Browsing by Author "Faculte de Medecine Pierre et Marie Curie"
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Publication Metadata only Case-control studies on host factors in severe malaria(2001-07-04) Mathieu Nacher; Pratap Singhasivanon; Frédérick Gay; Udomsak Silachamroon; Sornchai Looareesuwan; Faculte de Medecine Pierre et Marie Curie; Mahidol UniversityAlthough molecular biology has illustrated the phenotypic heterogeneity of Plasmodium falciparum, there are still no specific markers of virulence. As parasite virulence is an important determinant of severe malaria, the choice of comparison groups in the study of host factors influencing severity is a delicate issue. Ignoring parasite factors in the selection of controls potentially leads to biased comparisons between a majority of cases with virulent parasites and a majority of controls with non-virulent parasites. This article discusses how to avoid this virulence bias in the absence of specific markers of virulence.Publication Metadata only Effective and cheap removal of leukocytes and platelets from plasmodium vivax infected blood(2009-07-23) Kanlaya Sriprawat; Supaporn Kaewpongsri; Rossarin Suwanarusk; Mara L. Leimanis; Usa Lek-Uthai; Aung Pyae Phyo; Georges Snounou; Bruce Russell; Laurent Renia; François Nosten; Shoklo Malaria Research Unit; Agency for Science, Technology and Research, Singapore; Mahidol University; Hopital Pitie Salpetriere; Faculte de Medecine Pierre et Marie Curie; National University of Singapore, Faculty of Medicine; National University of Singapore; Nuffield Department of Clinical MedicineBackground. Investigations of Plasmodium vivax are restricted to samples collected from infected persons or primates, because this parasite cannot be maintained in in vitro cultures. Contamination of P. vivax isolates with host leukocytes and platelets is detrimental to a range of ex vivo and molecular investigations. Easy-to-produce CF11 cellulose filters have recently provided us with an inexpensive method for the removal of leukocytes and platelets. This contrasted with previous reports of unacceptably high levels of infected red blood cell (IRBC) retention by CF11. The aims of this study were to compare the ability of CF11 cellulose filters and the commercial filter Plasmodipur at removing leukocyte and platelet, and to investigate the retention of P. vivax IRBCs by CF11 cellulose filtration. Methods and Results. Side-by-side comparison of six leukocyte removal methods using blood samples from five healthy donor showed that CF11 filtration reduced the mean initial leukocyte counts from 9.4 × 103per μl [95%CI 5.213.5] to 0.01 × 103[95%CI 0.010.03]. The CF11 was particularly effective at removing neutrophils. CF11 treatment also reduced initial platelet counts from 211.6 × 103per μl[95%CI 107.5315.7] to 0.8 × 103per μl [95%CI -0.72.2]. Analysis of 30 P. vivax blood samples before and after CF11 filtration showed only a minor loss in parasitaemia ( ≤7.1% of initial counts). Stage specific retention of P. vivax IRBCs was not observed. Conclusion. CF11 filtration is the most cost and time efficient method for the production of leukocyte- and platelet-free P. vivax-infected erythrocytes from field isolates. © 2009 Sriprawat et al.; licensee BioMed Central Ltd.Publication Metadata only Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial(2010-11-01) Patrice Piola; Carolyn Nabasumba; Eleanor Turyakira; Mehul Dhorda; Niklas Lindegardh; Dan Nyehangane; Georges Snounou; Elizabeth A. Ashley; Rose McGready; Francois Nosten; Philippe J. Guerin; Epicentre; Epicentre; Mbarara University of Science and Technology; Mahidol University; Nuffield Department of Clinical Medicine; Inserm; Faculte de Medecine Pierre et Marie Curie; Imperial College Healthcare NHS Trust; Shoklo Malaria Research UnitBackground: Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on efficacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. Methods: We did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confirmed by PCR. The non-inferiority margin was a difference in cure rate of 5%. Analysis of efficacy was for all randomised patients without study deviations that could have affected the efficacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508. Findings: 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to follow-up and 25 were excluded from the analysis. At day 42, 137 (99·3%) of 138 patients taking artemether-lumefantrine and 122 (97·6%) of 125 taking quinine were cured-difference 1·7% (lower limit of 95% CI -0·9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group. Interpretation: Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy. Funding: Médecins Sans Frontières and the European Commission. © 2010 Elsevier Ltd.Publication Metadata only Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates(2012-03-05) Varakorn Kosaisavee; Usa Lek-Uthai; Rossarin Suwanarusk; Anne Charlotte Grüner; Bruce Russell; Francois Nosten; Laurent Rénia; Georges Snounou; Mahidol University; Agency for Science, Technology and Research, Singapore; Shoklo Malaria Research Unit; Center for Clinical Vaccinology and Tropical Medicine; Inserm; Faculte de Medecine Pierre et Marie CurieBackground: Plasmodium vivax merozoites specifically invade reticulocytes. Until recently, two reticulocyte-binding proteins (Pvrbp1 and Pvrbp2) expressed at the apical pole of the P. vivax merozoite were considered to be involved in reticulocyte recognition. The genome sequence recently obtained for the Salvador I (Sal-I) strain of P. vivax revealed additional genes in this family, and in particular Pvrbp2a, Pvrbp2b (Pvrbp2 has been renamed as Pvrbp2c) and two pseudogenes Pvrbp2d and Pvrbp3. It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1. The primary goal of this study was to ascertain the level of polymorphism of these new genes. Methodology/Princ ipal Findings: The sequence of the Pvrbp2a, Pvrbp2b, Pvrbp2d and Pvrbp3 genes were obtained by amplification/cloning using DNA purified from four isolates collected from patients that acquired the infection in the four cardinal regions of Thailand (west, north, south and east). An additional seven isolates from western Thailand were analyzed for gene copy number variation. There were significant polymorphisms exhibited by these genes (compared to the reference Sal-I strain) with the ratio of mutations leading to a non-synonymous or synonymous amino acid change close to 3:1 for Pvrbp2a and Pvrbp2b. Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c. It was interesting to note that variations in the copy number of Pvrbp2a and Pvrbp2b occurred in some isolates. Conclusions/Significance: The evolution of different members of the Pvrbp2 family and their relatively high degree of polymorphism suggests that the proteins encoded by these genes are important for parasite survival and are under immune selection. Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax. © 2012 Kosaisavee et al.Publication Metadata only Genetic marker suitable for identification and genotyping of Plasmodium Ovale Curtisi and Plasmodium Ovale Wallikeri(2013-12-01) Naowarat Tanomsing; Mallika Imwong; Colin J. Sutherland; Christiane Dolecek; Tran Tinh Hien; Francois Nosten; Nicholas P J Day; Nicholas J. White; Georges Snounou; Mahidol University; London School of Hygiene & Tropical Medicine; UCL; Churchill Hospital; Shoklo Malaria Research Unit; Inserm; Faculte de Medecine Pierre et Marie CurieWe present a seminested PCR method that specifically discriminates between Plasmodium ovale curtisi and P. ovale wallikeri with high sensitivity. The test is based on species-specific amplification of a size-polymorphic fragment of the tryptophan-rich antigen gene, potra, which also permits discrimination of intraspecific sequence variants at this locus. Copyright © 2013 Tanomsing et al. This is an open-Access article distributed.Publication Metadata only Microsatellite genotyping of Plasmodium vivax infections and their relapses in pregnant and non-pregnant patients on the Thai-Myanmar border(2013-08-09) Supinya Thanapongpichat; Rose McGready; Christine Luxemburger; Nicholas Pj Day; Nicholas J. White; Francois Nosten; Georges Snounou; Mallika Imwong; Mahidol University; Shoklo Malaria Research Unit; Churchill Hospital; Sanofi Pasteur SA; Inserm; Faculte de Medecine Pierre et Marie CurieBackground: Plasmodium vivax infections in pregnancy are associated with low birth weight and anaemia. This parasites species is also characterised by relapses, erythrocytic infections initiated by the activation of the dormant liver stages, the hypnozoites, to mature. Genotyping of P. vivax using microsatellite markers has opened the way to comparative investigations of parasite populations. The aim of the study was to assess whether there were any differences between the parasites found in pregnant and non-pregnant patients, and/or between the admission infections and recurrent episodes during follow-up. Methods. Blood samples were collected from 18 pregnant and 18 non-pregnant patients, who had at least two recurrent episodes during follow-up, that were recruited in two previous trials on the efficacy of chloroquine treatment of P. vivax infections on the Thai-Myanmar border. DNA was purified and the P. vivax populations genotyped with respect to eight polymorphic microsatellite markers. Analyses of the genetic diversity, multiplicity of infection (MOI), and a comparison of the genotypes in the samples from each patient were conducted. Results: The P. vivax parasites present in the samples exhibited high genetic diversity (6 to 15 distinct allelic variants found for the 8 loci). Similar expected heterozygosity (He) values were obtained for isolates from pregnant (0.837) and non-pregnant patients (0.852). There were modest differences between the MOI values calculated for both admission and recurrence samples from the pregnant patients (2.00 and 2.05, respectively) and the equivalent samples from the non-pregnant patients (1.67 and 1.64, respectively). Furthermore, the mean number of distinct alleles enumerated in the admission samples from the pregnant (6.88) and non-pregnant (7.63) patients were significantly lower than that found in the corresponding recurrent episodes samples (9.25 and 9.63, respectively). Conclusions: The P. vivax populations circulating in inhabitants along the Thai-Myanmar border, an area of low malaria transmission, displayed high genetic diversity. A subtle increase in the multiplicity of P. vivax infections in pregnant patients suggests a higher susceptibility to infection. The higher allelic diversity in the relapse as compared to the admission samples in both patient groups is consistent with the hypothesis that a febrile episode promotes the activation of hypnozoites. © 2013 Thanapongpichat et al.; licensee BioMed Central Ltd.Publication Metadata only Relationship between reactive nitrogen intermediates and total immunoglobulin E, soluble CD21 and soluble CD23: Comparison between cerebral malaria and nonsevere malaria(2002-11-26) Mathieu Nacher; Pratap Singhasivanon; Jaranit Kaewkungwal; Udomsak Silachamroon; Sombat Treeprasertsuk; Thanawat Tosukhowong; Suparp Vannaphan; Sornchai Looareesuwan; Faculte de Medecine Pierre et Marie Curie; Mahidol UniversityTo search for evidence of a protective role of the CD23/NO pathway against cerebral malaria, concentrations of reactive nitrogen intermediates (RNI) and sCD21, total immunoglobulin (Ig)E and sCD23 were compared between 17 cases of cerebral malaria and 33 controls. The geometric mean of sCD23 concentration was higher among cerebral malaria cases than among controls (optical density 2643/1495, P = 0.01). The ratio between sCD21 and sCD23 was significantly lower in cerebral malaria cases than in controls (0.67 ± 0.02 versus 0.77 ± 0.02, respectively, P = 0.009). Multiple linear regression analysis showed that, among cerebral malaria cases, there was a clear correlation between RNI and both IgE (P = 0.007) and sCD21 (P < 0.0001). Among controls, there was a strong negative correlation between RNI and sCD23 concentrations (r = -0.61, P < 0.0001). However, multivariate analysis unmasked the fact that, in controls, there was also a positive correlation between RNI and IgE (P = 0.045). Logistic regression showed that increased RNI concentrations were associated with a cerebral malaria adjusted odds ratio of 1.05 per unit increase [95% confidence interval (CI) 1.006-1.1, P = 0.02] and that an increased ratio between sCD21 and sCD23 was associated with protection from cerebral malaria (adjusted OR = 0.00001 per unit increase (95% CI 0-0.03, P = 0.005). These different immunological profiles suggest that, among controls, the CD23/NO pathway was chronically stimulated whereas, in cerebral malaria, its stimulation was acute, which could explain why some patients developed cerebral malaria and others did not.Publication Metadata only Socio-economic and environmental protective/risk factors for severe malaria in Thailand(2001-02-23) Mathieu Nacher; Pratap Singhasivanon; Suparp Vannaphan; Sombat Treeprasertsuk; Maninthorn Phanumaphorn; Boubacar Traore; Sornchai Looareesuwan; Frédérick Gay; Faculte de Medecine Pierre et Marie Curie; Mahidol UniversityWe conducted a cross-sectional study to identify the socio-economic and environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication, adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe malaria. Using stepwise logistic regression with all the variables inserted in the model yielded similar results. These findings suggest specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria. © 2001 Elsevier Science B.V.Publication Metadata only Two nonrecombining sympatric forms of the human malaria parasite plasmodium ovale occur globally(2010-05-15) Colin J. Sutherland; Naowarat Tanomsing; Debbie Nolder; Mary Oguike; Charlie Jennison; Sasithon Pukrittayakamee; Christiane Dolecek; Tran Tinh Hien; Virgilio E. Do Rosário; Ana Paula Arez; João Pinto; Pascal Michon; Ananias A. Escalante; Francois Nosten; Martina Burke; Rogan Lee; Marie Blaze; Thomas Dan Otto; John W. Barnwell; Arnab Pain; John Williams; Nicholas J. White; Nicholas P.J. Day; Georges Snounou; Peter J. Lockhart; Peter L. Chiodini; Mallika Imwong; Spencer D. Polley; Health Protection Agency; London School of Hygiene & Tropical Medicine; UCL; Churchill Hospital; Sanger Genome Centre; Mahidol University; Royal Institute; Shoklo Malaria Research Unit; University of Oxford; Universidade Nova de Lisboa, Instituto de Higiene e Medicina Tropical; Papua New Guinea Institute of Medical Research; Arizona State University; Centers for Disease Control and Prevention; Westmead Hospital; Inserm; Faculte de Medecine Pierre et Marie Curie; National University of Singapore; Massey UniversityBackground. Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. Methods. Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. Results. Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. Conclusions. We propose that P ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated. © 2010 by the Infectious Diseases Society of America. All rights reserved.Publication Metadata only Worms and malaria: Noisy nuisances and silent benefits(2002-11-20) Mathieu Nacher; Faculte de Medecine Pierre et Marie Curie; Mahidol UniversityThe burden of malaria mortality has been a major evolutionary influence on human immunity. The selection of the most successful immune responses against malaria has been in populations concomitantly infected by intestinal helminths. Animal models have shown that coinfections with helminths and protozoa in the same host elicit a range of antagonist and synergistic interactions. Recent findings suggest similar interactions take place between helminths, Plasmodium falciparum and humans. However, as the threat of HIV and tuberculosis becomes a major selective force, what used to be a successful ecological system may now prove detrimental. Nevertheless, the understanding of the ecological forces at play may expose new intervention targets for malaria control, and give a new perspective on our shortcomings against the deadliest of human parasites.