Targeted Antibiotics for Trachoma: A Cluster-Randomized Trial

Abstract

Background: Current guidelines recommend community-wide mass azithromycin for trachoma, but a targeted treatment strategy could reduce the volume of antibiotics required.

Methods: In total, 48 Ethiopian communities were randomized to mass, targeted, or delayed azithromycin distributions. In the targeted arm, only children aged 6 months to 5 years with evidence of ocular chlamydia received azithromycin, distributed thrice over the following year. The primary outcome was ocular chlamydia at months 12 and 24, comparing the targeted and delayed arms (0-5 year-olds, superiority analysis) and the targeted and mass azithromycin arms (8-12 year-olds, noninferiority analysis, 10% noninferiority margin).

Results: At baseline, the mean prevalence of ocular chlamydia in the 3 arms ranged from 7% to 9% among 0-5 year-olds and from 3% to 9% among 8-12 year-olds. Averaged across months 12-24, the mean prevalence of ocular chlamydia among 0-5 year-olds was 16.7% (95% confidence interval [CI]: 9.0%-24.4%) in the targeted arm and 22.3% (95% CI: 11.1%-33.6%) in the delayed arm (P = .61). The final mean prevalence of ocular chlamydia among 8-12 year-olds was 13.5% (95% CI: 7.9%-19.1%) in the targeted arm and 5.5% (95% CI: 0.3%-10.7%) in the mass treatment arm (adjusted risk difference 8.5 percentage points [pp] higher in the targeted arm, 95% CI: 0.9 pp-16.1 pp higher).

Conclusions: Antibiotic treatments targeted to infected preschool children did not result in significantly less ocular chlamydia infections compared with untreated communities and did not meet noninferiority criteria relative to mass azithromycin distributions. Targeted approaches may require treatment of a broader segment of the population in areas with hyperendemic trachoma.

Keywords: Africa; antibacterial agents; chlamydia; mass drug administration; trachoma.

Figure 1.

Schematic showing potential direct and indirect effects in the 3 treatment arms. Each box represents a community in one of the three treatment arms, stratified by age group (0–5 y on top, 8–12 y on bottom) and infection status at baseline (infected on bottom, not infected on top). Circles represent uninfected children and stars represent infected children. Red symbols receive antibiotic treatment and blue symbols do not. Arrows represent potential indirect effects of treatment through reduced transmission. Children in the mass drug administration (MDA) communities experienced both the direct and indirect effects of antibiotics. In the targeted communities, the infected children experienced both direct and indirect effects of antibiotics, but the uninfected children could only benefit from indirect effects. The delayed-treatment communities received no antibiotics at all. Primary analysis 1 assessed whether the overall effect (ie, the direct and indirect effects at the community level) of targeted treatments was superior to no treatment; secondary analyses (SA) 1A and 1B assessed whether the indirect effects of targeted treatment were superior to no treatment. Primary analysis 2 and SA 2 assessed whether the indirect effects of targeted treatments were noninferior to the overall effect (ie, community-level direct and indirect effects) of mass azithromycin.

Figure 2.

Trial flow. Abbreviation: SD, standard deviation.

Figure 3.

Village-level prevalence of ocular chlamydia, stratified by age group. The left-hand panel shows the prevalence in a random sample of 0–5 year-olds and the right-hand panel in a random sample of 8–12 year-olds; a new random sample was selected at each monitoring visit. Heavy lines summarize group averages. Abbreviation: MDA, mass drug administration.

Figure 4.

Incidence of new ocular chlamydia infections over 24 months among children ages 0–5 years not infected at baseline. Panel A depicts for each treatment arm the incidence estimate and 95% confidence interval for each village on the left, and a box and whiskers plot summarizing all villages on the right. Panel B depicts the same data on a map of the study area, with each marker corresponding to a village, and markers sized according to the magnitude of the incidence estimate. The dark gray line represents the Zonal border; the light gray lines represent the major roads; the blue lines represent surface water; and the stars represent the 2 district administrative centers in the study area (base map: OpenStreetMap). Abbreviation: MDA, mass drug administration.