Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum

Martha A. Clark, Morgan M. Goheen, Anthony Fulford, Andrew M. Prentice, Marwa A. Elnagheeb, Jaymin Patel, Nancy Fisher, Steve M. Taylor, Raj S. Kasthuri and Carla Cerami ()
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Martha A. Clark: University of North Carolina
Morgan M. Goheen: University of North Carolina
Anthony Fulford: Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine
Andrew M. Prentice: Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine
Marwa A. Elnagheeb: Gillings School of Global Public Health, University of North Carolina
Jaymin Patel: Gillings School of Global Public Health, University of North Carolina
Nancy Fisher: University of North Carolina
Steve M. Taylor: Duke University Medical Center
Raj S. Kasthuri: University of North Carolina
Carla Cerami: Gillings School of Global Public Health, University of North Carolina

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Iron deficiency and malaria have similar global distributions, and frequently co-exist in pregnant women and young children. Where both conditions are prevalent, iron supplementation is complicated by observations that iron deficiency anaemia protects against falciparum malaria, and that iron supplements increase susceptibility to clinically significant malaria, but the mechanisms remain obscure. Here, using an in vitro parasite culture system with erythrocytes from iron-deficient and replete human donors, we demonstrate that Plasmodium falciparum infects iron-deficient erythrocytes less efficiently. In addition, owing to merozoite preference for young erythrocytes, iron supplementation of iron-deficient individuals reverses the protective effects of iron deficiency. Our results provide experimental validation of field observations reporting protective effects of iron deficiency and harmful effects of iron administration on human malaria susceptibility. Because recovery from anaemia requires transient reticulocytosis, our findings imply that in malarious regions iron supplementation should be accompanied by effective measures to prevent falciparum malaria.

Date: 2014
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DOI: 10.1038/ncomms5446

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