Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised trial

Background Many individuals at risk of malaria also have micronutrient defi ciencies that may hamper protective immunity. Vitamin A is central to norma l immune function, and supplementation has been shown to lower the morbidit y of some infectious diseases. We investigated the effect of vitamin A supp lementation 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 Guin ea. Of 520 potentially eligible children aged 6-60 months, 480 were randoml y assigned high-dose vitamin A (n=239) or placebo (n=241), every 3 months f or 13 months. Malaria morbidity was assessed through weekly community-based case detection and surveillance of patients who self-reported to the healt h centre. Cross-sectional surveys were also done at the beginning, middle, and end of the study to assess malariometric indicators. Analyses were by i ntention to treat. Findings The number of P falciparum febrile episodes (temperature greater t han or equal to 37.5 degrees C with a parasite count of at least 8000/mu L) 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 th an the placebo group (1300 [907-1863] vs 2039 [1408-2951]) as was the propo rtion with spleen enlargement (125/196 [64%] vs 148/207 [71%]); neither dif ference was significant (p=0.093 and p=0.075). Children aged 12-36 months b enefited 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] v s 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 strat egy to lower morbidity due to P falciparum in young children. The findings suggest that clinical episodes, spleen enlargement, and parasite density ar e influenced by different immunological mechanisms from infection and anaem ia.