The Terai region of Nepal is endemic for visceral leishmaniasis (VL), a protozoal infection caused by the parasites of the Leishmania donovani complex and L tropica. The goals of this project are to (i) advance research for safe, easily administered, and cost-effective screening and diagnostic techniques for human infection with L. donovani, (ii) investigate the prevalence of and potential contribution asymptomatic and sub-clinical cases may have as parasite reservoffs in the transmission dynamics of L. donovani, and (iii) investigate the impact of malnutrition on the progression to active VL disease. We plan to implement our study in the Salempur District of Nepal. For this district, the prevalence of sero-positivity for anti-L donovani antibodies is estimated to be 7.5 percent, and the ratio of active cases to asymptomatic and sub-clinical cases to be 1:6. The target sample size is 5000, and all consenting persons >3 years of age will be screened. Through the use of a specially designed questionnaire, potential risk factors for infection with L donovani and the impact of malnutrition on progression to active VL disease will be studied. In addition, the applicability of the Dot-Direct Agglutination Test, recombinant K39 dipstick, and the Polymerase Chain Reaction diagnostic techniques will be tested in the field, and their correlation in the identification of individuals seropositive for anti-L. donovani antibodies will be compared. Household clustering of sero-positive individuals with and without active VL cases will be analyzed in the attempt to establish the potential contribution that asymptomatic and sub-clinical cases have on parasite transmission via the primary vector Phiebotomus argentipes. The L donovani transmission dynamics between the human host and Plebotomus sandfly vector are not well understood in this region, but are important as the transmission of L. donovan/is anthroponotic. Ideally, these data will serve to aid in the development of future interventions for the control of visceral leishmaniasis and its negative socio-economic impact in an already impoverished and resource constrained area.