Effect of Biannual Mass Azithromycin Distributions to Preschool-Aged Children on Trachoma Prevalence in Niger

Abstract

IMPORTANCEBecause transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. OBJECTIVE To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. DESIGN, SETTING, AND PARTICIPANTS In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. INTERVENTIONS Every 6 months, a single dose of either oral azithromycin (20 mg/kg using heightbased approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. MAIN OUTCOMES AND MEASURES Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens. RESULTS At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6]months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07).

Monitoring transmission intensity of trachoma with serology

“…District-level PCR from Alefa and Woreta town were estimated to be 0%, and a recent study from the same population in Dosso found no Ct in pooled metagenomic testing of ocular swabs. 36 In these three populations, 98% of clusters (60/61) fell below the serologic thresholds for 90% sensitivity, supporting the interpretation of low levels of infection below the estimated thresholds.…”

Monitoring transmission intensity of trachoma with serology

“…1 and 2 ). District-level PCR from Alefa and Woreta town, Ethiopia were estimated to be 0%, and a recent study from the same population in Dosso, Niger found no C. trachomatis in pooled metagenomic testing of ocular swabs 38 . In these three populations, 98% of clusters (60/61) fell below the serologic thresholds for 90% sensitivity, supporting the interpretation of low levels of infection below the estimated thresholds.…”

“…We combined serologic, molecular, and clinical measurements collected between 2012 and 2019 across nine studies in five countries (Supplementary Table 1 ) 26 – 38 . When possible, measurements within the same study were stratified into populations corresponding to trachoma evaluation units, resulting in 14 study populations.…”

“…Details of serologic, clinical, and PCR measurements can be found in the published reports for each study 26 – 38 . In Malawi, dried blood spots were tested for IgG antibodies against Pgp3 using ELISA.…”

Unravelling the Potential Mortality Benefits of Mass Drug Administration With Azithromycin in Niger

“…Careful follow-up studies of nasopharyngeal specimens among recipients of MAA in Niger show an increase in macrolide resistance among Streptococcus pneumoniae nasopharyngeal isolates, although this was not shown to persist by 36 months. 5 Given that no impact of MAA has been shown on ocular trachoma in Niger, 6 the original reason for mass azithromycin use, questions have to be asked as to the viability of this approach in the country, especially compared with other investments. No country has rolled out this strategy, more than 3 years following the conditional recommendation by the World Health Organization, 7 and findings from replication trials are still awaited.…”