The addition of azithromycin to seasonal malaria chemoprevention may reduce mortality and morbidity in African children, according to a study recently published in the New England Journal of Medicine.

A sustained reduction in all-cause mortality was seen in Ethiopian children after a mass administration of azithromycin for trachoma. Therefore, this study investigated whether adding azithromycin to the monthly sulfadoxine-pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention reduced mortality and morbidity in African children ( identifier: NCT02211729).

In Burkina Faso and Mali, 19,578 children aged 3 to 59 months were randomly assigned, on the basis of household, to receive seasonal malaria chemoprevention plus either azithromycin (n=9735) or placebo (n=9843). Once children reached age 5 years, they exited the trial and new children were enrolled. For 3 successive seasons, the interventions were administered in four 3-day cycles at monthly intervals. The primary end point was death or hospitalization for at least 24 hours that was not a result of elective surgery or trauma.

During 3 malaria-transmission seasons, the number of deaths and hospital admissions was 250 in the azithromycin group and 238 in the placebo group (incidence rate ratio [IRR], 1.1; 95% CI, 0.88-1.3). In the azithromycin group, the following events occurred less than in the placebo group: gastrointestinal infections (1647 vs 1985 episodes; IRR, 0.85; 95% CI, 0.79-0.91), upper respiratory tract infections (4893 vs 5763 episodes; IRR, 0.85; 95% CI, 0.81-0.90), and nonmalarial febrile illnesses (1122 vs 1424 episodes; IRR, 0.79; 95% CI, 0.73-0.87). In both groups, the incidence of adverse events and the prevalence of malaria parasitemia were similar.

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Overall, the study authors concluded that, in “children in Burkina Faso and Mali, the addition of azithromycin to the antimalarial agents used for seasonal malaria chemoprevention did not result in a lower incidence of death or hospital admission that was not due to trauma or surgery than antimalarial agents plus placebo, although a lower disease burden was noted with azithromycin than with placebo.”


Chandramohan D, Dicko A, Zongo I, et al. Effect of adding azithromycin to seasonal malaria chemoprevention [published online January 30, 2019]. N Engl J Med. doi: 10.1056/NEJMoa1811400