Abstract
Africa is often called the "heart" of malaria due to the impact of this disease on the continent. Over the past decade, evidences indicate that malaria burden around the world, including in most African countries, is declining. These changes are linked to major advances in prevention, diagnosis and treatment of malaria, linked to a massive increase of investment in the fight against malaria. Consequently, traditional entomological (Entomological Inoculation Rate, EIR) and parasitological (microscopy, Rapid Diagnostic Tests) methods used to estimate the risk of infection/transmission are becoming difficult and insensitive. News effective, sensitive and reliable monitoring tools are therefore needed to sustain control efforts and ensure malaria elimination. By an immuno-epidemiological approach and by using immunological properties of salivary proteins of Anopheles, a peptide was identified and validated as a biomarker to assess the risk of human exposure to Anopheles bites. This thesis is a contribution to the optimization of this biomarker as a tool for malaria surveillance and intends to evaluate its applications in low exposure/transmission settings,such as malaria pre-elimination areas.First, we demonstrated that the IgG antibody response to the An. gambiae gSG6-P1 salivary peptide is a sensitive and relevant tool for distinguishing a micro-geographical heterogeneity of human exposure to Anopheles bites in an overall context of low exposure. Subsequently, by associating anti-gSG6-P1 IgG responses with parasitological and clinical, we have shown that the biomarker of exposure to Anopheles bites could detect a risk of P. falciparum infection during the dry season which is generally free of malaria, and discriminate uninfected children from asymptomatic carriers of the parasite. Finally, by combining immunological biomarkers of human exposure to the Anopheles vectors and to the parasites, we have shown that this serological method could be a sensitive and reliable tool for identifying individuals that have been bitten by infectious Anopheles, so likely to be infected and develop malaria illness.Taken together, these results support the use of salivary biomarker as a new tool for malaria surveillance, especially in areas where malaria is low and seasonal