Reductions in
malaria morbidity have been reported following
azithromycin mass drug administration (MDA) for
trachoma. The recent
Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial reported a reduction in child mortality following biannual
azithromycin MDA. Here, we investigate the effects of
azithromycin MDA on
malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and
azithromycin or placebo syrup was distributed to children aged 1-59 months for a total of four biannual distributions. At baseline, 12-month, and 24-month follow-up visits, a random sample of 1,200 children was assessed for
malaria with thick and thin blood smears and
hemoglobin measurement. In the community-level analysis, there was no difference in the prevalence of
parasitemia (1.0% lower in
azithromycin-treated communities; 95% CI: -8.2 to 6.1), gametocytemia (0.7% lower in
azithromycin-treated communities; 95% CI: -2.8 to 1.5), or
anemia (1.7% lower in
azithromycin-treated communities; 95% CI: -8.1 to 4.6) between placebo and
azithromycin communities. Further interrogation of the data at the individual level, both per-protocol (including only those who received treatment 6 months previously) and by intention-to-treat, did not identify differences in
parasitemia between treatment arms. In contrast to several previous reports, this study did not show an effect of
azithromycin MDA on
malaria parasitemia at the community or individual levels.