A Single Dose of Azithromycin and Inflammation in Infants: A Cluster-Randomized Placebo-Controlled Trial

Azithromycin mass drug administration (MDA) reduces under-5 mortality in some African settings. The biomechanisms behind the mortality reduction are unknown. The aim of this study was to test the hypothesis that a dose of azithromycin reduces inflammation in infants in a West African setting. This cluster-randomized, double-blind, placebo-controlled trial was part of a large-scale trial in Mali conducted to test the effect of azithromycin MDA on infant mortality (LAKANA trial, ClinicalTrials.gov NCT04424511). In the LAKANA trial, villages were randomly assigned to placebo or azithromycin groups. All participants, investigators, and study personnel were masked. Whole-blood C-reactive protein (CRP) concentration was measured in 4- to 11-month-old infants in a subset of villages right before and 2 weeks after receiving either placebo or azithromycin. CRP values were log-transformed, and mixed-effects regression with random intercepts for clusters and identity link was used to compare the groups. Among 1,615 infants in 72 villages, the baseline geometric mean CRP level was 1.76 mg/L in the placebo group ( n = 696) and 1.81 mg/L in the azithromycin group ( n = 919). On day 14, the mean CRP level was 1.67 mg/L in the placebo group and 1.47 mg/L in the azithromycin group, accounting for an average 14% lower CRP with azithromycin (95% CI: 1%–26%; P = 0.048). There was no statistically significant difference in prevalence of elevated CRP levels (>5 mg/L). Those with two or more morbidities seemed to benefit most, with 42% lower CRP levels on average with azithromycin treatment (95% CI: 1%–67%; P = 0.047). These findings support the hypothesis that a single dose of azithromycin reduces inflammation in Malian infants.