Iron supplementation and malaria infection : results of a randomized controlled field trial

Gyorkos, Theresa W. (Supervisor) Iron deficiency anaemia is associated with several ill-health effects. Its treatment and/or control with iron preparations in malaria endemic areas has, however, been implicated to increase host susceptibility to malaria infection. Scientific evidence accumulated to date remains equivocal about the presence of this increased susceptibility. The present work was planned to address the existing controversy by assessing the effect of oral iron supplementation on host susceptibility to malaria infection. A randomized, double-blind, placebo-controlled field trial of oral ferrous sulphate supplementation in schoolchildren 5 to 14 years of age was carried out in northwest Ethiopia where transmission of malaria is high. A total of 500 school children, all with mild-to-moderate iron deficiency, were randomly assigned to receive either ferrous sulphate (60 mg elemental iron per day) or a look-alike placebo, over a period of 12 weeks. Follow-up continued for 24 weeks post-randomization. Children who received iron supplementation tended to develop more clinical attacks of malaria than those children who received placebo, although the difference between the groups was not statistically significant, either during the initial 12 week supplementation period (RR = 1.59; 95% CI: 0.92-2.75) or during the 24 weeks of follow-up (RR = 1.45; 95% CI: 0.95-2.20). Similarly, a trend of increased risk of malaria infection (parasitemia) was noted in the iron-supplemented group over the 24 week follow-up period (RR = 1.22; 95% CI: 0.98-1.52). No difference in any other outcome measure (spleen rate, average enlarged spleen index, and parasite density index) was observed between the groups either during the 12 weeks of supplementation or the 24 weeks of follow-up. This study suggests that iron supplementation, in areas where iron deficiency and malaria co-occur, may enhance host susceptibility to malaria infection. Thus, approaches to control or prevent iron deficiency anaemia in malaria endemic areas should be integrated with malaria control activities in order to minimize the unintended effects of malaria infection while providing the greatest benefit.