Differential acquisition of human antibody responses to Plasmodium falciparum according to intensity of exposure to Anopheles bites.

Malaria immunity is modulated by many environmental and epidemiological factors. This study evaluates the influence of a hitherto unstudied environmental-epidemiological factor, namely the impact of human exposure to Anopheles bites on the isotype profile of acquired antibody responses to Plasmodium falciparum. In two Senegalese villages where the intensity of exposure to Anopheles bites was markedly different (high and low exposure), specific IgG1 and IgG3 responses to P. falciparum whole schizont extract (WSE) and circumsporozoite protein (CSP) were evaluated at the peak of Anopheles exposure (September) and later (December) in a cohort of 120 children aged 3-8 years. Multivariate analysis showed a significantly lower IgG1 response against P. falciparum WSE and CSP in children highly exposed to Anopheles bites (Gankette) compared to those who were weakly exposed (Mboula). In contrast, in both villages, parasitemia and increasing age were strongly associated with higher IgG1 and IgG3 levels. We hypothesize that high exposure to Anopheles bites could inhibit IgG1-dependent responsiveness to P. falciparum known to induce protective immune responses against malaria. The impact of mosquito saliva on the regulation of specific protective immunity may need to be taken into account in epidemiological studies and trials for malaria vaccines.

Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays.

BACKGROUND: The evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years. RESULTS: Compared to other antigens, a high percentage of seropositivity and specific antibody levels were detected with Glurp, Salsa1, Lsa3NR2, and Lsa1J antigens. The seropositivity increased with age for all tested antigens. Specific IgG levels to Glurp, Salsa1, Lsa3NR2, and Lsa1J were significantly higher in P. falciparum infected children compared to non-infected and this increase is significantly correlated with parasite density. CONCLUSION: The multiplex assay represents a useful technology for a serological assessment of rapid variations in malaria transmission intensity, especially in a context of low parasite rates. The use of such combined serological markers (i.e. Glurp, Lsa1, Lsa3, and Salsa) could offer the opportunity to examine these variations over time, and to evaluate the efficacy of integrated malaria control strategies.

Immunoglobulin G antibody profiles against Anopheles salivary proteins in domestic animals in Senegal.

Although domestic animals may not be permissive for Plasmodium, they could nevertheless play a role in the epidemiology of malaria by attracting Anopheles away from humans. To investigate interactions between domestic animals and mosquitoes, we assayed immunoglobulin G (IgG) antibodies directed against the salivary proteins of Anopheles gambiae in domestic animals living in Senegalese villages where malaria is endemic. By Western blotting, sera from bovines (n=6), ovines (n=36), and caprines (n=36) did not react with Anopheles whole saliva. In contrast, equine sera recognized proteins in both saliva and salivary gland extracts. Two of the major immunogens (32 and 72 kDa) were also reactive in extracts from other major mosquito genera (Aedes and Culex), but reactions toAnopheles-specific antigens were detected in 12 of 17 horses. These data suggest that horses strongly react to Anopheles bites, and further experiments on horses are warranted to investigate the impact of this domestic animal species on the transmission of human malaria.

First attempt to validate the gSG6-P1 salivary peptide as an immuno-epidemiological tool for evaluating human exposure to Anopheles funestus bites.

SUMMARY OBJECTIVE: The development of a biomarker of exposure based on the evaluation of the human antibody response specific to Anopheles salivary proteins seems promising in improving malaria control. The IgG response specific to the gSG6-P1 peptide has already been validated as a biomarker of An. gambiae exposure. This study represents a first attempt to validate the gSG6-P1 peptide as an epidemiological tool evaluating exposure to An. funestus bites, the second main malaria vector in sub-Saharan Africa. METHODS: A multi-disciplinary survey was performed in a Senegalese village where An. funestus represents the principal anopheline species. The IgG antibody level specific to gSG6-P1 was evaluated and compared in the same children before, at the peak and after the rainy season. RESULTS: Two-thirds of the children developed a specific IgG response to gSG6-P1 during the study period and--more interestingly--before the rainy season, when An. funestus was the only anopheline species reported. The specific IgG response increased during the An. funestus exposure season, and a positive association between the IgG level and the level of exposure to An. funestus bites was observed. CONCLUSIONS: The results suggest that the evaluation of the IgG response specific to gSG6-P1 in children could also represent a biomarker of exposure to An. funestus bites. The availability of such a biomarker evaluating the exposure to both main Plasmodium falciparum vectors in Africa could be particularly relevant as a direct criterion for the evaluation of the efficacy of vector control strategies.

[Survey of diarrhoea survey in Kosovo Mitrovica. August 2001]. / Etude sur les diarrhées à Mitrovicè (Kosovo) en août 2001.

The upsurge of diarrhoea observed in children in Kosovo Mitrovica in the spring of 2001 led to a survey, jointly organized by the city health department, the GISPE association and the medical laboratory at the Val de Grâce Hospital (France). The available retrospective data showed an increase in cases of diarrhoea in which Giardia duodenalis was isolated. During the third week of August 2001, all children with diarrhoea consulting in the hospital south of city (n = 45) had a complete stool analysis. The analyses showed the presence of Giardia cysts and trophozoites in 40% of the cases, and no cases with helminthes or cryptosporidia. Moreover 3 strains of S. sonnei, a microorganism never previously identified, and different pathovars of E. coli in 11 patients were isolated. This "epidemic" appeared to be linked to the poor hygiene conditions that still prevailed 2 years after the events but not directly to the water supply, which was rehabilitated at the end of 1999. It is also necessary to strengthen the capacity of the public laboratories and health-care facilities of the province.

Bionomics of malaria vectors and relationship with malaria transmission and epidemiology in three physiographic zones in the Senegal River Basin.

Following the implementation of two dams in the Senegal River, entomological and parasitological studies were conducted in three different ecological zones in the Senegal River Basin (the low valley of Senegal River, the Guiers Lake area and the low valley of Ferlo) every 3 month in June 2004, September 2004, December 2004 and March 2005. The objective of this work was to study the influence of environmental heterogeneities on vector bionomics and malaria epidemiology. Mosquitoes were collected when landing on human volunteers and by pyrethrum spray catches. In the parasitological survey, blood samples were taken from a cohort of schoolchildren under 9 years during each entomology survey. Seven anopheline species were collected: Anopheles arabiensis, Anopheles gambiae M form, Anopheles funestus, Anopheles pharoensis, Anopheles coustani, Anopheles wellcomei and Anopheles rufipes. A. arabiensis, A. funestus and A. pharoensis were predominant in the low valley of the Senegal River, A. funestus in the Guiers Lake area and A. arabiensis in the low valley of Ferlo. Mosquito populations' dynamics varied temporally depending on the rainy season for each zone. The anthropophilic rates varied between 6 and 76% for A. gambiae s.l. and 23 and 80% for A. funestus. Only 4/396 A. pharoensis and 1/3076 A. funestus tested carried Plasmodium falciparum CS antigen. These results suggest the implication of A. pharoensis in malaria transmission. The related entomological inoculation rates were estimated to 10.44 in Mbilor and 3 infected bites in Gankette Balla and were due, respectively, to A. pharoensis and A. funestus. Overall, 1636 thick blood smears were tested from blood samples taken from schoolchildren with, respectively, a parasite and gametocyte average prevalence of 9 and 0.9%. The parasite prevalence was uniformly low in Mbilor and Gankette Balla whereas; it increased in September (16%) and then remained stable in December and March (22%) in Mboula where malaria transmission was not perceptible. However, significant differences were observed over time for parasite prevalence in Mbilor and Mboula villages whereas; it was only in Gankette Balla village where gametocyte prevalence was significantly different over time. Our study demonstrates the influence of ecological changes resulted from dams implementation in the Senegal River on the composition of vectorial system, malaria transmission and epidemiology. Such changes should be thoroughly surveyed in order to prevent any possible malaria outbreak in the Senegal River Basin.