<p>LAKANA trial original protocol, 2019-11-27.</p>

Azithromycin mass drug administration (MDA) has been shown to promote child survival in high mortality settings. Azithromycin has antimalarial effects, and one possible mechanism behind mortality reduction with azithromycin may be reduction in malaria. We aimed to test the effect of a single dose of azithromycin on malaria prevalence and parasite load in infants. This malaria substudy was part of a large double-blinded cluster-randomized clinical trial in Mali studying the effect of azithromycin MDA on infant mortality (ClinicalTrials.gov NCT04424511). Villages were randomized into either placebo or azithromycin MDA groups. We collected dry blood spot samples among 4–11-month-old infants right before and two weeks after an azithromycin MDA dose (20mg/kg). Malaria positivity and concentration of Plasmodium falciparum DNA (parasite load) were determined by quantitative PCR. Hemoglobin concentration was measured with a rapid test. A total of 1158 infants at baseline were treated, with 324 infants in 20 villages in the control group, and 834 infants in 38 villages in the azithromycin group. At baseline, prevalence of PCR-positive malaria was 9.4% in the control group and 9.9% in the azithromycin group. On day 14 after receiving the study drug, prevalence was 8.9% among controls and 8.0% in the azithromycin group. Adjusting for baseline and clusters, malaria prevalence risk ratio was 0.96 (95% CI: 0.63 to 1.48) favoring azithromycin. The prevalence risk ratio for baseline malaria PCR-positive infants was 0.81 (0.55 to 1.19). The ratio of means for parasite load was 0.91 (0.66 to 1.25) favoring azithromycin. Hemoglobin was 0.1 g/L (-3.9 to 4.1) higher with azithromycin. The findings do not conclusively support, but are consistent with, a hypothesis that a single dose of azithromycin reduces malaria prevalence and parasite load among infants in a malaria-endemic West African setting.