EPHAI

For numerous infectious diseases affecting humans, we observe a diversity of clinical manifestations caused by a given species of micro-organism, ranging from asymptomatic (without clinical manifestation) forms to severe pathologies. The originality of this project is to focus on asymptomatic carriers (animals or individuals who are infected with an infectious microorganism but display no symptoms). Indeed, it has been demonstrated that, for a great number of infectious diseases, healthy carriers represent a large part of human populations living in endemic areas. The fundamental interest of these asymptomatic subjects resides in the fact that they can be a reservoir of potentially pathogenic microorganisms and that they are a source of material to identify parasite factors involved in the observed clinical polymorphisms. However, to date, most studies on infectious diseases have focused on patients and on corresponding micro-organisms. This project is innovative since we will study parasitic factors from asymptomatic carriers and patients using the Leishmania model. These protozoan parasites are responsible of human leishmaniasis and can produce a wide spectrum of clinical manifestations. This includes Leishmania infantum, the species under study in this project. Indeed, this species is associated with benign cutaneous lesions as well as severe visceral disease, fatal without cure. Nevertheless, it is known that a large part of the reservoir population remains asymptomatic upon infection. The main goal of this project is to explore the role of asymptomatic carriers in an endemic Leishmania focus of the Southern of France (Nice region). In this frame, we will estimate the prevalence of asymptomatic carriers in L. infantum hosts, dogs (natural reservoirs) and humans; we will identify the circulating genotypes within these hosts and within the sandfly vectors (P. ariasi and P. perniciosus) and compare them with genotypes responsible for cutaneous and visceral leishmaniasis in this region. The second objective of this project is to explore the diversity of Leishmania parasites by investigating genetic polymorphisms and various biological characteristics (eg. behaviour within a laboratory maintained sandflies) of parasites isolated from patients and asymptomatic carriers (humans and dogs). Finally, this project will allow us (i) to better understand the contribution of asymptomatic carriers in leishmaniasis transmission and (ii) to improve our knowledge of the role of the parasite in pathogenesis by comparing genetic characters and experimental behaviours of Leishmania parasites in their vector sanflies.