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 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.
Methods: 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. 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.
Findings: 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]).
Interpretation: 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.
PIP: The impact of iron supplementation and malaria chemoprophylaxis was investigated in a double-blind, placebo-controlled study involving 832 infants born in a malaria-hyperendemic area of Tanzania in 1995. Infants were randomly assigned to receive daily oral iron (2 mg/kg) and weekly Deltaprim (3-125 mg pyrimethamine plus 25 mg dapsone), daily iron plus weekly placebo, or daily and weekly placebo. Daily supplementation was provided from 8 to 24 weeks of age, while weekly chemoprophylaxis was given from 8 to 48 weeks. The 2 groups that received iron supplementation had a lower frequency of severe anemia (packed cell volume under 25%) than those who received placebo (0.62 versus 0.87 cases per person-year; protective efficacy, 28.8%), but iron supplementation did not have a significant effect on malaria incidence (0.87 versus 1.00 cases per person-year; protective efficacy, 12.8%). Infants who received malaria prophylaxis had lower frequencies of both severe anemia (0.45 versus 1.04 episodes per person-year; protective efficacy, 57.3%) and malaria (0.53 versus 1.43 episodes per person-year; protective efficacy, 60.5%) than those who received placebo. However, after the end of the intervention period, children who had received malaria prophylaxis had higher rates of severe anemia and malaria than those in the non-chemoprophylaxis groups (relative risks, 2.2 and 1.8, respectively). These findings indicate that malaria chemoprophylaxis during the first year of life can impair the development of natural immunity, while iron supplementation effectively prevents severe anemia without increasing susceptibility to malaria.