Mass Drug Administration of Azithromycin to Reduce Child Mortality: Only for High-Mortality Settings?

Dramatic global reductions in child mortality over the past several decades have not been equitably realized across populations.1 Less than one quarter of sub-Saharan African countries achieved the child mortality targets outlined in the Millennium Development Goals. Without new approaches to improve child survival, these countries are also likely to fail to meet the 2030 Sustainable Development targets (less than 25 deaths before the age of 5 years per 1,000 live births).1,2 Biannual mass drug administration (MDA) of azithromycin has been shown to reduce child mortality in several large trials.

Delivery via MDA offers the opportunity to impact the most marginalized and disadvantaged communities, as MDA programs appear to be among the most equitable intervention platforms in low-resource settings. However, in the largest of these trials (Macrolide Oraux pour R ´eduire Les D ´ec `es avec un Oeil sur la R ´esistance [MORDOR]), conducted in three African countries, the site-specific effect size was only significant in Niger, where the baseline mortality rate was highest.

Although mortality reductions were observed in the other sites, the statistically nonsignificant effects and fact that the study was not powered to evaluate effect modification by site complicate their interpretation, especially when considering the balance of risk (including toxicity and emergence of antibiotic resistance) versus benefit. This has led to uncertainty surrounding whether such an intervention should be recommended in lower mortality settings.