Linear growth in preschool children treated with mass azithromycin distributions for trachoma: A cluster-randomized trial

Background Mass azithromycin distributions have been shown to reduce mortality among pre-school children in sub-Saharan Africa. It is unclear what mediates this mortality reduction, but one possibility is that antibiotics function as growth promoters for young children. Methods and findings 24 rural Ethiopian communities that had received biannual mass azithromycin distributions over the previous four years were enrolled in a parallel-group, cluster-randomized trial. Communities were randomized in a 1:1 ratio to either continuation of biannual oral azithromycin (20mg/kg for children, 1 g for adults) or to no programmatic antibiotics over the 36 months of the study period. All community members 6 months and older were eligible for the intervention. The primary outcome was ocular chlamydia; height and weight were measured as secondary outcomes on children less than 60 months of age at months 12 and 36. Study participants were not masked; anthropometrists were not informed of the treatment allocation. Anthropometric measurements were collected for 282 children aged 0-36 months at the month 12 assessment and 455 children aged 0-59 months at the month 36 assessment, including 207 children who had measurements at both time points. After adjusting for age and sex, children were slightly but not significantly taller in the biannually treated communities (84.0 cm, 95%CI 83.2-84.8, in the azithromycin-treated communities vs. 83.7 cm, 95%CI 82.9-84.5, in the untreated communities; mean difference 0.31 cm, 95%CI -0.85 to 1.47, P = 0.60). No adverse events were reported. Conclusions Periodic mass azithromycin distributions for trachoma did not demonstrate a strong impact on childhood growth. Trial registration The TANA II trial was registered on clinicaltrials.gov #NCT01202331. Author summary Mass distribution of a single dose of the broad-spectrum antibiotic azithromycin twice per year to pre-school children in Sub-Saharan Africa has been shown to reduce childhood mortality. The mechanism by which azithromycin reduces mortality is currently not clear, especially since the antibiotic is not targeted to sick children but rather given to all children in the community whether or not they have an infectious disease. In this study, we report the height and weight of children enrolled in a trial in Ethiopia in which communities were randomized either to twice annual mass azithromycin distributions for blinding trachoma or to no treatments. After accounting for age and sex, children from azithromycin-treated communities were on average slightly taller at the 12- and 36-month study visits than those from untreated communities, but the difference was not statistically significant.