Mass azithromycin distribution and cause-specific mortality among children aged 1-59 months: a secondary analysis of a cluster randomized controlled trial

Mass azithromycin distribution has been shown to reduce all-cause child mortality in several settings in the Sahel by 14-18%. A trial in Niger found that mass azithromycin distribution to children aged 1-59 months reduced cause-specific mortality due to malaria, dysentery, meningitis, and pneumonia. However, this study was done in the absence of seasonal malaria chemoprevention (SMC). Here, we assess the effect of mass azithromycin distribution on cause-specific child mortality in a setting receiving SMC. The Child Health with Azithromycin Treatment (CHAT) trial was a cluster randomized placebo-controlled trial of 341 communities in Nouna District, Burkina Faso. Eligible children (aged 1-59 months) received a single oral 20 mg/kg dose of azithromycin or matching placebo. Six rounds of distribution occurred over a 36-month period. An enumerative census was conducted during each twice-yearly distribution, during which vital status for all children in the community was collected. Verbal autopsy was performed to assess cause of death. Of 1,086 deaths recorded in the trial, verbal autopsy results were available for 992 (91%). The most common causes of death were infectious, including malaria (34%), diarrhea (24%), and pneumonia (9%). Children living in communities receiving azithromycin had significant reduction in malaria mortality (incidence rate ratio, IRR, 0.67, 95% confidence interval, CI, 0.50 to 0.90, P=0.008). Other infectious causes of mortality, including diarrhea and pneumonia, were lower in communities receiving azithromycin but were not statistically significantly different. Mass azithromycin distribution for child mortality has benefits in the context of SMC for reducing mortality, including for malaria mortality. Trial RegistrationClinicalTrials.gov NCT03676764. Trial registered 17 September 2018.