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Advancing research on the sexually transmitted female 'nuisance' pathogen Trichom

$253,688R21FY2009AINIH

New York University School Of Medicine, New York NY

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Abstract

DESCRIPTION (provided by applicant): Trichomoniasis is the most common non-viral STD, estimated to cause ~174 million infections world-wide each year. The Trichomonas vaginalis parasite resides in the urogenital tract of both sexes and can cause vaginitis in women and urethritis and prostatitis in men. However, the disease is known more as a female 'nuisance'condition, which has resulted in a lack of scientific and medical attention and scant interest by public health officials in developing trichomoniasis control programs. Acute infections among women are associated with pelvic inflammatory disease and adverse pregnancy outcomes. Most alarming is the recognition that T. vaginalis infection appears to increase women's susceptibility to HIV-1 infection. Because of the association between T. vaginalis and risk for HIV-1 acquisition, interventions to reduce T. vaginalis infection and transmission would likely result in fewer HIV-1 infections. Completion of the T. vaginalis genome sequence in 2007 has significantly increased our knowledge concerning the biology and mechanisms of pathogenesis of the parasite, but significant gaps remain. In particular, the genetic diversity of the parasite is not known, i.e. whether the parasite is maintained as a clonal population, or whether genetic exchange occurs between parasites in the urogenital tract. The extent of genetic diversity has implications for the control of the disease, for example it determines how virulent parasites spread or how they may evade a vaccine. The focus of this R21 proposal is to examine the genetic diversity of T. vaginalis infecting women attending eight New York City Bureau of STD clinics in inner city areas, and to use some of these isolates to develop a standardized and accessible in vitro model system for the study of colonization of the vagina by the parasite. A panel of polymorphic genetic markers - microsatellites and single copy genes - will be developed using the T. vaginalis genome sequence, and used to genotype T. vaginalis isolates identified in vaginal swabs taken from women attending the clinics. Knowledge of the genetic diversity and colonization characteristics of the parasite will provide important data points for subsequent studies, for example determining associations between T. vaginalis genotypes and the commensal microbes that make up the vaginal 'microbiome'. PUBLIC HEALTH RELEVANCE: Trichomoniasis, caused by the eukaryotic parasite Trichomonas vaginalis, is the most common, non-viral, sexually transmitted infection worldwide, but long considered a female 'nuisance'disease. The goal of this project is to determine the genetic diversity of the parasite in women attending STD clinics in New York City, and to use these extant isolates in the development of a model system for the study of colonization of the vagina.

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