RANDOMIZED PLACEBO-CONTROLLED TRIAL OF IRON SUPPLEMENTATION AND MALARIA CHEMOPROPHYLAXIS FOR PREVENTION OF SEVERE ANEMIA AND MALARIA IN TANZANIAN INFANTS

Background Malaria and anaemia, especially that due to iron deficiency , are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We u ndertook a randomised comparison of different strategies for control o f anaemia and malaria in infants, including an assessment of the effec t of iron supplementation on malaria susceptibility. Methods 832 infan ts born at one hospital in a malaria-hyperendemic area of Tanzania bet ween January and October, 1995, were randomly assigned to group DI, re ceiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 m g pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus wee kly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP, receiving daily placebo plus weekly placebo. Daily supple mentation was given from 8 to 24 weeks of age, and the weekly chemopro phylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-c ell volume <25%) and malaria episodes was assessed through a combinati on of passive case detection and cross-sectional surveys. Findings The groups that received iron supplementation had a lower frequency of se vere anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron sup plementation had no effect on the frequency of malaria (0.87 vs 1.00 c ases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective eff icacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person -year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, ch ildren who had received malaria chemoprophylaxis had higher rates of s evere anaemia and malaria than non-chemoprophylaxis groups (relative r isks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]). Interpretation Malaria chemopro phylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe ana emia without increasing susceptibility to malaria. Our findings suppor t iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.