Les aspects parasitologiques de l'épidémiologie du paludisme dans le Sahara malien

Dans le cadre de l'évaluation épidémiologique de la Transsaharienne, une enquête transversale paludométrique a été réalisée d'Août 1988 à Septembre 1988 le long du tronçon malien. Neuf localités ont été visitées : Douentza, Gossi, Bourem, Almoustarat, Anefis, Aguel-Hoc, Tarlit, Tessalit, Kidal, Bouressa. 2185 unités ont été prélevées pour les études cliniques, parasitologiques et immunologiques. L'indice plasmodique global est de 5,3 % avec une grande variation du Sud (44,6 %) au Nord (0 %). L'indice gamétocytique et l'indice splénique sont très faibles. #P. falciparum est l'espèce dominante. #P. malariae a été décrit une fois en association avec #P. falciparum. #P. ovale n'a jamais été observé. Par contre un cas de #P. vivax a été décrit chez une jeune fille leucoderme de 8 ans à Kidal. #A. gambiae s.s. (forme Mopti) et #A. arabiensis sont les principaux vecteurs au Nord du Mali. Une hypothèse de circulation de #P. vivax dans le Sahara malien est émise. (Résumé d'auteur

Exposure-Dependent Control of Malaria-Induced Inflammation in Children

In malaria-naïve individuals, Plasmodium falciparum infection results in high levels of parasite-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, individuals in endemic areas who are repeatedly infected are often asymptomatic and have low levels of iRBCs, even young children. We hypothesized that febrile malaria alters the immune system such that P. falciparum re-exposure results in reduced production of pro-inflammatory cytokines/chemokines and enhanced anti-parasite effector responses compared to responses induced before malaria. To test this hypothesis we used a systems biology approach to analyze PBMCs sampled from healthy children before the six-month malaria season and the same children seven days after treatment of their first febrile malaria episode of the ensuing season. PBMCs were stimulated with iRBC in vitro and various immune parameters were measured. Before the malaria season, children's immune cells responded to iRBCs by producing pro-inflammatory mediators such as IL-1β, IL-6 and IL-8. Following malaria there was a marked shift in the response to iRBCs with the same children's immune cells producing lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines (IL-10, TGF-β). In addition, molecules involved in phagocytosis and activation of adaptive immunity were upregulated after malaria as compared to before. This shift was accompanied by an increase in P. falciparum-specific CD4+Foxp3- T cells that co-produce IL-10, IFN-γ and TNF; however, after the subsequent six-month dry season, a period of markedly reduced malaria transmission, P. falciparum-inducible IL-10 production remained partially upregulated only in children with persistent asymptomatic infections. These findings suggest that in the face of P. falciparum re-exposure, children acquire exposure-dependent P. falciparum-specific immunoregulatory responses that dampen pathogenic inflammation while enhancing anti-parasite effector mechanisms. These data provide mechanistic insight into the observation that P. falciparum-infected children in endemic areas are often afebrile and tend to control parasite replication

Impact of Acute Malaria on Pre-Existing Antibodies to Viral and Vaccine Antigens in Mice and Humans

Vaccine-induced immunity depends on long-lived plasma cells (LLPCs) that maintain antibody levels. A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies--raising concerns that malaria may compromise pre-existing vaccine responses. We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge. We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B) before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season. On average, vaccine-specific IgG did not decrease following acute malaria. However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies

Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection

Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission

SummaryGlycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated the expression of the Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for the production of anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86:B7 express α-gal and that anti-α-gal Abs are associated with protection against malaria transmission in humans as well as in α1,3GT-deficient mice, which produce protective anti-α-gal Abs when colonized by E. coli O86:B7. Anti-α-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against α-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans.PaperFlic

The Influence of Physiological Status on age Prediction of Anopheles Arabiensis Using Near Infra-red spectroscopy

Determining the age of malaria vectors is essential for evaluating the impact of interventions that reduce the survival of wild mosquito populations and for estimating changes in vectorial capacity. Near infra-red spectroscopy (NIRS) is a simple and non-destructive method that has been used to determine the age and species of Anopheles gambiae s.l. by analyzing differences in absorption spectra. The spectra are affected by biochemical changes that occur during the life of a mosquito and could be influenced by senescence and also the life history of the mosquito, i.e., mating, blood feeding and egg-laying events. To better understand these changes, we evaluated the influence of mosquito physiological status on NIR energy absorption spectra. Mosquitoes were kept in individual cups to permit record keeping of each individual insect’s life history. Mosquitoes of the same chronological age, but at different physiological stages, were scanned and compared using cross-validations. We observed a slight trend within some physiological stages that suggest older insects tend to be predicted as being physiologically more mature. It was advantageous to include mosquitoes of different chronological ages and physiological stages in calibrations, as it increases the robustness of the model resulting in better age predictions. Progression through different physiological statuses of An. arabiensis influences the chronological age prediction by the NIRS. Entomologists that wish to use NIR technology to predict the age of field-caught An. gambiae s.l from their study area should use a calibration developed from their field strain using mosquitoes of diverse chronological ages and physiological stages to increase the robustness and accuracy of the predictions.\u

Different Plasmodium falciparum clearance times in two Malian villages following artesunate monotherapy.

BACKGROUND: Artemisinin resistance described as increased parasite clearance time (PCT) is rare in Africa. More sensitive methods such as qPCR might better characterize the clearance phenotype in sub-Saharan Africa. METHODS: PCT is explored in Mali using light microscopy and qPCR after artesunate for uncomplicated malaria. In two villages, patients were followed for 28 days. Blood smears and spots were collected respectively for microscopy and qPCR. Parasitemia slope half-life was calculated after microscopy. Patient residual parasitemia were measured by qPCR. RESULTS: Uncorrected adequate clinical and parasitological responses (ACPR) observed in Faladje and Bougoula-Hameau were 78% and 92%, respectively (p=0.01). This reached 100% for both after molecular correction. Proportions of 24H microscopy positive patients in Faladje and Bougoula-Hameau were 97.2% and 72%, respectively (p<0.0001). Slope half-life was 2.8h in Faladje vs 2H in Bougoula-Hameau (p<0.001) and Proportions of 72H patients with residual parasitemia were 68.5% and 40% in Faladje and Bougoula-Hameau, respectively (p=0.003). The mean residual parasitemia was 2.9 in Faladje vs. 0.008 in Bougoula-Hameau (p=0.002). Although artesunate is efficacious in Mali, the longer parasite clearance time with submicroscopic parasitemia observed may represent early signs of developing P. falciparum resistance to artemisinins