This proposal is for competitive renewal of the STD CRC consortium involving the University of Washington and the Fred Hutchinson Cancer Center, together with the Universities of Manitoba and Nairobi. The central theme is prevention of female reproductive tract infection morbidity -- specifically cervical neoplasia and PID -- through research on sexual behavior, and on the clinical epidemiology, immunobiology and pathogenesis of HPV, C. trachomatis, and N. gonorrhoeae. The proposal includes six projects, four scientific cores, and a developmental core. Project 1 (Acquisition and Natural History of Genital HPV Infection, Laura Koutsky PI) and Project 2 (HPV Capsid Antibodies Denise Galloway PI) represent continued collaborative research involving a long.term cohort of female University of Washington students, Project 3 (Cellular Immunity and Pathogenesis of Chlamydia trachomatis PID, Robert Brunham PI) and project 4 (Opa in the Pathogenesis of Gonococcal Infection and Disease, Frank Plummer PI) involve coordinated research involving a long- term cohort of female sex workers in Nairobi, Kenya who are at extremely high risk of gonococcal and chlamydia infection and PID. These projects offer complementary research on the immunobiology of PID, with Project 3 emphasizing the cellular immune response in what is probably a lymphocyte mediated disease; and Project 4 emphasizing the humoral immune response in what is likely primarily a neutrophil-mediated disease. Project 5 (Diversity of Epitopes in Chlamydia, Mary Lampe PI) further pursues the molecular specificity and protective role of Class I restricted CD8+ cylotoxic T cells in a murine model of C. trachomatis infection. Project 6 (Sexual Partnerships and STD Control Strategies, King Holmes PI) an ongoing multidisciplinary study of sexual partnerships and networks will undertake two randomized interventions in Seattle evaluating the impact of partner notification on rates of reinfection with N. gonorrhoeae and C. trachomatis, will undertake complementary qualitative research on social and psychological determinants of sexual partnerships, particularly those which are discordant for sexual activity class. Roy Anderson and Geoff Gernett, Oxford University collaboration on networking models of the epidemiology of gonococcal and chlamydia infection using empiric data from Project 6, and HPV infection, using data from Project 1. Cores A (Administration, King Holmes Director, Denise Galloway and Walter Stamm Co-Directors); and Core B (Biostatistics, Tim De Rouen Director and James Hughes Co-Director), support all 6 projects. Cores C (HPV Laboratory, Nancy Kiviat Director) and D (C. trachomatis and N. gonorrhoeae Laboratory, Walter Stamm, Director) both support multiple projects in the CRC. The Developmental Core (Sheila Lukehart Director will support two New Investigators throughout the program.
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