The influence of rectal Chlamydia trachomatis infections on immunity and incident urogenital infections in women without an indication forrectal screening

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ABSTRACT Chlamydia trachomatis (Ct) infections in the U.S. are increasing and no Ct vaccine exists. Annual urogenital tract (UGT) screening of <25 and high risk women of any age is recommended, but testing for rectal Ct infection is not recommended in women without rectal exposure. However, rectal Ct prevalence rates are similar in women regardless of anal sex exposures and up to 19% of Ct infections occur only in the rectum and would be missed by screening recommendations. Animal studies suggest that rectal infection is beneficial by inducing potent transmucosal immunity that protects the UGT against reinfection without pathological effects. It is critical that we understand whether rectal Ct infections in women are potentially harmful, by cross-contaminating the UGT, or beneficial, by inducing mucosal protection against UGT infection. Further, understanding if rectal Ct infections are immunogenic will establish if a mucosal chlamydia vaccine is feasible. We will enroll women at high-risk for chlamydia but who have never engaged in anal sex. Over 12 months, we will (1) obtain monthly oral, vaginal, and rectal swabs to detect incident Ct infections, (2) collect quarterly blood and cervical cytobrush specimens to study systemic and cervical T-cell responses, and (3) capture weekly sexual behavior and symptoms data to screen for exposure and Ct-related symptoms. The goal of this project is to test the hypothesis that (1) rectal Ct infections are frequent, long-lasting, asymptomatic, associated with specific rectal-tropic strains, and do not increase risk for UGT infection (Aim 1) and (2) assess their influence on systemic and cervical memory T-cell immunity and if they decrease incident UGT infections (Aim 2). By understanding if rectal Ct infections increase or decrease UGT infection risk, these studies may change screening guidelines and lay the foundation for development of an oral attenuated chlamydia vaccine.