Risk Factors for Ocular Chlamydia after Three Mass Azithromycin Distributions

Background: An important component of the World Health Organization's comprehensive trachoma elimination strategy is the provision of repeated annual mass azithromycin distributions, which are directed at reducing the burden of ocular chlamydia. Knowledge of characteristics associated with infection after mass antibiotic treatments could allow trachoma programs to focus resources to those most likely to be infected with ocular chlamydia. Methodology/Principal Findings: We monitored 12 communities in rural Ethiopia that had received 3 annual mass azithromycin treatments as part of a cluster-randomized trial for trachoma. One year after the third treatment, a random sample of children from each village received conjunctival examination for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI), conjunctival swabbing for chlamydial RNA and DNA, and a household survey. The primary outcome for this study was RNA evidence of ocular chlamydia, which we detected in 41 of 573 swabbed children (7.2%, 95%CI 2.7–17.8). In multivariate mixed effects logistic regression models, ocular chlamydial RNA was significantly associated with ocular discharge (OR 2.82, 95%CI 1.07–7.42), missing the most recent mass azithromycin treatment (OR 2.49, 95%CI 1.02–6.05), having a sibling with ocular chlamydia (OR 4.44, 95%CI 1.60–12.29), and above-median community population (OR 7.81, 95%CI 1.56–39.09). Ocular chlamydial infection was also independently associated with TF (OR 3.42, 95%CI 1.56–7.49) and TI (OR 5.39, 95%CI 2.43–11.98). Conclusions/Significance: In areas with highly prevalent trachoma treated with multiple rounds of mass azithromycin, trachoma programs could consider continuing mass azithromycin treatments in households that have missed prior mass antibiotic treatments, in households with clinically active trachoma, and in larger communities. Author Summary: Trachoma, which is the leading infectious cause of blindness worldwide, is caused by repeated ocular infection with Chlamydia trachomatis. Treatment for trachoma includes mass azithromycin treatments to the entire community. The World Health Organization recommends at least 3 rounds of annual mass antibiotic distributions in areas with trachoma, with further mass treatments based on the prevalence of trachoma. However, there are other options for communities that have received several rounds of treatment. For example, programs could continue antibiotic treatments only in those households most likely to have infected individuals. In this study, we performed trachoma monitoring on children from 12 Ethiopian communities one year after a third mass azithromycin treatment, and conducted a household survey at the same time. We found that children were more likely to be infected with ocular chlamydia if they had ocular inflammatory signs or ocular discharge, or if they had missed the preceding antibiotic treatment, had an infected sibling, or came from a larger community. These risk factors suggest that after mass azithromycin treatments, trachoma programs could consider continuing antibiotic distributions to households that have missed prior antibiotic distributions, in households with children who have the clinical signs of trachoma, and in larger communities.