Mass Azithromycin Distribution to Prevent Childhood Mortality: A Pooled Analysis of Cluster-Randomized Trials

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.

Figure 1.

Forest plot of incidence rate ratios for studies included in the pooled analysis. Studies evaluated child mortality rates in communities receiving mass drug administration with azithromycin compared with control (placebo distribution in Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance [MORDOR], annual azithromycin in Partnership for the Rapid Elimination of Trachoma [PRET], and delayed treatment in Trachoma Amelioration in Northern Amhara [TANA]). Data were included for children aged 1–59 months in MORDOR, 6–59 months in PRET, and 12–59 months in TANA.

Figure 2.

Risk differences and 95% confidence intervals for rate of mortality in azithromycin-treated communities compared with placebo-treated communities. The red dotted line with short dashes indicates 0 deaths averted per 1,000 person-years (no effect). The gray dotted line with long dashes indicates the pooled effect estimate (−2.9 deaths averted per 1,000 person-years). MORDOR = Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance; PRET = Partnership for the Rapid Elimination of Trachoma; TANA = Trachoma Amelioration in Northern Amhara. This figure appears in color at www.ajtmh.org.