Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa
Jeremy D Keenan1, Robin L Bailey1, Sheila K West1
1From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O., T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.); the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for Community Outreach and the College of Medicine, University of Malawi, Blantyre (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); and the International Trachoma Initiative, Decatur (P.M.E.), and Emory University, Atlanta (P.M.E.) - both in Georgia.
Insights
Mass antibiotic distribution of azithromycin to preschool children in sub-Saharan Africa significantly reduced overall childhood mortality. This intervention showed the most impact in Niger, highlighting its potential for improving child survival rates.
Area of Science:
- Global Health
- Infectious Diseases
- Pediatrics
Background:
- Sub-Saharan Africa faces significant challenges in meeting United Nations Sustainable Development Goals, particularly concerning child mortality.
- Mass distribution of broad-spectrum antibiotics is being explored as an intervention to reduce mortality in vulnerable populations.
Purpose of the Study:
- To evaluate the impact of mass azithromycin distribution on all-cause mortality in preschool children in sub-Saharan Africa.
- To assess country-specific effects and identify age groups with the greatest benefit.
Main Methods:
- A cluster-randomized trial involving mass distribution of oral azithromycin or placebo to children aged 1-59 months in Malawi, Niger, and Tanzania.
- Twice-yearly distributions over a defined period, with vital status determined through censuses.
- Primary outcome was aggregate all-cause mortality, with subgroup analyses by country and age.
Main Results:
- Overall mortality was 13.5% lower in communities receiving azithromycin compared to placebo (P<0.001).
- Significant reductions were observed in Niger (18.1% lower mortality) and overall, with the greatest impact in infants aged 1-5 months (24.9% lower mortality).
- Serious adverse events were rare and comparable between groups.
Conclusions:
- Mass distribution of azithromycin effectively reduced childhood mortality in preschool-aged children in sub-Saharan Africa.
- The intervention demonstrated notable efficacy, particularly in Niger and for younger children.
- Consideration of antibiotic resistance is crucial for policy implementation.
Background:
We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations.
Methods:
In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses.
Results:
A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing.
Conclusions:
Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).
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