Projected health impact of post-discharge malaria chemoprevention among children under the age of five years with severe malarial anaemia in Africa: a modelling analysis

Background Children discharged from hospital after recovery from severe malarial anaemia (SMA) are at high risk of readmission and death in subsequent months. Clinical trial results show that three months of post-discharge malaria chemoprevention (PMC) with dihydroartemisinin-piperaquine reduces this risk. Methods We developed a compartmental mathematical model describing the daily post-discharge incidence of uncomplicated and severe malaria requiring readmission among a cohort of 0-5 year-old children. We fitted the model to PMC and placebo groups from nine trial hospitals in areas of moderate-to-intense malaria transmission in Uganda and Kenya using Bayesian methods. The cohort model was then embedded within a full population model of SMA to predict impact of PMC across malaria-endemic African countries. Results The incidence of hospitalised malaria episodes during the first 6 months post-discharge is estimated to be ~23-60 times higher than the average for children of this age, depending on transmission intensity. We estimate that repeat SMA episodes within 6 months of the original episode constitute 18-27% of all SMA episodes in high transmission settings. In the 20 highest-burden countries in Africa, only 2-5 children need to be given PMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised cases access PMC, we estimate that 36,000 (range 16,000-82,000) malaria-associated readmissions could be prevented annually, depending on the proportion accessing hospital care. Interpretation PMC has high potential impact per child treated across a range of epidemiological settings in Africa.