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

• Published in: The Lancet (British edition) Vol. 354; no. 9174; pp. 203 - 209
• Main Authors: Shankar, Anuraj H, Genton, Blaise, Semba, Richard D, Baisor, Moses, Paino, Joseph, Tamja, Steven, Adiguma, Thomas, Wu, Lee, Rare, Lawrence, Tielsch, James M, Alpers, Michael P, West, Keith P
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 17-07-1999; Lancet
• Subjects: Biological and medical sciences; Child, Preschool; Chromatography, High Pressure Liquid; Double-Blind Method; Female; General and cellular metabolism. Vitamins; Humans; Infant; Malaria, Falciparum - epidemiology; Malaria, Falciparum - immunology; Malaria, Falciparum - mortality; Malaria, Falciparum - prevention & control; Male; Medical sciences; New Guinea - epidemiology; Pharmacology. Drug treatments; Population; Population Surveillance; Prevalence; Survival Analysis; Tropical medicine; Vitamin A - blood; Vitamin A - therapeutic use; Vitamin A Deficiency - immunology; Papua New Guinea; Melanesia; Oceania; New Guinea; Human; Protozoa; Apicomplexa; Protozoal disease; Chemoprophylaxis; Malaria; Parasitosis; Morbidity; Retinol; Infection; Prevention; Plasmodium falciparum; Randomization; Double blind study; Supplementation; High dose; Child; Papua New Guinea; Health Services; Age Factors; Biology; Delivery Of Health Care; Research Methodology; Oceania; Double-blind Studies; Population Characteristics; Population; Research Report; Physiology; Parasitic Diseases; Vitamin A > beneficial effects; Demographic Factors; Health; Youth; Food Supplementation > beneficial effects; Vitamins; Diseases; Studies; Micronutrients; Treatment; Melanesia; Developing Countries; Primary Health Care; Nutrition Programs
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(98)08293-2

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.
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.
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% Cl 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% Cl 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.
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.