Malaria is a life-threatening disease typically transmitted through the bite of an infected Anopheles mosquito. The common malaria chemoprevention included monthly sulfadoxine-pyrimethamine plus amodiaquine. Some evidence suggests that adding azithromycin to the chemoprevention may reduce the risk of mortality. The objective of this study is to evaluate the efficacy of adding azithromycin to seasonal malaria chemoprevention therapy.

This is a randomized study conducted on a total of 19,578 children aged 3-19 months. Out of all participants, 9,735 children received chemoprevention plus azithromycin, and 9,843 received chemoprevention plus a placebo. The effect of the drug combination was administered in four three-day cycles at monthly intervals for three consecutive seasons. The primary outcome of the study was death or hospital admission, not due to trauma or elective surgery. 

The overall deaths were 250 in the azithromycin group and 238 in the placebo group. Adverse events, including gastrointestinal infections, upper respiratory tract infections, and non-malarial febrile illnesses, were less prevalent in the azithromycin group. The incidence of other adverse events, along with the prevalence of malaria parasitemia was comparable in the two groups.

The research concluded that the addition of azithromycin to seasonal malaria chemoprevention of sulfadoxine-pyrimethamine plus amodiaquine did not lower the overall survival or hospital admission. However, the disease burden was lower with azithromycin than with a placebo.