Epidemiological linkages between sexually transmitted infections
Interactions between STIs can be complex and difficult to disentangle. These conditions share a common group of sexual risk factors, which may lead to the identification of non-causal associations. Studies that aim to determine the temporal sequence of STIs require prospective data collection with frequent STI assessment, as well as careful control for potential confounding factors. We conducted three studies to further characterize the complex inter-relationships between several STIs including HIV, utilizing data from a cohort of female sex workers (FSWs) in Mombasa, Kenya. The specific aims of these studies were: 1) To explore the contribution (population attributable risk percent) of STIs to HIV acquisition among Kenyan FSWs, and how this has changed over time since the cohort was established 2) To assesses the incidence and correlates of Chlamydia trachomatis infection among HIV seropositive and seronegative women enrolled in the cohort and 3) To determine the effect of incident HSV-2 on subsequent BV episodes among HIV-seronegative women.
We conducted longitudinal follow-up and prospective cohort analyses to complete the three specific aims. The study was conducted within the Mombasa cohort, an established, open cohort study of high-risk women. Follow-up began in February 1993, with over 3500 women enrolled to date. The eligibility criteria to join the cohort are: age 16 – 50 years, residing in the Mombasa area, self-identifying as exchanging sex for payment in cash or in kind, and able to provide informed consent. Participants were seen monthly at the research clinic, where a standardized interview addressing past medical and sexual history is administered. They also receive a physical and pelvic examination, with collection of genital samples to test for STIs.
Aim 1: Between 1993 and 2012, 1,964 women contributed 6,135 person-years of follow-up. The overall PAR% for each infection was; prevalent HSV-2 (48.3%), incident HSV-2 (4.5%), BV (15.1%), intermediate microbiota (7.5%), vaginal yeast (6.4%), T. vaginalis (1.1%), N. gonorrhoeae (0.9%), non-specific cervicitis (0.7%), GUD (0.8%), genital warts (-0.2%). The PAR% for prevalent HSV-2 (40.4%, 61.8%, 58.4%, 48.3%) and BV (17.1%, 19.5%, 14.7%, 17.1%), were high but did not change significantly over time. The PAR% for trichomoniasis, gonorrhea, GUD and genital warts all remained <3% across the four study periods. Aim 2: Between August 2006 and December 2010, 865 women contributed 2011 person-years of observation. Sixty-four women experienced 101 episodes of C. trachomatis infection (incidence rate of 5.0/100 person-years). In multivariate analyses, younger age (<25 years and 25-34 years versus ≥35 years; hazard ratio [HR] 8.49 95% CI 4.1-17.7 and HR 2.9 95% CI 1.7 5.0 respectively), depot medroxyprogesterone acetate use (HR 1.8 95% CI 1.1-3.0) and recent Neisseria gonorrhoeae infection (HR 3.3 95% CI 1.5-7.4) were significantly associated with increased risk of acquiring C. trachomatis infection. Aim 3: Between 1993 and December 2010, one hundred and sixty four of 406 HSV-2/HIV-1 seronegative Kenyan women acquired HSV-2, incidence rate 21/100 person-years. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR 1.28; 95% CI 1.05-1.56; p=0.01).
At the population level, abnormal vaginal microbiota and HSV-2 have consistently been the largest contributors to these high-risk women’s risk for HIV acquisition over the past 20 years. Interventions that prevent these conditions would benefit women’s health generally, and also hold potential for reducing HIV risk in women. Secondly, we found a high incidence of C. trachomatis among younger high-risk women suggesting the need for screening as an important public health intervention for this population. Finally, our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota.