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Malaria is a cause of iron deficiency in African children

Muriuki JM 1 , Mentzer AJ 2 , Mitchell R 3 , Webb EL 4 , Etyang AO 5 , Kyobutungi C 6 Show all authors , Morovat A 7 , Kimita W 5 , Ndungu FM 5 , Macharia AW 5 , Ngetsa CJ 5 , Makale J 5 , Lule SA 8 , Musani SK 9 , Raffield LM 10 , Cutland CL 11 , Sirima SB 12 , Diarra A 12 , Tiono AB 12 , Fried M 13 , Gwamaka M 14 , Adu-Afarwuah S 15 , Wirth JP 16 , Wegmüller R 16 , Madhi SA 11 , Snow RW 5 , Hill AVS 2 , Rockett KA 2 , Sandhu MS 17 , Kwiatkowski DP 2 , Prentice AM 18 , Byrd KA 19 , Ndjebayi A 20 , Stewart CP 21 , Engle-Stone R 21 , Green TJ 22 , Karakochuk CD 23 , Suchdev PS 24 , Bejon P 5 , Duffy PE 13 , Davey Smith G 3 , Elliott AM 8 , Williams TN 5 , Atkinson SH 25

Affiliations 

  • 1 Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. jmuriuki@kemri-wellcome.org
  • 2 Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  • 3 Medical Research Council (MRC) Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • 4 MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  • 5 Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
  • 6 African Population and Health Research Centre, Nairobi, Kenya
  • 7 Department of Clinical Biochemistry, Oxford University Hospitals, Oxford, UK
  • 8 MRC/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
  • 9 Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
  • 10 Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
  • 11 South African Medical Research Council: Vaccines and Infectious Diseases Analytical Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • 12 Groupe de Recherche Action en Sante (GRAS), 06 BP 10248, Ouagadougou, Burkina Faso
  • 13 Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
  • 14 Mother Offspring Malaria Studies (MOMS) Project, Seattle Biomedical Research Institute, Seattle, WA, USA
  • 15 Department of Nutrition and Food Science, University of Ghana, Legon, Ghana
  • 16 GroundWork, Fläsch, Switzerland
  • 17 Wellcome Sanger Institute, Hinxton, UK
  • 18 MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia
  • 19 WorldFish, Bayan Lepas, Malaysia
  • 20 Helen Keller International, Yaoundé, Cameroon
  • 21 Department of Nutrition, University of California, Davis, Davis, CA, USA
  • 22 SAHMRi Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  • 23 Food, Nutrition, and Health, University of British Columbia, Vancouver, British Columbia, Canada
  • 24 Department of Pediatrics, Emory University and Emory Global Health Institute, Atlanta, GA, USA
  • 25 Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya. satkinson@kemri-wellcome.org
Nat Med, 2021 Apr;27(4):653-658.
PMID: 33619371 DOI: 10.1038/s41591-021-01238-4

Abstract

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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