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Objective Using human IgG antibody response to the Aedes Nterm-34 kDa salivary peptide as an indicator of human exposure to Aedes bites in surveying exposed populations from areas at risk of dengue virus (DENV) transmission in urban settings of Vientiane city, Lao PDR. Methods Enzyme-linked immunosorbent assay tests were performed to measure the IgG response to Nterm-34 kDa peptide in blood samples collected within a flavivirus seroprevalence survey carried out in 2006 including 3558 randomly selected individuals. The level of IgG response to the Nterm-34 kDa peptide in individuals was analysed in relation to the level of urbanisation of the individual's residence, areas that presented significant differences in the prevalence of recent DENV infection. Results No differences were observed in the anti-Nterm-34 kDa IgG level between DENV-positive and DENV-negative individuals. However, the level of specific IgG response was higher among individuals living in slightly urbanised neighbourhoods than among those in more highly urbanised areas (P

Study of the human antibody (Ab) response to Aedes salivary proteins can provide new biomarkers to evaluate human exposure to vector bites. The identification of genus- and/or species-specific proteins is necessary to improve the accuracy of biomarkers. We analysed Aedes albopictus immunogenic salivary proteins by 2D immunoproteomic technology and compared the profiles according to human individual exposure to Ae. albopictus or Ae. aegypti bites. Strong antigenicity to Ae. albopictus salivary proteins was detected in all individuals whatever the nature of Aedes exposure. Amongst these antigenic proteins, 68% are involved in blood feeding, including D7 protein family, adenosine deaminase, serpin and apyrase. This study provides an insight into the repertoire of Ae. albopictus immunogenic salivary proteins for the first time.

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. Premiere tentative de validation du peptide salivaire gSG6-P1 comme un outil immuno-epidemiologique d’evaluation de l’exposition humaine aux piqures de An. funestus Objectif: Valider le peptide gSG6-P1 comme un outil epidemiologique evaluant l’exposition aux piqures de An. funestus, le second principal vecteur de la malaria en Afrique subsaharienne. Methodes: Etude multidisciplinaire dans un village senegalais ouAn. funestus est la principale espece d’anophele. Le taux d’anticorps IgG specifiques a gSG6-P1 a eteevalue et compare chez les memes enfants avant, durant le pic et a la fin de la saison des pluies. Resultats: Deux tiers des enfants ont developpe une reponse IgG specifique a gSG6-P1 durant la periode etudiee et - plus interessant - avant la saison des pluies, quand An. funestus etait la seule espece d’anophele signalee. La reponse IgG specifique augmentait au cours de saison d’exposition a l’An. funestus et une association positive entre le taux d’IgG et le niveau d’exposition aux piqures de An. funestus a ete observee. Conclusions: Les resultats suggerent que l’evaluation de la reponse IgG specifique a gSG6-P1 chez les enfants pourrait egalement representer un biomarqueur de l’exposition aux piqures de An. funestus. La disponibilite d’un tel biomarqueurs evaluant l’exposition aux deux principaux vecteurs de P. falciparum en Afrique pourrait etre particulierement pertinente en tant que critere pour l’evaluation directe de l’efficacite des strategies de lutte antivectorielle. Primer ensayo para validar el peptido salivar gSG6-P1 como herramienta inmuno-epidemiologica que evalue la exposicion humana frente a picaduras de An. funestus Objetivo: Validar el peptido gSG6-P1 como herramienta epidemiologica que evalue la exposicion a picaduras de An. funestus, el segundo vector de malaria mas importante en Africa sub-Sahariana. Metodos: Estudio multidisciplinar, en un poblado senegales en donde An. funestus es la principal especie anofelina. Los niveles de anticuerpos IgG especificos para gSG6-P1 se evaluaron y compararon en los mismos ninos antes, durante el pico y despues de la estacion de lluvias. Resultados: Dos tercios de los ninos desarrollaron una IgG especifica para gSG6-P1 durante el periodo de estudio y – mas interesante aun – antes de la epoca lluviosa, cuando An. funestus era la unica especie anofelina reportada. La respuesta IgG especifica aumento durante el periodo de exposicion a An. funestus y se observo una asociacion positiva entre el nivel de IgG y el nivel de exposicion a picaduras de An. funestus. Conclusiones: Los resultados sugieren que la evaluacion de la respuesta IgG especifica para gSG6-P1 en ninos tambien podria utilizarse como un biomarcador de exposicion a picaduras de An. funestus. La disponibilidad de un biomarcador que evalua la exposicion a los dos principales vectores de P. falciparum en Africa podria ser particularmente relevante como un criterio directo para la evaluacion de la eficacia de estrategias de control vectorial.

Malaria and schistosomiasis are the two major parasite diseases present in developing countries. The epidemiological co-infection with schistosomiasis could influence the development of the physiological reaction associated with Plasmodium falciparum infection in human. Most studies have demonstrated the association of circulating levels of interferon-gamma (IFN-gamma), tumour necrosis factor-a (TNF-alpha), interleukin-10 (IL-10), transforming growth factor (TGF-beta) and soluble Tumour Necrosis Factor Receptors (sTNF-RI and sTNF-RII) with the morbidity of malaria. In the present study, we showed that Schistosoma haematobium co-infection influences, in an age-dependent manner, the unbalance between pro- and anti-inflammatory circulating cytokines that play a key role during malaria infection. Indeed, children co-infected by S. haematobium have higher levels of IFN-gamma and sTNF-RII than children infected only by P. falciparum. In contrast, co-infected adults presented a significant increase of IFN-gamma, IL-10, TGF-beta, sTNF-RI and sTNF-RII rates and IL-10/TNF-alpha ratio. Taken together, this study indicates that schistosomiasis co-infection can unbalance the regulation of inflammatory factors in uncomplicated P. falciparum malaria. The possible consequences of the schistosomiasis co-infection for age-dependent malaria morbidity are discussed.

A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).