Project 1: Human epidemiology in the context of the VL elimination initiative Project Summary Project 1 ?Human epidemiology in the context of the VL elimination initiative? seeks to provide essential epidemiological evidence in the context of the VL elimination initiative in Bihar State, India. The project combines epidemiological field work with laboratory work, all study designs are observational. There are 4 specific aims in the project, the first is to consolidate the TMRC-supported KAMRC as a center of excellence for surveillance and monitoring of L.donovani transmission and VL incidence. We plan to continue the registration of new VL cases and vital events that occur in the study population we have enrolled in the Health and Demographical Surveillance Site (HDSS) in Muzaffarpur district. In a subset of this HDSS population we will conduct a repeat sero-survey to allow us to compare the current prevalence of L. donovani infection with that in the 2007 survey, conducted in the early years of the VL elimination initiative. Other aims of Project 1 are (1) to use global metabolomic profiling to understand the role of asymptomatic individuals in transmission (cross reference to Project 2) and progression to disease, especially those that fall into different classes according to parasite load in the blood and/or ability to make antigen-specific antibody versus T cell responses, (2) to study co-infections with other neglected tropical diseases (NTDs) as a determinant for progression to VL, and opening up to a wider scope for understanding NTDs in the project area, and (3) to use gut metagenomics to determine the contribution of the gut microbiome, and the broader burden of gut pathogens, as risk factors for progression to clinical VL. The project is linked to transmission studies described in Project 2 andimmunological work described in Project 3, and is firmly rooted in the research infrastructure provided by the HDSS described as Scientific Core, which we have been gradually developing over the past ten years.