Implications of Malaria On Iron Deficiency Control Strategies

The populations in greatest need of iron supplementation are also those at greatest risk of malaria: pregnant women and young children. Iron supplementation has been shown to increase malaria risk in these groups in numerous studies, although this effect is likely diminished by factors such as host immunity, host iron status, and effective malaria surveillance and control. Conversely, the risk of anemia is increased by malaria infections and preventive measures against malaria decrease anemia prevalence in susceptible populations without iron supplementation. Studies have shown that subjects with malaria experience diminished absorption of orally administered iron, so that as a consequence, iron supplementation may have generally reduced efficacy in malarious populations. A possible mechanistic link between malaria, poor absorption of iron, and anemia is provided by recent research on hepcidin, the human iron control hormone. Our improved understanding of iron metabolism may contribute to the control of malaria and the treatment of anemia. Malaria surveillance and control are necessary components of programs to control iron deficiency and may enhance the efficacy of iron supplementation. Adv. Nutr. 3: 570–578, 2012. Introduction For a decade or more, controversy has persisted over whether the benefit of iron supplementation in vulnerable individuals in malaria-endemic areas outweighs a possible increase in risk of malarial infection. A recent Cochrane review suggests that iron is not harmful when “regular malaria surveillance and treatment services are provided” (1). An updated version of this review concurred that across all studies, iron did not increase malaria risk, but the authors qualified this view by stating that there was a significantly increased risk of malaria associated with iron supplementation in areas without adequate malaria surveillance and treatment programs (2). Both Cochrane reviews and the many studies that preceded or followed them still leave nutritionists asking to what extent must malaria be prevalent and surveillance and treatment programs inadequate before it is no longer safe to provide iron supplementation. Are there other, safer methods of addressing the problem of widespread anemia? Aside from the risk of increasedmalaria, is iron supplementation in a population highly at risk of infection likely to be efficacious and why or why not? Simultaneously, novel research into iron biology has in the past 10 y vastly increased our understanding of iron metabolism and its interactions with infection. Significantly, the small molecule hepcidin has been identified as a crucial controller of iron bioavailability. This review attempts to synthesize what is known about the links between iron and malaria as well as exploring the underlying mechanisms that might explain them. Iron status affects malaria risk in children and pregnant women The target populations for iron supplementation are exactly those most susceptible to malaria: pregnant women and children. It has long been unclear whether iron supplementation renders children and pregnant women more vulnerable to malarial infections. Global attention to this problem 1 Published as a supplement to Advances in Nutrition. Presented as part of the symposium entitled “Tackling Iron Deficiency and Anemia in Infants and Young Children in Malaria-Endemic Areas: Moving from Controversy towards Guidance for Safe, Effective and Feasible Policies and Programs” given at the Experimental Biology 2011 meeting, April 10, 2011, in Washington, DC. The symposium was sponsored by the American Society for Nutrition and supported in part by the U.S. Army Military Infectious Disease Research Program. The symposium was chaired by Lynnette M. Neufeld and Angus Scrimgeour. The Guest Editors for this symposium were Lynnette M. Neufeld and Rafael Flores-Ayala. Guest Editor disclosures: Neither Guest Editor had conflicts to disclose. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of Advances in Nutrition. 2 N. Spottiswoode is supported by the National Institutes of Health Oxford-Cambridge Scholars Program. H. Drakesmith was supported by a Beit Memorial Fellowship for Medical Research and a MRC new investigator award. During this period, P. Duffy and M. Fried were funded by the Division of Intramural Research, NIAID, National Institutes of Health and the Bill and Melinda Gates Foundation grant 1364. 3 Author disclosures: N. Spottiswoode, M. Fried, H. Drakesmith, and P. E. Duffy, no conflicts of