Background. Many individuals at risk of malaria also have micronutrient deficiencies that may hamper protective immunity. Vitamin A is central to normal immune function, and supplementation has been shown to lower the morbidity of some infectious diseases. We investigated the effect of vitamin A supplementation on malaria morbidity. Methods. This randomised double-blind placebo-controlled trial of vitamin A supplementation took place in a P falciparum endemic area of Papua New Guinea. Of 520 potentially eligible children aged 6-60 months, 480 were randomly assigned high-dose Vitamin A (n = 239) or placebo (n = 241), every 3 months for 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the health centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by intention to treat. Findings. The number of P falciparum febrile episodes (temperature ≥ 37.5°C with a parasite count of at least 8000/μL) was 30% lower in the vitamin A group than in the placebo group (178 vs 249 episodes; relative risk 0.70 [95% CI 0.57-0.87], p = 0.0013). At the end of the study P falciparum geometric mean density was lower in the vitamin A than the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the proportion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither difference was significant (p = 0.093 and p = 0.075). Children aged 12-36 months benefited most, having 35% fewer febrile episodes (89 vs 141; relative risk 0.65 [14-50], p = 0.0023), 26% fewer enlarged spleens (46/79 [58%] vs 67/90 [74%], p = 0.0045), and a 68% lower parasite density (1160 [95% CI 665-2022] vs 3569 [2080-6124] p = 0.0054). Vitamin A had no consistent effect on cross-sectional indices of proportion infected or with anaemia. Interpretation. Vitamin A supplementation may be an effective low-cost strategy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density are influenced by different immunological mechanisms from infection and anaemia.
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