Background Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by Chlamydia trachomatis (CT) infections, a leading cause of pelvic inflammatory disease (PID), infertility, and increased HIV susceptibility. CT-induced genital inflammation disrupts mucosal barriers and activates HIV target cells, compounding reproductive and immunological risks. We investigated the impact of CT infection in AGYW from two South African regions, focusing on genital inflammation and immune activation.

Methods An observational cohort of 298 sexually active AGYW (16–22 years) from Cape Town and Johannesburg was enrolled. Those in Johannesburg attended one visit while those in Cape Town were followed for three visits over 6-8 months. Cytokine profiling of cervicovaginal samples assessed inflammatory responses, while cervical cytobrush-derived CD4+ T cells were analyzed for CD38, Ki67 and CCR5 expression. CT ompA genotyping examined strain diversity.

Results CT prevalence was 2.4 times higher in Cape Town (41.6%) than in Johannesburg (17.4%). Infection with CT led to an upregulation of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, with a stronger inflammatory response observed in Johannesburg. Genotypic analysis revealed regional variations: genovar D, which was predominant in Cape Town, was associated with lower IFN-γ levels, whereas genovar E, prevalent in Johannesburg, was linked to higher IFN-γ levels. AGYW who experienced CT infection across multiple study visits did not exhibit elevated genital tract cytokine levels compared to those with a single infection. However, they did show an increase in activated and proliferating cervical CD4+ T cells, which may contribute to heightened HIV susceptibility.

Conclusions CT genotypic diversity and regional variations significantly influence immune responses in AGYW. Region-specific vaccines and integrated sexual health services would support mitigating STI and HIV risks in this vulnerable population.

The authors have declared no competing interest.

This research was funded by the EDCTP Strategic Primer grant (SP.2011.41304.038; PI J. Passmore, UCT) and a self-initiated grant from the South African Medical Research Council (2017-2020; PI J. Passmore, UCT).

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The ethics committees/IRB of the University of Cape Town and Witwatersrand gave ethical approval for this work (#267/2013 and #M130745, respectively)

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