Chlamydia trachomatis ompA Genotype and Clinical Signs of Trachoma in a Longitudinal Tanzanian Cohort.

Trachoma, caused by Chlamydia trachomatis (Ct), persists as a major cause of preventable blindness despite the global SAFE strategy. Understanding how Ct genovars and genovariants influence infection dynamics and clinical outcomes is crucial for sustaining elimination efforts and informing vaccine development. A four-year longitudinal study was conducted in a trachoma-endemic region of Tanzania across multiple rounds of mass drug administration (MDA) with azithromycin. Ct infections were genotyped by ompA sequencing to identify genovars and genovariants. Associations between genetic variants, bacterial load, and clinical signs of trachoma were assessed. Following MDA, a shift in Ct genovar prevalence occurred from genovar B to genovar A. Genovar B was associated with more severe clinical signs, including follicles, papillae, and scarring, whereas genovar A infections exhibited higher bacterial loads. Among 121 individuals with recurrent infections, 94% were re-infected with the same genovar, indicating limited protective immunity and incomplete clearance despite MDA coverage exceeding 60%. The genovariants B2, B9, and A2 predominated, with an A → T amino acid substitution in B9 potentially modifying antigenic recognition. Post-MDA, normalized genovariant diversity increased, suggesting ongoing transmission or strain reintroduction. Distinct genovar-associated clinical and immunological patterns underscore the need to elucidate genovar-specific virulence and immune evasion mechanisms. These findings provide key insights for optimizing trachoma control and advancing vaccine development.