Mass azithromycin distribution for reducing childhood mortality in sub-Saharan Africa

BACKGROUND. Interventions to reduce under-5 mortality can either target the vulnerable or include all children regardless of state of health. Here, we assess whether mass distribution of a broad-spectrum antibiotic to pre-school children reduces mortality in sub-Saharan Africa. METHODS. MORDOR was a large simple trial that randomized communities in Malawi, Niger, and Tanzania to 4 biannual mass distributions of either oral azithromycin or placebo. Children aged 1-59 months were enumerated and offered treatment. Vital status was assessed at the subsequent biannual census. The primary outcome was aggregate all-cause mortality, with country-specific rates as pre-specified subgroup analyses. RESULTS. In total, 1533 communities were randomized, 190,238 children censused at baseline, and 323,302 person-years monitored. Mean antibiotic coverage over the 4 biannual distributions was 90.4% (SD 10.4%) of the censused population. The overall annual mortality rate in placebo- treated communities was 16.5 per 1000 person-years (9.6 per 1000 person-years in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Antibiotic-treated communities had an estimated 13.5% lower mortality overall (95% CI 6.7%—19.8%, P<0.001). Mortality was 5.7% lower in Malawi (CI - 9.7%—18.9%, P=0.45), 18.1% lower in Niger (CI 10.0%—25.5%, P<0.001), and 3.4% lower in Tanzania (CI -21.2%—23.0%, P=0.77). The greatest reduction was observed in 1-5 month-old children (24.9% lower, CI 10.6%—37.0%, P=0.001). CONCLUSIONS. Mass azithromycin distribution to post-neonatal, pre-school children may reduce childhood mortality in sub-Saharan Africa, particularly in high mortality areas such as Niger. Any implementation would need to consider selection for antibiotic resistance.