Use of Plasmodium falciparum culture-adapted field isolates for in vitro exflagellation-blocking assay

International audienceA major requirement for malaria elimination is the development of transmission-blocking interventions. In vitro transmission-blocking bioassays currently mostly rely on the use of very few Plasmodium falciparum reference laboratory strains isolated decades ago. To fill a piece of the gap between laboratory experimental models and natural systems, the purpose of this work was to determine if culture-adapted field isolates of P. falciparum are suitable for in vitro transmission-blocking bioassays targeting functional maturity of male gametocytes: exflagellation. Plasmodium falciparum isolates were adapted to in vitro culture before being used for in vitro gametocyte production. Maturation was assessed by microscopic observation of gametocyte morphology over time of culture and the functional viability of male gametocytes was assessed by microscopic counting of exflagellating gametocytes. Suitability for in vitro exflagellation-blocking bioassays was determined using dihydroartemisinin and methylene blue. In vitro gametocyte production was achieved using two isolates from French Guiana and two isolates from Cambodia. Functional maturity of male gametocytes was assessed by exflagellation observations and all four isolates could be used in exflagellation-blocking bioassays with adequate response to methylene blue and dihydroartemisinin. This work shows that in vitro culture-adapted P. falciparum field isolates of different genetic background, from South America and Southeast Asia, can successfully be used for bioassays targeting the male gametocyte to gamete transition, exflagellation

Drug Resistance in Eukaryotic Microorganisms

Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies

Predictors of antimalarial self-medication in illegal gold miners in French Guiana: a pathway towards artemisinin resistance.

International audienceBackground:Malaria is endemic in French Guiana (FG), South America. Despite the decrease in cases in the local population, illegal gold miners are very affected by malaria (22.3% of them carried Plasmodium spp.). Self-medication seems to be very common, but its modalities and associated factors have not been studied. The aim of this study was to evaluate parasite susceptibility to drugs and to document behaviours that could contribute to resistance selection in illegal gold miners.Methods:This multicentric cross-sectional study was conducted in resting sites along the FG-Surinamese border. Participating gold miners working in FG completed a questionnaire and provided a blood sample.Results:From January to June 2015, 421 illegal gold miners were included. Most were Brazilian (93.8%) and 70.5% were male. During the most recent malaria attack, 45.5% reported having been tested for malaria and 52.4% self-medicated, mainly with artemisinin derivatives (90%). Being in FG during the last malaria attack was the main factor associated with self-medication (adjusted OR = 22.1). This suggests that access to malaria diagnosis in FG is particularly difficult for Brazilian illegal gold miners. Treatment adherence was better for persons who reported being tested. None of the 32 samples with Plasmodium falciparum presented any mutation on the pfK13 gene, but one isolate showed a resistance profile to artemisinin derivatives in vitro.Conclusions:The risk factors for the selection of resistance are well known and this study showed that they are present in FG with persons who self-medicated with poor adherence. Interventions should be implemented among this specific population to avoid the emergence of artemisinin resistance

heterogeneous distribution of Plasmodium vivax and falciparum carriage on the border area between Brazil and French Guiana

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Portage asymptomatique de plasmodies dans le quartier Blondin de Saint-Georges-de-l’Oyapock, Guyane

International audienceOptimized elimination strategies are needed to control transmission of malaria. As part of an elimination campaign, active detection of asymptomatic Plasmodium carriers by highly sensitive methods is deemed necessary. Asymptomatic carriage leads to complex scientific, ethical, and operational issues regarding individual or collective detection and treatment. To address this issue, a crosssectional study was carried out in French Guiana to determine the prevalence of asymptomatic Plasmodium carriage during an inter-epidemic season in the whole population of a neighborhood of Saint-Georges-de-l’Oyapock, along the Brazilian border. Fifty-eight participants out of 63 residents were screened. The median age was 23.3 years (range: 2 months–72 years), with a male/female sex-ratio of 0.56. The majority of the participants (74%, N = 43/58) reported a history of malaria, 12% (N = 7/58) during the past 12 months. All rapid diagnostic tests for malaria were negative. Among the 58 participants, malaria prevalence detected by nested-PCR (Polymerase Chain Reaction) was 3.6% (N = 2/56). Two asymptomatic carriers of Plasmodium were identified: one child with Plasmodium vivax and one adult with Plasmodium falciparum. These two carriers were treated and did not develop malaria within the eight months following the diagnosis. This study confirmed the presence of asymptomatic parasitaemias outside hyperendemic areas. However, the benefits of such an active detection and patient treatment to eliminate malaria in French Guiana need to be evaluated at a larger scale.Une fois la transmission du paludisme contrôlée, les stratégies d'élimination s'imposent. Ces dernières ciblent tout particulièrement les porteurs asymptomatiques de plasmodies. Ces parasitémies asymptomatiques posent des questions scientifiques, éthiques et opérationnelles complexes en termes de détection et d'intérêt individuel et collectif de proposer un traitement. Afin de préciser la part jouée par ces porteurs asymptomatiques en Guyane dans la transmission, il est nécessaire de connaître leur prévalence. Nous avons réalisé une étude transversale, en période interépidémique, en population générale, dans un quartier de la commune de Saint-Georges-de-l'Oyapock, à la frontière brésilienne, caractérisé par une transmission régulière endémoépidémique de paludisme dit autochtone. Cinquante-huit des 63 habitants du quartier ont été inclus. La moyenne d'âge était de 23,3 ans (min–max : 2 mois-72 ans) et le sex-ratio homme/femme de 0,56. Soixante-quatorze pour cent (n = 43/58) de la population d'étude déclaraient au moins un antécédent palustre au cours de leur vie, dont 12 % (n = 7/58) au cours de l'année précé-dente. Tous les tests de diagnostic rapide du paludisme (n = 58/58) étaient négatifs. La Polymerase Chain Reaction (PCR) a permis d'identifier deux porteurs asymptoma-tiques : un enfant porteur de Plasmodium vivax et un adulte porteur de Plasmodium falciparum. Cela représentait une prévalence totale de 3,6 % (n = 2/56). Ces deux patients ont été traités comme pour un accès symptomatique et n'ont pas développé d'accès palustre symptomatique dans les huit mois qui ont suivi. Cette étude montre que le por-tage asymptomatique de plasmodies existe en dehors des zones hyperendémiques. L'efficacité de cette stratégie de dépistage et de traitement dans un but d'élimination du paludisme en Guyane reste cependant à objectiver au tra-vers d'une étude à plus large échelle

Imaging exhumed lower continental crust in the distal Jequitinhonha basin, Brazil

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