Mass azithromycin distribution to prevent childhood mortality: A pooled analysis of cluster-randomized trials

• Type of Material: Article
• Authors: Catherine E. Oldenburg, University of California San Francisco; Ahmed M. Arzika, The Carter Center; Abdou Amza, Universite Abdou Moumouni; Teshome Gebre, The Carter Center; Khumbo Kalua, University of Malawi College of Medicine; Zakayo Mrango, National Institute for Medical Research Tanga; Sun Y. Cotter, University of California San Francisco; Sheila K. West, Johns Hopkins School of Medicine; Robin L. Bailey, London School of Hygiene & Tropical Medicine; Paul Emerson, Emory University; Kieran S. O Brien, University of California San Francisco; Travis C. Porco, University of California San Francisco; Jeremy D. Keenan, University of California San Francisco; Thomas M. Lietman, University of California San Francisco
• Language: English
• Date: 2019-01-01
• Publisher: American Society of Tropical Medicine and Hygiene
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by The American Society of Tropical Medicine and Hygiene
• Final Published Version (URL): http://dx.doi.org/10.4269/ajtmh.18-0846
• Title of Journal or Parent Work: American Journal of Tropical Medicine and Hygiene
• ISSN: 0002-9637
• Volume: 100
• Issue: 3
• Start Page: 691
• End Page: 695
• Grant/Funding Information: The studies included in this analysis were supported by the Bill & Melinda Gates Foundation (T. M. L.) and the National Eye Institute (U10 EY016214; T. M. L.).
• Keywords: multisite study; community; Children; sub-Saharan Africa; Mortality; heterogeneity; Azithromycin; mass drug administration; cluster-randomized trials
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Mass drug administration (MDA) with azithromycin may reduce under-5 child mortality (U5M) in sub-Saharan Africa. Here, we conducted a pooled analysis of all published cluster-randomized trials evaluating the effect of azithromycin MDA on child mortality. We pooled data from cluster-randomized trials randomizing communities to azithromycin MDA versus control. We calculated mortality rates in the azithromycin and control arms in each study, and by country for multisite studies including multiple countries. We conducted a two-stage individual community data meta-analysis to estimate the effect of azithromycin for prevention of child mortality. Three randomized controlled trials in four countries (Ethiopia, Malawi, Niger, and Tanzania) were identified. The overall pooled mortality rate was 15.9 per 1,000 person-years (95% confidence interval [CI]: 15.5–16.3). The pooled mortality rate was lower in azithromycin-treated communities than in placebo-treated communities (14.7 deaths per 1,000 person-years, 95% CI: 14.2–15.3 versus 17.2 deaths per 1,000 person-years, 95% CI: 16.5–17.8). There was a 14.4% reduction in all-cause child mortality in communities receiving azithromycin MDA (95% CI: 6.3–21.7% reduction, P = 0.0007). All-cause U5M was lower in communities receiving azithromycin MDA than in control communities, suggesting that azithromycin MDA could be a new tool to reduce child mortality in sub-Saharan Africa. However, heterogeneity in effect estimates suggests that the magnitude of the effect may vary in time and space and is currently not predictable.