Pathogenesis of Leishmaniasis:Host,Parasite and Vector

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DESCRIPTION (provided by applicant): The main objective of this program is to perform epidemiological, clinical, immunological and genetic studies to expand our knowledge of the pathogenesis and control of visceral, cutaneous and mucosal leishmaniasis. The UFBA, UFRN, FIOCRUZ, Tropical Medicine Research Center consortium was formed in 1996 and has now built a highly synergistic and productive collaboration among researchers from the major academic centers in Northeast Brazil where these diseases are endemic. The overall pragmatic theme is to determine the role of host (immunological response, genetics), pathogens (genetical and phenotypic markers) and environment (sand fly) factors in disease expression and adverse outcome. These studies will contribute to the identification of new forms of interventions to control and ameliorate disease outcomes due to these common endemic diseases. Project "Host and Parasite Factors in Mucosal Leishmaniasis", will determine the roles played by the host immune response and genetics, as well as parasite polymorphism, in driving the clinical outcome to mucosal leishmaniasis. Project "Human Immunological Responses to Phlebotomine Saliva", will evaluate how the effect of phlebotomine's salivary products in the initial host immune response to Leishmania and how the established host immune response to these products influence disease outcome. Project "Determinants of Disease in Visceral Leishmaniasis", will attempt to identify specific host genetic and environmental determinants of infection and disease progression in a family cohort followed prospectively in an area endemic for L chagasi. Host immunological response plays an important role in the control of leishmaniasis. This project will explore a new area in the parasite host interaction by evaluating how immunological response to salivary gland products correlate with clinical outcome of L. chagasi infection. Emphasis will be placed on the understanding of the pathogenesis of mucosal leishmaniasis, which eventually will contribute to new source of therapy and prophylactic measures to decrease the burden of this leishmaniasis.