Malaria is a cause of iron deficiency in African children


Nat Med

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 ID(1). To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria(2), 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%.

Muriuki, J. M., Mentzer, A. J., Mitchell, R., Webb, E. L., Etyang, A. O., Kyobutungi, C., Morovat, A., Kimita, W., Ndungu, F. M., Macharia, A. W., Ngetsa, C. J., Makale, J., Lule, S. A., Musani, S. K., Raffield, L. M., Cutland, C. L., Sirima, S. B., Diarra, A., Tiono, A. B., Fried, M., Gwamaka, M., Adu-Afarwuah, S., Wirth, J. P., Wegmuller, R., Madhi, S. A., Snow, R. W., Hill, A. V. S., Rockett, K. A., Sandhu, M. S., Kwiatkowski, D. P., Prentice, A. M., Byrd, K. A., Ndjebayi, A., Stewart, C. P., Engle-Stone, R., Green, T. J., Karakochuk, C. D., Suchdev, P. S., Bejon, P., Duffy, P. E., Davey Smith, G., Elliott, A. M., Williams, T. N., Atkinson, S. H.

Pages:653-658, Volume:27, Edition:2/24/2021, Date,Apr


Notes:Muriuki, John Muthii|Mentzer, Alexander J|Mitchell, Ruth|Webb, Emily L|Etyang, Anthony O|Kyobutungi, Catherine|Morovat, Alireza|Kimita, Wandia|Ndungu, Francis M|Macharia, Alex W|Ngetsa, Caroline J|Makale, Johnstone|Lule, Swaib A|Musani, Solomon K|Raffield, Laura M|Cutland, Clare L|Sirima, Sodiomon B|Diarra, Amidou|Tiono, Alfred B|Fried, Michal|Gwamaka, Moses|Adu-Afarwuah, Seth|Wirth, James P|Wegmuller, Rita|Madhi, Shabir A|Snow, Robert W|Hill, Adrian V S|Rockett, Kirk A|Sandhu, Manjinder S|Kwiatkowski, Dominic P|Prentice, Andrew M|Byrd, Kendra A|Ndjebayi, Alex|Stewart, Christine P|Engle-Stone, Reina|Green, Tim J|Karakochuk, Crystal D|Suchdev, Parminder S|Bejon, Philip|Duffy, Patrick E|Davey Smith, George|Elliott, Alison M|Williams, Thomas N|Atkinson, Sarah H|eng|202800/Z/16/Z/WT_/Wellcome Trust/United Kingdom|R25 TW009343/TW/FIC NIH HHS/|064693/WT_/Wellcome Trust/United Kingdom|HHSN268201800015I/HB/NHLBI NIH HHS/|095778/WT_/Wellcome Trust/United Kingdom|107769 /WT_/Wellcome Trust/United Kingdom|U1232661351/MRC_/Medical Research Council/United Kingdom|MC_U123292699/MRC_/Medical Research Council/United Kingdom|103951/WT_/Wellcome Trust/United Kingdom|098051 /WT_/Wellcome Trust/United Kingdom|204911/Z/16/Z/WT_/Wellcome Trust/United Kingdom|103602/WT_/Wellcome Trust/United Kingdom|203077/WT_/Wellcome Trust/United Kingdom|MC_UU_00027/5/MRC_/Medical Research Council/United Kingdom|203141 /WT_/Wellcome Trust/United Kingdom|MR/R010161/1/MRC_/Medical Research Council/United Kingdom|110255/WT_/Wellcome Trust/United Kingdom|MC_PC_MR/R020183/1/MRC_/Medical Research Council/United Kingdom|U105960371/MRC_/Medical Research Council/United Kingdom|202800/WT_/Wellcome Trust/United Kingdom|MC_UU_00026/3/MRC_/Medical Research Council/United Kingdom|R01 HL120393/HL/NHLBI NIH HHS/|090532 /WT_/Wellcome Trust/United Kingdom|206194 /WT_/Wellcome Trust/United Kingdom|T32 HL129982/HL/NHLBI NIH HHS/|212176/WT_/Wellcome Trust/United Kingdom|MC-A760-5QX00/MRC_/Medical Research Council/United Kingdom|MR/M006212/1/MRC_/Medical Research Council/United Kingdom|079110/WT_/Wellcome Trust/United Kingdom|HHSN268201800013I/MD/NIMHD NIH HHS/|106289/WT_/Wellcome Trust/United Kingdom|HHSN268201100037C/HL/NHLBI NIH HHS/|R01 HL117626/HL/NHLBI NIH HHS/|MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom|Research Support, N.I.H., Extramural|Research Support, N.I.H., Intramural|Research Support, Non-U.S. Gov’t|Research Support, U.S. Gov’t, Non-P.H.S.|2021/02/24 06:00|Nat Med. 2021 Apr;27(4):653-658. doi: 10.1038/s41591-021-01238-4. Epub 2021 Feb 22.

ISBN: 1546-170X (Electronic)|1078-8956 (Linking) Permanent ID: PMC7610676 Accession Number: 33619371

Author Address: Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.|Open University, KEMRI-Wellcome Trust Research Programme, Accredited Research Centre, Kilifi, Kenya.|Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.|Medical Research Council (MRC) Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.|MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.|Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.|African Population and Health Research Centre, Nairobi, Kenya.|Department of Clinical Biochemistry, Oxford University Hospitals, Oxford, UK.|MRC/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.|Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.|South African Medical Research Council: Vaccines and Infectious Diseases Analytical Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Groupe de Recherche Action en Sante (GRAS), 06 BP 10248, Ouagadougou, Burkina Faso.|Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.|Mother Offspring Malaria Studies (MOMS) Project, Seattle Biomedical Research Institute, Seattle, WA, USA.|Muheza Designated District Hospital, Muheza, Tanzania.|University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania.|Department of Nutrition and Food Science, University of Ghana, Legon, Ghana.|GroundWork, Flasch, Switzerland.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Centre for Clinical Vaccinology and Tropical Medicine and the Jenner Institute Laboratories, University of Oxford, Oxford, UK.|Wellcome Sanger Institute, Hinxton, UK.|MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.|WorldFish, Bayan Lepas, Malaysia.|Helen Keller International, Yaounde, Cameroon.|Department of Nutrition, University of California, Davis, Davis, CA, USA.|SAHMRi Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.|School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.|Food, Nutrition, and Health, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Pediatrics, Emory University and Emory Global Health Institute, Atlanta, GA, USA.|Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.|Department of Infectious Diseases and Institute of Global Health Innovation, Imperial College, London, UK.|Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.|Department of Paediatrics, University of Oxford, Oxford, UK.