Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants

• Published in: The Lancet (British edition) Vol. 350; no. 9081; pp. 844 - 850
• Main Authors: Menendez, Clara, Kahigwa, Elizeus, Hirt, Rosmarie, Vounatsou, Penelope, Aponte, John J, Font, Fidel, Acosta, Camilo J, Schellenberg, David M, Galindo, Claudia M, Kimario, John, Urassa, Honorathy, Brabin, Bernard, Smith, Tom A, Kitua, Andrew Y, Tanner, Marcel, Alonso, Pedro L
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 20.09.1997; Lancet; Elsevier Limited
• Subjects: Adult; Anemia; Anemia, Iron-Deficiency - epidemiology; Anemia, Iron-Deficiency - prevention & control; Antimalarials - therapeutic use; Babies; Biological and medical sciences; Dapsone - therapeutic use; Delayed-Action Preparations; Dietary supplements; Double-Blind Method; Drug Combinations; Female; Ferrous Compounds - therapeutic use; Follow-Up Studies; Human protozoal diseases; Humans; Incidence; Infant; Infectious diseases; Iron; Malaria; Malaria, Falciparum - epidemiology; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Male; Medical sciences; Parasitic diseases; Population; Protozoal diseases; Pyrimethamine - therapeutic use; Tanzania - epidemiology; Time Factors; Tropical medicine; Africa; Tanzania; Human; Protozoa; Antimalarial; Protozoal disease; Chemoprophylaxis; Malaria; Iron deficiency anemia; Pyrimethamine; Controlled therapeutic trial; Hemopathy; Iron; Parasitosis; Infection; Prevention; Plasmodium falciparum; Diet therapy; Parasiticid; Supplementation; Sideropenia; Sporozoa; Child; Comparative Studies; Eastern Africa; Health Services; Immunological Effects; Age Factors; Malaria > prevention and control; Metals; Infant; Biology; Delivery Of Health Care; Research Methodology; English Speaking Africa; Immunity; Inorganic Chemicals; Population Characteristics; Population; Research Report; Physiology; Parasitic Diseases; Demographic Factors; Anemia > prevention and control; Health; Africa; Tanzania; Youth; Diseases; Studies; Treatment; Developing Countries; Drugs > therapeutic use; Food Supplementation; Ingredients And Chemicals; Primary Health Care; Africa South Of The Sahara; Nutrition Programs
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(97)04229-3

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 undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility. 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3·125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP, receiving daily placebo plus weekly placebo. Daily supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume <25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys. The groups that received iron supplementation had a lower frequency of severe 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 supplementation had no effect on the frequency of malaria (0·87 vs 1·00 cases 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 efficacy 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, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2·2 [1·3–3·7] and 1·8 [1·3–2·6]). Malaria chemoprophylaxis 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 anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.