title: Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum.
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.
authors: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Martha A
authors: MA
authors: Clark
authors: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Morgan M
authors: MM
authors: Goheen
authors: 1] Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK [2] Medical Research Council, Keneba, The Gambia.
authors: Anthony
authors: A
authors: Fulford
authors: 1] Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK [2] Medical Research Council, Keneba, The Gambia.
authors: Andrew M
authors: AM
authors: Prentice
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Marwa A
authors: MA
authors: Elnagheeb
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Jaymin
authors: J
authors: Patel
authors: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Nancy
authors: N
authors: Fisher
authors: Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: Steve M
authors: SM
authors: Taylor
authors: Division of Hematology Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Raj S
authors: RS
authors: Kasthuri
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors: Carla
authors: C
authors: Cerami
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000469:parasitology; D019587:Dietary Supplements; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D007501:Iron / Q000097:blood* / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D055815:Young Adult
chemical_list: D007501:Iron