The focus of this multidisciplinary proposal is to elucidate the epidemiology of the genetic lineages of T. cruzi, for improved understanding and prevention of Chagas disease. The project will unite skills in genotyping, genomics, genetics and pathogenesis in Europe with considerable compatible skills in South America, and with key research in endemic areas that have distinct characteristics. The proposal is intended to be high impact in terms of both research progress and fostering of collaborative networks. Aim: Elucidate the epidemiology of the genetic lineages of T. cruzi, for improved understanding and prevention of Chagas disease. Technology development: 1. Develop further and apply MLST; PCR-RFLP and MLMT to the analysis of genetic populations of T. cruzi, 2. Sequence the unresolved genome of T. cruzi I, 3. Develop lineage specific diagnosis, 4. Develop an oligochromatography PCR-dipstick procedure for detection of T. cruzi. Molecular epidemiology: 5. Pilot studies of association between genetic lineage, clinical outcome, and prevalence of congenital infection, 6. Map the silvatic vector, silvatic mammal, human and ecological associations of the T. cruzi genotypes IId,e,b,a. 7. Compare lineage specific pathogenesis and transmissibility of congenital infection in a mouse model, and compare lineage susceptibility to drugs in vitro. Population genetics and phylogenetics: 8. Re-evaluate the population genetics and evolution of T. cruzi lineages. International cryobank and database: 9. Establish in South America an accessible, expanded, international cryobank for T. cruzi, 10. Establish a website and database for outputs of the project. The project encompasses the desirable characteristics prescribed by the call, in that they include: genomics/proteomics; effective, innovative relevance to disease, pathogenesis, drugs, interventions; an integrated multidisciplinarity, and capacity building, networking and training in endemic regions.