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Background  As part of the SAFE strategy, mass antibiotic treatments are useful in controlling the ocular strains of chlamydia that cause trachoma. The World Health Organization recommends treating at least 80% of individuals per community. However, the role of antibiotic coverage for trachoma control has been poorly characterized.    Methodology/Principal Findings  In a collection of cluster-randomized clinical trials, mass oral azithromycin was administered to 40 villages in Ethiopia. The village prevalence of ocular chlamydia was determined before treatment, and at two and six months post-treatment. The mean prevalence of ocular chlamydia was 48.9% (95% CI 42.8 to 55.0%) before mass treatments, decreased to 5.4% (95% CI 3.9 to 7.0%) at two months after treatments ( p <0.0001), and returned to 7.9% (95% CI 5.4 to 10.4%) by six months after treatment ( p  = 0.03). Antibiotic coverage ranged from 73.9% to 100%, with a mean of 90.6%. In multivariate regression models, chlamydial prevalence two months after treatment was associated with baseline infection ( p <0.0001) and antibiotic coverage ( p  = 0.007). However, by six months after treatment, chlamydial prevalence was associated only with baseline infection ( p <0.0001), but not coverage ( p  = 0.31).    Conclusions/Significance  In post-hoc analyses of a large clinical trial, the amount of endemic chlamydial infection was a strong predictor of chlamydial infection after mass antibiotic treatments. Antibiotic coverage was an important short-term predictor of chlamydial infection, but no longer predicted infection by six months after mass antibiotic treatments. A wider range of antibiotic coverage than found in this study might allow an assessment of a more subtle association.

Importance of Coverage and Endemicity on the Return of Infectious Trachoma after a Single Mass Antibiotic Distribution