Impact of community management of fever (using antimalarials with or without antibiotics) on childhood mortality: A cluster-randomized controlled trial in Ghana

Malaria and pneumonia are leading causes of childhood mortality. Home Management of fever as Malaria (HMM) enables presumptive treatment with antimalarial drugs but excludes pneumonia.We aimed to evaluate the impact of adding an antibiotic, amoxicillin (AMX) to an antimalarial, artesunate amodiaquine (AAQ+AMX) for treating fever among children 2-59 months of age within the HMM strategy on all-cause mortality. In a stepped-wedge clusterrandomized, open trial, children 2-59 months of age with fever treated with AAQ or AAQ+AMX within HMM were compared with standard care. Mortality reduced significantly by 30% (rate ratio [RR] = 0.70, 95% confidence interval [CI] = 0.53-0.92, P = 0.011) in AAQ clusters and by 44% (RR = 0.56, 95% CI = 0.41-0.76, P = 0.011) in AAQ+AMX clusters compared with control clusters. The 21% mortality reduction between AAQ and AAQ+AMX (RR = 0.79, 95% CI = 0.56-1.12, P = 0.195) was however not statistically significant. Community fever management with antimalarials significantly reduces under-five mortality. Given the lower mortality trend, adding an antibiotic is more beneficial.