Prevention of Chlamydia trachomatis infections: Evaluation of vaccination and post-exposure prophylactic antibiotic use as population-level strategies

PROJECT SUMMARY The global burden of sexually transmitted infections has increased over the last several decades. In 2020 alone, the World Health Organization estimated that 128.5 million incident cases of Chlamydia trachomatis (CT) occurred among individuals of reproductive age. Although risk of infection persists across the general

population, young women aged 15–24-years, as well as gay, bisexual, and other men who have sex with men (MSM), have a significantly greater risk for acquiring CT. Successful interruption of CT infections and subsequent sequalae requires the implementation of wide-scale public health prevention measures. However,

effective primary- and secondary-level prevention strategies, including prophylactic antibiotic use and vaccines, are underutilized or unavailable. Interest in the use of doxycycline prophylaxis has grown in recent years but concerns of antibiotic resistance in Neisseria gonorrhoea and future resistance in CT limit its feasibility and

warrant additional research on considerations for successful implementation. Given these concerns, an effective vaccine is likely required for enduring population-level declines in CT infections. Testing of vaccines to protect against CT infections has thus far been limited to Phase I trials and further testing is needed to

understand the efficacy and safety among broader populations. The vaccine development process could be strengthened by parallel investigations using mathematical models and health economic evaluations to assess the impact of a CT vaccine. This proposal addresses the following questions: Among individuals potentially

eligible for antibiotic prophylaxis, what is the frequency of, and characteristics associated with, antibiotic use that can inform the utility of doxycycline as a preventative measure? What are the potential impacts of a proposed CT vaccine on disease burden? Is CT vaccination a cost-effective prevention strategy compared to

current screen-and-treat practices in the United States? To answer these questions, the project will characterize the frequency and factors associated with antibiotic use among MSM in Seattle, WA (Aim 1) using longitudinal data from the ExGen Study, a prospective cohort study of MSM. Second, a mathematical

model will be developed to predict the 50-year impact of national rollout of a theoretical vaccine on the burden of urogenital and rectal CT infections in the United States (Aim 2). Model structure and parameters will be sourced from peer-reviewed published literature, publicly available surveillance systems,

and vaccine target product profiles. Finally, the cost-effectiveness of CT vaccination strategies, in combination with screen-and-treat interventions, will be compared to screen-and-treat alone in the United States (Aim 3) using the mathematical model developed in Aim 2, alongside cost data from peer-

reviewed and public sources. This research addresses critical knowledge gaps about CT prevention strategies and serves as a training opportunity for the applicant to develop into an independent, academic researcher.