Original Investigation 

February 13, 2024

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial

Catherine E. Oldenburg, Mamadou Ouattara, Mamadou Bountogo, et al

JAMA. 2024;331(6):482-490. doi:10.1001/jama.2023.27393

Key Points

Question  Does twice-annual mass azithromycin distribution prevent all-cause childhood mortality among children in Burkina Faso aged 1 to 59 months in the setting of seasonal malaria chemoprevention distribution?

Findings  In this randomized trial of twice-yearly mass azithromycin distribution, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years) in the azithromycin group compared with 588 deaths over 58 547 person-years (10.0 deaths/1000 person-years) in the placebo group. The difference was not statistically significant.

Meaning  Communities with mass azithromycin distribution had lower child mortality than controls, although the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.

Abstract

Importance  Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions.

Objective  To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention.

Design, Setting, and Participants  This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities.

Interventions  Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023.

Main Outcomes and Measures  The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census.

Results  A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months.

Conclusions and Relevance  Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.

Trial Registration  ClinicalTrials.gov Identifier: NCT03676764