Trachoma, caused by Chlamydia trachomatis (Ct), remains a leading cause of preventable infection induced blindness worldwide. We conducted a four-year longitudinal study in three trachoma-endemic villages in Northern Tanzania, tracking infection dynamics and factors influencing trachomatous scarring progression and persistence pre- and post-Mass Drug Administration (MDA) interventions.
We analysed 118 whole genomes of Ct originating from ocular swabs of children. Sample collection was conducted at three-month intervals over four years, encompassing 15 timepoints. We studied Ct phylogeny, patterns of single nucleotide polymorphism (SNP) accumulation in individual isolates and single nucleotide variation (SNV) in the population, with association of clinical signs of trachoma and scarring progression.
Seventy-one (60.2%) samples were classified as serovar A (SvA) and 47 (39.8%) as serovar B (SvB) genomes. Initially, SvB dominated among pre-MDA samples (36/40, 90%), but SvA gradually became dominant after the first round of MDA (67/78, 85.9%) (P<0.0001). Two distinct subsets of SvA were found: subset_1 (29 sequences) pre-MDA, aligning with Tanzanian reference strain A/2497; subset_2 (42 sequences) post-MDA, showing a mutation rate roughly twice as high as subset_1, a 6 kbp genome reduction in the PZ, and forming a distinct cluster. Similarly, 13 SvB sequences exhibited diverse PZ genome reduction (~4 and ~10 kbp), yet all grouped with Tanzanian reference strain B/TZ1A828/OT.
Importantly, we observed a shift in the types of Ct serovars after the first round of MDA, with the emergence of a unique SvA subset with distinct genetic characteristics compared to those circulating before MDA. The observed decrease in the size of the Ct genome suggests a process where the Tanzanian ocular Ct strains may be streamlining, highlighting ongoing evolution. Further research is needed to understand the factors driving these changes and their impact on Ct biology and response to azithromycin.