The Effect of Multiple Rounds of Mass Drug Administration on the Association between Ocular Chlamydia trachomatis Infection and Follicular Trachoma in Preschool-Aged Children

Abstract

Purpose

To examine the relationship between ocular Chlamydia trachomatis infection and follicular trachoma (TF) in children prior to and following multiple rounds of annual mass drug administration (MDA) with azithromycin.

Methodology/principal findings

Thirty-two communities with endemic trachoma in Kongwa District, Tanzania, were offered annual MDA as part of a district-wide trachoma control program. Presence of ocular C. trachomatis infection and TF were assessed in 3,200 randomly sampled children aged five years and younger, who were examined prior to each MDA. Infection was detected using the Amplicor CT/NG assay and TF was identified by clinical examination using the World Health Organization (WHO) simplified grading system. The association between chlamydial infection and TF in children was evaluated at baseline prior to any treatment, and 12 months after each of three annual rounds of mass treatment. Factors associated with infection were examined using generalized estimating equation models.

At baseline, the overall prevalence of chlamydial infection and TF was 22% and 31%, respectively. Among children with clinical signs of TF, the proportion of those with infection was 49% prior to treatment and declined to 30% after three MDAs. The odds of infection positivity among children with clinical signs of TF decreased by 26% (OR 0.74, 95% CI 0.65 to 0.84, p = <0.01) with each MDA, after adjusting for age. For children aged under one year, who did not receive treatment, the relationship was unchanged.

Conclusions/significance

The association between ocular C. trachomatis infection and TF weakened in children with each MDA, as both infection and clinical disease prevalence declined. However, there was still a significant proportion of TF cases with infection after three rounds of MDA. New strategies are needed to assess this residual infection for optimal treatment distribution.

Author Summary

Trachoma, which is caused by infection by the bacterium Chlamydia trachomatis, is the leading preventable cause of blindness worldwide. Annual mass drug administration with azithromycin is recommended for trachoma control; however, monitoring the impact of azithromycin, which targets C. trachomatis, relies on the clinical assessment of follicular trachoma. If the relationship between chlamydial infection and the presence or absence of follicular trachoma were to remain unchanged with each round of treatment, we would be able to predict the level of residual infection, and the need for additional treatment, from the prevalence of follicular trachoma. In this study, we examined the association between infection and presence or absence of follicular trachoma in children prior to and following multiple rounds of treatment. Findings suggest that with increasing rounds of treatment, the prevalence of infection declines in children both with and without signs of follicular trachoma. Newer strategies, including tests that can rapidly detect infection under field conditions, may be needed to assess residual infection in treated communities.