title: Combinatorial effects of malaria season, iron deficiency, and inflammation determine plasma hepcidin concentration in African children.
abstract: Hepcidin is the master regulatory hormone that governs iron homeostasis and has a role in innate immunity. Although hepcidin has been studied extensively in model systems, there is less information on hepcidin regulation in global health contexts where iron deficiency (ID), anemia, and high infectious burdens (including malaria) all coexist but fluctuate over time. We evaluated iron status, hepcidin levels, and determinants of hepcidin in 2 populations of rural children aged ≤8 years, in the Gambia and Kenya (total n = 848), at the start and end of a malaria season. Regression analyses and structural equation modeling demonstrated, for both populations, similar combinatorial effects of upregulating stimuli (iron stores and to a lesser extent inflammation) and downregulating stimuli (erythropoietic drive) on hepcidin levels. However, malaria season was also a significant factor and was associated with an altered balance of these opposing factors. Consistent with these changes, hepcidin levels were reduced whereas the prevalence of ID was increased at the end of the malaria season. More prevalent ID and lower hepcidin likely reflect an enhanced requirement for iron and an ability to efficiently absorb it at the end of the malaria season. These results, therefore, have implications for ID and malaria control programs.
authors.affiliation: Department of Paediatrics, Oxford University Hospitals, University of Oxford, Oxford, United Kingdom; Oxford University Clinical Academic Graduate School, Oxford, United Kingdom; Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya;
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Atkinson
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford University Hospitals, United Kingdom;
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Armitage
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya; Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford University Hospitals, United Kingdom;
authors.forename: Shivani
authors.initials: S
authors.lastname: Khandwala
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya;
authors.forename: Tabitha W
authors.initials: TW
authors.lastname: Mwangi
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya;
authors.forename: Sophie
authors.initials: S
authors.lastname: Uyoga
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya;
authors.forename: Philip A
authors.initials: PA
authors.lastname: Bejon
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya; Department of Medicine, Imperial College, London, United Kingdom;
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.affiliation: Medical Research Council International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom; and Medical Research Council Keneba, Keneba, The Gambia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford University Hospitals, United Kingdom;
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D007501:Iron / Q000097:blood*; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D008297:Male; D012621:Seasons
chemical_list: D064451:Hepcidins; D007501:Iron