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.

BackgroundTrachoma is targeted for elimination by 2020. World Health Organization advises districts to undertake surveillance when follicular trachoma (TF) <5% in children 1–9 years and mass antibiotic administration has ceased. There is a question if other tools could be used for surveillance as well. We report data from a test for antibodies to C. trachomatis antigen pgp3 as a possible tool.MethodologyWe randomly sampled 30 hamlets in Kilosa district, Tanzania, and randomly selected 50 children ages 1–9 per hamlet. The tarsal conjunctivae were graded for trachoma (TF), tested for C. trachomatis infection (Aptima Combo2 assay: Hologic, San Diego, CA), and a dried blood spot processed for antibodies to C. trachomatis pgp3 using a multiplex bead assay on a Luminex 100 platform.Principal findingsThe prevalence of trachoma (TF) was 0.4%, well below the <5% indicator for re-starting a program. Infection was also low, 1.1%. Of the 30 hamlets, 22 had neither infection nor TF. Antibody positivity overall was low, 7.5% and increased with age from 5.2% in 1–3 year olds, to 9.3% in 7–9 year olds (p = 0.015). In 16 of the 30 hamlets, no children ages 1–3 years had antibodies to pgp3.ConclusionsThe antibody status of the 1–3 year olds indicates low cumulative exposure to infection during the surveillance period. Four years post MDA, there is no evidence for re-emergence of follicular trachoma.

Background The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. MethodsIn this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1-59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov, NCT02047981.