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.

In developed countries the major tuberculosis epidemics declined long before the disease became curable in the 1940s. We present a theoretical framework for assessing the intrinsic transmission dynamics of tuberculosis. We demonstrate that it takes one to several hundred years for a tuberculosis epidemic to rise, fall and reach a stable endemic level. Our results suggest that some of the decline of tuberculosis is simply due to the natural behaviour of an epidemic. Although other factors must also have contributed to the decline, these causal factors were constrained to operate within the slow response time dictated by the intrinsic dynamics.