Leptospirosis, a zoonotic disease transmitted by rats, is an important health problem in slum settlements. Large epidemics occur during periods of rainfall which are associated with life-threatening manifestations such as pulmonary haemorrhage syndrome (LPHS), for which case fatality is >50%. No efficient interventions are available. An interdisciplinary evaluation of the reservoir host, pathogen and environmental determinants of urban poverty is proposed needed to understand intensity of lep tospirosis epidemics and disease progression. We aim to determine the contribution of environmental and host and pathogen genetic factors in influencing (spatio-temporal) variation in rates of leptospire shedding and their relation with leptospirosis transmission and LPHS. We will carry out field studies on the demographics and genetics of Norway rats, coupled with quantification, isolation and sequencing of leptospires from rats. Leptospire shedding variations and its determinants will be li nk to variations in the risk of human disease over space and time by prospectively following a cohort of slum residents. In addition, leptospires shedding will be linked to the risk of severe leptospirosis and LPHS in a population-based case control study in Salvador city. Identification and quantification of factors contributing to variations in environmental Leptospira contamination may serve to stratify disease risk and prioritize prevention in resource-poor settings.