SCHISTOSOMIASIS AND CHAGAS DISEASE IN BRAZIL

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We propose to build a research program of interdisciplinary studies on human schistosomiasis mansoni and Chagas' disease in Minas Gerias, Brazil. The disciplines will include immunology, molecular biology, biochemistry, pathology, epidemiology and clinical medicine. This program is rooted in the collaborative research being pursued in schistosomal immunoregulation by 3 of the senior investigators on this application. Our goals are to understand the pathogenesis of these diseases, and develop vaccines or other modalities to control the morbidity and mortality of these infections. Studies on the immunoregulation of schistosomiasis: comparisons of T cell clones/hybridomas from patients with different clinical forms, and their abilities to induce/regulate in vitro granuloma formation; comparisons of multi/monoclonal anti-schistosome idiotypes (Ids) from patients in clinical groups. Schistosomal pathogenesis: ability of patients to stimulate/regulate fibrogenesis, and to produce fibrogenic extracellular matrix proteins, at the protein and gene activation levels. Studies on the immunology of Chagas' disease: cellular immune responses and regulation in patients with different clinical forms of Chagas' disease; Id analysis of patients' anti-T. cruzi antibodies and retrospective and longitudinal studies of maternal/perinatal immune effects on subsequent responsiveness, morbidity and mortality; autoimmune studies and HLA-typing, with analysis in relationship to clinical patterns. Studies of the Molecular Biology of S. mansoni: identification, cloning and production of parasite encoded antigens useful in both diagnosis and immunoregulatory studies of schistosomiasis. Studies of the Molecular Biology of T cruzi: identification, cloning and production of parasite encoded antigens related to patients' cellular immunity and useful in diagnosis of Chagas' disease, and potentially involved in cross-reactivity and autoimmune reactions with host tissues.