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

Abstract

In 2023, over 1.6 million cases of Chlamydia trachomatis (CT) were reported in the United States, making it the most common notifiable sexually transmitted infection (STI). Although CT affects the broader population, young women aged 15 to 24 years and gay, bisexual, and other men who have sex with men (MSM) face disproportionately higher risk of CT acquisition. Prevention of CT and its sequelae from untreated infections requires large-scale public health interventions, including annual screening and health education campaigns. Interest has grown in augmenting current prevention strategies with novel approaches, particularly doxycycline post-exposure prophylaxis (doxy-PEP) and CT vaccination. This dissertation addresses critical knowledge gaps related to these two emerging population-level prevention strategies. Aim 1 (Chapter 2) used data from a prospective cohort of men who have sex with men (MSM) in Seattle, WA to characterize longitudinal antibiotic use, providing a foundation for understanding how doxy-PEP may influence antibiotic consumption and the dissemination of antibiotic resistance in this population. In Aim 2 (Chapter 3), we developed a deterministic, compartmental model of CT transmission in the United States among males and females aged 15 to 64 years, simulating trends from 2000 to 2075. We then modeled the introduction of a CT vaccine in 2025, estimating its impact on disease burden under a range of implementation strategies and vaccine characteristics. Aim 3 (Chapter 4) builds on this model to evaluate the cost-effectiveness of CT vaccination in the United States from 2025 to 2050 through the incorporation of cost and health utilities data. In Aim 1, we found that antibiotic consumption among our cohort of MSM was very high, primarily driven by treatment for STIs and other health conditions. Participants with a recent history of bacterial STIs and those aged 25 to 39 years had significantly higher rates of antibiotic initiation. These findings provide a critical foundation for understanding antibiotic use behaviors in MSM and underscore the importance of evaluating how doxy-PEP may influence antibiotic consumption in this already high-using population. In Aims 2 and 3, we found that a partially efficacious vaccine, introduced through routine vaccination of adolescent girls only or adolescent girls and boys, could prevent up to 160 million CT infections and lead to meaningful reductions in CT incidence by 2075. Catch-up vaccination of older, unvaccinated females offered additional gains, but these were relatively modest compared to the impact of sustained routine vaccination. Our findings also suggest that routine CT vaccination has the potential to be a cost-saving or highly cost-effective intervention, even across a range of assumptions about vaccine efficacy, duration of protection, and vaccine coverage. Incremental cost-effectiveness ratios were most influenced by uncertainty in vaccine price per dose and treatment costs for pelvic inflammatory disease, though all results remained cost-effective under the highest accepted willingness-to-pay thresholds in the United States. We hope this work contributes to a growing body of evidence informing the design, implementation, and scale-up of effective CT prevention strategies, ultimately helping to reduce infections and improve sexual health outcomes.