light traps were reliable, simple to operate, and proved to be satisfactory to study the mosquito vector population. PMID:7548942

  18. Tumour necrosis factor production in Falciparum malaria and its association with schizont rupture.

    PubMed Central

    Kwiatkowski, D; Cannon, J G; Manogue, K R; Cerami, A; Dinarello, C A; Greenwood, B M

    1989-01-01

    To investigate the involvement of tumour necrosis factor (TNF) in human malaria, we studied TNF production in patients infected with Plasmodium falciparum, and in co-cultures of human mononuclear cells and malaria parasites in vitro. In the examined sample, plasma TNF levels of over 39 pg/ml were detected in the plasma of 59% of Gambian children with acute malaria, 17% of convalescents, 9% of children with mild infections other than malaria, and 7% of healthy Gambian adults. Mononuclear cells of acute malaria patients, when stimulated with endotoxin in vitro, secreted twice as much TNF as did those of convalescent individuals, and three times that of healthy adult controls. Erythrocytic cultures of P. falciparum stimulated increased TNF secretion by mononuclear cells from uninfected individuals, and a sharp rise in the rate of secretion occurred shortly after schizont rupture. We suggest that malaria fever is mediated, at least in part, through paroxysmal TNF release associated with schizont rupture. PMID:2680183

  19. Plasmodium falciparum Malaria Challenge by the Bite of Aseptic Anopheles stephensi Mosquitoes: Results of a Randomized Infectivity Trial

    PubMed Central

    Lyke, Kirsten E.; Laurens, Matthew; Adams, Matthew; Billingsley, Peter F.; Richman, Adam; Loyevsky, Mark; Chakravarty, Sumana; Plowe, Christopher V.; Sim, B. Kim Lee; Edelman, Robert; Hoffman, Stephen L.

    2010-01-01

    Background Experimental infection of malaria-naïve volunteers by the bite of Plasmodium falciparum-infected mosquitoes is a preferred means to test the protective effect of malaria vaccines and drugs. The standard model relies on the bite of five infected mosquitoes to induce malaria. We examined the efficacy of malaria transmission using mosquitoes raised aseptically in compliance with current Good Manufacturing Practices (cGMPs). Methods and Findings Eighteen adults aged 18–40 years were randomized to receive 1, 3 or 5 bites of Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of P. falciparum. Seventeen participants developed malaria; fourteen occurring on Day 11. The mean prepatent period was 10.9 days (9–12 days). The geometric mean parasitemia was 15.7 parasites/µL (range: 4–70) by microscopy. Polymerase chain reaction (PCR) detected parasites 3.1 (range: 0–4) days prior to microscopy. The geometric mean sporozoite load was 16,753 sporozoites per infected mosquito (range: 1,000–57,500). A 1-bite participant withdrew from the study on Day 13 post-challenge and was PCR and smear negative. Conclusions The use of aseptic, cGMP-compliant P. falciparum-infected mosquitoes is safe, is associated with a precise prepatent period compared to the standard model and appears more efficient than the standard approach, as it led to infection in 100% (6/6) of volunteers exposed to three mosquito bites and 83% (5/6) of volunteers exposed to one mosquito bite. Trial Registration ClinicalTrials.gov NCT00744133 PMID:21042404

  20. Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis

    PubMed Central

    Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

    2013-01-01

    A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. PMID:23355576

  1. Antibodies to Malaria Vaccine Candidates Pvs25 and Pvs28 Completely Block the Ability of Plasmodium vivax To Infect Mosquitoes

    PubMed Central

    Hisaeda, Hajime; Stowers, Anthony W.; Tsuboi, Takafumi; Collins, William E.; Sattabongkot, Jetsumon S.; Suwanabun, Natavadee; Torii, Motomi; Kaslow, David C.

    2000-01-01

    Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently cloned Plasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivax malaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed in Saccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response. PMID:11083773

  2. Placental Malaria: Decreased Transfer of Maternal Antibodies Directed to Plasmodium falciparum and Impact on the Incidence of Febrile Infections in Infants

    PubMed Central

    Dechavanne, Celia; Cottrell, Gilles; Garcia, André; Migot-Nabias, Florence

    2015-01-01

    The efficacy of mother-to-child placental transfer of antibodies specific to malaria blood stage antigens was investigated in the context of placental malaria infection, taking into account IgG specificity and maternal hypergammaglobulinemia. The impact of the resulting maternal antibody transfer on infections in infants up to the age of 6 months was also explored. This study showed that i) placental malaria was associated with a reduced placental transfer of total and specific IgG, ii) antibody placental transfer varied according to IgG specificity and iii) cord blood malaria IgG levels were similar in infants born to mothers with or without placental malaria. The number of malaria infections was negatively associated with maternal age, whereas it was not associated with the transfer of any malaria-specific IgG from the mother to the fetus. These results suggest that i) malaria-specific IgG may serve as a marker of maternal exposure but not as a useful marker of infant protection from malaria and ii) increasing maternal age contributes to diminishing febrile infections diagnosed in infants, perhaps by means of the transmission of an effective antibody response. PMID:26698578

  3. Experiential relationship between malaria parasite density and some haematological parameters in malaria infected male subjects in Port Harcourt, Nigeria.

    PubMed

    M, Eze Evelyn; Ezeiruaku, F C; Ukaji, D C

    2012-07-01

    This study examined the experiential relationship between the parasite density and haematological parameters in male patients with Plasmodium falciparum infection in Port Harcourt, Nigeria reporting to malaria clinics. A total of one hundred and thirty-six (136) male patients were recruited. QBC haematological analysis, QBC malaria parasite specie identification and quantification and thin blood film for differential leucocytes count was used. The mean values of the haematological parameters in each quartile of parasite densities were determined using Microsoft Excel statistical package. Regression analysis was employed to model the experiential relationship between parasite density and haematological parameters. All regression relationships were tested and the relationship with the highest coefficient of determination (R2) was accepted as the valid relationship. The relationships tested included linear, polynomial, exponential, logarithmic and power relationships. The X- axis of the regression graphs stand for the parasite density while Y-axis stands for the respective haematological parameters  Neutrophil count had a negative  exponential relationship with the parasite density and is related to the parasite density by a polynomial equation model: ynm = -7E-07x2 - 0.0003x + 56.685.The coefficient of determination (R2) was 0.6140. This means that the rate of change of the parasitemia will depend on the initial value of the neutrophil. As the neutrophil increases, the parasitemia will tend to decrease in a double, triple and quadruple manner. The relationship between lymphocyte count, monocyte count and eosinophil count and parasite density was logarithmic and expressed by the following linear equation models: ylm = -2.371ln(x) + 37.296, ymm = 0.6965ln(x) + 5.7692 and yem = 0.9334ln(x) + 4.1718 in the same order. Their respective high coefficients of determination (R2) were 0.8027, 0.8867 and 0.9553. This logarithmic relationship means that each doubling of

  4. Acute hemiplegia with lacunar infarct after varicella infection in childhood.

    PubMed

    Eda, I; Takashima, S; Takeshita, K

    1983-01-01

    We report 4 cases of acute hemiplegia and a small low-density lesion on computerized tomography (CT) after varicella infection. In 3 of them, CT in the acute hemiplegic stage, and later, reveals the development of lacunar infarct around the internal capsule. Focal low density may be caused by occlusive vascular lesions of the penetrating arteries. Varicella infection may play an important role as one of the causes of acute hemiplegia in childhood producing lacunar infarct, as well as delayed hemiplegia, reported previously in herpes zoster ophthalmicus. PMID:6660422

  5. A Research Agenda for Malaria Eradication: Drugs

    PubMed Central

    2011-01-01

    Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission. PMID:21311580

  6. Natural infection in anopheline species and its implications for autochthonous malaria in the Atlantic forest in Brazil

    PubMed Central

    2013-01-01

    Background A descriptive study was carried out in an area of the Atlantic Forest with autochthonous malaria in the Parelheiros subdistrict on the periphery of the municipality of São Paulo to identify anopheline fauna and anophelines naturally infected with Plasmodium as well as to discuss their role in this peculiar epidemiological context. Methods Entomological captures were made from May 2009 to April 2011 using Shannon traps and automatic CDC traps in four areas chosen for their different patterns of human presence and incidences of malaria (anthropic zone 1, anthropic zone 2, transition zone and sylvatic zone). Natural Plasmodium infection was detected by nested PCR based on amplification of the 18S rRNA gene. Results In total, 6,073 anophelines were collected from May 2009 to April 2011, and six species were identified in the four zones. Anopheles cruzii was the predominant species in the three environments but was more abundant in the sylvatic zone. Anopheles (Kerteszia) cruzii specimens from the anthropic and sylvatic zones were positive for P. vivax and P. malariae. An. (Ker.) bellator, An. (Nys.) triannulatus, An. (Nys.) strodei, An. (Nys.) lutzi and An. (Ano) maculipes were found in small numbers. Of these, An. (Nys.) triannulatus and An. (Nys.) lutzi, which were collected in the anthropic zone, were naturally infected with P. vivax while An. (Nys.) triannulatus from the anthropic zones and An. (Nys.) strodei from the transition zone were positive for P. malariae. Conclusion These results confirm that Anopheles (Kerteszia) cruzii plays an important role as a major Plasmodium vector. However, the finding of other naturally infected species may indicate that secondary vectors are also involved in the transmission of malaria in the study areas. These findings can be expected to help in the implementation of new measures to control autochthonous malaria in areas of the Atlantic Forest. PMID:23497493

  7. Acute intestinal infections of non-dysenteric etiology*

    PubMed Central

    Linetskaya-Novgorodskaya, E. M.

    1959-01-01

    Recent work on the epidemiology and microbiology of acute intestinal infections has brought about a revision of long-held views as to many of their characteristics and as to their grouping. This paper deals with these infections in the light of this recent work, with particular reference to findings made in Leningrad. PMID:14417237

  8. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2016-04-08

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. Facilitation through altered resource availability in a mixed-species rodent malaria infection.

    PubMed

    Ramiro, Ricardo S; Pollitt, Laura C; Mideo, Nicole; Reece, Sarah E

    2016-09-01

    A major challenge in disease ecology is to understand how co-infecting parasite species interact. We manipulate in vivo resources and immunity to explain interactions between two rodent malaria parasites, Plasmodium chabaudi and P. yoelii. These species have analogous resource-use strategies to the human parasites Plasmodium falciparum and P. vivax: P. chabaudi and P. falciparum infect red blood cells (RBC) of all ages (RBC generalist); P. yoelii and P. vivax preferentially infect young RBCs (RBC specialist). We find that: (1) recent infection with the RBC generalist facilitates the RBC specialist (P. yoelii density is enhanced ~10 fold). This occurs because the RBC generalist increases availability of the RBC specialist's preferred resource; (2) co-infections with the RBC generalist and RBC specialist are highly virulent; (3) and the presence of an RBC generalist in a host population can increase the prevalence of an RBC specialist. Thus, we show that resources shape how parasite species interact and have epidemiological consequences. PMID:27364562

  10. Acute Cytomegalovirus Infection as a Cause of Venous Thromboembolism

    PubMed Central

    Rinaldi, Francesca; Lissandrin, Raffaella; Mojoli, Francesco; Baldanti, Fausto; Brunetti, Enrico; Pascarella, Michela; Giordani, Maria Teresa

    2014-01-01

    Acute Human Cytomegalovirus (HCMV) infection is an unusual cause of venous thromboembolism, a potentially life-threatening condition. Thrombus formation can occur at the onset of the disease or later during the recovery and may also occur in the absence of acute HCMV hepatitis. It is likely due to both vascular endothelium damage caused by HCMV and impairment of the clotting balance caused by the virus itself. Here we report on two immunocompetent women with splanchnic thrombosis that occurred during the course of acute HCMV infection. Although the prevalence of venous thrombosis in patients with acute HCMV infection is unknown, physicians should be aware of its occurrence, particularly in immunocompetent patients presenting with fever and unexplained abdominal pain. PMID:24959338

  11. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  12. Effects of malaria (Plasmodium relicturm) on activity budgets of experimentally-infected juvenile Apapane (Himatione sanquinea)

    USGS Publications Warehouse

    Yorinks, N.; Atkinson, C.T.

    2000-01-01

    We used behavioral, physiological, and parasitological measures to document effects of acute malarial infections on activity budgets of experimentally infected juvenile Apapane (Himatione sanguinea). Five of eight birds died within 20 to 32 days after exposure to a single infective mosquito bite. Infected Apapane devoted less time to locomotory activities involving flight, walking or hopping, and stationary activities such as singing, preening, feeding, and probing. The amount of time spent sitting was positively correlated with parasitemia and increased dramatically after infection and between treatment and control groups. Birds that succumbed to infection experienced a significant loss of body mass and subcutaneous fat, whereas surviving Apapane were better able to maintain body condition and fat levels. When rechallenged with the parasite five months after initial infection, surviving birds experienced no increase in parasitemia, indicating that they had become immune to reinfection. Regardless of the outcome, infected birds experienced acute illness that would have left them unable to forage or to escape from predators in the wild.

  13. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community

    PubMed Central

    Branch, OraLee; Casapia, W Martin; Gamboa, Dionicia V; Hernandez, Jean N; Alava, Freddy F; Roncal, Norma; Alvarez, Eugenia; Perez, Enrique J; Gotuzzo, Eduardo

    2005-01-01

    Background There is a low incidence of malaria in Iquitos, Peru, suburbs detected by passive case-detection. This low incidence might be attributable to infections clustered in some households/regions and/or undetected asymptomatic infections. Methods Passive case-detection (PCD) during the malaria season (February-July) and an active case-detection (ACD) community-wide survey (March) surveyed 1,907 persons. Each month, April-July, 100-metre at-risk zones were defined by location of Plasmodium falciparum infections in the previous month. Longitudinal ACD and PCD (ACP+PCD) occurred within at-risk zones, where 137 houses (573 persons) were randomly selected as sentinels, each with one month of weekly active sampling. Entomological captures were conducted in the sentinel houses. Results The PCD incidence was 0.03 P. falciparum and 0.22 Plasmodium vivax infections/person/malaria-season. However, the ACD+PCD prevalence was 0.13 and 0.39, respectively. One explanation for this 4.33 and 1.77-fold increase, respectively, was infection clustering within at-risk zones and contiguous households. Clustering makes PCD, generalized to the entire population, artificially low. Another attributable-factor was that only 41% and 24% of the P. falciparum and P. vivax infections were associated with fever and 80% of the asymptomatic infections had low-density or absent parasitaemias the following week. After accounting for asymptomatic infections, a 2.6-fold increase in ACD+PCD versus PCD was attributable to clustered transmission in at-risk zones. Conclusion Even in low transmission, there are frequent highly-clustered asymptomatic infections, making PCD an inadequate measure of incidence. These findings support a strategy of concentrating ACD and insecticide campaigns in houses adjacent to houses were malaria was detected one month prior. PMID:15975146

  14. Malaria-Infected Female Collared Flycatchers (Ficedula albicollis) Do Not Pay the Cost of Late Breeding

    PubMed Central

    Kulma, Katarzyna; Low, Matthew; Bensch, Staffan; Qvarnström, Anna

    2014-01-01

    Life-history theory predicts that the trade-off between parasite defense and other costly traits such as reproduction may be most evident when resources are scarce. The strength of selection that parasites inflict on their host may therefore vary across environmental conditions. Collared flycatchers (Ficedula albicollis) breeding on the Swedish island Öland experience a seasonal decline in their preferred food resource, which opens the possibility to test the strength of life-history trade-offs across environmental conditions. We used nested-PCR and quantitative-PCR protocols to investigate the association of Haemosporidia infection with reproductive performance of collared flycatcher females in relation to a seasonal change in the external environment. We show that despite no difference in mean onset of breeding, infected females produced relatively more of their fledglings late in the season. This pattern was also upheld when considering only the most common malaria lineage (hPHSIB1), however there was no apparent link between the reproductive output and the intensity of infection. Infected females produced heavier-than-average fledglings with higher-than-expected recruitment success late in the season. This reversal of the typical seasonal trend in reproductive output compensated them for lower fledging and recruitment rates compared to uninfected birds earlier in the season. Thus, despite different seasonal patterns of reproductive performance the overall number of recruits was the same for infected versus uninfected birds. A possible explanation for our results is that infected females breed in a different microhabitat where food availability is higher late in the season but also is the risk of infection. Thus, our results suggest that another trade-off than the one we aimed to test is more important for explaining variation in reproductive performance in this natural population: female flycatchers appear to face a trade-off between the risk of infection and

  15. Fetal Immune Activation to Malaria Antigens Enhances Susceptibility to In Vitro HIV Infection in Cord Blood Mononuclear Cells

    PubMed Central

    Steiner, Kevin; Myrie, Latoya; Malhotra, Indu; Mungai, Peter; Muchiri, Eric; Dent, Arlene; King, Christopher L.

    2010-01-01

    Mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) remains a significant cause of new HIV infections in many countries. To examine whether fetal immune activation as a consequence of prenatal exposure to parasitic antigens increases the risk of MTCT, cord blood mononuclear cells (CBMCs) from Kenyan and North American newborns were examined for relative susceptibility to HIV infection in vitro. Kenyan CBMCs were 3-fold more likely to be infected with HIV than were North American CBMCs (P = .03). Kenyan CBMCs with recall responses to malaria antigens demonstrated enhanced susceptibility to HIV when compared with Kenyan CBMCs lacking recall responses to malaria (P = .03). CD4+ T cells from malaria-sensitized newborns expressed higher levels of CD25 and human leukocyte antigen DR ex vivo, which is consistent with increased immune activation. CD4+ T cells were the primary reservoir of infection at day 4 after virus exposure. Thus, prenatal exposure and in utero priming to malaria may increase the risk of MTCT. PMID:20687848

  16. Immunopathology of nephropathies associated with malaria*

    PubMed Central

    Houba, V.

    1975-01-01

    Immune complexes play an important role in the pathogenesis of malaria-associated nephropathies. Two main types of lesion are demonstrable: (a) acute (transient—reversible) lesions typical of falciparum infections in man, with mild clinical symptoms developing a week or two after infection. Renal biopsies at that time show deposits of immunoglobulins, complement, and sometimes antigen. The lesions respond to antimalarials. (b) Chronic (progressive) lesions characteristic of quartan infections in man, developing slowly into a chronic stage with persistent proteinuria and gradually deteriorating renal function and hypertension. Renal biopsies at the onset of the disease show deposits of immunoglobulins, complement, and P. malariae antigens in glomerular capillary walls. Antimalarial therapy has no effect. Recent immunochemical findings confirm that these lesions are of the immune-complex type and are associated with malaria infection. However, several questions remain to be solved. PMID:1083308

  17. Epstein-Barr Virus Infection with Acute Acalculous Cholecystitis

    PubMed Central

    Kim, Ahlee; Moon, Jin Soo; Chang, Ju Young; Ko, Jae Sung

    2014-01-01

    Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. PMID:24749090

  18. Epstein-barr virus infection with acute acalculous cholecystitis.

    PubMed

    Kim, Ahlee; Yang, Hye Ran; Moon, Jin Soo; Chang, Ju Young; Ko, Jae Sung

    2014-03-01

    Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature. PMID:24749090

  19. Clinical signs and symptoms cannot reliably predict Plasmodium falciparum malaria infection in pregnant women living in an area of high seasonal transmission

    PubMed Central

    2013-01-01

    Background Malaria in pregnancy is a major public health problem in endemic countries. Though the signs and symptoms of malaria among pregnant women have been already described, clinical presentation may vary according to intensity of transmission and local perceptions. Therefore, determining common signs and symptoms among pregnant women with a malaria infection may be extremely useful to identify those in need of further investigation by rapid diagnostic test or microscopy. Methods Six hundred pregnant women attending the maternity clinic of Nanoro District Hospital, Burkina Faso were recruited, 200 with suspected clinical malaria and 400 as controls. Cases were matched with controls by gestational age and parity. Signs and symptoms were collected and a blood sample taken for rapid diagnostic test, microscopy and haemoglobin measurement. A multivariate model was used to assess the predictive value of signs and symptoms for malaria infection. Results The overall prevalence of malaria was 42.6% (256/600) while anaemia was found in 60.8% (365/600) of the women. Nearly half (49%) of the cases and 39.5% of the controls had a malaria infection (p = 0.03). The most common signs and symptoms among the cases were fever (36%,72/200), history of fever (29%,58/200) and headache (52%,104/200). The positive predictive value for fever was 53% (95% CI:41–64), history of fever 58% (95% CI:37–63) and headache 51% (95% CI:41–61). Conclusion Signs and symptoms suggestive of malaria are frequent among pregnant women living in areas of intense transmission. Common malaria symptoms are not strong predictors of infection. For a better management of malaria in pregnancy, active screening to detect and treat malaria infection early should be performed on all pregnant women attending a health facility. PMID:24373481

  20. Defining the relationship between infection prevalence and clinical incidence of Plasmodium falciparum malaria.

    PubMed

    Cameron, Ewan; Battle, Katherine E; Bhatt, Samir; Weiss, Daniel J; Bisanzio, Donal; Mappin, Bonnie; Dalrymple, Ursula; Hay, Simon I; Smith, David L; Griffin, Jamie T; Wenger, Edward A; Eckhoff, Philip A; Smith, Thomas A; Penny, Melissa A; Gething, Peter W

    2015-01-01

    In many countries health system data remain too weak to accurately enumerate Plasmodium falciparum malaria cases. In response, cartographic approaches have been developed that link maps of infection prevalence with mathematical relationships to predict the incidence rate of clinical malaria. Microsimulation (or 'agent-based') models represent a powerful new paradigm for defining such relationships; however, differences in model structure and calibration data mean that no consensus yet exists on the optimal form for use in disease-burden estimation. Here we develop a Bayesian statistical procedure combining functional regression-based model emulation with Markov Chain Monte Carlo sampling to calibrate three selected microsimulation models against a purpose-built data set of age-structured prevalence and incidence counts. This allows the generation of ensemble forecasts of the prevalence-incidence relationship stratified by age, transmission seasonality, treatment level and exposure history, from which we predict accelerating returns on investments in large-scale intervention campaigns as transmission and prevalence are progressively reduced. PMID:26348689

  1. Defining the relationship between infection prevalence and clinical incidence of Plasmodium falciparum malaria

    PubMed Central

    Cameron, Ewan; Battle, Katherine E.; Bhatt, Samir; Weiss, Daniel J.; Bisanzio, Donal; Mappin, Bonnie; Dalrymple, Ursula; Hay, Simon I.; Smith, David L.; Griffin, Jamie T.; Wenger, Edward A.; Eckhoff, Philip A.; Smith, Thomas A.; Penny, Melissa A.; Gething, Peter W.

    2015-01-01

    In many countries health system data remain too weak to accurately enumerate Plasmodium falciparum malaria cases. In response, cartographic approaches have been developed that link maps of infection prevalence with mathematical relationships to predict the incidence rate of clinical malaria. Microsimulation (or ‘agent-based') models represent a powerful new paradigm for defining such relationships; however, differences in model structure and calibration data mean that no consensus yet exists on the optimal form for use in disease-burden estimation. Here we develop a Bayesian statistical procedure combining functional regression-based model emulation with Markov Chain Monte Carlo sampling to calibrate three selected microsimulation models against a purpose-built data set of age-structured prevalence and incidence counts. This allows the generation of ensemble forecasts of the prevalence–incidence relationship stratified by age, transmission seasonality, treatment level and exposure history, from which we predict accelerating returns on investments in large-scale intervention campaigns as transmission and prevalence are progressively reduced. PMID:26348689

  2. Numerical modelling of a healthy/malaria-infected erythrocyte in shear flow using dissipative particle dynamics method

    NASA Astrophysics Data System (ADS)

    Ye, Ting; Phan-Thien, Nhan; Cheong Khoo, Boo; Teck Lim, Chwee

    2014-06-01

    In the present paper, the dynamics of healthy and malaria-infected erythrocytes in the shear flow are investigated using dissipative particle dynamics (DPD), a particle-based method. A discrete model is developed, where the computational domain is discretized into a set of particles to represent the suspending liquid, as well as erythrocytes as suspended deformable particles. The particles on an erythrocyte surface are connected into a triangular network to represent the membrane. The interaction between any two particles is modelled by the DPD method, which conserves both mass and momentum. In order to validate this model, the deformation of a spherical capsule in the shear flow is firstly simulated, and a good agreement is found with previously published works. Then, the dynamics of a healthy biconcave erythrocyte in a shear flow is investigated. The results demonstrate that a healthy erythrocyte undergoes a tank-treading motion at a high capillary number, and a tumbling motion at a low capillary number or at a high viscosity ratio, internal (erythrocyte) to external fluids. Two other types of trembling motions, breathing with tumbling and swinging with tank-treading, are also found at an intermediate capillary number or viscosity ratio. Finally, the dynamics of malaria-infected erythrocyte in a shear flow is studied. At the same shear rate, if the healthy erythrocyte undergoes a tumbling motion, the malaria-infected one will exhibit a tumbling motion only. If the healthy erythrocyte undergoes a trembling motion, the malaria-infected one cannot exhibit tank-treading motion. If the healthy erythrocyte undergoes a tank-treading motion, the malaria-infected one will exhibit one of three dynamic motions: tumbling, trembling or tank-treading motion.

  3. Human bocavirus in children with acute respiratory infections in Vietnam.

    PubMed

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. PMID:24123072

  4. Automated system for characterization and classification of malaria-infected stages using light microscopic images of thin blood smears.

    PubMed

    Das, D K; Maiti, A K; Chakraborty, C

    2015-03-01

    In this paper, we propose a comprehensive image characterization cum classification framework for malaria-infected stage detection using microscopic images of thin blood smears. The methodology mainly includes microscopic imaging of Leishman stained blood slides, noise reduction and illumination correction, erythrocyte segmentation, feature selection followed by machine classification. Amongst three-image segmentation algorithms (namely, rule-based, Chan-Vese-based and marker-controlled watershed methods), marker-controlled watershed technique provides better boundary detection of erythrocytes specially in overlapping situations. Microscopic features at intensity, texture and morphology levels are extracted to discriminate infected and noninfected erythrocytes. In order to achieve subgroup of potential features, feature selection techniques, namely, F-statistic and information gain criteria are considered here for ranking. Finally, five different classifiers, namely, Naive Bayes, multilayer perceptron neural network, logistic regression, classification and regression tree (CART), RBF neural network have been trained and tested by 888 erythrocytes (infected and noninfected) for each features' subset. Performance evaluation of the proposed methodology shows that multilayer perceptron network provides higher accuracy for malaria-infected erythrocytes recognition and infected stage classification. Results show that top 90 features ranked by F-statistic (specificity: 98.64%, sensitivity: 100%, PPV: 99.73% and overall accuracy: 96.84%) and top 60 features ranked by information gain provides better results (specificity: 97.29%, sensitivity: 100%, PPV: 99.46% and overall accuracy: 96.73%) for malaria-infected stage classification. PMID:25523795

  5. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection.

    PubMed

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  6. Acute hantavirus infection induces galectin-3-binding protein.

    PubMed

    Hepojoki, Jussi; Strandin, Tomas; Hetzel, Udo; Sironen, Tarja; Klingström, Jonas; Sane, Jussi; Mäkelä, Satu; Mustonen, Jukka; Meri, Seppo; Lundkvist, Ake; Vapalahti, Olli; Lankinen, Hilkka; Vaheri, Antti

    2014-11-01

    Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection. PMID:25013204

  7. First malaria infections in a cohort of infants in Benin: biological, environmental and genetic determinants. Description of the study site, population methods and preliminary results

    PubMed Central

    Cottrell, Gilles; Martin-Prevel, Yves; Migot-Nabias, Florence; Cot, Michel; Garcia, André

    2012-01-01

    Objectives Malaria infection of the placenta during pregnancy was found to be associated with infant susceptibility to malaria. Other factors such as the intensity of malaria transmission and the nutritional status of the child might also play a role, which has not been adequately taken into account in previous studies. The aim of this study was to assess precisely the parts played by environmental, nutritional and biological determinants in first malaria infections, with a special interest in the role of placental infection. The objective of this paper is not to present final results but to outline the rationale of the study, to describe the methods used and to report baseline data. Design A cohort of infants followed with a parasitological (symptomatic and asymptomatic parasitaemia) and nutritional follow-up from birth to 18 months. Ecological, entomological and behavioural data were collected along the duration of the study. Setting A rural area in Benin with two seasonal peaks in malaria transmission. Participants 656 infants of women willing to participate in the study, giving birth in one of the three maternity clinics and living in one of the nine villages of the study area. Primary Outcome Measures The time and frequency of first malaria parasitaemias in infants, according to Plasmodium falciparum infection of the placenta. Results 11% of mothers had a malaria-infected placenta at delivery. Mosquito catches made every 6 weeks in the area showed an average annual P falciparum entomological inoculation rate of 15.5, with important time and space variations depending on villages. Similarly, the distribution of rainfalls, maximal during the two rainy seasons, was heterogeneous over the area. Conclusions Considering the multidisciplinary approach of all factors potentially influencing the malaria status of newborn babies, this study should bring evidence on the implication of placental malaria in the occurrence of first malaria infections in infants. PMID

  8. Parasitic procrastination: late-presenting ovale malaria and schistosomiasis.

    PubMed

    Davis, T M; Singh, B; Sheridan, G

    2001-08-01

    A 29-year-old woman with ovale malaria (most likely contracted, together with asymptomatic schistosomiasis, in East Africa two years previously) had fever, nausea and confusion, jaundice, anaemia, thrombocytopenia, hyponatraemia and hypokalaemia. She was initially diagnosed with and treated for blood-smear-positive vivax malaria. Because of the unusual clinical presentation, blood was analysed by a malaria species-specific nested polymerase chain reaction (PCR) assay which identified Plasmodium ovale as the only infecting species. This case illustrates (i) that a detailed travel history remains a vital part of clinical assessment, (ii) ovale malaria can have an exceptionally long incubation period and features of a moderately severe acute infection, and (iii) PCR assay may prove a valuable adjunct to blood film examination in the diagnosis and speciation of malaria. PMID:11548081

  9. Differential Spleen Remodeling Associated with Different Levels of Parasite Virulence Controls Disease Outcome in Malaria Parasite Infections

    PubMed Central

    Huang, Ximei; Huang, Sha; Ong, Lai Chun; Lim, Jason Chu-Shern; Hurst, Rebecca Joan Mary; Mushunje, Annals Tatenda; Matsudaira, Paul Thomas; Han, Jongyoon

    2015-01-01

    ABSTRACT Infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. Differences in the ability of the spleen to deal with the infected red blood cells (iRBCs) are linked to differences in virulence. Using virulent and avirulent strains of the rodent malaria parasite Plasmodium yoelii, we investigated how parasite virulence modulates overall spleen function. Following parasite invasion, a difference in parasite virulence was observed in association with different levels of spleen morphology and iRBC rigidity, both of which contributed to enhanced parasite clearance. Moreover, iRBC rigidity as modulated by the spleen was demonstrated to correlate with disease outcome and thus can be used as a robust indicator of virulence. The data indicate that alterations in the biomechanical properties of iRBCs are the result of the complex interaction between host and parasite. Furthermore, we confirmed that early spleen responses are a key factor in directing the clinical outcome of an infection. IMPORTANCE The spleen and its response to parasite infection are important in eliminating parasites in malaria. By comparing P. yoelii parasite lines with different disease outcomes in mice that had either intact spleens or had had their spleens removed, we showed that upon parasite infection, the spleen exhibits dramatic changes that can affect parasite clearance. The spleen itself directly impacts RBC deformability independently of parasite genetics. The data indicated that the changes in the biomechanical properties of malaria parasite-infected RBCs are the result of the complex interaction between host and parasite, and RBC deformability itself can serve as a novel predictor of clinical outcome. The results also suggest that early responses in the spleen are a key factor directing the clinical outcome of an infection. PMID:27303680

  10. Characteristic Age Distribution of Plasmodium vivax Infections after Malaria Elimination on Aneityum Island, Vanuatu

    PubMed Central

    Chaves, Luis F.; Taleo, George; Kalkoa, Morris; Isozumi, Rie; Wickremasinghe, Renu; Perlmann, Hedvig; Takeo, Satoru; Tsuboi, Takafumi; Tachibana, Shin-Ichiro; Kimura, Masatsugu; Björkman, Anders; Troye-Blomberg, Marita; Tanabe, Kazuyuki; Drakeley, Chris

    2014-01-01

    Resurgence is a major concern after malaria elimination. After the initiation of the elimination program on Aneityum Island in 1991, microscopy showed that Plasmodium falciparum disappeared immediately, whereas P. vivax disappeared from 1996 onward, until P. vivax cases were reported in January 2002. By conducting malariometric surveys of the entire population of Aneityum, we investigated the age distribution of individuals with parasites during this epidemic in the context of antimalarial antibody levels and parasite antigen diversity. In July 2002, P. vivax infections were detected by microscopy in 22/759 individuals: 20/298 born after the beginning of the elimination program in 1991, 2/126 born between 1982 and 1991, and none of 335 born before 1982. PCR increased the number of infections detected to 77, distributed among all age groups. Prevalences were 12.1%, 16.7%, and 6.0%, respectively (P < 0.001). In November, a similar age pattern was found, but with fewer infections: 6/746 and 39/741 individuals were found to be infected by microscopy and PCR, respectively. The frequencies of antibody responses to P. vivax were significantly higher in individuals born before 1991 than in younger age groups and were similar to those on Malakula Island, an area of endemicity. Remarkably low antigen diversity (h, 0.15) of P. vivax infections was observed on Aneityum compared with the other islands (h, 0.89 to 1.0). A P. vivax resurgence was observed among children and teenagers on Aneityum, an age distribution similar to those before elimination and on islands where P. vivax is endemic, suggesting that in the absence of significant exposure, immunity may persist, limiting infection levels in adults. The limited parasite gene pool on islands may contribute to this protection. PMID:24166950

  11. The Effect of Intestinal Parasitic Infection on the Clinical Outcome of Malaria in Coinfected Children in Cameroon

    PubMed Central

    Kwenti, Tebit E.; Nkume, Franklin A.; Tanjeko, Ajime T.; Kwenti, Tayong D. B.

    2016-01-01

    Background The interaction between intestinal parasites and malaria is still not clear. Data in published literature are conflicting. We studied the effect of intestinal parasitic infection (IPI) on the clinical outcome of malaria in coinfected children. Methods In a cross sectional study performed between October 2014 and September 2015, children infected with malaria, as demonstrated by the presence of asexual parasites in Giemsa stained blood films, were enrolled. Stool samples were obtained from participants and subjected to the formol-ether concentration technique for the detection of intestinal parasites. The Complete blood count was performed using an automated haematology analyser (Mindray, BC-2800). The risk ratio, Pearson’s chi-square and the student T test were all performed as part of the statistical analyses. Statistical significance was set at p < 0.05. Results In all, 405 children successfully took part in the study. The children were between 1 week and 120 months of age (mean ± SD = 41.5 ± 33.5). Coinfection with intestinal parasites was observed in 11.6%. The rate of severe malaria (SM) attack in this study was 10.9%. SM was not observed to be associated with age (p = 0.377) or gender (p = 0.387), meanwhile coinfection with intestinal parasites was associated with age (p = 0.003). Among SM cases, IPI prevalence was higher in children with mild (WHO group 3) severe malaria (p = 0.027). Overall, IPI was not observed to be associated with SM (p = 0.656) or malaria parasite density (p = 0.185) or haemoglobin concentration (p = 0.205). The main clinical features of SM observed were hyperpyrexia (68.2%), severe malarial anaemia (61.4%), and multiple convulsion (52.3%). Conclusion IPI was not observed to be associated with the severity of malaria, the malaria parasite density, and the haemoglobin concentration in coinfected children in Cameroon. The clinical outcome of malaria in children coinfected with intestinal parasites may depend on the

  12. Malaria and Helminth Co-Infections in School and Preschool Children: A Cross-Sectional Study in Magu District, North-Western Tanzania

    PubMed Central

    Kinung'hi, Safari M.; Magnussen, Pascal; Kaatano, Godfrey M.; Kishamawe, Coleman; Vennervald, Birgitte J.

    2014-01-01

    Background Malaria, schistosomiasis and soil transmitted helminth infections (STH) are important parasitic infections in Sub-Saharan Africa where a significant proportion of people are exposed to co-infections of more than one parasite. In Tanzania, these infections are a major public health problem particularly in school and pre-school children. The current study investigated malaria and helminth co-infections and anaemia in school and pre-school children in Magu district, Tanzania. Methodology School and pre-school children were enrolled in a cross-sectional study. Stool samples were examined for Schistosoma mansoni and STH infections using Kato Katz technique. Urine samples were examined for Schistosoma haematobium using the urine filtration method. Blood samples were examined for malaria parasites and haemoglobin concentrations using the Giemsa stain and Haemoque methods, respectively. Principal Findings Out of 1,546 children examined, 1,079 (69.8%) were infected with one or more parasites. Malaria-helminth co-infections were observed in 276 children (60% of all children with P. falciparum infection). Malaria parasites were significantly more prevalent in hookworm infected children than in hookworm free children (p = 0.046). However, this association was non-significant on multivariate logistic regression analysis (OR = 1.320, p = 0.064). Malaria parasite density decreased with increasing infection intensity of S. mansoni and with increasing number of co-infecting helminth species. Anaemia prevalence was 34.4% and was significantly associated with malaria infection, S. haematobium infection and with multiple parasite infections. Whereas S. mansoni infection was a significant predictor of malaria parasite density, P. falciparum and S. haematobium infections were significant predictors of anaemia. Conclusions/Significance These findings suggest that multiple parasite infections are common in school and pre-school children in Magu district. Concurrent

  13. Incidence of malaria by cotrimoxazole use in HIV-infected Ugandan adults on antiretroviral therapy: a randomised, placebo-controlled study

    PubMed Central

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

    2016-01-01

    Introduction: Previous unblinded trials have shown increased malaria among HIV-infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV-infected adults on ART in a double-blind, placebo-controlled trial. Methods: HIV-infected Ugandan adults stable on ART and CTX with CD4+ cell count at least 250 cells/μl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes. Results: A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2–10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74–4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18–0.49). There was one malaria-related death (CTX arm). Conclusion: HIV-infected adults – who are stable on ART and stop prophylactic CTX – experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis. PMID:26558729

  14. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed. PMID:27018033

  15. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  16. Co-infection of Long-Term Carriers of Plasmodium falciparum with Schistosoma haematobium Enhances Protection from Febrile Malaria: A Prospective Cohort Study in Mali

    PubMed Central

    Sangala, Jules; Li, Shanping; Doumtabe, Didier; Kone, Younoussou; Traoré, Abdrahamane; Bathily, Aboudramane; Sogoba, Nafomon; Coulibaly, Michel E.; Huang, Chiung-Yu; Ongoiba, Aissata; Kayentao, Kassoum; Diallo, Mouctar; Dramane, Zongo; Nutman, Thomas B.; Crompton, Peter D.; Doumbo, Ogobara; Traore, Boubacar

    2014-01-01

    Background Malaria and schistosomiasis often overlap in tropical and subtropical countries and impose tremendous disease burdens; however, the extent to which schistosomiasis modifies the risk of febrile malaria remains unclear. Methods We evaluated the effect of baseline S. haematobium mono-infection, baseline P. falciparum mono-infection, and co-infection with both parasites on the risk of febrile malaria in a prospective cohort study of 616 children and adults living in Kalifabougou, Mali. Individuals with S. haematobium were treated with praziquantel within 6 weeks of enrollment. Malaria episodes were detected by weekly physical examination and self-referral for 7 months. The primary outcome was time to first or only malaria episode defined as fever (≥37.5°C) and parasitemia (≥2500 asexual parasites/µl). Secondary definitions of malaria using different parasite densities were also explored. Results After adjusting for age, anemia status, sickle cell trait, distance from home to river, residence within a cluster of high S. haematobium transmission, and housing type, baseline P. falciparum mono-infection (n = 254) and co-infection (n = 39) were significantly associated with protection from febrile malaria by Cox regression (hazard ratios 0.71 and 0.44; P = 0.01 and 0.02; reference group: uninfected at baseline). Baseline S. haematobium mono-infection (n = 23) did not associate with malaria protection in the adjusted analysis, but this may be due to lack of statistical power. Anemia significantly interacted with co-infection (P = 0.009), and the malaria-protective effect of co-infection was strongest in non-anemic individuals. Co-infection was an independent negative predictor of lower parasite density at the first febrile malaria episode. Conclusions Co-infection with S. haematobium and P. falciparum is significantly associated with reduced risk of febrile malaria in long-term asymptomatic carriers of P. falciparum. Future studies are

  17. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  18. Assessment of Immune Interference, Antagonism and Diversion following Human Immunization with Bi-Allelic Blood-Stage Malaria Viral Vectored Vaccines and Controlled Malaria Infection

    PubMed Central

    Elias, Sean C.; Collins, Katharine A.; Halstead, Fenella D.; Choudhary, Prateek; Bliss, Carly M.; Ewer, Katie J.; Sheehy, Susanne H.; Duncan, Christopher J. A.; Biswas, Sumi; Hill, Adrian V. S.; Draper, Simon J.

    2012-01-01

    Overcoming antigenic variation is one of the major challenges in the development of an effective vaccine against Plasmodium falciparum, a causative agent of human malaria. Inclusion of multiple antigen variants in subunit vaccine candidates is one strategy that has aimed to overcome this problem for the leading blood-stage malaria vaccine targets, merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). However previous studies, utilizing malaria antigens, have concluded that inclusion of multiple allelic variants, encoding altered peptide ligands (APL), in such a vaccine may be detrimental to both the priming and in vivo re-stimulation of antigen-experienced T cells. Here we analyze the T cell responses to two alleles of MSP1 and AMA1 induced by vaccination of malaria-naïve adult volunteers with bi-valent viral vectored vaccine candidates. We show a significant bias to the 3D7/MAD20 allele compared to the Wellcome allele for the 33kDa region of MSP1, but not for the 19kDa fragment or the AMA1 antigen. Whilst this bias could be caused by ‘immune interference’ at priming, the data don’t support a significant role for ‘immune antagonism’ during memory T cell re-stimulation, despite observation of the latter at a minimal epitope level in vitro. A lack of class I HLA epitopes in the Wellcome allele that are recognized by vaccinated volunteers may in fact contribute to the observed bias. We also show that controlled infection with 3D7 strain P. falciparum parasites neither boosts existing 3D7-specific T cell responses nor appears to ‘immune divert’ cellular responses towards the Wellcome allele. PMID:23293353

  19. Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria

    PubMed Central

    Ray, Sandipan; Patel, Sandip K.; Venkatesh, Apoorva; Bhave, Amruta; Kumar, Vipin; Singh, Vaidhvi; Chatterjee, Gangadhar; Shah, Veenita G.; Sharma, Sarthak; Renu, Durairaj; Nafis, Naziya; Gandhe, Prajakta; Gogtay, Nithya; Thatte, Urmila; Sehgal, Kunal; Verma, Sumit; Karak, Avik; Khanra, Dibbendhu; Talukdar, Arunansu; Kochar, Sanjay K.; S. B, Vijeth; Kochar, Dhanpat K.; Rojh, Dharmendra; Varma, Santosh G.; Gandhi, Mayuri N.; Srikanth, Rapole; Patankar, Swati; Srivastava, Sanjeeva

    2016-01-01

    In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity. PMID:27090372

  20. Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

    PubMed

    Ray, Sandipan; Patel, Sandip K; Venkatesh, Apoorva; Bhave, Amruta; Kumar, Vipin; Singh, Vaidhvi; Chatterjee, Gangadhar; Shah, Veenita G; Sharma, Sarthak; Renu, Durairaj; Nafis, Naziya; Gandhe, Prajakta; Gogtay, Nithya; Thatte, Urmila; Sehgal, Kunal; Verma, Sumit; Karak, Avik; Khanra, Dibbendhu; Talukdar, Arunansu; Kochar, Sanjay K; S B, Vijeth; Kochar, Dhanpat K; Rojh, Dharmendra; Varma, Santosh G; Gandhi, Mayuri N; Srikanth, Rapole; Patankar, Swati; Srivastava, Sanjeeva

    2016-01-01

    In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity. PMID:27090372

  1. Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX)

    PubMed Central

    Birch, Christina M.; Hou, Han Wei; Han, Jongyoon; Niles, Jacquin C.

    2015-01-01

    Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly characterized. Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selectively recognize distinct epitopes uniquely present on parasite-infected RBCs. Based on inertial focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficiency ≥ 106) from unbound oligonucleotides at high volume throughput (~2 × 106 cells min−1). Using an RBC model displaying a single, non-native antigen and live malaria parasite-infected RBCs as targets, we establish suitability of this strategy for de novo aptamer selections. We demonstrate recovery of a diverse set of aptamers that recognize distinct, surface-displayed epitopes on parasite-infected RBCs with nanomolar affinity, including an aptamer against the protein responsible for placental sequestration, var2CSA. These findings validate I-SELEX as a broadly applicable aptamer discovery platform that enables identification of new reagents for mapping the parasite-infected RBC surface proteome at higher molecular resolution to potentially contribute to malaria diagnostics, therapeutics and vaccine efforts. PMID:26126714

  2. Identification of malaria parasite-infected red blood cell surface aptamers by inertial microfluidic SELEX (I-SELEX)

    NASA Astrophysics Data System (ADS)

    Birch, Christina M.; Hou, Han Wei; Han, Jongyoon; Niles, Jacquin C.

    2015-07-01

    Plasmodium falciparum malaria parasites invade and remodel human red blood cells (RBCs) by trafficking parasite-synthesized proteins to the RBC surface. While these proteins mediate interactions with host cells that contribute to disease pathogenesis, the infected RBC surface proteome remains poorly characterized. Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selectively recognize distinct epitopes uniquely present on parasite-infected RBCs. Based on inertial focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficiency ≥ 106) from unbound oligonucleotides at high volume throughput (~2 × 106 cells min-1). Using an RBC model displaying a single, non-native antigen and live malaria parasite-infected RBCs as targets, we establish suitability of this strategy for de novo aptamer selections. We demonstrate recovery of a diverse set of aptamers that recognize distinct, surface-displayed epitopes on parasite-infected RBCs with nanomolar affinity, including an aptamer against the protein responsible for placental sequestration, var2CSA. These findings validate I-SELEX as a broadly applicable aptamer discovery platform that enables identification of new reagents for mapping the parasite-infected RBC surface proteome at higher molecular resolution to potentially contribute to malaria diagnostics, therapeutics and vaccine efforts.

  3. Evaluation of serum chemistry values associated with avian malaria infections in African black-footed penguins (Spheniscus demersus).

    PubMed

    Graczyk, T K; Cranfield, M R; Bicknese, E J

    1995-01-01

    The value profiles of 5 intracellular enzymes, 15 metabolites (with 2 associated ratios), and 3 electrolytes were monitored over time in 9 captive-reared African black-footed penguins (Spheniscus demersus) with different avian malaria clinical status: uninfected, subclinically infected, and clinically infected with fatal outcome. Fatal infections were caused by Plasmodium relictum. Numerous schizonts were visible in the lungs, liver, spleen, and interstitial tissue of the kidneys. The reference ranges of 23 serum clinical chemistry parameters and 2 ratios were established for S. demersus. The mean values obtained for 8 of 23 parameters of the infected penguins were significantly different from those recorded for the uninfected birds, indicating impaired renal function, hepatic dysfunction, and nonspecific tissue damage related to the infestation with exoerythrocytic schizonts. Analysis of sensitivity, specificity, and negative and positive predictive values (PPVs) showed that gamma-glutamyltranspeptidase (GGTP), alanine aminotransferase (ALT), and creatinine reached PPVs and a specificity over 57% for avian malaria infections in penguins. Creatinine, ALT, and GGTP values should be consulted in evaluation of the clinical malaria status of S. demersus. PMID:7624290

  4. An analysis of the spatial distribution of Plasmodium sporozoites and effects of climatic correlates on malaria infection in Anyigba town, Nigeria.

    PubMed

    Ifatimehin, Olarewaju Oluseyi; Falola, O O; Odogbo, E V

    2014-01-01

    The infectivity of sporozoites on both mosquitoes and human is the major cause of malaria infection on its host, Man. Malaria infection had continued to blossom despite measures to curb it. Clinically diagnosed malaria data for 3 years, capture of mosquitoes for laboratory analysis to determining the infectivity of sporozoites, responses from the population on the number of episode of malaria in the last 60 days were all collected and generated, and also subjected to various analysis using methods accepted tools and methods. A fifteen weeks climatic data was also collected. It was discovered that malaria incidence of 467.2853/1000 persons is very high. This high rate is possible as out of every 10 mosquitoes in Anyigba, 4 are infected by sporozoites and can possibly transmit these sporozoites during blood feeding on the population. This is affirmed by the prevalence of malaria by 54.75% among Anyigba's population. At p>001 (0.829), climatic variables and sporozoites rate showed a strong affinity with the prevalence of malaria. The risk map showed that the university community and the surrounding students' lodges are areas of very high risk. Therefore, the populace is strongly advised to employed practicable measures such as regular environmental sanitation and the use of Insecticidal Treated Nets (ITN) in order to drastically address this epidemic. PMID:24373271

  5. An Analysis of the Spatial Distribution of Plasmodium sporozoites and Effects of Climatic Correlates on Malaria Infection in Anyigba Town, Nigeria

    PubMed Central

    Ifatimehin, O. O.; Falola, O. O.; Odogbo, E. V.

    2014-01-01

    The infectivity of sporozoites on both mosquitoes and human is the major cause of malaria infection on its host, Man. Malaria infection had continued to blossom despite measures to curb it. Clinically diagnosed malaria data for 3 years, capture of mosquitoes for laboratory analysis to determining the infectivity of sporozoites, responses from the population on the number of episode of malaria in the last 60 days were all collected and generated, and also subjected to various analysis using methods accepted tools and methods. A fifteen weeks climatic data was also collected. It was discovered that malaria incidence of 467.2853/1000 persons is very high. This high rate is possible as out of every 10 mosquitoes in Anyigba, 4 are infected by sporozoites and can possibly transmit these sporozoites during blood feeding on the population. This is affirmed by the prevalence of malaria by 54.75% among Anyigba’s population. At p>001 (0.829), climatic variables and sporozoites rate showed a strong affinity with the prevalence of malaria. The risk map showed that the university community and the surrounding students’ lodges are areas of very high risk. Therefore, the populace is strongly advised to employed practicable measures such as regular environmental sanitation and the use of Insecticidal Treated Nets (ITN) in order to drastically address this epidemic. PMID:24373271

  6. Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria.

    PubMed

    Warimwe, George M; Abdi, Abdirahman I; Muthui, Michelle; Fegan, Gregory; Musyoki, Jennifer N; Marsh, Kevin; Bull, Peter C

    2016-05-01

    Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical P. falciparum samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation per se and disease severity within these data. This contrasts with the simple hypothesis that P. falciparum isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria. PMID:26883585

  7. Malaria-induced changes in host odors enhance mosquito attraction

    PubMed Central

    De Moraes, Consuelo M.; Stanczyk, Nina M.; Betz, Heike S.; Pulido, Hannier; Sim, Derek G.; Read, Andrew F.; Mescher, Mark C.

    2014-01-01

    Vector-borne pathogens may alter traits of their primary hosts in ways that influence the frequency and nature of interactions between hosts and vectors. Previous work has reported enhanced mosquito attraction to host organisms infected with malaria parasites but did not address the mechanisms underlying such effects. Here we document malaria-induced changes in the odor profiles of infected mice (relative to healthy individuals) over the course of infection, as well as effects on the attractiveness of infected hosts to mosquito vectors. We observed enhanced mosquito attraction to infected mice during a key period after the subsidence of acute malaria symptoms, but during which mice remained highly infectious. This attraction corresponded to an overall elevation in the volatile emissions of infected mice observed during this period. Furthermore, data analyses—using discriminant analysis of principal components and random forest approaches—revealed clear differences in the composition of the volatile blends of infected and healthy individuals. Experimental manipulation of individual compounds that exhibited altered emission levels during the period when differential vector attraction was observed also elicited enhanced mosquito attraction, indicating that compounds being influenced by malaria infection status also mediate vector host-seeking behavior. These findings provide important insights into the cues that mediate vector attraction to hosts infected with transmissible stages of malaria parasites, as well as documenting characteristic changes in the odors of infected individuals that may have potential value as diagnostic biomarkers of infection. PMID:24982164

  8. Stress dependent infection cost of the human malaria agent Plasmodium falciparum on its natural vector Anopheles coluzzii.

    PubMed

    Sangare, I; Dabire, R; Yameogo, B; Da, D F; Michalakis, Y; Cohuet, A

    2014-07-01

    Unraveling selective forces that shape vector-parasite interactions has critical implications for malaria control. However, it remains unclear whether Plasmodium infection induces a fitness cost to their natural mosquito vectors. Moreover, environmental conditions are known to affect infection outcome and may impact the effect of infection on mosquito fitness. We investigated in the laboratory the effects of exposition to and infection by field isolates of Plasmodium falciparum on fecundity and survival of a major vector in the field, Anopheles coluzzii under different conditions of access to sugar resources after blood feeding. The results evidenced fitness costs induced by exposition and infection. When sugar was available after blood meal, infected and exposed mosquitoes had either reduced or equal to survival to unexposed mosquitoes while fecundity was either increased or decreased depending on the blood donor. Under strong nutritional stress, survival was reduced for exposed and infected mosquitoes in all assays. We therefore provide here evidence of an environmental-dependant reduced survival in mosquitoes exposed to infection in a natural and one of the most important parasite-mosquito species associations for human malaria transmission. PMID:24747607

  9. Acute Infection in Total Knee Arthroplasty: Diagnosis and Treatment

    PubMed Central

    Martínez-Pastor, Juan Carlos; Maculé-Beneyto, Francisco; Suso-Vergara, Santiago

    2013-01-01

    Infection is one of the most serious complications after total knee arthroplasty (TKA). The current incidence of prosthetic knee infection is 1-3%, depending on the series. For treatment and control to be more cost effective, multidisciplinary groups made up of professionals from different specialities who can work together to eradicate these kinds of infections need to be assembled. About the microbiology, Staphylococcus aureus and coagulase-negative staphylococcus were among the most frequent microorganisms involved (74%). Anamnesis and clinical examination are of primary importance in order to determine whether the problem may point to a possible acute septic complication. The first diagnosis may then be supported by increased CRP and ESR levels. The surgical treatment for a chronic prosthetic knee infection has been perfectly defined and standardized, and consists in a two-stage implant revision process. In contrast, the treatment for acute prosthetic knee infection is currently under debate. Considering the different surgical techniques that already exist, surgical debridement with conservation of the prosthesis and polythene revision appears to be an attractive option for both surgeon and patient, as it is less aggressive than the two-stage revision process and has lower initial costs. The different results obtained from this technique, along with prognosis factors and conclusions to keep in mind when it is indicated for an acute prosthetic infection, whether post-operative or haematogenous, will be analysed by the authors. PMID:23919094

  10. Plasmodium falciparum msp2 Genotypes and Multiplicity of Infections among Children under Five Years with Uncomplicated Malaria in Kibaha, Tanzania

    PubMed Central

    Kidima, W.; Nkwengulila, G.

    2015-01-01

    Genetic diversity of Plasmodium falciparum may pose challenges in malaria treatment and prevention through chemotherapy and vaccination. We assessed Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) of P. falciparum infections and sort relationship of parasitaemia with P. falciparum msp2 genotypes as well as with the number of infecting clones. The study was carried out in Kibaha, Tanzania. Ninety-nine children under five years with uncomplicated malaria were recruited. Genetic diversity was analyzed by genotyping the msp2 gene using PCR-Restriction Fragment Length Polymorphism. Thirty-two different msp2 alleles were obtained. The msp2 3D7 allelic frequency was higher (48.1%) and more prevalent than FC27 (27.3%) (p < 0.05). Twenty-four percent of the infections were mixed alleles. The individuals with FC27 had high parasitemia compared to those with 3D7 alleles (p = 0.038). The mean MOI was low (1.4 clones, 95% CI 1.2–1.5). The P. falciparum population among children at Kibaha is composed of distinct P. falciparum clones, and parasites having 3D7 are more frequent than those with FC27 alleles. Individuals with parasite having FC27 alleles have high parasite densities suggesting that parasites with FC27 alleles may associate with severity of disease in Kibaha. Low MOI at Kibaha suggests low malaria transmission rate. PMID:26770821

  11. TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection

    PubMed Central

    Gonçalves, Lígia Antunes; Rodrigues-Duarte, Lurdes; Rodo, Joana; Vieira de Moraes, Luciana; Marques, Isabel; Penha-Gonçalves, Carlos

    2013-01-01

    Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2−/− Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2−/− mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer–hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite. PMID:24218563

  12. Maturation of Plasmodium falciparum in multiply infected erythrocytes and the potential role in malaria pathogenesis.

    PubMed

    Orjih, Augustine U

    2014-11-01

    Erythrocytes containing two or more parasites, referred to here as multiply infected erythrocytes (MIEs), are common in the blood of humans infected by Plasmodium falciparum. It is necessary to study these cells closely because the excess numbers of parasites they contain suggest that they could be overloaded with virulence factors. Here, microscopic examinations of blood smears from patients showed that up to seven merozoites can successfully invade an erythrocyte and mature to ring stage. However, in vitro culture showed that only up to three parasites can mature to late schizont stage. These observations were made by culturing the parasites in erythrocytes containing hemoglobin AA (HbAA), HbAS, and HbSS. Biochemical analysis of saponin-concentrated culture suggests that more hemozoin is produced in a MIE than in a singly infected erythrocyte (SIE). Studies have shown that ingestion of excessive hemozoin destroys monocytes and neutrophils, which could impair the immune system. Cultured parasites were also examined by transmission electron microscopy, and it was found that the quantity of knobs was dramatically increased on the membranes of erythrocytes containing multiple schizonts, compared to those containing only one schizont. Knobs contain, among other things, P. falciparum erythrocyte membrane protein 1 (PfEMP1) complex which mediates sequestration and promotes severe malaria. These findings suggest that P. falciparum increases its virulence by producing MIEs. On sexual life cycle of the parasite, microphotographs are presented in this report showing, for the first time, that two gametocytes can develop in one erythrocyte; they are referred to here as twin gametocytes. It is not known whether they can infect mosquitoes. PMID:25120031

  13. Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

    PubMed Central

    Page, Anne-Laure; de Rekeneire, Nathalie; Sayadi, Sani; Aberrane, Said; Janssens, Ann-Carole; Rieux, Claire; Djibo, Ali; Manuguerra, Jean-Claude; Ducou-le-Pointe, Hubert; Grais, Rebecca F.; Schaefer, Myrto; Guerin, Philippe J.; Baron, Emmanuel

    2013-01-01

    Background Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger. Methods Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission. Results Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses. Conclusions These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data. PMID:23874731

  14. Immunochromatography-based Diagnosis of Rotavirus Infection in Acute Diarrhea.

    PubMed

    Vashishtha, Vipin M; Thacker, Sandeep; Namjoshi, Gajanan Sudhir

    2016-07-01

    Documentation of rotavirus diarrhea in a rural, resource-poor setting is a difficult task. We analyzed stool samples of 103 children admitted for acute diarrhea in a pediatric hospital in Bijnor, UP, India, using a simple bedside immunochromatography kit. Rotavirus infection was detected in 47 out of total of 103 children (45.6%). PMID:27508549

  15. Acute Borrelia infection inducing an APMPPE-like picture.

    PubMed

    Al Mousa, Munjid; Koch, Frank

    2016-12-01

    Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon disorder of unknown etiology affecting the retina, the retinal pigment epithelium, and the choroid. Although several etiological factors have been suggested, none has been confirmed. We report a case of APMPPE associated with acute infection of Borreliosis. A 30-year-old man presented with a decrease in vision in the right eye of about 1-week duration. His visual acuity in the right eye was 6/36. Fundus exam revealed the presence of multiple placoid creamy retinal/subretinal lesions in the right eye. Fundus fluorescein angiography supported the diagnosis of APMPPE. Blood tests revealed the presence of concomitant acute Borreliosis infection, as confirmed by IgM. The patient received oral prednisone therapy and amoxicillin. Six weeks later, the visual acuity returned to 6/6, and the patient was symptom free. Borreliosis can have several manifestations in the eye. One of the less common presentations is an APMPPE-like picture. The clinician should suspect acute Borreliosis infection in patients presenting with APMPPE, especially when there is a history of a tick bite, when the patient has systemic symptoms, or when living in/visiting endemic areas. This may help in the prompt management of APMPPE, avoiding complications due to the condition itself, or systemic involvement secondary to the Borreliosis infection. PMID:27294731

  16. Synchrony in malaria infections: How intensifying within-host competition can be adaptive

    PubMed Central

    Greischar, Megan A.; Read, Andrew F.; Bjørnstad, Ottar N.

    2015-01-01

    Malaria parasites exhibit great diversity in the coordination of their asexual life cycle within the host, ranging from asynchronous growth to tightly synchronized cycles of invasion and emergence from red blood cells. Synchronized reproduction should come at a high cost— intensifying competition among offspring—so why would some Plasmodium species engage in such behavior and others not? We use a delayed differential equation model to show that synchronized infections can be favored when: (1) there is limited interference among parasites competing for red blood cells; (2) transmission success is an accelerating function of sexual parasite abundance; (3) the target of saturating immunity is short-lived; and (4) coinfections with asynchronous parasites are rare. As a consequence, synchrony may be beneficial or costly, in line with the diverse patterns of synchronization observed in natural and lab infections. By allowing us to characterize diverse temporal dynamics, the model framework provides a basis for making predictions about disease severity and for projecting evolutionary responses to interventions. PMID:24464205

  17. Molecular dynamics simulation of soft grains: Malaria-infected red blood cells motion within obstructed 2-D capillary vessel

    NASA Astrophysics Data System (ADS)

    Haris, L.; Khotimah, S. N.; Haryanto, F.; Viridi, S.

    2014-02-01

    Molecular dynamics has been widely used to numerically solve equation of motion of classical many-particle system. It can be used to simulate many systems including biophysics, whose complexity level is determined by the involved elements. Based on this method, a numerical model had been constructed to mimic the behaviour of malaria-infected red blood cells within capillary vessel. The model was governed by three forces namely Coulomb force, normal force, and Stokes force. By utilizing two dimensional four-cells scheme, theoretical observation was carried out to test its capability. Although the parameters were chosen deliberately, all of the quantities were given arbitrary value. Despite this fact, the results were quite satisfactory. Combined with the previous results, it can be said that the proposed model were sufficient enough to mimic the malaria-infected red blood cells motion within obstructed capillary vessel.

  18. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  19. Hemiparesis post cerebral malaria

    PubMed Central

    Taiaa, Oumkaltoum; Amil, Touriya; Darbi, Abdelatif

    2015-01-01

    Cerebral malaria is one of the most serious complications in the Plasmodium falciparum infection. In endemic areas, the cerebral malaria interested mainly children. The occurrence in adults is very rare and most interested adult traveling in tropical zones. This case report describes a motor deficit post cerebral malaria in a young adult traveling in malaria endemic area. This complication has been reported especially in children and seems very rare in adults. PMID:25995798

  20. Evidence for spleen dysfunction in malaria-HIV co-infection in a subset of pediatric patients

    PubMed Central

    Joice, Regina; Frantzreb, Charles; Pradham, Alana; Seydel, Karl B.; Kamiza, Steve; Wirth, Dyann F.; Duraisingh, Manoj T.; Molyneux, Malcolm E; Taylor, Terrie E.; Marti, Matthias; Milner, Danny A.

    2015-01-01

    The spleen has an important role in the clearance of malaria parasites, and the role of HIV co-infection on this process is yet to be described. Using a combination of histological and molecular methods, we systematically evaluated parasite load across multiple organs from HIV-positive and HIV-negative cases of an autopsy study of pediatric comatose children with malaria infection (n = 103) in Blantyre, Malawi. Quantification of parasite load across organs was done using histology. A subset of cases was further characterized for parasite localization and stage of development using immunohistochemistry-based labeling of parasite and host cells (5 HIV-positive, 10 HIV-negative), and quantitative RT-PCR (qRT-PCR) of asexual and sexual-specific genes (4 HIV-positive, 5 HIV-negative). The results were compared with clinical information including HIV status. The HIV positive rate was 21% for the group studied (20 of 95) and HIV-positive patients had a significantly shorter duration of time between onset of illness and death, and were significantly older than HIV-negative patients. We found that spleens of HIV-positive cases had significantly higher parasite loads compared to those of HIV-negative cases in each the three methods we used: (i) standard histology, (ii) immunohistochemistry-based labeling of Plasmodium lactate dehydrogenase (pLDH), and (iii) molecular detection of asexual parasite transcript apical membrane antigen 1 (AMA1). Immunohistochemistry-based labeling of macrophage marker CD163 in a subset of spleens revealed fewer activated macrophages containing engulfed parasites and a greater number of free unphagocytosed parasites in the HIV-positive cases. The mechanism by which HIV infection is associated with more rapid progression to severe cerebral malaria disease is possibly impairment of parasite destruction by splenic macrophages, supported by published in vitro studies showing inefficient phagocytosis of malaria parasites by HIV-infected macrophages

  1. A second-order high resolution finite difference scheme for a structured erythropoiesis model subject to malaria infection.

    PubMed

    Ackleh, Azmy S; Ma, Baoling; Thibodeaux, Jeremy J

    2013-09-01

    We develop a second-order high-resolution finite difference scheme to approximate the solution of a mathematical model describing the within-host dynamics of malaria infection. The model consists of two nonlinear partial differential equations coupled with three nonlinear ordinary differential equations. Convergence of the numerical method to the unique weak solution with bounded total variation is proved. Numerical simulations demonstrating the achievement of the designed accuracy are presented. PMID:23541675

  2. Insights Into Circulating Cytokine Dynamics During Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria.

    PubMed

    Ibitokou, Samad A; Denoeud-Ndam, Lise; Ezinmegnon, Sèm; Ladékpo, Rodolphe; Zannou, Djimon-Marcel; Massougbodji, Achille; Girard, Pierre-Marie; Cot, Michel; Luty, Adrian J F; Ndam, Nicaise Tuikue

    2015-08-01

    We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array. Significantly elevated levels of IL-10 and lower levels of TNF-α were observed at delivery compared with inclusion (P = 0.005). At inclusion, the presence of circulating IFN-γ, a higher CD4(+) T cell count and having initiated intermittent preventive treatment of malaria with sulfadoxine pyrimethamine (SP-IPTp) were all associated with a lower likelihood of Plasmodium falciparum infection. At delivery, the inverse relationship between the presence of infection and circulating IFN-γ persisted, although there was a positive association between the likelihood of infection and the presence of circulating TNF-α. Initiation of antiretroviral therapy was associated with elevated IL-5 production. Consistent with our own and others' observations in HIV seronegative subjects, this study shows circulating IL-10 to be a marker of infection with P. falciparum during pregnancy even in HIV-infected women, although plasma IFN-γ may be a marker of anti-malarial protection in such women. PMID:26101276

  3. High resolution FTIR imaging provides automated discrimination and detection of single malaria parasite infected erythrocytes on glass.

    PubMed

    Perez-Guaita, David; Andrew, Dean; Heraud, Philip; Beeson, James; Anderson, David; Richards, Jack; Wood, Bayden R

    2016-06-23

    New highly sensitive tools for malaria diagnostics are urgently needed to enable the detection of infection in asymptomatic carriers and patients with low parasitemia. In pursuit of a highly sensitive diagnostic tool that can identify parasite infections at the single cell level, we have been exploring Fourier transform infrared (FTIR) microscopy using a Focal Plane Array (FPA) imaging detector. Here we report for the first time the application of a new optic configuration developed by Agilent that incorporates 25× condenser and objective Cassegrain optics with a high numerical aperture (NA = 0.81) along with additional high magnification optics within the microscope to provide 0.66 micron pixel resolution (total IR system magnification of 61×) to diagnose malaria parasites at the single cell level on a conventional glass microscope slide. The high quality images clearly resolve the parasite's digestive vacuole demonstrating sub-cellular resolution using this approach. Moreover, we have developed an algorithm that first detects the cells in the infrared image, and secondly extracts the average spectrum. The average spectrum is then run through a model based on Partial Least Squares-Discriminant Analysis (PLS-DA), which diagnoses unequivocally the infected from normal cells. The high quality images, and the fact this measurement can be achieved without a synchrotron source on a conventional glass slide, shows promise as a potential gold standard for malaria detection at the single cell level. PMID:27071693

  4. Wildlife disease and conservation in Hawaii: pathogenicity of avian malaria (Plasmodium relictum) in experimentally infected Iiwi (Vestiaria coccinea)

    USGS Publications Warehouse

    Atkinson, C.T.; Woods, K.L.; Dusek, R.J.; Sileo, L.S.; Iko, W.M.

    1995-01-01

    Native Hawaiian forest birds are facing a major extinction crisis with more than 75% of species recorded in historical times either extinct or endangered. Reasons for this catastrophe include habitat destruction, competition with non-native species, and introduction of predators and avian diseases. We tested susceptibility of Iiwi (Vestiaria coccinea), a declining native species, and Nutmeg Mannikins (Lonchura punctulata), a common non-native species, to an isolate of Plasmodium relictum from the island of Hawaii. Food consumption, weight, and parasitaemia were monitored in juvenile Iiwi that were infected by either single (low-dose) or multiple (high-dose) mosquito bites. Mortality in both groups was significantly higher than in uninfected controls, reaching 100% of high-dose birds and 90% of low-dose birds. Significant declines in food consumption and a corresponding loss of body weight occurred in malaria-infected birds. Both sex and body weight had significant effects on survival time, with males more susceptible than females and birds with low initial weights more susceptible than those with higher initial weights. Gross and microscopic lesions in malaria fatalities included massive enlargement of the spleen and liver, hyperplasia of the reticuloendothelial system with extensive deposition of malarial pigment, and overwhelming anaemia in which over 30% of the circulating erythrocytes were parasitized. Nutmeg Mannikins, by contrast, were completely refractory to infection. Our findings support previous studies documenting high susceptibility of native Hawaiian forest birds to avian malaria. This disease continues to threaten remaining high elevation populations of endangered native birds.

  5. [Anaerobic-aerobic infection in acute appendicitis].

    PubMed

    Mamchich, V I; Ulitovskiĭ, I V; Savich, E I; Znamenskiĭ, V A; Beliaeva, O A

    1998-01-01

    362 patients with acute appendicitis (AA) were examined. For microbiological diagnosis of aerobic and anaerobic nonclostridial microflora we used complex accelerated methods (including evaluation of gram-negative microorganisms in comparison with tinctorial-fermentative method of differential staining according to oxygen sensitivity of catalasopositive together with aerobic and cathalasonegative anaerobic microorganisms) as well as complete bacteriologic examination with determination of sensitivity of the above microorganism to antimicrobial remedies. High rate of aerobic-anaerobic microbial associations and substantial identity of microflora from appendicis and exudate from abdominal cavity was revealed, which evidenced the leading role of endogenous microorganisms in etiology and pathogenesis of AA and peritonitis i. e. autoinfection. In patients with destructive forms of AA, complicated by peritonitis it is recommended to use the accelerated method of examination of pathologic material as well as the complete scheme of examination with the identification of the isolated microorganisms and the correction of antibiotic treatment. PMID:9511291

  6. CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo.

    PubMed

    Ayi, Kodjo; Lu, Ziyue; Serghides, Lena; Ho, Jenny M; Finney, Constance; Wang, Jean C Y; Liles, W Conrad; Kain, Kevin C

    2016-07-01

    CD47 engagement by the macrophage signal regulatory protein alpha (SIRPα) inhibits phagocytic activity and protects red blood cells (RBCs) from erythrophagocytosis. The role of CD47-SIRPα in the innate immune response to Plasmodium falciparum infection is unknown. We hypothesized that disruption of SIRPα signaling may enhance macrophage uptake of malaria parasite-infected RBCs. To test this hypothesis, we examined in vivo clearance in CD47-deficient mice infected with Plasmodium berghei ANKA and in vitro phagocytosis of P. falciparum-infected RBCs by macrophages from SHP-1-deficient (Shp-1(-/-)) mice and NOD.NOR-Idd13.Prkdc(scid) (NS-Idd13) mice, as well as human macrophages, following disruption of CD47-SIRPα interactions with anti-SIRPα antibodies or recombinant SIRPα-Fc fusion protein. Compared to their wild-type counterparts, Cd47(-/-) mice displayed significantly lower parasitemia, decreased endothelial activation, and enhanced survival. Using macrophages from SHP-1-deficient mice or from NS-Idd13 mice, which express a SIRPα variant that does not bind human CD47, we showed that altered SIRPα signaling resulted in enhanced phagocytosis of P. falciparum-infected RBCs. Moreover, disrupting CD47-SIRPα engagement using anti-SIRPα antibodies or SIRPα-Fc fusion protein also increased phagocytosis of P. falciparum-infected RBCs. These results indicate an important role for CD47-SIRPα interactions in innate control of malaria and suggest novel targets for intervention. PMID:27091932

  7. Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

    PubMed Central

    Bousema, Teun; Drakeley, Chris

    2011-01-01

    Summary: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed. PMID:21482730

  8. Nematode infection: A rare mimic of acute appendicitis

    PubMed Central

    Hotchen, Andrew; Chin, Kian; Raja, Mahzar

    2014-01-01

    INTRODUCTION Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures. PRESENTATION OF CASE A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved. DISCUSSION Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided. CONCLUSION This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix. PMID:25024022

  9. Hemoglobin degradation in malaria-infected erythrocytes determined from live cell magnetophoresis

    PubMed Central

    Moore, Lee R.; Fujioka, Hisashi; Williams, P. Stephen; Chalmers, Jeffrey J.; Grimberg, Brian; Zimmerman, Peter; Zborowski, Maciej

    2013-01-01

    During intra-erythrocytic development, malaria trophozoites digest hemoglobin, which leads to parasite growth and asexual replication while accumulating toxic heme. To avoid death, the parasite synthesizes insoluble hemozoin crystals in the digestive vacuole through polymerization of β-hematin dimers. In the process, the heme is converted to a high-spin ferriheme whose magnetic properties were studied as early as 1936 by Pauling et al. Here, by magnetophoretic cell motion analysis, we provide evidence for a graduated increase of live cell magnetic susceptibility with developing blood-stage parasites, compatible with the increase in hemozoin content and the mechanism used by P. falciparum to avoid heme toxicity. The measured magnetophoretic mobility of the erythrocyte infected with a late-stage schizont form was m = 2.94 × 10−6 mm3 s/kg, corresponding to the net volume magnetic susceptibility (relative to water) of Δχ = 1.80 × 10−6, significantly higher than that of the oxygenated erythrocyte (−0.18×10−6) but lower than that of the fully deoxygenated erythrocyte (3.33×10−6). The corresponding fraction of hemoglobin converted to hemozoin, calculated based on the known magnetic susceptibilities of hemoglobin heme and hemozoin ferriheme, was 0.50, in agreement with the published biochemical and crystallography data. Magnetophoretic analysis of live erythrocytes could become significant for antimalarial drug susceptibility and resistance determination. PMID:16461330

  10. Azithromycin plus chloroquine: combination therapy for protection against malaria and sexually transmitted infections in pregnancy

    PubMed Central

    Chico, R Matthew; Chandramohan, Daniel

    2011-01-01

    Introduction: The first-line therapy for the intermittent preventive treatment of malaria in pregnancy (IPTp) is sulphadoxine-pyrimethamine (SP). There is an urgent need to identify safe, well-tolerated and efficacious alternatives to SP due to widespread Plasmodium falciparum resistance. Combination therapy using azithromycin and chloroquine is one possibility that has demonstrated adequate parasitological response > 95% in clinical trials of non-pregnant adults in sub-Saharan Africa and where IPTp is a government policy in 33 countries. Areas covered: Key safety, tolerability and efficacy data are presented for azithromycin and chloroquine, alone and/or in combination, when used to prevent and/or treat P. falciparum, P. vivax, and several curable sexually transmitted and reproductive tract infections (STI/RTI). Pharmacokinetic evidence from pregnant women is also summarized for both compounds. Expert opinion: The azithromycin-chloroquine regimen that has demonstrated consistent efficacy in non-pregnant adults has been a 3-day course containing daily doses of 1 g of azithromycin and 600 mg base of chloroquine. The pharmacokinetic evidence of these compounds individually suggests that dose adjustments may not be necessary when used in combination for treatment efficacy against P. falciparum, P. vivax, as well as several curable STI/ RTI among pregnant women, although clinical confirmation will be necessary. Mass trachoma-treatment campaigns have shown that azithromycin selects for macrolide resistance in the pneumococcus, which reverses following the completion of therapy. Most importantly, no evidence to date suggests that azithromycin induces pneumococcal resistance to penicillin. PMID:21736423

  11. Considerations for Comprehensive Analyses of Sporozoite-Based Controlled Human Malaria Infection Studies

    PubMed Central

    Lover, Andrew A.

    2015-01-01

    There has been renewed interest in the use of sporozoite-based approaches for controlled human malaria infections (CHMIs), and several sets of human challenge studies have recently completed. A study undertaken in Tanzania and published in 2014 found dose dependence between 10,000 and 25,000 sporozoite doses, as well as divergent times-to-parasitemia relative to earlier studies in European volunteers, with important implications for planning future studies. Analysis of time-to-event data has had extensive development in recent years, but these methods have had limited exposure outside biostatistics. Expansion of the published analyses to include recent methodological approaches optimized for the types of data used could provide a richer analysis of these studies and may result in alternative findings. Specifically, in a re-analysis of these data using survival analysis techniques, the differences recorded in prepatent periods between the two dosing regimens do not reach statistical significance, and there is no evidence for statistically significant differences in prepatent periods between the Dutch and Tanzanian study sites. Although these findings do not impact the reported safety and tolerability of challange with cryopreserved Plasmodium falciparum sporozoites (PfSPZ), or invalidate the authors' hypotheses regarding naturally acquired immunity and its effect on parasite growth rates and prepatent periods, they highlight important opportunities to more fully use datasets from these trials and related CHMI experiments in the planning of future challenge studies. PMID:26392161

  12. The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection

    PubMed Central

    van Ooij, Christiaan; Tamez, Pamela; Bhattacharjee, Souvik; Hiller, N. Luisa; Harrison, Travis; Liolios, Konstantinos; Kooij, Taco; Ramesar, Jai; Balu, Bharath; Adams, John; Waters, Andy; Janse, Chris; Haldar, Kasturi

    2008-01-01

    The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct from, the closely related Plasmodium Export Element [PEXEL]). Previous attempts to determine the entire secretome, using either the HT-motif or the PEXEL, have yielded large sets of proteins, which have not been comprehensively tested. We present here an expanded secretome that is optimized for both P. falciparum signal sequences and the HT-motif. From the most conservative of these three secretome predictions, we identify 11 proteins that are preserved across human- and rodent-infecting Plasmodium species. The conservation of these proteins likely indicates that they perform important functions in the interaction with and remodeling of the host erythrocyte important for all Plasmodium parasites. Using the piggyBac transposition system, we validate their export and find a positive prediction rate of ∼70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed ∼75%. Attempted deletions of the genes encoding the conserved exported proteins were not successful, but additional functional analyses revealed the first conserved secretome function. This gave new insight into mechanisms for the assembly of the parasite-induced tubovesicular network needed for import of nutrients into the infected erythrocyte. Thus, genomic screens combined with functional assays provide unexpected and fundamental insights into host remodeling by this major human pathogen. PMID:18551176

  13. Field performance of malaria rapid diagnostic test for the detection of Plasmodium falciparum infection in Odisha State, India

    PubMed Central

    Sahu, S.S.; Gunasekaran, K.; Jambulingam, P.

    2015-01-01

    Background & objectives: Rapid diagnostic tests (RDTs) have become an essential surveillance tool in the malaria control programme in India. The current study aimed to assess the performance of ParaHIT-f, a rapid test in diagnosis of Plasmodium falciparum infection through detecting its specific antigen, histidine rich protein 2 (PfHRP-2), in Odisha State, India. Methods: The study was undertaken in eight falciparum malaria endemic southern districts of Odisha State. Febrile patients included through active case detection, were diagnosed by Accredited Social Health Activists (ASHAs) for P. falciparum infection using the RDT, ParaHIT-f. The performance of ParaHIT-f was evaluated using microscopy as the gold standard. Results: A total of 1030 febrile patients were screened by both microscopy and the RDT for P. falciparum infection. The sensitivity of ParaHIT-f was 63.6% (95% CI: 56.0-70.6) and specificity was 98.9% (95% CI: 97.9-99.5), with positive and negative predictive values (PPV and NPV) of 92.6% (95% CI: 86.0-96.3) and 93.0% (95% CI: 91.0-94.5), respectively. When related to parasitaemia, the RDT sensitivity was 47.8% at the low parasitaemia of 4 to 40 parasites/μl of blood. Interpretation & conclusions: The results showed that the performance of the RDT, ParaHIT-f, was not as sensitive as microscopy in detecting true falciparum infections; a high specificity presented a low frequency of false-positive RDT results. The sensitivity of ParaHIT-f was around 60 per cent. It is, therefore, essential to improve the efficiency (sensitivity) of the kit so that the true falciparum infections will not be missed especially in areas where P. falciparum has been the predominant species causing cerebral malaria. PMID:26905242

  14. Current Perspectives of Prophylaxis and Management of Acute Infective Endophthalmitis.

    PubMed

    Tranos, Paris; Dervenis, Nikolaos; Vakalis, Athanasios N; Asteriadis, Solon; Stavrakas, Panagiotis; Konstas, Anastasios G P

    2016-05-01

    Endophthalmitis is an intraocular inflammatory condition which may or may not be caused by infective agents. Noninfectious (sterile) endophthalmitis may be attributable to various causes including postoperative retained soft lens matter or toxicity following introduction of other agents into the eye. Infectious endophthalmitis is further subdivided into endogenous and exogenous. In endogenous endophthalmitis there is hematogenous spread of organisms from a distant source of infection whereas in exogenous endophthalmitis direct microbial inoculation may occur usually following ocular surgery or penetrating eye injury with or without intraocular foreign bodies. Acute infective endophthalmitis is usually exogenous induced by inoculation of pathogens following ocular surgery, open-globe injury and intravitreal injections. More infrequently the infective source is internal and septicemia spreads to the eye resulting in endogenous endophthalmitis. Several risk factors have been implicated including immunosuppression, ocular surface abnormalities, poor surgical wound construction, complicated cataract surgery with vitreous loss and certain types of intraocular lens. Comprehensive guidelines and recommendations on prophylaxis and monitoring of surgical cases have been proposed to minimize the risk of acute endophthalmitis. Early diagnosis and prompt management of infective endophthalmitis employing appropriately selected intravitreal antibiotics are essential to optimize visual outcome. PMID:26935830

  15. ANA testing in the presence of acute and chronic infections.

    PubMed

    Litwin, Christine M; Binder, Steven R

    2016-01-01

    Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings. PMID:27050929

  16. Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. PMID:26790932

  17. Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection

    PubMed Central

    Rai, Birendra; Ali, Muhammad; Kumar, Varun; Krebit, Ibraheem

    2014-01-01

    We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients. PMID:24928932

  18. Pteropine orthoreovirus infection among out-patients with acute upper respiratory tract infection in Malaysia.

    PubMed

    Voon, Kenny; Tan, Yeh Fong; Leong, Pooi Pooi; Teng, Cheong Lieng; Gunnasekaran, Rajasekaran; Ujang, Kamsiah; Chua, Kaw Bing; Wang, Lin-Fa

    2015-12-01

    This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co-infection with other pathogens may potentially lead to different clinical outcomes. PMID:26106066

  19. The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

    PubMed Central

    Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

    2014-01-01

    Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

  20. The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

    PubMed

    Antonelli, Lis R V; Leoratti, Fabiana M S; Costa, Pedro A C; Rocha, Bruno C; Diniz, Suelen Q; Tada, Mauro S; Pereira, Dhelio B; Teixeira-Carvalho, Andrea; Golenbock, Douglas T; Gonçalves, Ricardo; Gazzinelli, Ricardo T

    2014-09-01

    Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+)CD16- (classical), CD14(+)CD16(+) (inflammatory), and CD14loCD16(+) (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+) cells, in particular the CD14(+)CD16(+) monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+) were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+)CD16(+) monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+)CD16(+) cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

  1. A Child with Acute Encephalopathy Associated with Quadruple Viral Infection

    PubMed Central

    Nakata, Keiko; Kashiwagi, Mitsuru; Masuda, Midori; Shigehara, Seiji; Oba, Chizu; Murata, Shinya; Kase, Tetsuo; Komano, Jun A.

    2015-01-01

    Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. Conclusion: an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE. PMID:25883930

  2. Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

    PubMed

    Hahn, D M; Schimpff, S C; Fortner, C L; Smyth, A C; Young, V M; Wiernik, P H

    1978-06-01

    During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections. PMID:98107

  3. The Effect of Cotrimoxazole Prophylactic Treatment on Malaria, Birth Outcomes, and Postpartum CD4 Count in HIV-Infected Women

    PubMed Central

    Dow, Anna; Hudgens, Michael G.; Van Rie, Annelies; King, Caroline C.; Ellington, Sascha; Chome, Nelecy; Turner, Abigail Norris; Kacheche, Zebrone; Jamieson, Denise J.; Chasela, Charles; van der Horst, Charles

    2013-01-01

    Background. Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). Methods. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. Results. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (−77.6 cells/μL, 95% CI: −125.2, −30.1) and not receiving antiretrovirals (−33.7 cells/μL, 95% CI: −58.6, −8.8). Conclusions. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination. PMID:24363547

  4. Antimalarial properties of SAABMAL®: an ethnomedicinal polyherbal formulation for the treatment of uncomplicated malaria infection in the tropics

    PubMed Central

    Obidike, I.C.; Amodu, B.; Emeje, M.O.

    2015-01-01

    Background & objectives: Malaria is a serious problem in the countries of the developing world. As the malaria parasite has become resistant to most of the antimalaria drugs available currently, there is a need to search for newer drugs. This study reports the pharmaceutical quality and in vivo antimalarial activities of a polyherbal formulation (SAABMAL®) used as malarial remedy in Nigeria. Methods: The antiplasmodial activity of SAABMAL® was determined by using the 4-day suppressive test in Plasmodium berghei-infected mice. The formulation was tried on three different experimental animal models for in vivo antimalarial activities, which are prophylactic, suppressive and curative in mice. Chloroquine and pyrimethamine were used as standard drugs for comparison. Results: The suppressive study showed that, SAABMAL® (200 and 400 mg/kg/bw) significantly (P<0.01) produced a suppression (29.39 - 100%) of parasitaemia in a dose-dependent manner, while the curative study showed that SAABMAL® at 400 mg significantly (P<0.01) reduced (95.80%) parasitaemia compared with controls. The mean survival time of SAABMAL®-treated groups (100 and 200 mg/kg) was higher than that of the chloroquine-treated group. Histopathologically, no changes were found in the spleen of both untreated and treated groups. SAABMAL® capsules were of good mechanical properties with low weight variation and high degree of content mass uniformity. Interpretation & conclusions: The results obtained in this study showed the efficacy of SAABMAL®, a herbal antimalarial formulation against chloroquine sensitive malaria and its potential use in the treatment of uncomplicated malaria infection. Further studies need to be done in humans to test its efficacy and safety for its potential use as an antimalarial drug. PMID:25900958

  5. Development and evaluation of a prototype non-woven fabric filter for purification of malaria-infected blood

    PubMed Central

    2011-01-01

    Background Many malaria-related studies depend on infected red blood cells (iRBCs) as fundamental material; however, infected blood samples from human or animal models include leukocytes (white blood cells or WBCs), especially difficult to separate from iRBCs in cases involving Plasmodium vivax. These host WBCs are a source of contamination in biology, immunology and molecular biology studies, requiring their removal. Non-woven fabric (NWF) has the ability to adsorb leukocytes and is already used as filtration material to deplete WBCs for blood transfusion and surgery. The present study describes the development and evaluation of a prototype NWF filter designed for purifying iRBCs from malaria-infected blood. Methods Blood samples of P. vivax patients were processed separately by NWF filter and CF11 column methods. WBCs and RBCs were counted, parasite density, morphology and developing stage was checked by microscopy, and compared before and after treatment. The viability of filtrated P. vivax parasites was examined by in vitro short-term cultivation. Results A total of 15 P. vivax-infected blood samples were treated by both NWF filter and CF11 methods. The WBC removal rate of the NWF filter method was 99.03%, significantly higher than the CF11 methods (98.41%, P < 0.01). The RBC recovery rate of the NWF filter method was 95.48%, also significantly higher than the CF11 method (87.05%, P < 0.01). Fourteen in vitro short-term culture results showed that after filter treatment, P. vivax parasite could develop as normal as CF11 method, and no obvious density, developing stage difference were fund between two methods. Conclusions NWF filter filtration removed most leukocytes from malaria-infected blood, and the recovery rate of RBCs was higher than with CF11 column method. Filtrated P. vivax parasites were morphologically normal, viable, and suitable for short-term in vitro culture. NWF filter filtration is simple, fast and robust, and is ideal for purification of

  6. Notes from the Field: Imported Cases of Malaria--Puerto Rico, July-October 2015.

    PubMed

    Dirlikov, Emilio; Rodríguez, Carmen; Morales, Shirley; Martínez, Laura Castro; Mendez, Juan B; Sanchez, Anibal Cruz; Burgos, Jesús Hernández; Santiago, Zobeida; Cuevas-Ruis, Rosa Ivette; Camacho, Sheila Adorno; Mercado, Enid Román; Guzmán, Jessica Falcón; Ryff, Kyle; Luna-Pinto, Carolina; Arguin, Paul M; Chenet, Stella M; Silva-Flannery, Luciana; Ljolje, Dragan; Velázquez, Julio Cadiz; Thomas, Dana; Garcia, Brenda Rivera

    2016-01-01

    On July 16 2015, the Puerto Rico Department of Health (PRDH) was notified of a case of malaria, diagnosed by a hospital parasitology laboratory in a student who had traveled to Punta Cana, Dominican Republic, during late June for a school-organized graduation trip. Malaria is a mosquito-borne parasitic infection, characterized by fever, shaking chills, headaches, muscle pains, nausea, general malaise, and vomiting (1). Malaria can be clinically difficult to distinguish from other acute febrile illnesses, and a definitive diagnosis requires demonstration of malaria parasites using microscopy or molecular diagnostic tests. The student's initial diagnosis on July 10 was suspected dengue virus infection. Puerto Rico eliminated local malaria transmission during the mid-1950s (2); however, reintroduction remains a risk because of the presence of a competent vector (Anopheles albimanus) and ease of travel to areas where the disease is endemic, including Hispaniola, the island shared by the Dominican Republic and Haiti, and the only island in the Caribbean with endemic malaria (3). During 2014, the Dominican Republic reported 496 confirmed malaria cases and four associated deaths; Haiti reported 17,662 confirmed cases and nine deaths (4). During 2000-2014, Puerto Rico reported a total of 35 imported malaria cases (range = 0-7 per year); three cases were imported from Hispaniola. During June-August 2015, eight confirmed malaria cases among travelers to the Dominican Republic were reported to CDC's National Malaria Surveillance System (CDC, unpublished data, 2015). PMID:27030910

  7. The requirements of protein & amino acid during acute & chronic infections.

    PubMed

    Kurpad, Anura V

    2006-08-01

    Nutrition and infection interact with each other in a synergistic vicious cycle, leading to an adverse nutritional status and increased susceptibility to infection. Infectious episodes result in hypermetabolism and a negative nitrogen balance which is modulated by hormones, cytokines and other pro-inflammatory mediators, and is compounded by a reduced food intake. The extent of the negative nitrogen balance varies with the type of infection and its duration; however, it is reasonable to suggest that the loss of body protein could be minimized by the provision of dietary nitrogen, although anorexia will limit this. Further, distinctions need to be made about the provision of nutrients or protein during the catabolic and anabolic or recovery phase of the infection, since the capacity of the body to retain protein is enhanced in the anabolic recovery phase. Meeting the increased requirement for protein (and other nutrients) in infection does not imply a complete therapeutic strategy. Infections need to be treated appropriately, with nutrition as an adjunct to the treatment. Prior undernutrition could also impair the body's response to infection, although the weight of the evidence would suggest that this happens more particularly in oedematous undernutrition. In general, the amount of extra protein that would appear to be needed is of the order of 20-25 per cent of the recommended intake, for most infections. In acute infections, this is particularly relevant during the convalescence period. Community trials have suggested that lysine supplementation to the level required for normal daily nutriture, in predominantly wheat eating or potentially lysine deficient communities, improves immune function among other functional nutritional parameters; however, there is as yet insufficient evidence to suggest a specific requirement for amino acids in infections over and above the normal daily requirement as based on recent evidence. Some clinical studies that have showed

  8. The Plasmodium translocon of exported proteins component EXP2 is critical for establishing a patent malaria infection in mice.

    PubMed

    Kalanon, Ming; Bargieri, Daniel; Sturm, Angelika; Matthews, Kathryn; Ghosh, Sreejoyee; Goodman, Christopher D; Thiberge, Sabine; Mollard, Vanessa; McFadden, Geoffrey I; Ménard, Robert; de Koning-Ward, Tania F

    2016-03-01

    Export of most malaria proteins into the erythrocyte cytosol requires the Plasmodium translocon of exported proteins (PTEX) and a cleavable Plasmodium export element (PEXEL). In contrast, the contribution of PTEX in the liver stages and export of liver stage proteins is unknown. Here, using the FLP/FRT conditional mutatagenesis system, we generate transgenic Plasmodium berghei parasites deficient in EXP2, the putative pore-forming component of PTEX. Our data reveal that EXP2 is important for parasite growth in the liver and critical for parasite transition to the blood, with parasites impaired in their ability to generate a patent blood-stage infection. Surprisingly, whilst parasites expressing a functional PTEX machinery can efficiently export a PEXEL-bearing GFP reporter into the erythrocyte cytosol during a blood stage infection, this same reporter aggregates in large accumulations within the confines of the parasitophorous vacuole membrane during hepatocyte growth. Notably HSP101, the putative molecular motor of PTEX, could not be detected during the early liver stages of infection, which may explain why direct protein translocation of this soluble PEXEL-bearing reporter or indeed native PEXEL proteins into the hepatocyte cytosol has not been observed. This suggests that PTEX function may not be conserved between the blood and liver stages of malaria infection. PMID:26347246

  9. Early effector cells survive the contraction phase in malaria infection and generate both central and effector memory T cells.

    PubMed

    Opata, Michael M; Carpio, Victor H; Ibitokou, Samad A; Dillon, Brian E; Obiero, Joshua M; Stephens, Robin

    2015-06-01

    CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection. PMID:25911759

  10. Pivmecillinam for the treatment of acute uncomplicated urinary infection.

    PubMed

    Nicolle, L E

    1999-12-01

    Pivmecillinam is a beta-lactam antimicrobial marketed almost two decades ago. It has been used widely for the treatment of acute cystitis in selected areas of the world, particularly in Scandinavia. With increasing resistance of community Escherichia coli isolates to trimethoprim and trimethoprim/sulphamethoxazole, as previously observed for ampicillin and sulphonamides, reassessment of empiric antimicrobial regimens for acute uncomplicated urinary infection is necessary. Thus, it is timely to revisit the role of pivmecillinam for the treatment of acute cystitis. Clinical studies document the efficacy of this antimicrobial with short course therapy for acute cystitis, and clinical practice in countries where it has been used for many years confirms its efficacy and tolerability. If this agent were more widely used for empiric treatment for acute cystitis, use of antimicrobials such as the quinolones might be avoided. Further trials to define the comparative efficacy of pivmecillinam with other antimicrobials, and further studies of community resistance in E. coli isolates to this agent are needed. PMID:10692756

  11. Glucocorticosteroids in Nano-Sterically Stabilized Liposomes Are Efficacious for Elimination of the Acute Symptoms of Experimental Cerebral Malaria

    PubMed Central

    Waknine-Grinberg, Judith H.; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K.; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage. PMID:23991146

  12. Bone and Joint Infections in Children: Acute Hematogenous Osteomyelitis.

    PubMed

    Agarwal, Anil; Aggarwal, Aditya N

    2016-08-01

    Acute hematogenous osteomyelitis (AHO) is one of the commonest bone infection in childhood. Staphylococcus aureus is the commonest organism causing AHO. With use of advanced diagnostic methods, fastidious Kingella kingae is increasingly becoming an important organism in etiology of osteoarticular infections in children under the age of 3 y. The diagnosis of AHO is primarily clinical. The main clinical symptom and sign in AHO is pain and tenderness over the affected bone especially in the metaphyseal region. However, in a neonate the clinical presentation may be subtle and misleading. Laboratory and radiological investigations supplement the clinical findings. The acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are frequently elevated. Ultrasonography and MRI are key imaging modalities for early detection of AHO. Determination of infecting organism in AHO is the key to the correct antibiotic choice, treatment duration and overall management and therefore, organism isolation using blood cultures and site aspiration should be attempted. Several effective antibiotics regimes are available for managing AHO in children. The choice of antibiotic and its duration and mode of delivery requires individualization depending upon severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and child's presentation and the clinical and laboratory response to the treatment. If pus has been evidenced in the soft tissues or bone region, surgical decompression of abscess is mandatory. PMID:26096866

  13. Efficacy of integrated school based de-worming and prompt malaria treatment on helminths -Plasmodium falciparum co-infections: A 33 months follow up study

    PubMed Central

    2011-01-01

    Background The geographical congruency in distribution of helminths and Plasmodium falciparum makes polyparasitism a common phenomenon in Sub Saharan Africa. The devastating effects of helminths-Plasmodium co-infections on primary school health have raised global interest for integrated control. However little is known on the feasibility, timing and efficacy of integrated helminths-Plasmodium control strategies. A study was conducted in Zimbabwe to evaluate the efficacy of repeated combined school based antihelminthic and prompt malaria treatment. Methods A cohort of primary schoolchildren (5-17 years) received combined Praziquantel, albendazole treatment at baseline, and again during 6, 12 and 33 months follow up surveys and sustained prompt malaria treatment. Sustained prompt malaria treatment was carried out throughout the study period. Children's infection status with helminths, Plasmodium and helminths-Plasmodium co-infections was determined by parasitological examinations at baseline and at each treatment point. The prevalence of S. haematobium, S. mansoni, STH, malaria, helminths-Plasmodium co-infections and helminths infection intensities before and after treatment were analysed. Results Longitudinal data showed that two rounds of combined Praziquantel and albendazole treatment for schistosomiasis and STHs at 6 monthly intervals and sustained prompt malaria treatment significantly reduced the overall prevalence of S. haematobium, S. mansoni, hookworms and P. falciparum infection in primary schoolchildren by 73.5%, 70.8%, 67.3% and 58.8% respectively (p < 0.001, p < 0.001, p < 0.001, p < 0.001 respectively). More importantly, the prevalence of STH + schistosomes, P. f + schistosomes, and P. f + STHs + schistosomes co-infections were reduced by 68.0%, 84.2%, and 90.7%, respectively. The absence of anti-helminthic treatment between the 12 mth and 33 mth follow-up surveys resulted in the sharp increase in STHs + schistosomes co-infection from 3.3% at 12 months

  14. Host-microbiome interactions in acute and chronic respiratory infections.

    PubMed

    Taylor, Steven L; Wesselingh, Steve; Rogers, Geraint B

    2016-05-01

    Respiratory infection is a leading cause of global morbidity and mortality. Understanding the factors that influence risk and outcome of these infections is essential to improving care. We increasingly understand that interactions between the microbial residents of our mucosal surfaces and host regulatory systems is fundamental to shaping local and systemic immunity. These mechanisms are most well defined in the gastrointestinal tract, however analogous systems also occur in the airways. Moreover, we now appreciate that the host-microbiota interactions at a given mucosal surface influence systemic host processes, in turn, affecting the course of infection at other anatomical sites. This review discusses the mechanisms by which the respiratory microbiome influences acute and chronic airway disease and examines the contribution of cross-talk between the gastrointestinal and respiratory compartments to microbe-mucosa interactions. PMID:26972325

  15. Contemporary management of infected necrosis complicating severe acute pancreatitis

    PubMed Central

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  16. Effect of zinc added to a daily small-quantity lipid-based nutrient supplement on diarrhoea, malaria, fever and respiratory infections in young children in rural Burkina Faso: a cluster-randomised trial

    PubMed Central

    Somé, Jérôme W; Abbeddou, Souheila; Yakes Jimenez, Elizabeth; Hess, Sonja Y; Ouédraogo, Zinéwendé P; Guissou, Rosemonde M; Vosti, Stephen A; Ouédraogo, Jean-Bosco; Brown, Kenneth H

    2015-01-01

    Objective Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children. Design, setting and populations This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso. Interventions Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community. Main outcomes Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group. Results The incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1–0.2%) and of upper RTI (7.8%; 95% IC 7.1–8.4%) did not differ among groups (p=0.234 and p=0.501, respectively). Conclusions Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea

  17. Testosterone-induced permanent changes of hepatic gene expression in female mice sustained during Plasmodium chabaudi malaria infection.

    PubMed

    Delić, Denis; Gailus, Nicole; Vohr, Hans-Werner; Dkhil, Mohamed; Al-Quraishy, Saleh; Wunderlich, Frank

    2010-12-01

    Testosterone has been previously shown to induce persistent susceptibility to Plasmodium chabaudi malaria in otherwise resistant female C57BL/6 mice. Here, we investigate as to whether this conversion coincides with permanent changes of hepatic gene expression profiles. Female mice aged 10-12 weeks were treated with testosterone for 3 weeks; then, testosterone treatment was discontinued for 12 weeks before challenging with 10⁶ P. chabaudi-infected erythrocytes. Hepatic gene expression was examined after 12 weeks of testosterone withdrawal and after subsequent infection with P. chabaudi at peak parasitemia, using Affymetrix microarrays with 22 ,690 probe sets representing 14, 000 genes. The expression of 54 genes was found to be permanently changed by testosterone, which remained changed during malaria infection. Most genes were involved in liver metabolism: the female-prevalent genes Cyp2b9, Cyp2b13, Cyp3a41, Cyp3a44, Fmo3, Sult2a2, Sult3a1, and BC014805 were repressed, while the male-prevalent genes Cyp2d9, Cyp7b1, Cyp4a10, Ugt2b1, Ugt2b38, Hsd3b5, and Slco1a1 were upregulated. Genes encoding different nuclear receptors were not persistently changed. Moreover, testosterone induced persistent upregulation of genes involved in hepatocellular carcinoma such as Lama3 and Nox4, whereas genes involved in immune response such as Ifnγ and Igk-C were significantly decreased. Our data provide evidence that testosterone is able to induce specific and robust long-term changes of gene expression profiles in the female mouse liver. In particular, those changes, which presumably indicate masculinized liver metabolism and impaired immune response, may be critical for the testosterone-induced persistent susceptibility of mice to P. chabaudi malaria. PMID:20844152

  18. Comparing the Bacterial Diversity of Acute and Chronic Dental Root Canal Infections

    PubMed Central

    Santos, Adriana L.; Siqueira, José F.; Rôças, Isabela N.; Jesus, Ederson C.; Rosado, Alexandre S.; Tiedje, James M.

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  19. Comparing the bacterial diversity of acute and chronic dental root canal infections.

    PubMed

    Santos, Adriana L; Siqueira, José F; Rôças, Isabela N; Jesus, Ederson C; Rosado, Alexandre S; Tiedje, James M

    2011-01-01

    This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections. PMID:22132218

  20. The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

    PubMed Central

    Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

    2015-01-01

    Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

  1. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection.

    PubMed

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  2. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection

    PubMed Central

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M.; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  3. Actinomyces infection causing acute right iliac fossa pain

    PubMed Central

    Govindarajah, Narendranath; Hameed, Waseem; Middleton, Simon; Booth, Michael

    2014-01-01

    This is a case of a 75-year-old man being admitted to the on-call surgical department with acute abdominal pain. On arrival he was clinically dehydrated and shocked with localised pain over McBurney's point and examination findings were suggestive of appendiceal or other colonic pathology. Full blood testing revealed a white cell count of 38×109/L and a C reactive protein (CRP) of 278 mg/L. A CT scan revealed a gallbladder empyema that extended into the right iliac fossa. This case highlights the potential for a hyperdistended gallbladder empyema to present as acute right iliac fossa pain with blood tests suggestive of complicated disease. Further analysis confirmed Actinomyces infection as the underlying aetiology prior to a laparoscopic subtotal cholecystectomy. This case serves to remind clinicians of this as a rare potential cause of atypical gallbladder pathology. PMID:24872493

  4. Microbial transformation from normal oral microbiota to acute endodontic infections

    PubMed Central

    2012-01-01

    Background Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections). Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites. Results On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples. Conclusions We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals. PMID:22839737

  5. The Effect of Indoor Residual Spraying on the Prevalence of Malaria Parasite Infection, Clinical Malaria and Anemia in an Area of Perennial Transmission and Moderate Coverage of Insecticide Treated Nets in Western Kenya

    PubMed Central

    Gimnig, John E.; Otieno, Peter; Were, Vincent; Marwanga, Doris; Abong’o, Daisy; Wiegand, Ryan; Williamson, John; Wolkon, Adam; Zhou, Ying; Bayoh, M. Nabie; Lobo, Neil F.; Laserson, Kayla; Kariuki, Simon; Hamel, Mary J.

    2016-01-01

    Background Insecticide treated nets (ITNs) and indoor residual spraying (IRS) have been scaled up for malaria prevention in sub-Saharan Africa. However, there are few studies on the benefit of implementing IRS in areas with moderate to high coverage of ITNs. We evaluated the impact of an IRS program on malaria related outcomes in western Kenya, an area of intense perennial malaria transmission and moderate ITN coverage (55–65% use of any net the previous night). Methods The Kenya Division of Malaria Control, with support from the US President’s Malaria Initiative, conducted IRS in one lowland endemic district with moderate coverage of ITNs. Surveys were conducted in the IRS district and a neighboring district before IRS, after one round of IRS in July-Sept 2008 and after a second round of IRS in April-May 2009. IRS was conducted with pyrethroid insecticides. At each survey, 30 clusters were selected for sampling and within each cluster, 12 compounds were randomly selected. The primary outcomes measured in all residents of selected compounds included malaria parasitemia, clinical malaria (P. falciparum infection plus history of fever) and anemia (Hb<8) of all residents in randomly selected compounds. At each survey round, individuals from the IRS district were matched to those from the non-IRS district using propensity scores and multivariate logistic regression models were constructed based on the matched dataset. Results At baseline and after one round of IRS, there were no differences between the two districts in the prevalence of malaria parasitemia, clinical malaria or anemia. After two rounds of IRS, the prevalence of malaria parasitemia was 6.4% in the IRS district compared to 16.7% in the comparison district (OR = 0.36, 95% CI = 0.22–0.59, p<0.001). The prevalence of clinical malaria was also lower in the IRS district (1.8% vs. 4.9%, OR = 0.37, 95% CI = 0.20–0.68, p = 0.001). The prevalence of anemia was lower in the IRS district but only in children

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

    PubMed Central

    2014-01-01

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

  7. Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease.

    PubMed

    Ioannidis, Lisa J; Nie, Catherine Q; Ly, Ann; Ryg-Cornejo, Victoria; Chiu, Chris Y; Hansen, Diana S

    2016-02-01

    CXCL10, or IFN-γ-inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum-mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10(-/-) mice with bone marrow from either WT or CXCL10(-/-) mice. Similar to CXCL10(-/-) mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3(+)CD4(+) T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs. PMID:26718341

  8. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  9. Acute prevertebral abscess secondary to infected pancreatic pseudocyst

    PubMed Central

    Bhandarkar, Ajay M; Pillai, Suresh; Venkitachalam, Shruti; Anand, Aishwarya

    2014-01-01

    We report a case of a middle aged, man with diabetes who presented with dysphagia and odynophagia. On evaluation, he was diagnosed to have an acute prevertebral abscess with an unusual aetiology, an infected pseudocyst of pancreas. Contrast-enhanced CT revealed an enhancing collection in the prevertebral space extending to the retrogastric space and communicating with the body of the pancreas via the oesophageal hiatus. Transoral incision and drainage of the prevertebral abscess were performed. Nasogastric tube was placed in the prevertebral space for continuous drainage and daily irrigation. Supportive intravenous broad spectrum antibiotic therapy along with the surgical intervention led to the resolution of the prevertebral abscess and the infected pancreatic pseudocyst. PMID:24408943

  10. Cerebral aspergillus infection in pediatric acute lymphoblastic leukemia induction therapy

    PubMed Central

    Prakash, Gaurav; Thulkar, Sanjay; Arava, Sudheer Kumar; Bakhshi, Sameer

    2012-01-01

    Angioinvasive pulmonary infection from filamentous fungi is not an uncommon occurrence in immunocompromised patients like acute lymphoblastic leukemia (ALL). Rarely, these lesions can spread via the hematogenous route and involve multiple visceral organs. We report a case of a 14-year-old boy with ALL who developed angioinvasive pulmonary aspergillosis early in the course of induction therapy, which was followed by hematogenous dissemination and formation of multiple brain abscesses. The patient was treated with intravenous amphotericin B. There was no response to the therapy and the patient succumbed to disseminated infection. Postmortem lung biopsy confirmed angioinvasive pulmonary aspergillosis. Poor penetration of amphotericin B across the blood-brain barrier could be one of the contributory factors for poor response to antifungal therapy. We discuss the various antifungal agents with respect to their penetration in brain. PMID:23580827

  11. Prevalence of Malaria Infection and Risk Factors Associated with Anaemia among Pregnant Women in Semiurban Community of Hazaribag, Jharkhand, India

    PubMed Central

    Sohail, Mohammad; Shakeel, Shayan; Kumari, Shweta; Bharti, Aakanksha; Zahid, Faisal; Anwar, Shadab; Singh, Krishn Pratap; Islam, Mazahirul; Sharma, Ajay Kumar; Lata, Sneh; Ali, Vahab; Adak, Tridibes; Das, Pradeep; Raziuddin, Mohammad

    2015-01-01

    The escalating burden, pathogenesis, and clinical sequel of malaria during pregnancy have combinatorial adverse impact on both mother and foetus that further perplexed the situation of diagnosis, treatment, and prevention. This prompted us to evaluate the status of population at risk of MIP in Hazaribag, Jharkhand, India. Cross-sectional study was conducted over a year at Sadar Hospital, Hazaribag. Malaria was screened using blood smear and/or RDT. Anaemia was defined as haemoglobin concentration. Pretested questionnaires were used to gather sociodemographic, clinical, and obstetrical data. The prevalence of MIP was 5.4% and 4.3% at ANC and DU, and 13.2% malaria was in women without pregnancy. Interestingly, majority were asymptomatically infected with P. vivax (over 85%) at ANC and DU. Peripheral parasitemia was significantly associated with fever within past week, rural origin of subjects, and first/second pregnancies in multivariate analysis, with the highest risk factor associated with fever followed by rural residence. Strikingly in cohort, anaemia was prevalent in 86% at ANC as compared to 72% at DU, whereas severe anaemia was 13.6% and 7.8% at ANC and DU. Even more anaemia prevalence was observed in MIP group (88% and 89% at ANC and DU), whereas severe anaemia was 23% and 21%, respectively. In view of observed impact of anaemia, parasitemia and asymptomatic infection of P. vivax during pregnancy and delivery suggest prompt diagnosis regardless of symptoms and comprehensive drug regime should be offered to pregnant women in association with existing measures in clinical spectrum of MIP, delivery, and its outcome. PMID:26783526

  12. Prevalence of Malaria Infection and Risk Factors Associated with Anaemia among Pregnant Women in Semiurban Community of Hazaribag, Jharkhand, India.

    PubMed

    Sohail, Mohammad; Shakeel, Shayan; Kumari, Shweta; Bharti, Aakanksha; Zahid, Faisal; Anwar, Shadab; Singh, Krishn Pratap; Islam, Mazahirul; Sharma, Ajay Kumar; Lata, Sneh; Ali, Vahab; Adak, Tridibes; Das, Pradeep; Raziuddin, Mohammad

    2015-01-01

    The escalating burden, pathogenesis, and clinical sequel of malaria during pregnancy have combinatorial adverse impact on both mother and foetus that further perplexed the situation of diagnosis, treatment, and prevention. This prompted us to evaluate the status of population at risk of MIP in Hazaribag, Jharkhand, India. Cross-sectional study was conducted over a year at Sadar Hospital, Hazaribag. Malaria was screened using blood smear and/or RDT. Anaemia was defined as haemoglobin concentration. Pretested questionnaires were used to gather sociodemographic, clinical, and obstetrical data. The prevalence of MIP was 5.4% and 4.3% at ANC and DU, and 13.2% malaria was in women without pregnancy. Interestingly, majority were asymptomatically infected with P. vivax (over 85%) at ANC and DU. Peripheral parasitemia was significantly associated with fever within past week, rural origin of subjects, and first/second pregnancies in multivariate analysis, with the highest risk factor associated with fever followed by rural residence. Strikingly in cohort, anaemia was prevalent in 86% at ANC as compared to 72% at DU, whereas severe anaemia was 13.6% and 7.8% at ANC and DU. Even more anaemia prevalence was observed in MIP group (88% and 89% at ANC and DU), whereas severe anaemia was 23% and 21%, respectively. In view of observed impact of anaemia, parasitemia and asymptomatic infection of P. vivax during pregnancy and delivery suggest prompt diagnosis regardless of symptoms and comprehensive drug regime should be offered to pregnant women in association with existing measures in clinical spectrum of MIP, delivery, and its outcome. PMID:26783526

  13. Malaria zoonoses.

    PubMed

    Baird, J Kevin

    2009-09-01

    The genus Plasmodium includes many species that naturally cause malaria among apes and monkeys. The 2004 discovery of people infected by Plasmodium knowlesi in Malaysian Borneo alerted to the potential for non-human species of plasmodia to cause human morbidity and mortality. Subsequent work revealed what appears to be a surprisingly high risk of infection and relatively severe disease, including among travelers to Southeast Asia. The biology and medicine of this zoonosis is reviewed here, along with an examination of the spectrum of Plasmodium species that may cause infection of humans. PMID:19747661

  14. Mixed-genotype infections of malaria parasites: within-host dynamics and transmission success of competing clones.

    PubMed Central

    Taylor, L H; Walliker, D; Read, A F

    1997-01-01

    Mixed-genotype infections of microparasites are common, but almost nothing is known about how competitive interactions within hosts affect the subsequent transmission success of individual genotypes. We investigated changes in the composition of mixed-genotype infections of the rodent malaria Plasmodium chabaudi clones CR and ER by monoclonal antibody analysis of the asexual infection in mice, and by PCR amplification of clone-specific alleles in oocysts sampled from mosquitoes which had fed on these mice. Mixed-clone infections were initiated with a 9:1 ratio of the two clones, with ER as the minority in the first experiment and CR as the minority in the second experiment. When beginning as the majority, clones achieved parasite densities in mice comparable to those achieved in control (single-clone) infections. When they began as the minority, clones were suppressed to less than 10% of control parasitaemias during the early part of the infections. However, in mosquitoes, the frequency of the initially rare clone was substantially greater than it was in mice at the start of the infection or four days prior to the feed. In both experiments, the minority clone in the inocula produced as many, or more, oocysts than it did as a single-clone infection. These experiments show that asexual dominance during most of the infection is poorly correlated to transmission probability, and therefore that the assumption that within-host population size correlates to transmission probability may not be warranted. They also raise the fundamental question of why transmission rates of individual genotypes are often higher from mixed than single-clone infections. PMID:9225482

  15. Malaria in pregnancy

    PubMed Central

    Soma-Pillay, P; Macdonald, A P

    2012-01-01

    Malaria is a complex parasitic disease affecting about 32 million pregnancies each year in sub-Saharan Africa. Pregnant women are especially susceptible to malarial infection and have the risk of developing severe disease and birth complications. The target of Millennium Development Goal 6 is to end malaria deaths by 2015. Maternal and perinatal morbidity and mortality due to malaria may be reduced by implementing preventive measures, early diagnosis of suspected cases, effective antimalarial therapy and treatment of complications.

  16. Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice

    PubMed Central

    Sarr, Demba; Bracken, Tara C.; Owino, Simon O.; Cooper, Caitlin A.; Smith, Geoffrey M.; Nagy, Tamas; Moore, Julie M.

    2015-01-01

    Introduction Plasmodium chabaudi AS-infection in pregnant A/J and C57BL/6J mice results in mid-gestational pregnancy loss. Although associated with increased systemic and placental pro-inflammatory responses and coagulopathy, the molecular mechanisms that underlie poor pregnancy outcomes in these mice are not yet fully understood. This study investigates the relationships between inflammation, apoptosis and malaria-induced pregnancy loss. Methods Infection with Plasmodium chabaudi AS in early murine pregnancy and term human placental tissues from an endemic setting were assessed by histology, immunohistochemistry, TUNEL staining, real-time PCR, flow cytometry, western blot, and ELISA. Results Quantitative PCR reveals accumulation of lymphocytes and monocytes and upregulation of chemokines that attract these cell types in malaria-exposed mid-gestational A/J conceptuses. Monocyte accumulation is confirmed by flow cytometry and placental immunohistochemistry. Concurrent with initiation of malaria-induced abortion, markers of apoptosis are evident in the junctional zone, but not the labyrinth, of A/J placentae. In contrast, mid-gestation conceptuses in infected C57BL/6J lack evidence for monocyte accumulation, exhibiting low or no in situ placental staining despite trophoblast immunoreactivity for the monokine, CCL2. Additionally, placental apoptosis is not consistently observed, and when evident, appears after malaria-induced abortion typically initiates. Similarly, trophoblast apoptosis in term human placental malaria is not observed. Of those studied, a sole common feature of malaria-induced abortion in A/J and C57BL/6J mice is elevation of plasma tumor necrosis factor. Discussion Consistent with our previous observations, tumor necrosis factor is likely to be a central driver of malaria-induced pregnancy loss in both strains, but likely operates through mechanisms distinct from placental apoptosis in C57BL/6J mice. PMID:25956987

  17. [Circulating immune complexes in acute and prolonged hepatitis A infection].

    PubMed

    Dautović-Krkić, Sajma; Gribajcević, Mehmed

    2002-01-01

    Level and dynamics activity of circulating immune complexes (CiC) and persistence CiC in the sera in the acute and prolonged HAV-infection was examined. In the same time we explored the relation of level and dynamics CiC compared with level, dynamics and persistence length ALT and IgM anti-HAV in sera, longitude excretion HAV Ag in stool and intensity patohistological damage in liver. Research have been undertaken in the prospected study on two groups with 90 patients in total: 60 patients with prolonged form of the hepatitis A, and 30 patients with HAV-infection with normal development. CiC was prescribe with fotometer in sediment of poliethilenglicol, and IgM anti HAV with ELISA technique. Ag-HAV in stool was prescribe with methodImmuno/electro/osmophoresis. Results of examination showed that high level values of CiC had present in all patients with HAV-infection, bat yet middle values of CiC had significantly higher in prolonged forms (p < 0.01). In a case of patients with PTHA CiC persistence almost three times longer than in HAV infection with normal development. The highest value of CiC have been found from one to two weeks after e peak ALT in HAV and in PTHA 4-6 weeks later. Persistence of elevated values CiC responded to the middle length persistence of Igm anti HAV-in the sera. PMID:12378858

  18. Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo

    PubMed Central

    Fonager, Jannik; Pasini, Erica M.; Braks, Joanna A.M.; Klop, Onny; Ramesar, Jai; Remarque, Edmond J.; Vroegrijk, Irene O.C.M.; van Duinen, Sjoerd G.; Thomas, Alan W.; Khan, Shahid M.; Mann, Matthias; Kocken, Clemens H.M.; Janse, Chris J.

    2012-01-01

    Adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of Plasmodium falciparum malaria. The prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. Irbc of the rodent parasite Plasmodium berghei ANKA sequester in a fashion analogous to P. falciparum by adhering to the host receptor CD36. To experimentally determine the significance of sequestration for parasite growth, we generated a mutant P. berghei ANKA parasite with a reduced CD36-mediated adherence. Although the cognate parasite ligand binding to CD36 is unknown, we show that nonsequestering parasites have reduced growth and we provide evidence that in addition to avoiding spleen removal, other factors related to CD36-mediated sequestration are beneficial for parasite growth. These results reveal for the first time the importance of sequestration to a malaria infection, with implications for the development of strategies aimed at reducing pathology by inhibiting tissue sequestration. PMID:22184632

  19. ‘Manipulation’ without the parasite: altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites

    PubMed Central

    Cator, Lauren J.; George, Justin; Blanford, Simon; Murdock, Courtney C.; Baker, Thomas C.; Read, Andrew F.; Thomas, Matthew B.

    2013-01-01

    Previous studies have suggested that Plasmodium parasites can manipulate mosquito feeding behaviours such as probing, persistence and engorgement rate in order to enhance transmission success. Here, we broaden analysis of this ‘manipulation phenotype’ to consider proximate foraging behaviours, including responsiveness to host odours and host location. Using Anopheles stephensi and Plasmodium yoelii as a model system, we demonstrate that mosquitoes with early stage infections (i.e. non-infectious oocysts) exhibit reduced attraction to a human host, whereas those with late-stage infections (i.e. infectious sporozoites) exhibit increased attraction. These stage-specific changes in behaviour were paralleled by changes in the responsiveness of mosquito odourant receptors, providing a possible neurophysiological mechanism for the responses. However, we also found that both the behavioural and neurophysiological changes could be generated by immune challenge with heat-killed Escherichia coli and were thus not tied explicitly to the presence of malaria parasites. Our results support the hypothesis that the feeding behaviour of female mosquitoes is altered by Plasmodium, but question the extent to which this is owing to active manipulation by malaria parasites of host behaviour. PMID:23698008

  20. Finding those at risk: Acute HIV infection in Newark, NJ

    PubMed Central

    Martin, Eugene G.; Salaru, Gratian; Mohammed, Debbie; Coombs, Robert W.; Paul, Sindy M.; Cadoff, Evan M.

    2014-01-01

    Background A screening strategy combining rapid HIV-1/2 (HIV) antibody testing with pooled HIV-1 RNA testing increases identification of HIV infections, but may have other limitations that restrict its usefulness to all but the highest incidence populations. Objective By combining rapid antibody detection and pooled nucleic acid amplification testing (NAAT) testing, we sought to improve detection of early HIV-1 infections in an urban Newark, NJ hospital setting. Study design Pooled NAAT HIV-1 RNA testing was offered to emergency department patients and out-patients being screened for HIV antibodies by fingerstick-rapid HIV testing. For those negative by rapid HIV and agreeing to NAAT testing, pooled plasma samples were prepared and sent to the University of Washington where real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification was performed. Results Of 13,226 individuals screened, 6381 had rapid antibody testing alone, and 6845 agreed to add NAAT HIV screening. Rapid testing identified 115 antibody positive individuals. Pooled NAAT increased HIV-1 case detection by 7.0% identifying 8 additional cases. Overall, acute HIV infection yield was 0.12%. While males represent only 48.1% of those tested by NAAT, all samples that screened positive for HIV-1 RNA were obtained from men. Conclusion HIV-1 RNA testing of pooled, HIV antibody-negative specimens permits identification of recent infections. In Newark, pooled NAAT increased HIV-1 case detection and provided an opportunity to focus on treatment and prevention messages for those most at risk of transmitting infection. Although constrained by client willingness to participate in testing associated with a need to return to receive further results, use of pooled NAAT improved early infection sensitivity. PMID:23953941

  1. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

    PubMed Central

    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  2. Malaria Research

    MedlinePlus

    ... Malaria > Research Malaria Understanding Research NIAID Role Basic Biology Prevention and Control Strategies Strategic Partnerships and Research ... the malaria parasite. Related Links Global Research​ Vector Biology International Centers of Excellence for Malaria Research (ICEMR) ...

  3. Abnormal PfEMP1/knob display on Plasmodium falciparum-infected erythrocytes containing hemoglobin variants: fresh insights into malaria pathogenesis and protection

    PubMed Central

    Fairhurst, Rick M.; Bess, Cameron D.; Krause, Michael A.

    2012-01-01

    Hemoglobin (Hb) variants are associated with reduced risk of life-threatening Plasmodium falciparum malaria syndromes, including cerebral malaria and severe malarial anemia. Despite decades of research, the mechanisms by which common Hb variants – sickle HbS, HbC, α-thalassemia, fetal HbF – protect African children against severe and fatal malaria have not been fully elucidated. In vitro experimental and epidemiological data have long suggested that Hb variants do not confer malaria protection by restricting the growth of parasites in red blood cells (RBCs). Recently, four Hb variants were found to impair cytoadherence, the binding of P. falciparum-infected RBCs (PfRBCs) to microvascular endothelial cells (MVECs), a centrally important event in both parasite survival and malaria pathogenesis in humans. Impaired cytoadherence is associated with abnormal display of P. falciparum erythrocyte membrane protein 1 (PfEMP1), the parasite’s major cytoadherence ligand and virulence factor, on the surface of host RBCs. We propose a model in which Hb variants allow parasites to display relatively low levels of PfEMP1, sufficient for sequestering PfRBCs in microvessels and avoiding their clearance from the bloodstream by the spleen. By preventing the display of high levels of PfEMP1, Hb variants may weaken the binding of PfRBCs to MVECs, compromising their ability to activate endothelium and initiate the downstream microvascular events that drive the pathogenesis of malaria. PMID:22634344

  4. Monitoring, characterization and control of chronic, symptomatic malaria infections in rural Zambia through monthly household visits by paid community health workers

    PubMed Central

    2014-01-01

    Background Active, population-wide mass screening and treatment (MSAT) for chronic Plasmodium falciparum carriage to eliminate infectious reservoirs of malaria transmission have proven difficult to apply on large national scales through trained clinicians from central health authorities. Methodology Fourteen population clusters of approximately 1,000 residents centred around health facilities (HF) in two rural Zambian districts were each provided with three modestly remunerated community health workers (CHWs) conducting active monthly household visits to screen and treat all consenting residents for malaria infection with rapid diagnostic tests (RDT). Both CHWs and HFs also conducted passive case detection among residents who self-reported for screening and treatment. Results Diagnostic positivity was higher among symptomatic patients self-reporting to CHWs (42.5%) and HFs (24%) than actively screened residents (20.3%), but spatial and temporal variations of diagnostic positivity were highly consistent across all three systems. However, most malaria infections (55.6%) were identified through active home visits by CHWs rather than self-reporting to CHWs or HFs. Most (62%) malaria infections detected actively by CHWs reported one or more symptoms of illness. Most reports of fever and vomiting, plus more than a quarter of history of fever, headache and diarrhoea, were attributable to malaria infection. The minority of residents who participated >12 times had lower rates of malaria infection and associated symptoms in later contacts but most residents were tested <4 times and high malaria diagnostic positivity (32%) in active surveys, as well as incidence (1.7 detected infections per person per year) persisted in the population. Per capita cost for active service delivery by CHWs was US$5.14 but this would rise to US$10.68 with full community compliance with monthly testing at current levels of transmission, and US$6.25 if pre-elimination transmission levels and

  5. Expression of senescent antigen on erythrocytes infected with a knobby variant of the human malaria parasite Plasmodium falciparum

    SciTech Connect

    Winograd, E.; Greenan, J.R.T.; Sherman, I.W.

    1987-04-01

    Erythrocytes infected with a knobby variant of Plasmodium falciparum selectively bind IgG autoantibodies in normal human serum. Quantification of membrane-bound IgG, by use of /sup 125/I-labeled protein A, revealed that erythrocytes infected with the knobby variant bound 30 times more protein A than did noninfected erythrocytes; infection with a knobless variant resulted in less than a 2-fold difference compared with noninfected erythrocytes. IgG binding to knobby erythrocytes appeared to be related to parasite development, since binding of /sup 125/I-labeled protein A to cells bearing young trophozoites (less than 20 hr after parasite invasion) was similar to binding to uninfected erythrocytes. By immunoelectron microscopy, the membrane-bound IgG on erythrocytes infected with the knobby variant was found to be preferentially associated with the protuberances (knobs) of the plasma membrane. The removal of aged or senescent erythrocytes from the peripheral circulation is reported to involve the binding of specific antibodies to an antigen (senescent antigen) related to the major erythrocyte membrane protein band 3. Since affinity-purified autoantibodies against band 3 specifically bound to the plasma membrane of erythrocytes infected with the knobby variant of P. falciparum, it is clear that the malaria parasite induces expression of senescent antigen.

  6. Cytokine response to pregnancy-associated recrudescence of Plasmodium berghei infection in mice with pre-existing immunity to malaria

    PubMed Central

    2013-01-01

    Background During childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. However, susceptibility to infection reappears in pregnant women, particularly primigravidae. This is due to appearance of antigenic parasite variants that are restricted to pregnancy. Variant-specific immunity also governs pregnancy-associated recrudescence of Plasmodium berghei infection in pregnant mice. Pregnancy-related changes in the plasma cytokine levels of mice with immunity acquired prior to first pregnancy have not been studied in detail previously, and were the topic of the present study. Methods A multiplexed bead assay was used to measure plasma levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF in BALB/c mice immunized against P. berghei K173 by repeated infection and drug cure before the first pregnancy. The association between cytokine levels on the one hand and parasitaemia and haemoglobin levels on the other, in mice that had never been pregnant or were pregnant for the first, second or third time were evaluated by Mann–Whitney test and Spearman rank-order correlation analysis. Results Pregnancy per se did not further increase the already high cytokine levels in mice previously immunized by repeated infection and drug cure. Levels of all the cytokines except IL-10 were correlated with each other, and with parasitaemia and haemoglobin levels. Furthermore, levels of all cytokines were positively correlated with parity, except IL-10, which was negatively correlated with parity. High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome. Conclusions High levels of IL-10 and low levels of the other cytokines were associated with poor pregnancy outcome in this mouse model of placental malaria. Since the model replicates key parasitological and immunological features of placental P

  7. Epstein-Barr virus-carrying B cells are large, surface IgM, IgD-bearing cells in normal individuals and acute malaria patients.

    PubMed Central

    Lam, K M; Whittle, H; Grzywacz, M; Crawford, D H

    1994-01-01

    In this study the presence of Epstein-Barr virus (EBV) carrying B lymphocytes in different B-cell subpopulations from peripheral blood was determined by spontaneous outgrowth which gives rise to lymphoblastoid cell lines. In healthy seropositive adults, the EBV-carrying B cell was predominantly within the IgM- and IgD-positive but not the IgG-positive subpopulations. Furthermore, these B lymphocytes were in the low-density (large cell) Percoll fraction. The IgM- and IgD-positive B cell phenotype suggests the EBV-carrying B cells to be circulating virgin B cells recently released from the bone marrow. These B cells have an estimated life span of only 6-8 weeks suggesting that long-term EBV persistence in the body may be the result of infection of a more primitive B-cell type. Similar experiments were carried out in children with acute malaria from the Gambia, West Africa, where Burkitt lymphoma (BL) is endemic in order to determine whether a population of EBV-carrying B cells could be identified which had a similar phenotype to the BL cell. The EBV-carrying B cells in this patient group were also found in the IgM-positive, IgG-negative B-cell subpopulation. The majority of these cells were found in the low-density (large cell) Percoll fraction although in some patients a proportion was derived from the high-density (small cell) fraction. This cellular phenotype is not representative of a BL cell. PMID:7959872

  8. Plasmodium knowlesi: the emerging zoonotic malaria parasite.

    PubMed

    Antinori, Spinello; Galimberti, Laura; Milazzo, Laura; Corbellino, Mario

    2013-02-01

    Plasmodium knowlesi was initially identified in the 30s as a natural Plasmodium of Macaca fascicularis monkey also capable of experimentally infecting humans. It gained a relative notoriety in the mid-30s as an alternative to Plasmodium vivax in the treatment of the general paralysis of the insane (neurosyphilis). In 1965 the first natural human infection was described in a US military surveyor coming back from the Pahang jungle of the Malaysian peninsula. P. knowlesi was again brought to the attention of the medical community when in 2004, Balbir Singh and his co-workers reported that about 58% of malaria cases observed in the Kapit district of the Malaysian Borneo were actually caused by P. knowlesi. In the following years several reports showed that P. knowlesi is much more widespread than initially thought with cases reported across Southeast Asia. This infection should also be considered in the differential diagnosis of any febrile travellers coming back from a recent travel to forested areas of Southeast Asia. P. knowlesi can cause severe malaria with a rate of 6-9% and with a case fatality rate of 3%. Respiratory distress, acute renal failure, shock and hyperbilirubinemia are the most frequently observed complications of severe P. knowlesi malaria. Chloroquine is considered the treatment of choice of uncomplicated malaria caused by P. knowlesi. PMID:23088834

  9. An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso

    PubMed Central

    2012-01-01

    Background A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. Methods Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. Results Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. Conclusion Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy. PMID:22433778

  10. Variation in haematological parameters in children less than five years of age with asymptomatic Plasmodium infection: implication for malaria field studies

    PubMed Central

    Gansane, Adama; Ouedraogo, Issa Nebie; Henry, Noelie Bere; Soulama, Issiaka; Ouedraogo, Esperance; Yaro, Jean-Baptiste; Diarra, Amidou; Benjamin, Sombie; Konate, Amadou Tidiani; Tiono, Alfred; Sirima, Sodiomon Bienvenu

    2013-01-01

    During the season of high malaria transmission, most children are infected by Plasmodium, which targets red blood cells (RBCs), affecting haematological parameters. To describe these variations, we examined the haematological profiles of two groups of children living in a malaria-endemic area. A cross-sectional survey was conducted at the peak of the malaria transmission season in a rural area of Burkina Faso. After informed consent and clinical examination, blood samples were obtained from the participants for malaria diagnosis and a full blood count. Of the 414 children included in the analysis, 192 were not infected with Plasmodium, whereas 222 were asymptomatic carriers of Plasmodium infection. The mean age of the infected children was 41.8 months (range of 26.4-57.2) compared to 38.8 months (range of 22.4-55.2) for the control group (p = 0.06). The asymptomatic infected children tended to have a significantly lower mean haemoglobin level (10.8 g/dL vs. 10.4 g/dL; p < 0.001), mean lymphocyte count (4592/µL vs. 5141/µL; p = 0.004), mean platelet count (266 x 103/µL vs. 385 x 103/µL; p < 0.001) and mean RBC count (4.388 x 106/µL vs. 4.158 x 106/µL; p < 0.001) and a higher mean monocyte count (1403/µL vs. 1192/µL; p < 0.001) compared to the control group. Special attention should be applied when interpreting haematological parameters and evaluating immune responses in asymptomatic infected children living in malaria-endemic areas and enrolled in vaccine trials. PMID:23903982

  11. Vivax malaria

    PubMed Central

    Price, Ric N; Tjitra, Emiliana; Guerra, Carlos A; Yeung, Shunmay; White, Nicholas J; Anstey, Nicholas M

    2009-01-01

    Plasmodium vivax threatens almost 40% of the world’s population, resulting in 132 - 391 million clinical infections each year. Most of these cases originate from South East Asia and the Western Pacific, although a significant number also occur in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates and the parasite’s ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers and funding bodies. PMID:18165478

  12. Co-existence of urinary tract infection and malaria among children under five years old: a report from Benin City, Nigeria.

    PubMed

    Okunola, P O; Ibadin, M O; Ofovwe, G E; Ukoh, G

    2012-05-01

    Children with fever are a majority in the various emergency rooms all over the world, and especially in the tropics. Most in sub-Saharan Africa will be treated for malaria, whether confirmed or not. It therefore follows that some of the morbidities other than malaria may go undiagnosed. The comorbidities with malaria that may have similar presentation among under-fives therefore are difficult to detect, and diseases like respiratory tract infections and urinary tract infections (UTI) are left to debilitate affected children. The exact burden of UTI co-existing with malaria in Nigeria remains ill defined. This study looks at the co-existence of UTI in under- fives with a primary diagnosis of malaria. Well-nourished children aged less than five years with confirmed malaria seen at the Children Emergency Room of the University of Benin Teaching Hospital were recruited into a prospective cross-sectional study between June and August 2006. The prevalence of UTI was 9% (27 of 300 children), with those aged less than 24 months comprising the majority. The uropathogens isolated included Staphylococcus aureus (55.6%), Escherichia coli (29.6%) and Kleibsiella pneumonia (14.8%). The isolates demonstrated high in vitro sensitivity to clavulanic acid-potentiated amoxicillin, ciprofloxacin and gentamicin, but were resistant to other commonly used antibiotics like amoxicillin and co-trimoxazole. The study indicates that UTI is a silent comorbidity in children aged less than 5 years with malaria and there is a need to evaluate these children in order to prevent the long-term morbidity of chronic renal diseases. PMID:22569460

  13. Concurrent meningitis and vivax malaria

    PubMed Central

    Santra, Tuhin; Datta, Sumana; Agrawal, Neha; Bar, Mita; Kar, Arnab; Adhikary, Apu; Ranjan, Kunal

    2015-01-01

    Malaria is an endemic infectious disease in India. It is often associated with other infective conditions but concomitant infection of malaria and meningitis are uncommon. We present a case of meningitis with vivax malaria infection in a 24-year-old lady. This case emphasizes the importance of high index of clinical suspicion to detect other infective conditions like meningitis when fever does not improve even after anti-malarial treatment in a patient of malaria before switching therapy suspecting drug resistance, which is quite common in this part of world. PMID:26985423

  14. Molecular Identification of Falciparum Malaria and Human Tuberculosis Co-Infections in Mummies from the Fayum Depression (Lower Egypt)

    PubMed Central

    Bianucci, Raffaella; Welte, Beatrix; Nerlich, Andreas G.; Kun, Jürgen F. J.; Pusch, Carsten M.

    2013-01-01

    Due to the presence of the lake Quarun and to the particular nature of its irrigation system, it has been speculated that the Fayum, a large depression 80 kilometers south- west of modern Cairo, was exposed to the hazards of malaria in historic times. Similarly, it has been speculated that, in the same area, also human tuberculosis might have been far more widespread in the antiquity than in its recent past. If these hypotheses were confirmed, it would imply that frequent cases of co-infection between the two pathogens might have occurred in ancient populations. To substantiate those speculations, molecular analyses were carried out on sixteen mummified heads recovered from the necropolis of Abusir el Meleq (Fayum) dating from the 3rd Intermediate Period (1064- 656 BC) to the Roman Period (30 BC- 300 AD). Soft tissue biopsies were used for DNA extractions and PCR amplifications using well-suited protocols. A partial 196-bp fragment of Plasmodium falciparum apical membrane antigen 1 gene and a 123-bp fragment of the Mycobacterium tuberculosis complex insertion sequence IS6110 were amplified and sequenced in six and five of the sixteen specimens, respectively. A 100% concordance rates between our sequences and those of P. falciparum and M. tuberculosis complex ones were obtained. Lastly, concomitant PCR amplification of P. falciparum and M. tuberculosis complex DNA specific fragments was obtained in four mummies, three of which are 14 C dated to the Late and Graeco-Roman Periods. Our data confirm that the hydrography of Fayum was extremely conducive to the spread of malaria. They also support the notion that the agricultural boom and dense crowding occurred in this region, especially under the Ptolemies, highly increased the probability for the manifestation and spread of tuberculosis. Here we extend back-wards to ca. 800 BC new evidence for malaria tropica and human tuberculosis co-occurrence in ancient Lower Egypt. PMID:23565222

  15. Molecular identification of falciparum malaria and human tuberculosis co-infections in mummies from the Fayum depression (Lower Egypt).

    PubMed

    Lalremruata, Albert; Ball, Markus; Bianucci, Raffaella; Welte, Beatrix; Nerlich, Andreas G; Kun, Jürgen F J; Pusch, Carsten M

    2013-01-01

    Due to the presence of the lake Quarun and to the particular nature of its irrigation system, it has been speculated that the Fayum, a large depression 80 kilometers south-west of modern Cairo, was exposed to the hazards of malaria in historic times. Similarly, it has been speculated that, in the same area, also human tuberculosis might have been far more widespread in the antiquity than in its recent past. If these hypotheses were confirmed, it would imply that frequent cases of co-infection between the two pathogens might have occurred in ancient populations. To substantiate those speculations, molecular analyses were carried out on sixteen mummified heads recovered from the necropolis of Abusir el Meleq (Fayum) dating from the 3(rd) Intermediate Period (1064-656 BC) to the Roman Period (30 BC-300 AD). Soft tissue biopsies were used for DNA extractions and PCR amplifications using well-suited protocols. A partial 196-bp fragment of Plasmodium falciparum apical membrane antigen 1 gene and a 123-bp fragment of the Mycobacterium tuberculosis complex insertion sequence IS6110 were amplified and sequenced in six and five of the sixteen specimens, respectively. A 100% concordance rates between our sequences and those of P. falciparum and M. tuberculosis complex ones were obtained. Lastly, concomitant PCR amplification of P. falciparum and M. tuberculosis complex DNA specific fragments was obtained in four mummies, three of which are (14)C dated to the Late and Graeco-Roman Periods. Our data confirm that the hydrography of Fayum was extremely conducive to the spread of malaria. They also support the notion that the agricultural boom and dense crowding occurred in this region, especially under the Ptolemies, highly increased the probability for the manifestation and spread of tuberculosis. Here we extend back-wards to ca. 800 BC new evidence for malaria tropica and human tuberculosis co-occurrence in ancient Lower Egypt. PMID:23565222

  16. 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

  17. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  18. First report of the infection of insecticide-resistant malaria vector mosquitoes with an entomopathogenic fungus under field conditions

    PubMed Central

    2011-01-01

    Background Insecticide-resistant mosquitoes are compromising the ability of current mosquito control tools to control malaria vectors. A proposed new approach for mosquito control is to use entomopathogenic fungi. These fungi have been shown to be lethal to both insecticide-susceptible and insecticide-resistant mosquitoes under laboratory conditions. The goal of this study was to see whether entomopathogenic fungi could be used to infect insecticide-resistant malaria vectors under field conditions, and to see whether the virulence and viability of the fungal conidia decreased after exposure to ambient African field conditions. Methods This study used the fungus Beauveria bassiana to infect the insecticide-resistant malaria vector Anopheles gambiae s.s (Diptera: Culicidae) VKPER laboratory colony strain. Fungal conidia were applied to polyester netting and kept under West African field conditions for varying periods of time. The virulence of the fungal-treated netting was tested 1, 3 and 5 days after net application by exposing An. gambiae s.s. VKPER mosquitoes in WHO cone bioassays carried out under field conditions. In addition, the viability of B. bassiana conidia was measured after up to 20 days exposure to field conditions. Results The results show that B. bassiana infection caused significantly increased mortality with the daily risk of dying being increased by 2.5× for the fungus-exposed mosquitoes compared to the control mosquitoes. However, the virulence of the B. bassiana conidia decreased with increasing time spent exposed to the field conditions, the older the treatment on the net, the lower the fungus-induced mortality rate. This is likely to be due to the climate because laboratory trials found no such decline within the same trial time period. Conidial viability also decreased with increasing exposure to the net and natural abiotic environmental conditions. After 20 days field exposure the conidial viability was 30%, but the viability of control

  19. Malaria Infection, Poor Nutrition and Indoor Air Pollution Mediate Socioeconomic Differences in Adverse Pregnancy Outcomes in Cape Coast, Ghana

    PubMed Central

    Amegah, Adeladza K.; Damptey, Obed K.; Sarpong, Gideon A.; Duah, Emmanuel; Vervoorn, David J.; Jaakkola, Jouni J. K.

    2013-01-01

    Background The epidemiological evidence linking socioeconomic deprivation with adverse pregnancy outcomes has been conflicting mainly due to poor measurement of socioeconomic status (SES). Studies have also failed to evaluate the plausible pathways through which socioeconomic disadvantage impacts on pregnancy outcomes. We investigated the importance of maternal SES as determinant of birth weight and gestational duration in an urban area and evaluated main causal pathways for the influence of SES. Methods A population-based cross-sectional study was conducted among 559 mothers accessing postnatal services at the four main health facilities in Cape Coast, Ghana in 2011. Information on socioeconomic characteristics of the mothers was collected in a structured questionnaire. Results In multivariate linear regression adjusting for maternal age, parity and gender of newborn, low SES resulted in 292 g (95% CI: 440–145) reduction in birth weight. Important SES-related determinants were neighborhood poverty (221 g; 95% CI: 355–87), low education (187 g; 95% CI: 355–20), studentship during pregnancy (291 g; 95% CI: 506–76) and low income (147 g; 95% CI: 277–17). In causal pathway analysis, malaria infection (6–20%), poor nutrition (2–51%) and indoor air pollution (10–62%) mediated substantial proportions of the observed effects of socioeconomic deprivation on birth weight. Generalized linear models adjusting for confounders indicated a 218% (RR: 3.18; 95% CI: 1.41–7.21) risk increase of LBW and 83% (RR: 1.83; 95% CI: 1.31–2.56) of PTB among low income mothers. Low and middle SES was associated with 357% (RR: 4.57; 95% CI: 1.67–12.49) and 278% (RR: 3.78; 95% CI: 1.39–10.27) increased risk of LBW respectively. Malaria infection, poor nutrition and indoor air pollution respectively mediated 10–21%, 16–44% and 31–52% of the observed effects of socioeconomic disadvantage on LBW risk. Conclusion We provide evidence of the effects of socioeconomic

  20. Acute disseminated encephalomyelitis associated with hepatitis A virus infection.

    PubMed

    Alehan, Füsun K; Kahveci, Suat; Uslu, Yasemin; Yildirim, Tülin; Yilmaz, Başak

    2004-06-01

    We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM. PMID:15186542

  1. Genome expression analysis of Anopheles gambiae: responses to injury, bacterial challenge, and malaria infection.

    PubMed

    Dimopoulos, George; Christophides, George K; Meister, Stephan; Schultz, Jörg; White, Kevin P; Barillas-Mury, Carolina; Kafatos, Fotis C

    2002-06-25

    The complex gene expression responses of Anopheles gambiae to microbial and malaria challenges, injury, and oxidative stress (in the mosquito and/or a cultured cell line) were surveyed by using cDNA microarrays constructed from an EST-clone collection. The expression profiles were broadly subdivided into induced and down-regulated gene clusters. Gram+ and Gram- bacteria and microbial elicitors up-regulated a diverse set of genes, many belonging to the immunity class, and the response to malaria partially overlapped with this response. Oxidative stress activated a distinctive set of genes, mainly implicated in oxidoreductive processes. Injury up- and down-regulated gene clusters also were distinctive, prominently implicating glycolysis-related genes and citric acid cycle/oxidative phosphorylation/redox-mitochondrial functions, respectively. Cross-comparison of in vivo and in vitro responses indicated the existence of tightly coregulated gene groups that may correspond to gene pathways. PMID:12077297

  2. Genome expression analysis of Anopheles gambiae: Responses to injury, bacterial challenge, and malaria infection

    PubMed Central

    Dimopoulos, George; Christophides, George K.; Meister, Stephan; Schultz, Jörg; White, Kevin P.; Barillas-Mury, Carolina; Kafatos, Fotis C.

    2002-01-01

    The complex gene expression responses of Anopheles gambiae to microbial and malaria challenges, injury, and oxidative stress (in the mosquito and/or a cultured cell line) were surveyed by using cDNA microarrays constructed from an EST-clone collection. The expression profiles were broadly subdivided into induced and down-regulated gene clusters. Gram+ and Gram− bacteria and microbial elicitors up-regulated a diverse set of genes, many belonging to the immunity class, and the response to malaria partially overlapped with this response. Oxidative stress activated a distinctive set of genes, mainly implicated in oxidoreductive processes. Injury up- and down-regulated gene clusters also were distinctive, prominently implicating glycolysis-related genes and citric acid cycle/oxidative phosphorylation/redox-mitochondrial functions, respectively. Cross-comparison of in vivo and in vitro responses indicated the existence of tightly coregulated gene groups that may correspond to gene pathways. PMID:12077297

  3. Airway microbiota and acute respiratory infection in children.

    PubMed

    Hasegawa, Kohei; Camargo, Carlos A

    2015-01-01

    Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the leading cause of hospitalization of infants in the US. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a 'risk and resilience' model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity and, thereby, decrease ARI incidence and severity in children. PMID:25961472

  4. Acute phase response to Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum' infection in FIV-infected and non-FIV-infected cats.

    PubMed

    Korman, R M; Cerón, J J; Knowles, T G; Barker, E N; Eckersall, P D; Tasker, S

    2012-08-01

    The pathogenicity of Haemoplasma spp. in cats varies with 'Candidatus Mycoplasma haemominutum' (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7-14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16-44 pi to half of the Mhf-infected cats, and on days 49-77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species. PMID:22763129

  5. [Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].

    PubMed

    de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V

    2015-05-01

    Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199

  6. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.

    PubMed

    Mooney, Jason P; Lokken, Kristen L; Byndloss, Mariana X; George, Michael D; Velazquez, Eric M; Faber, Franziska; Butler, Brian P; Walker, Gregory T; Ali, Mohamed M; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M M; Luckhart, Shirley; Tsolis, Renée M

    2015-01-01

    Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections. PMID:26434367

  7. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection

    PubMed Central

    Mooney, Jason P.; Lokken, Kristen L.; Byndloss, Mariana X.; George, Michael D.; Velazquez, Eric M.; Faber, Franziska; Butler, Brian P.; Walker, Gregory T.; Ali, Mohamed M.; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M. M.; Luckhart, Shirley; Tsolis, Renée M.

    2015-01-01

    Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections. PMID:26434367

  8. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  9. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults.

    PubMed

    Riddle, Mark S; DuPont, Herbert L; Connor, Bradley A

    2016-05-01

    Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. PMID:27068718

  10. Audit of imported and domestic malaria cases at Kuala Lumpur Hospital.

    PubMed

    Moore, C S; Cheong, I

    1995-01-01

    The clinical, haematological and biochemical profiles of all domestic and imported malaria cases admitted to the Hospital Kuala Lumpur were analysed. The most common malaria types were Plasmodium falciparum (39.5%) and Plasmodium vivax (42%). The most common patient type was men aged 29-40 years (reflecting the high mobility of this group, many of whom were illegal immigrants). Misdiagnosis on admission was frequently due to the variable clinical presentation of the disease and the difficulties of obtaining an accurate history. Associated haematological abnormalities were common. Chloroquine resistance was diagnosed in four P. falciparum patients and in one P. falciparum/vivax patient. Overall, imported malaria did not seem more severe than domestic. The three patients with cerebral malaria survived. One patient died of acute liver failure. The large influx of illegal immigrants to Malaysia has resulted in a surge in malaria infection; illegal immigrants remain a source of chloroquine resistance. PMID:8554954

  11. Immunopathology of malaria*

    PubMed Central

    Voller, Alister

    1974-01-01

    Antibodies with different spectra of reactivity are produced during malarial infections and marked changes in IgG and IgM levels occur. In addition malaria elicits serological changes that are usually associated with connective tissue disease. The excessive anaemia associated with malaria may, in part, be an autoimmune phenomenon. Transient nephritis accompanies many plasmodial infections but chronic malarial nephrotic syndrome is specifically associated with quartan malaria. Malarial infection leads to splenomegaly, the most extreme form of which is idiopathic tropical splenomegaly, which probably represents an aberrant immune response to the infection. Malaria can affect the humoral immune response to unrelated antigens and infectious agents. This may be relevant to the etiology of Burkitt's lymphoma. During pregnancy there is some loss of acquired immunity to P. falciparum and the placenta appears to be an immunologically privileged site for the multiplication of this parasite. PMID:4216408

  12. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method.

    PubMed

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S; Butykai, Adam; Kézsmárki, István

    2016-01-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66-76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method - besides being label and reagent-free, automated and rapid - has a high in vivo sensitivity and is ready for in-field evaluation. PMID:26983695

  13. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    PubMed Central

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-01-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66–76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method – besides being label and reagent-free, automated and rapid – has a high in vivo sensitivity and is ready for in-field evaluation. PMID:26983695

  14. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    NASA Astrophysics Data System (ADS)

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-03-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66–76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method – besides being label and reagent-free, automated and rapid – has a high in vivo sensitivity and is ready for in-field evaluation.

  15. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  16. Crowdsourcing Malaria Parasite Quantification: An Online Game for Analyzing Images of Infected Thick Blood Smears

    PubMed Central

    Arranz, Asier; Frean, John

    2012-01-01

    Background There are 600,000 new malaria cases daily worldwide. The gold standard for estimating the parasite burden and the corresponding severity of the disease consists in manually counting the number of parasites in blood smears through a microscope, a process that can take more than 20 minutes of an expert microscopist’s time. Objective This research tests the feasibility of a crowdsourced approach to malaria image analysis. In particular, we investigated whether anonymous volunteers with no prior experience would be able to count malaria parasites in digitized images of thick blood smears by playing a Web-based game. Methods The experimental system consisted of a Web-based game where online volunteers were tasked with detecting parasites in digitized blood sample images coupled with a decision algorithm that combined the analyses from several players to produce an improved collective detection outcome. Data were collected through the MalariaSpot website. Random images of thick blood films containing Plasmodium falciparum at medium to low parasitemias, acquired by conventional optical microscopy, were presented to players. In the game, players had to find and tag as many parasites as possible in 1 minute. In the event that players found all the parasites present in the image, they were presented with a new image. In order to combine the choices of different players into a single crowd decision, we implemented an image processing pipeline and a quorum algorithm that judged a parasite tagged when a group of players agreed on its position. Results Over 1 month, anonymous players from 95 countries played more than 12,000 games and generated a database of more than 270,000 clicks on the test images. Results revealed that combining 22 games from nonexpert players achieved a parasite counting accuracy higher than 99%. This performance could be obtained also by combining 13 games from players trained for 1 minute. Exhaustive computations measured the parasite

  17. Phase-diverse Fresnel coherent diffractive imaging of malaria parasite-infected red blood cells in the water window.

    PubMed

    Jones, M W M; Abbey, B; Gianoncelli, A; Balaur, E; Millet, C; Luu, M B; Coughlan, H D; Carroll, A J; Peele, A G; Tilley, L; van Riessen, G A

    2013-12-30

    Phase-diverse Fresnel coherent diffractive imaging has been shown to reveal the structure and composition of biological specimens with high sensitivity at nanoscale resolution. However, the method has yet to be applied using X-ray illumination with energy in the so-called 'water-window' that lies between the carbon and oxygen K edges. In this range, differences in the strength of the X-ray interaction for protein based biological materials and water is increased. Here we demonstrate a proof-of-principle application of FCDI at an X-ray energy within the water-window to a dehydrated cellular sample composed of red blood cells infected with the trophozoite stage of the malaria parasite, Plasmodium falciparum. Comparison of the results to both optical and electron microscopy shows that the correlative imaging methods that include water-window FCDI will find utility in studying cellular architecture. PMID:24514809

  18. Oritavancin for acute bacterial skin and skin structure infection

    PubMed Central

    Messina, Julia A.; Fowler, Vance G.; Corey, G. Ralph

    2015-01-01

    Introduction Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapidly bactericidal agent approved for the treatment of ABSSSI. Its prolonged half-life with one-time intravenous (IV) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of IV therapy. Areas covered This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/ pharmacokinetics, efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability. Expert Opinion If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged IV therapy, it will be sought as an alternative antibiotic therapy for ABSSSI. In addition, further clinical data demonstrating efficacy in gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market. PMID:25803197

  19. Mosquito-Borne Infections in the Aftermath of Hurricane Jeanne— Gonaïves, Haiti, 2004

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Following Hurricane Jeanne in September 2004, surveillance for mosquito-borne diseases in Gonaïves Haiti identified three patients with malaria, two with acute dengue infections, and two with acute West Nile virus infections among 116 febrile patients. These are the first reported human West Nile vi...

  20. Immunogenicity and protection from malaria infection in BK-SE36 vaccinated volunteers in Uganda is not influenced by HLA-DRB1 alleles.

    PubMed

    Tougan, Takahiro; Ito, Kazuya; Palacpac, Nirianne Marie Q; Egwang, Thomas G; Horii, Toshihiro

    2016-10-01

    SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Designated as BK-SE36, the SE36 antigen was formulated with aluminum hydroxyl gel (AHG) and produced under Good Manufacturing Practice (GMP) constraints. In a Phase Ib clinical trial and follow-up study in Uganda, the risk for malaria symptoms was reduced by 72% compared with the control group. Although promising, the number of responders to the vaccine in 6-20years-olds was approximately 30% with the majority in the younger cohort. This is in contrast to the phase Ia clinical trial where response to the vaccine was 100% in Japanese malaria naive adults. A consideration that can be of importance is the involvement of host genetic factors that may influence the ability to mount an effective immune response to vaccination as well as susceptibility to malaria infection. We, therefore, analyzed allelic polymorphism of human leukocyte antigen (HLA)-DRB1 alleles using sequence-based typing (SBT). In this study, DRB1 alleles did not influence antibody response to BK-SE36 and the vaccinees susceptibility to clinical malaria. PMID:27343834

  1. Gestational malaria associated to Plasmodium vivax and Plasmodium falciparum placental mixed-infection followed by foetal loss: a case report from an unstable transmission area in Brazil.

    PubMed

    Carvalho, Bruna O; Matsuda, Joycenéa S; Luz, Sergio L B; Martinez-Espinosa, Flor E; Leite, Juliana A; Franzin, Fernanda; Orlandi, Patrícia P; Gregoracci, Gustavo B; Lacerda, Marcus V G; Nogueira, Paulo A; Costa, Fabio T M

    2011-01-01

    Gestational malaria is a multi-factorial syndrome leading to poor outcomes for both the mother and foetus. Although an unusual increasing in the number of hospitalizations caused by Plasmodium vivax has been reported in Brazil, mortality is rarely observed. This is a report of a gestational malaria case that occurred in the city of Manaus (Amazonas State, Brazil) and resulted in foetal loss. The patient presented placental mixed-infection by Plasmodium vivax and Plasmodium falciparum after diagnosis by nested-PCR, however microscopic analysis failed to detect P. falciparum in the peripheral blood. Furthermore, as the patient did not receive proper treatment for P. falciparum and hospitalization occurred soon after drug treatment, it seems that P. falciparum pathology was modulated by the concurrent presence of P. vivax. Collectively, this case confirms the tropism towards the placenta by both of these species of parasites, reinforces the notion that co-existence of distinct malaria parasites interferes on diseases' outcomes, and opens discussions regarding diagnostic methods, malaria treatment during pregnancy and prenatal care for women living in unstable transmission areas of malaria, such as the Brazilian Amazon. PMID:21708032

  2. Mhc supertypes confer both qualitative and quantitative resistance to avian malaria infections in a wild bird population

    PubMed Central

    Sepil, Irem; Lachish, Shelly; Hinks, Amy E.; Sheldon, Ben C.

    2013-01-01

    Major histocompatibility complex (Mhc) genes are believed to play a key role in the genetic basis of disease control. Although numerous studies have sought links between Mhc and disease prevalence, many have ignored the ecological and epidemiological aspects of the host–parasite interaction. Consequently, interpreting associations between prevalence and Mhc has been difficult, whereas discriminating alleles for qualitative resistance, quantitative resistance and susceptibility remains challenging. Moreover, most studies to date have quantified associations between genotypes and disease status, overlooking the complex relationship between genotype and the properties of the Mhc molecule that interacts with parasites. Here, we address these problems and demonstrate avian malaria (Plasmodium) parasite species-specific associations with functional properties of Mhc molecules (Mhc supertypes) in a wild great tit (Parus major) population. We further show that correctly interpreting these associations depends crucially on understanding the spatial variation in risk of infection and the fitness effects of infection. We report that a single Mhc supertype confers qualitative resistance to Plasmodium relictum, whereas a different Mhc supertype confers quantitative resistance to Plasmodium circumflexum infections. Furthermore, we demonstrate common functional properties of Plasmodium-resistance alleles in passerine birds, suggesting this is a model system for parasite–Mhc associations in the wild. PMID:23516242

  3. Congenital toxoplasmosis and pregnancy malaria detection post-partum: Effective diagnosis and its implication for efficient management of congenital infection.

    PubMed

    Blay, Emmanuel Awusah; Ghansah, Anita; Otchere, Joseph; Koku, Roberta; Kwofie, Kofi Dadzie; Bimi, Langbong; Takashi, Suzuki; Ohta, Nobuo; Ayi, Irene

    2015-12-01

    Congenital toxoplasmosis (CT) and pregnancy malaria (PM) have been individually reported to cause severe negative outcomes in pregnancies but the diagnostic method is still debatable. This study sought to estimate the prevalence of PM and CT single and co-infections in pregnant women by using various specimens including plasma and placental tissues. Genomic DNA extracted from the placenta, cord blood or blood of mothers was tested by PCR. Conventional method of immunodiagnosis was done for CT. We tested 79 pregnant women aged 18-42 years (mean: 28±1.06). Prevalence of Plasmodium falciparum infection determined by PCR on mother's peripheral blood specimen was 6.3% whiles 57.3% was recorded for placental tissues (p<0.01). PCR testing for placental tissues showed 29.2% positive for Toxoplasma gondii, whiles 76.0% of mothers had serum IgG against T. gondii. It should be noted that 6.3% of the placental tissues showed PCR positive for SAG 3, a marker of active infection in T. gondii. Although there were no enhanced foetal disorders at birth in our study, there is a possibility of active transmission of T. gondii from mothers to foetuses even in immune mothers. Our study suggests that foetuses were exposed to P. falciparum and T. gondii in utero, and placenta is a better specimen for PCR in detecting such episodes. In cases of PCR-positive samples, clinical follow-up after birth may be important. PMID:26264261

  4. Shedding of TRAP by a Rhomboid Protease from the Malaria Sporozoite Surface Is Essential for Gliding Motility and Sporozoite Infectivity

    PubMed Central

    Ejigiri, Ijeoma; Ragheb, Daniel R. T.; Pino, Paco; Coppi, Alida; Bennett, Brandy Lee; Soldati-Favre, Dominique; Sinnis, Photini

    2012-01-01

    Plasmodium sporozoites, the infective stage of the malaria parasite, move by gliding motility, a unique form of locomotion required for tissue migration and host cell invasion. TRAP, a transmembrane protein with extracellular adhesive domains and a cytoplasmic tail linked to the actomyosin motor, is central to this process. Forward movement is achieved when TRAP, bound to matrix or host cell receptors, is translocated posteriorly. It has been hypothesized that these adhesive interactions must ultimately be disengaged for continuous forward movement to occur. TRAP has a canonical rhomboid-cleavage site within its transmembrane domain and mutations were introduced into this sequence to elucidate the function of TRAP cleavage and determine the nature of the responsible protease. Rhomboid cleavage site mutants were defective in TRAP shedding and displayed slow, staccato motility and reduced infectivity. Moreover, they had a more dramatic reduction in infectivity after intradermal inoculation compared to intravenous inoculation, suggesting that robust gliding is critical for dermal exit. The intermediate phenotype of the rhomboid cleavage site mutants suggested residual, albeit inefficient cleavage by another protease. We therefore generated a mutant in which both the rhomboid-cleavage site and the alternate cleavage site were altered. This mutant was non-motile and non-infectious, demonstrating that TRAP removal from the sporozoite surface functions to break adhesive connections between the parasite and extracellular matrix or host cell receptors, which in turn is essential for motility and invasion. PMID:22911675

  5. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

    PubMed Central

    Messacar, Kevin; Pastula, Daniel M.; Robinson, Christine C.; Leshem, Eyal; Sejvar, James J.; Nix, W. Allan; Oberste, M. Steven; Feikin, Daniel R.; Dominguez, Samuel R.

    2016-01-01

    During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  6. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

    PubMed

    Aliabadi, Negar; Messacar, Kevin; Pastula, Daniel M; Robinson, Christine C; Leshem, Eyal; Sejvar, James J; Nix, W Allan; Oberste, M Steven; Feikin, Daniel R; Dominguez, Samuel R

    2016-08-01

    During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  7. Acute Middle East Respiratory Syndrome Coronavirus Infection in Livestock Dromedaries, Dubai, 2014

    PubMed Central

    Corman, Victor M.; Wong, Emily Y.M.; Tsang, Alan K.L.; Muth, Doreen; Lau, Susanna K. P.; Khazanehdari, Kamal; Zirkel, Florian; Ali, Mansoor; Nagy, Peter; Juhasz, Jutka; Wernery, Renate; Joseph, Sunitha; Syriac, Ginu; Elizabeth, Shyna K.; Patteril, Nissy Annie Georgy; Woo, Patrick C. Y.; Drosten, Christian

    2015-01-01

    Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother–calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk. PMID:25989145

  8. Effect of a Clostridium difficile Infection Prevention Initiative in Veterans Affairs Acute Care Facilities.

    PubMed

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Jain, Rajiv; Roselle, Gary A

    2016-06-01

    Rates of clinically confirmed hospital-onset healthcare facility-associated Clostridium difficile infections from July 1, 2012, through March 31, 2015, in 127 acute care Veterans Affairs facilities were evaluated. Quarterly pooled national standardized infection ratios decreased 15% from baseline by the final quarter of the analysis period (P=.01, linear regression). Infect Control Hosp Epidemiol 2016;37:720-722. PMID:26864803

  9. SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections.

    PubMed Central

    Johnson, L L

    1992-01-01

    Lymphodeficient scid/scid (SCID) mice died from acute infection with a strain of Toxoplasma gondii that causes chronic infection with mild symptoms in immunocompetent non-SCID mice. However, most SCID mice reconstituted with spleen cells from immunocompetent mice 1 month prior to T. gondii infection survived in good health after a transient period during which they appeared ill. Unreconstituted SCID mice given sulfadiazine in their drinking water from day 10 of Toxoplasma infection onward survived the acute phase of infection and lived for many weeks without overt symptoms. Histological examination revealed Toxoplasma cysts in their brains. However, if sulfadiazine was withdrawn from the drinking water of these chronically infected SCID mice, the mice died within 1 week with large numbers of trophozoites throughout their brains. These findings establish SCID mice as a potentially useful resource with which to study various aspects of immunological control of T. gondii infection during either its acute or chronic phase. Furthermore, the ability to produce chronic infections with avirulent T. gondii in SCID mice and to cause acute relapsing infections at will suggests that SCID mice may be helpful in evaluating potential therapies for acute and chronic T. gondii infections in immunocompromised patients. Images PMID:1500181

  10. Acute cholecystitis associated with infection of Enterobacteriaceae from gut microbiota.

    PubMed

    Liu, J; Yan, Q; Luo, F; Shang, D; Wu, D; Zhang, H; Shang, X; Kang, X; Abdo, M; Liu, B; Ma, Y; Xin, Y

    2015-09-01

    Acute cholecystitis (AC) is one of the most common surgical diseases. Bacterial infection accounts for 50% to 85% of the disease's onset. Since there is a close relationship between the biliary system and the gut, the aims of this study were to characterize and determine the influence of gut microbiota on AC, to detect the pathogenic microorganism in the biliary system, and to explore the relationship between the gut and bile microbiota of patients with AC. A total of 185 713 high-quality sequence reads were generated from the faecal samples of 15 patients and 13 healthy controls by 16S rRNA gene pyrosequencing. Patients' samples were significantly enriched in Akkermansia, Enterobacter and Escherichia/Shigella group. The healthy controls, however, showed significant enrichment of Clostridiales, Coprococcus, Coprobacillaceae, Paraprevotella, Turicibacter and TM7-3 in their faecal samples. Escherichia coli was the main biliary pathogenic microorganism, among others such as Klebsiella spp., Clostridium perfringens, Citrobacter freundii and Enterobacter cloacae in the bile of the patients. Additionally, the amount of bile endotoxin significantly correlated with the number of Enterobacteriaceae, especially E. coli. Our data indicate that Enterobacteriaceae might play essential role in the pathogenesis and/or progress of AC. This was verified in an in vivo model using a pathogenic E. coli isolated from one of the patients in guinea pigs and observed marked gallbladder inflammation and morphologic changes. This study thus provides insight which could be useful for the prevention, diagnosis and treatment of AC and related diseases by controlling the growth of Enterobacteriaceae to alleviate the infection. PMID:26025761

  11. Incubation periods of acute respiratory viral infections: a systematic review

    PubMed Central

    Lessler, Justin; Reich, Nicholas G; Brookmeyer, Ron; Perl, Trish M; Nelson, Kenrad E; Cummings, Derek A T

    2015-01-01

    Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications. PMID:19393959

  12. Detection Of Viral And Bacterial Pathogens In Acute Respiratory Infections

    PubMed Central

    Obasi, Chidi N.; Barrett, Bruce; Brown, Roger; Vrtis, Rose; Barlow, Shari; Muller, Daniel; Gern, James

    2013-01-01

    Objectives The role of bacteria in acute respiratory illnesses (ARI) of adults and interactions with viral infections is incompletely understood. This study tested the hypothesis that bacterial co-infection during ARI adds to airway inflammation and illness severity. Methods Two groups of 97 specimens each were randomly selected from multiplex-PCR identified virus-positive and virus-negative nasal specimens obtained from adults with new onset ARI, and 40 control specimens were collected from healthy adults. All specimens were analyzed for Haemophilus influenza(HI), Moraxella catarrhalis(MC) and Streptococcus pneumonia(SP) by quantitative-PCR. General linear models tested for relationships between respiratory pathogens, biomarkers (nasal wash neutrophils and CXCL8), and ARI-severity. Results Nasal specimens from adults with ARIs were more likely to contain bacteria (37% overall; HI=28%, MC=14%, SP=7%) compared to specimens from healthy adults (5% overall; HI=0%, MC=2.5%, SP=2.5%;p<0.001). Among ARI specimens, bacteria were more likely to be detected among virus-negative specimens compared to virus-positive specimens (46% vs. 27%;p=0.0046). The presence of bacteria was significantly associated with increased CXCL8 and neutrophils, but not increased symptoms. Conclusion Pathogenic bacteria were more often detected in virus-negative ARI, and also associated with increased inflammatory biomarkers. These findings suggest the possibility that bacteria may augment virus-induced ARI and contribute to airway inflammation. Summary We tested whether bacterial pathogens were associated with ARI illness and inflammation. Bacteria were detected more often in nasal secretions during ARI, especially in samples without detectable viruses, and were associated with increased airway inflammation, but not increased symptoms. PMID:24211414

  13. Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania

    PubMed Central

    2012-01-01

    Background In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania. Methods From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages. Results A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4

  14. Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria: effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells.

    PubMed

    Ginsburg, H; Atamna, H; Shalmiev, G; Kanaani, J; Krugliak, M

    1996-07-01

    The balanced polymorphism of glucose-6-phosphate dehydrogenase deficiency (G6PD-) is believed to have evolved through the selective pressure of malarial combined with consumption of fava beans. The implicated fava bean constituents are the hydroxypyrimidine glucosides vicine and convicine, which upon hydrolysis of their beta-O-glucosidic bond, became protein pro-oxidants. In this work we show that the glucosides inhibit the growth of Plasmodium falciparum, increase the hexose-monophosphate shunt activity and the phagocytosis of malaria-infected erythrocytes. These activities are exacerbated in the presence of beta-glucosidase, implicating their pro-oxidant aglycones in the toxic effect, and are more pronounced in infected G6PD- erythrocytes. These results suggest that G6PD- infected erythrocytes are more susceptible to phagocytic cells, and that fava bean pro-oxidants are more efficiently suppressing parasite propagation in G6PD- erythrocytes, either by directly affecting parasite growth, or by means of enhanced phagocytic elimination of infected cells. The present findings could account for the relative resistance of G6PD- bearers to falciparum malaria, and establish a link between dietary habits and malaria in the selection of the G6PD- genotype. PMID:8710417

  15. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  16. Profiling Acute Respiratory Tract Infections in Children from Assam, India

    PubMed Central

    Islam, Farzana; Sarma, Ratna; Debroy, Arup; Kar, Sumit; Pal, Ranabir

    2013-01-01

    Background: Acute respiratory infections (ARI) are leading global cause of under-five mortality and morbidity. Objective: To elicit the prevalence and risk factors associated with ARI among under-five children. Materials and Methods: A community-based cross-sectional study was undertaken in 21 registered urban slums of Guwahati in Assam to determine the prevalence and risk factors associated with ARI among 370 under-five children from 184 households and 370 families. Results: The prevalence of ARI was found to be 26.22%; infants and female children were more affected. Majority of the ARI cases were from nuclear families (84.54%), living in kutcha houses (90.72%) with inadequate ventilation (84.54%), overcrowded living condition (81.44%), with kitchen attached to the living room (65.98%) and using biomass fuel for cooking (89.69%). ARI was significantly associated with ventilation, location of kitchen in household; presence of overcrowding, nutritional status, and primary immunization status also had impacts on ARI. Conclusion: The present study had identified a high prevalence of the disease among under-fives. It also pointed out various socio-demographic, nutritional, and environmental modifiable risk factors which can be tackled by effective education of the community. PMID:23599611

  17. Effect of acute cytomegalovirus infection on drug-induced SLE.

    PubMed Central

    Schattner, A.; Sthoeger, Z.; Geltner, D.

    1994-01-01

    A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity. PMID:7831173

  18. Nef gene evolution from a single transmitted strain in acute SIV infection

    PubMed Central

    Bimber, Benjamin N; Chugh, Pauline; Giorgi, Elena E; Kim, Baek; Almudevar, Anthony L; Dewhurst, Stephen; O'Connor, David H; Lee, Ha Youn

    2009-01-01

    Background The acute phase of immunodeficiency virus infection plays a crucial role in determining steady-state virus load and subsequent progression of disease in both humans and nonhuman primates. The acute period is also the time when vaccine-mediated effects on host immunity are likely to exert their major effects on virus infection. Recently we developed a Monte-Carlo (MC) simulation with mathematical analysis of viral evolution during primary HIV-1 infection that enables classification of new HIV-1 infections originating from multiple versus single transmitted viral strains and the estimation of time elapsed following infection. Results A total of 322 SIV nef SIV sequences, collected during the first 3 weeks following experimental infection of two rhesus macaques with the SIVmac239 clone, were analyzed and found to display a comparable level of genetic diversity, 0.015% to 0.052%, with that of env sequences from acute HIV-1 infection, 0.005% to 0.127%. We confirmed that the acute HIV-1 infection model correctly identified the experimental SIV infections in rhesus macaques as "homogenous" infections, initiated by a single founder strain. The consensus sequence of the sampled strains corresponded to the transmitted sequence as the model predicted. However, measured sequential decrease in diversity at day 7, 11, and 18 post infection violated the model assumption, neutral evolution without any selection. Conclusion While nef gene evolution over the first 3 weeks of SIV infection originating from a single transmitted strain showed a comparable rate of sequence evolution to that observed during acute HIV-1 infection, a purifying selection for the founder nef gene was observed during the early phase of experimental infection of a nonhuman primate. PMID:19505314

  19. Acute Scedosporium apiospermum Endobronchial Infection in Cystic Fibrosis.

    PubMed

    Padoan, Rita; Poli, Piercarlo; Colombrita, Domenico; Borghi, Elisa; Timpano, Silviana; Berlucchi, Marco

    2016-06-01

    Fungi are known pathogens in cystic fibrosis patients. A boy with cystic fibrosis boy presented with acute respiratory distress. Bronchoscopy showed airways obstruction by mucus plugs and bronchial casts. Scedosporium apiospermum was identified as the only pathogen. Bronchoalveolar lavage successfully resolved the acute obstruction. Plastic bronchitis is a new clinical picture of acute Scedosporium endobronchial colonization in cystic fibrosis patients. PMID:26967814

  20. Molecular Detection of Malaria at Delivery Reveals a High Frequency of Submicroscopic Infections and Associated Placental Damage in Pregnant Women from Northwest Colombia

    PubMed Central

    Arango, Eliana M.; Samuel, Roshini; Agudelo, Olga M.; Carmona-Fonseca, Jaime; Maestre, Amanda; Yanow, Stephanie K.

    2013-01-01

    Plasmodium infection in pregnancy causes substantial maternal and infant morbidity and mortality. In Colombia, both P. falciparum and P. vivax are endemic, but the impact of either species on pregnancy is largely unknown in this country. A cross-sectional study was carried out with 96 pregnant women who delivered at their local hospital. Maternal, placental, and cord blood were tested for malaria infection by microscopy and real-time quantitative polymerase chain reaction (qPCR). A high frequency of infection was detected by qPCR (45%). These infections had low concentrations of parasite DNA, and 79% were submicroscopic. Submicroscopic infections were associated with placental villitis and intervillitis. In conclusion, the overall frequency of Plasmodium infection at delivery in Colombia is much higher than previously reported. These data prompt a re-examination of the local epidemiology of malaria using molecular diagnostics to establish the clinical relevance of submicroscopic infections during pregnancy as well as their consequences for mothers and newborns. PMID:23716408

  1. Maladjusted host immune responses induce experimental cerebral malaria-like pathology in a murine Borrelia and Plasmodium co-infection model.

    PubMed

    Normark, Johan; Nelson, Maria; Engström, Patrik; Andersson, Marie; Björk, Rafael; Moritz, Thomas; Fahlgren, Anna; Bergström, Sven

    2014-01-01

    In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1β and TNF-α, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells. PMID:25075973

  2. Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model

    PubMed Central

    Normark, Johan; Nelson, Maria; Engström, Patrik; Andersson, Marie; Björk, Rafael; Moritz, Thomas; Fahlgren, Anna; Bergström, Sven

    2014-01-01

    In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1β and TNF-α, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells. PMID:25075973

  3. Clinical and laboratory predictive markers for acute dengue infection

    PubMed Central

    2013-01-01

    Background Early diagnosis of dengue virus infection during the febrile stage is essential for adjusting appropriate management. This study is to identify the predictive markers of clinical and laboratory findings in the acute stage of dengue infection during a major outbreak of dengue virus type 1 that occurred in southern Taiwan during 2007. A retrospective, hospital-based study was conducted at a university hospital in southern Taiwan from January to December, 2007. Patient who was reported for clinically suspected dengue infection was enrolled. Laboratory-positive dengue cases are confirmed by enzyme-linked immunosorbent assay of specific dengue IgM, fourfold increase of dengue-specific IgG titers in convalescent serum, or by reverse transcription-polymerase chain reaction (RT-PCR) of dengue virus. Results The suspected dengue cases consist of 100 children (≤ 18 years) and 481 adults. Among the 581 patients, 67 (67%) children and 309 (64.2%) adults were laboratory-confirmed. Patients who had laboratory indeterminate were excluded. Most cases were uncomplicated and 3.8% of children and 2.9% of adults developed dengue hemorrhagic fever or dengue shock syndrome (DHF/DSS). The overall mortality rate in those with DHF/DSS was 7.1%, and the average duration of hospitalization was 20 days. The most common symptoms/signs at admission were myalgia (46.8%), petechiae (36.9%) and nausea/vomiting (33.5%). The most notable laboratory findings included leukopenia (2966 ± 1896/cmm), thrombocytopenia (102 ± 45 × 103/cmm), prolonged activated partial thromboplastin time (aPTT) (45 ± 10 s), and elevated serum levels of aminotransferase (AST, 166 ± 208 U/L; ALT, 82 ± 103 U/L) and low C - reactive protein (CRP) (6 ± 11 mg/L). Based on the clinical features for predicting laboratory-confirmed dengue infection, the sensitivities of typical rash, myalgia, and positive tourniquet test are 59.2%, 46.8%, and 34.2%, while the specificities for

  4. Disseminated Neocosmospora vasinfecta infection in a patient with acute nonlymphocytic leukemia.

    PubMed Central

    Cornely, O. A.; Chemnitz, J.; Brochhagen, H. G.; Lemmer, K.; Schütt, H.; Söhngen, D.; Staib, P.; Wickenhauser, C.; Diehl, V.; Tintelnot, K.

    2001-01-01

    We report Neocosmospora vasinfecta infection following chemotherapy for acute nonlymphocytic leukemia. N. vasinfecta, a plant pathogen, was identified by culture and genetic sequencing. Susceptibility testing revealed in vitro resistance for common antifungals. PMID:11266308

  5. Changes in ovarian follicles following acute infection with bovine viral diarrhea virus.

    PubMed

    Grooms, D L; Brock, K V; Pate, J L; Day, M L

    1998-02-01

    Bovine viral diarrhea virus (BVDV) has been associated with several reproductive problems in cattle, including poor fertility, early embryonic deaths, abortion and congenital anomalies. Little is known about the cause of poor fertility in cows acutely infected with BVDV. The purpose of this study was to identify changes in ovarian function following acute infection with noncytopathic BVDV. The ovaries of 5 BVDV sero-negative and virus-negative pubertal heifers were monitored daily for 4 consecutive estrous cycles. The position and diameter of all follicles (> 5 mm) and luteal structures were recorded. Daily plasma samples were collected to measure peripheral progesterone and estradiol levels. Each heifer was infected intranasally with noncytopathic BVDV following ovulation of the second estrous cycle. The maximum diameter and growth rate of dominant anovulatory and ovulatory follicles were significantly reduced following acute BVDV infection. Similarly, the number of subordinate follicles associated with both the anovulatory and ovulatory follicle was reduced following infection. There were no significant differences in other follicle or luteal dynamic parameters or in peripheral progesterone or estradiol levels. Ovarian follicular growth was different during the first 2 estrous cycles following acute infection with BVDV when compared with the 2 estrous cycles preceding infection. These differences may be important in explaining reduced fertility in herds with acute BVDV infection. PMID:10732038

  6. Enhancing the detection and management of acute hepatitis C virus infection.

    PubMed

    Martinello, Marianne; Matthews, Gail V

    2015-10-01

    Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID. PMID:26254495

  7. Radiculoplexopathy with conduction block caused by acute Epstein-Barr virus infection.

    PubMed

    Vucic, Steve; Palmer, William; Cros, Didier

    2005-02-01

    The authors report a case of cervicobrachial radiculoplexopathy with proximal conduction block (CB), associated with acute Epstein-Barr virus (EBV) infection. The patient presented with pain, paresthesias, and monomelic weakness in the left C7-8, and T1 myotomes. The illness was monophasic with rapid recovery. Neurophysiologic studies demonstrated CB in the proximal left median and ulnar nerve segments. The authors conclude that this syndrome resulted from a postinfectious process following acute EBV infection. PMID:15699388

  8. Acute Hepatitis as a Manifestation of Parvovirus B19 Infection

    PubMed Central

    Hatakka, Aleisha; Klein, Julianne; He, Runtao; Piper, Jessica; Tam, Edward; Walkty, Andrew

    2011-01-01

    There are few reports in the literature of hepatitis as a manifestation of parvovirus B19 infection. We describe a case of parvovirus B19-associated acute hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in a liver biopsy specimen. Parvovirus B19 infection should be considered in the differential diagnosis of patients presenting with acute hepatitis. PMID:21734024

  9. Varicella Zoster Infection: A Rare Cause of Abdominal Pain Mimicking Acute Abdomen

    PubMed Central

    Olmez, Deniz; Boz, Alper; Erkan, Nazif

    2009-01-01

    Varicella zoster is an acute viral infection that results from reactivation of a latent varicella zoster virus. It usually occurs in adult population and immune compromised patients. It rarely occurs in healthy children. Here we present a 14 years old male with varicella zoster that had abdominal pain mimicking acute abdomen to alert others who are consulted for the differentiation of acute abdomen and others who may be consulted for pain management. Keywords Varicella zoster; Abdominal pain PMID:22461879

  10. Tsunami, post-tsunami malaria situation in Nancowry group of islands, Nicobar district, Andaman and Nicobar Islands

    PubMed Central

    Manimunda, Sathya Prakash; Sugunan, Attayoor Purushottaman; Sha, Wajid Ali; Singh, Shiv Shankar; Shriram, Ananganallur Nagarajan; Vijayachari, Paluru

    2011-01-01

    Background & objectives: Due to tsunami in 2004 a large proportion of population in Nicobar group of Islands become homeless, and in 2006 large scale labour migration took place to construct the houses. In 2008, a significant increase in malaria incidence was observed in this area. Therefore, in March 2008, the situation of malaria was assessed in Nancowry Islands in Nicobar District to study the reasons for the observed upsurge in the number of cases, and to suggest public health measures to control the infection. Methods: The methods included a retrospective analysis of long term trend in the behaviour of malaria over the years from 2001 to 2008, analysis of the acute malaria situation, and rapid fever and malaria parasitemia survey along with environmental component. Mass radical therapy (MRT) and post-intervention parasitemia survey were carried out. The malaria situation in the aftermath of MRT was analysed. Results: During the post tsunami year (2005) there was a large increase in the incidence of malaria and this trend continued till 2008. The percentage of Plasmodium falciparum increased from 23 to 53 per cent from 2006 to 2007 that coincides with the labour influx from mainland. The study showed that Nancowry was highly endemic, with high transmission setting, and high risk area for malaria. Though, more number of migrant labourers suffered fever (75 vs 20%) and sought malaria treatment over past month but parasitemia survey showed higher point prevalence of malaria among native tribes (7.4 vs 6.5%). Post-MRT, there was a decline in the occurrence of malaria, though it did not last long. Interpretation & conclusions: The study findings suggest that the migrant workers hailing from non-endemic or moderately endemic settings became victims of malaria in epidemic proportion in high endemic and high transmission setting. To find out the reasons for deterioration of malaria situation at Nancowry in the aftermath of tsunami requires further research. PMID

  11. [Current malaria situation in the Republic of Uzbekistan].

    PubMed

    Razakov, Sh A; Shakhgunova, G Sh

    2001-01-01

    1998). The remaining cases were diagnosed as having acute respiratory viral infections, tropical and parasitic diseases, viral hepatitis, or influenza. Early diagnosis of malaria was made in 60% of cases (77% in 1998). Three cases of imported tertian malaria were recorded in the Tashkent Region in the first quarter of 2000. They were imported from Tajikistan into rural areas and the patients had been infected during the 1999 season. Epidemiological surveillance of malaria in Uzbekistan is regularly carried out by the general network of health facilities and by the departments of parasitology of state epidemiological surveillance centers in collaboration with medical administrative departments, the Ministry of Agriculture and Fisheries, the L.M. Isayev Research Institute of Medical Parasitology, and other agencies. Active links are maintained with WHO under the Roll Back Malaria programme. Great emphasis is laid on medical staff training at all levels. During the 1999 epidemiological survey, 672,536 laboratory tests were performed on blood samples from suspected malaria patients and individuals who had visited malaria-endemic countries, 55% of them suffering from fever. A total area of 17 million m2 of dwelling and nondwelling buildings 20 ha of water areas were treated against mosquitoes and the larvivorous fish Gambusia was put into the water areas occupying 6,500 ha. In all cases of malaria, the focus of infection was epidemiologically surveyed and required epidemic preventive measures were implemented. All malaria patients received a full course of radical therapy and recovered completely. The epidemiological surveillance system for malaria is affected by staff shortages at the parasitology departments of state epidemiological surveillance centers and by shortages of microscopes, reagents, sterilizing equipment, insecticides, etc. There are still difficulties in obtaining supplies of primaquine although a small stock is locally available as due to WHO humanitarian

  12. Chlamydia trachomatis Antigens Recognized by Women With Tubal Factor Infertility, Normal Fertility, and Acute Infection

    PubMed Central

    Budrys, Nicole M.; Gong, Siqi; Rodgers, Allison K.; Wang, Jie; Louden, Christopher; Shain, Rochelle; Schenken, Robert S.; Zhong, Guangming

    2015-01-01

    Objective To identify Chlamydia trachomatis antigens associated with tubal factor infertility and acute infection. Methods A C. trachomatis proteome array was used to compare antibody profiles among women with tubal factor infertility, normal fertility, and acute C. trachomatis infection. Results Thirteen immunodominant antigens reacted with 50% or more sera from all women (N=73). Six C. trachomatis antigens were uniquely recognized by women diagnosed with tubal factor infertility. Combining fragmentation of the six antigens with serum sample dilution, chlamydial antigens HSP60, CT376, CT557, and CT443 could discriminate between women with tubal factor infertility and women with normal fertility with a sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.91–1), respectively. These antigens were designated as tubal factor infertility-associated antigens. However, these tubal factor antigens were unable to distinguish tubal factor infertility patients from those with acute infection. A combination of CT875 and CT147 distinguished women with acute infection from all other C. trachomatis-exposed women with a detection sensitivity of 63% (95% CI: 0.41–0.77) and specificity of 100% (95% CI: 0.95–1), respectively. Thus, CT875 and CT147 were designated as acute infection-associated antigens. Conclusion A sequential screening of antibodies against panels of C. trachomatis antigens can be used to identify women with tubal factor infertility and acute C. trachomatis infection. PMID:22525912

  13. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    PubMed Central

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette; Poulsen, Karin T.; Campbell, Fiona M.; Eckersall, P. David; Heegaard, Peter M.H.

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14–18 h after lung infection in pigs. The lung infection was established with the pig specific respiratory pathogen Actinobacillus pleuropneumoniae. Quantitative real-time PCR based expression analysis were performed on samples from liver, tracheobronchial lymph node, tonsils, spleen and on blood leukocytes, supplemented with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14–18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase protein response occurring concomitantly with the hepatic response. This suggests that the acute phase protein response is a more disseminated systemic response than previously thought. The current study provides to our knowledge the first example of porcine extrahepatic expression and regulation of C-reactive protein, haptoglobin, fibrinogen, pig major acute phase protein, and transferrin in peripheral lymphoid tissues. PMID:19236838

  14. Prevalence of dengue viral and malaria parasitic co-infections in an epidemic district, Angul of Odisha, India: An eco-epidemiological and cross-sectional study for the prospective aspects of public health.

    PubMed

    Rao, M Rajesh Kumar; Padhy, Rabindra N; Das, Manoj K

    2016-01-01

    The co-existence of dengue and malaria infection in an individual and the primary and secondary dengue infection during co-infection were assessed. Over 1 year, 1980 blood samples were collected from suspected cases of dengue fever and analyzed by rapid diagnostic test (RDT), enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods to detect dengue infection. RDT and microscopic methods were used to detect malaria. Of the 1980 samples, only 22 (3.0%) cases were identified as dengue-malaria co-infection cases, out of which 13 were male and 9 were female. The highest number of confirmed cases were found during the hot and humid months of September and October (7 cases, 31.8%) and within the over 15 years age group. Of the cases of co-infection, dengue primary infection (21 cases, 95.5%) was significantly more common than dengue secondary infection (1 case, 4.5%) among all of the age groups. There were 12 cases of Plasmodium falciparum and 10 cases of Plasmodium vivax infection among malarial cases. A high prevalence of concurrence of dengue and malaria infection was recorded in this ecosystem. In light of the severity of co-infection and overlapping symptoms, a multidimensional diagnostic approach is suggested. PMID:26653975

  15. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    PubMed

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. PMID:27434148

  16. A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

    PubMed Central

    2010-01-01

    Background Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. Methods During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. Results A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P

  17. Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series

    PubMed Central

    Panichsillapakit, Theppharit; Patel, Derek; Santangelo, Joanne; Richman, Douglas D.; Little, Susan J.; Smith, Davey M.

    2016-01-01

    Background. The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection. Methods. We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment. Results. Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20–54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis. Conclusions. To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract. PMID:26925432

  18. Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria

    PubMed Central

    Boyle, Michelle J.; Jagannathan, Prasanna; Farrington, Lila A.; Eccles-James, Ijeoma; Wamala, Samuel; McIntyre, Tara I; Vance, Hilary M.; Bowen, Katherine; Nankya, Felistas; Auma, Ann; Nalubega, Mayimuna; Sikyomu, Esther; Naluwu, Kate; Rek, John; Katureebe, Agaba; Bigira, Victor; Kapisi, James; Tappero, Jordan; Muhindo, Mary K; Greenhouse, Bryan; Arinaitwe, Emmanuel; Dorsey, Grant; Kamya, Moses R.; Feeney, Margaret E.

    2015-01-01

    FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations. PMID:26182204

  19. BOVINE VIRAL DIARRHEA VIRUS PERSISTENTLY INFECTED AND ACUTELY INFECTED CALVES: ASSAYS FOR VIRAL INFECTIVITY, POLYMERASE CHAIN REACTION ANALYSIS, AND ANTIGEN DETECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are numerous assays for bovine viral diarrhea virus (BVDV) detecting infectious virus, nucleic material, and antigen. Persistently infected (PI) and acutely/transiently infected calves with BVDV represent two different manifestations. Diagnostic test results impact on differentiation of PI o...

  20. Identification of malaria infected red blood samples by digital holographic quantitative phase microscope

    NASA Astrophysics Data System (ADS)

    Patel, Nimit R.; Chhaniwal, Vani K.; Javidi, Bahram; Anand, Arun

    2015-07-01

    Development of devices for automatic identification of diseases is desired especially in developing countries. In the case of malaria, even today the gold standard is the inspection of chemically treated blood smears through a microscope. This requires a trained technician/microscopist to identify the cells in the field of view, with which the labeling chemicals gets attached. Bright field microscopes provide only low contrast 2D images of red blood cells and cell thickness distribution cannot be obtained. Quantitative phase contrast microscopes can provide both intensity and phase profiles of the cells under study. The phase information can be used to determine thickness profile of the cell. Since cell morphology is available, many parameters pertaining to the 3D shape of the cell can be computed. These parameters in turn could be used to decide about the state of health of the cell leading to disease diagnosis. Here the investigations done on digital holographic microscope, which provides quantitative phase images, for comparison of parameters obtained from the 3D shape profile of objects leading to identification of diseased samples is described.

  1. Interactive cost of Plasmodium infection and insecticide resistance in the malaria vector Anopheles gambiae.

    PubMed

    Alout, Haoues; Dabiré, Roch K; Djogbénou, Luc S; Abate, Luc; Corbel, Vincent; Chandre, Fabrice; Cohuet, Anna

    2016-01-01

    Insecticide resistance raises concerns for the control of vector-borne diseases. However, its impact on parasite transmission could be diverse when considering the ecological interactions between vector and parasite. Thus we investigated the fitness cost associated with insecticide resistance and Plasmodium falciparum infection as well as their interactive cost on Anopheles gambiae survival and fecundity. In absence of infection, we observed a cost on fecundity associated with insecticide resistance. However, survival was higher for mosquito bearing the kdr mutation and equal for those with the ace-1(R) mutation compared to their insecticide susceptible counterparts. Interestingly, Plasmodium infection reduced survival only in the insecticide resistant strains but not in the susceptible one and infection was associated with an increase in fecundity independently of the strain considered. This study provides evidence for a survival cost associated with infection by Plasmodium parasite only in mosquito selected for insecticide resistance. This suggests that the selection of insecticide resistance mutation may have disturbed the interaction between parasites and vectors, resulting in increased cost of infection. Considering the fitness cost as well as other ecological aspects of this natural mosquito-parasite combination is important to predict the epidemiological impact of insecticide resistance. PMID:27432257

  2. Interactive cost of Plasmodium infection and insecticide resistance in the malaria vector Anopheles gambiae

    PubMed Central

    Alout, Haoues; Dabiré, Roch K.; Djogbénou, Luc S.; Abate, Luc; Corbel, Vincent; Chandre, Fabrice; Cohuet, Anna

    2016-01-01

    Insecticide resistance raises concerns for the control of vector-borne diseases. However, its impact on parasite transmission could be diverse when considering the ecological interactions between vector and parasite. Thus we investigated the fitness cost associated with insecticide resistance and Plasmodium falciparum infection as well as their interactive cost on Anopheles gambiae survival and fecundity. In absence of infection, we observed a cost on fecundity associated with insecticide resistance. However, survival was higher for mosquito bearing the kdr mutation and equal for those with the ace-1R mutation compared to their insecticide susceptible counterparts. Interestingly, Plasmodium infection reduced survival only in the insecticide resistant strains but not in the susceptible one and infection was associated with an increase in fecundity independently of the strain considered. This study provides evidence for a survival cost associated with infection by Plasmodium parasite only in mosquito selected for insecticide resistance. This suggests that the selection of insecticide resistance mutation may have disturbed the interaction between parasites and vectors, resulting in increased cost of infection. Considering the fitness cost as well as other ecological aspects of this natural mosquito-parasite combination is important to predict the epidemiological impact of insecticide resistance. PMID:27432257

  3. Explaining variance of avian malaria infection in the wild: the importance of host density, habitat, individual life-history and oxidative stress

    PubMed Central

    2013-01-01

    Background Avian malaria (Plasmodium sp.) is globally widespread, but considerable variation exists in infection (presence/absence) patterns at small spatial scales. This variation can be driven by variation in ecology, demography, and phenotypic characters, in particular those that influence the host’s resistance. Generation of reactive oxygen species (ROS) is one of the host’s initial immune responses to combat parasitic invasion. However, long-term ROS exposure can harm the host and the redox response therefore needs to be adjusted according to infection stage and host phenotype. Here we use experimental and correlational approaches to assess the relative importance of host density, habitat composition, individual level variation and redox physiology for Plasmodium infection in a wild population of great tits, Parus major. Results We found that 36% of the great tit population was infected with Plasmodium (22% P. relictum and 15% P. circumflexum prevalence) and that patterns of infection were Plasmodium species-specific. First, the infection of P. circumflexum was significantly higher in areas with experimental increased host density, whereas variation in P. relictum infection was mainly attributed to age, sex and reproduction. Second, great tit antioxidant responses – total and oxidizied glutathione - showed age- , sex- and Plasmodium species-specific patterns between infected and uninfected individuals, but reactive oxygen metabolites (ROM) showed only a weak explanatory power for patterns of P. relictum infection. Instead ROM significantly increased with Plasmodium parasitaemia. Conclusions These results identify some key factors that influence Plasmodium infection in wild birds, and provide a potential explanation for the underlying physiological basis of recently documented negative effects of chronic avian malaria on survival and reproductive success. PMID:23565726

  4. A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice.

    PubMed

    Moon, Deuk Kyu; Tripathi, Abhai; Sullivan, David; Siegler, Maxime A; Parkin, Sean; Posner, Gary H

    2011-05-01

    Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally. PMID:20952197

  5. High Rates of Asymptomatic, Sub-microscopic Plasmodium vivax Infection and Disappearing Plasmodium falciparum Malaria in an Area of Low Transmission in Solomon Islands

    PubMed Central

    Waltmann, Andreea; Darcy, Andrew W.; Harris, Ivor; Koepfli, Cristian; Lodo, John; Vahi, Ventis; Piziki, David; Shanks, G. Dennis; Barry, Alyssa E.; Whittaker, Maxine; Kazura, James W.; Mueller, Ivo

    2015-01-01

    Introduction Solomon Islands is intensifying national efforts to achieve malaria elimination. A long history of indoor spraying with residual insecticides, combined recently with distribution of long lasting insecticidal nets and artemether-lumefantrine therapy, has been implemented in Solomon Islands. The impact of these interventions on local endemicity of Plasmodium spp. is unknown. Methods In 2012, a cross-sectional survey of 3501 residents of all ages was conducted in Ngella, Central Islands Province, Solomon Islands. Prevalence of Plasmodium falciparum, P. vivax, P. ovale and P. malariae was assessed by quantitative PCR (qPCR) and light microscopy (LM). Presence of gametocytes was determined by reverse transcription quantitative PCR (RT-qPCR). Results By qPCR, 468 Plasmodium spp. infections were detected (prevalence = 13.4%; 463 P. vivax, five mixed P. falciparum/P. vivax, no P. ovale or P. malariae) versus 130 by LM (prevalence = 3.7%; 126 P. vivax, three P. falciparum and one P. falciparum/P. vivax). The prevalence of P. vivax infection varied significantly among villages (range 3.0–38.5%, p<0.001) and across age groups (5.3–25.9%, p<0.001). Of 468 P. vivax infections, 72.9% were sub-microscopic, 84.5% afebrile and 60.0% were both sub-microscopic and afebrile. Local residency, low education level of the household head and living in a household with at least one other P. vivax infected individual increased the risk of P. vivax infection. Overall, 23.5% of P. vivax infections had concurrent gametocytaemia. Of all P. vivax positive samples, 29.2% were polyclonal by MS16 and msp1F3 genotyping. All five P. falciparum infections were detected in residents of the same village, carried the same msp2 allele and four were positive for P. falciparum gametocytes. Conclusion P. vivax infection remains endemic in Ngella, with the majority of cases afebrile and below the detection limit of LM. P. falciparum has nearly disappeared, but the risk of re-introductions and

  6. Enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis in 7 dogs from Saskatchewan.

    PubMed

    Kjaergaard, Astrid B; Carr, Anthony P; Gaunt, M Casey

    2016-09-01

    Seven dogs diagnosed with enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis are described. Disease severity ranged from mild in adults to fatal disease in young dogs. Enteropathogenic E. coli infection should be considered as a possible differential diagnosis in dogs with diarrhea. PMID:27587889

  7. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  8. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.