Active Surveillance for Cutaneous Leishmaniasis in Mali

The overarching aim of the research program is to develop a vaccine against cutaneous leishmaniasis (CL) based on sandfly salivary proteins (SFSPs). In order to determine whether vaccination with SFSPs can reduce the subsequent incidence of Leishmania major infections or CL in humans, it is first necessary to establish baseline rates of parasite infection and disease. We have selected two rural villages in central Mali where we have readily observed CL lesions in individuals of all ages and large numbers of sandflies that are known to transmit L. major in West Africa. The main objectives of this study are to estimate a cross-sectional prevalence of L. major exposure; to determine the prevalence of CL; to determine an annual incidence rate of L. major infection; and to determine whether robust in vitro T and B cell responses to SFSPs correlate with protection against newly acquired L. major infection or CL. To meet these objectives, a standard leishmanin skin test (LST) will be administered to all residents of two Malian villages in order to identify a cohort of subjects who are at risk for newly acquired L. major. After the sandfly biting and disease transmission seasons, all subjects will be examined for the development of CL lesions every month for 5 months total. CL lesions will be treated topically with paromomycin- methylbenzethonium chloride ointment twice daily for 20 days. Response to therapy will be documented on days 28 and 42 of the protocol. After allowing adequate time for the development of delayed-type hypersensitivity responses to parasite antigens, LSTs will be re-administered to all subjects. Conversion from a negative to positive LST will be taken as evidence of newly acquired L. major infection. LST conversion data and clinical diagnosis of CL lesions will allow us to calculate both the incidence of new L. major infections and CL in our study population. In vitro T and B cell responses to SFSPs will be measured from a subset of individuals and correlated with relative resistance to both L. major infection and the development of clinically apparent lesions.