title: Malaria and Age Variably but Critically Control Hepcidin Throughout Childhood in Kenya.
abstract: Both iron deficiency (ID) and malaria are common among African children. Studies show that the iron-regulatory hormone hepcidin is induced by malaria, but few studies have investigated this relationship longitudinally. We measured hepcidin concentrations, markers of iron status, and antibodies to malaria antigens during two cross-sectional surveys within a cohort of 324 Kenyan children ≤ 8 years old who were under intensive surveillance for malaria and other febrile illnesses. Hepcidin concentrations were the highest in the youngest, and female infants, declined rapidly in infancy and more gradually thereafter. Asymptomatic malaria and malaria antibody titres were positively associated with hepcidin concentrations. Recent episodes of febrile malaria were associated with high hepcidin concentrations that fell over time. Hepcidin concentrations were not associated with the subsequent risk of either malaria or other febrile illnesses. Given that iron absorption is impaired by hepcidin, our data suggest that asymptomatic and febrile malaria contribute to the high burden of ID seen in African children. Further, the effectiveness of iron supplementation may be sub-optimal in the presence of asymptomatic malaria. Thus, strategies to prevent and eliminate malaria may have the added benefit of addressing an important cause of ID for African children.
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya ; Department of Paediatrics, Oxford University Hospitals, University of Oxford, Oxford, UK ; Oxford University Clinical Academic Graduate School, Oxford, UK.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Atkinson
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Uyoga
authors.affiliation: Medical Research Unit (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford University Hospitals, UK ; National Institute for Health Research Biomedical Research Centre Oxford, UK.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Armitage
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya ; Medical Research Unit (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford University Hospitals, UK.
authors.forename: Shivani
authors.initials: S
authors.lastname: Khandwala
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya ; Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Cleopatra K
authors.initials: CK
authors.lastname: Mugyenyi
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia ; Department of Microbiology, Monash University, Victoria, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.affiliation: Medical Research Council (MRC) Unit, The Gambia ; Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Medical Research Unit (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford University Hospitals, UK ; National Institute for Health Research Biomedical Research Centre Oxford, UK.
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
authors.affiliation: Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme (KWTRP), PO Box 230-80108, Kilifi, Kenya ; Department of Medicine, Imperial College, London, UK.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
mesh_terms: D000367:Age Factors; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology / Q000209:etiology; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007223:Infant; D007501:Iron / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000097:blood* / Q000150:complications / Q000453:epidemiology* / Q000276:immunology / Q000469:parasitology; D016778:Malaria, Falciparum / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000276:immunology / Q000469:parasitology; D008297:Male; D011159:Population Surveillance; D016016:Proportional Hazards Models; D012306:Risk; D012680:Sensitivity and Specificity; D017085:alpha-Thalassemia / Q000150:complications / Q000453:epidemiology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015415:Biomarkers; D064451:Hepcidins; D007501:Iron
keywords: Africa; Age; Children; Hepcidin; Iron deficiency; Malaria