Malaria is a cause of iron deficiency in African children

John Muthii Muriuki; Alexander J. Mentzer; Ruth Mitchell; Emily L. Webb; Anthony O. Etyang; Catherine Kyobutungi; Alireza Morovat; Wandia Kimita; Francis M. Ndungu; Alex W. Macharia; Caroline J. Ngetsa; Johnstone Makale; Swaib A. Lule; Solomon K. Musani; Laura M. Raffield; Clare L. Cutland; Sodiomon B. Sirima; Amidou Diarra; Alfred B. Tiono; Michal Fried; Moses Gwamaka; Seth Adu-Afarwuah; James P. Wirth; Rita Wegmüller; Shabir A. Madhi; Robert W. Snow; Adrian V.S. Hill; Kirk A. Rockett; Manjinder S. Sandhu; Dominic P. Kwiatkowski; Andrew M. Prentice; Kendra A. Byrd; Alex Ndjebayi; Christine P. Stewart; Reina Engle-Stone; Tim J. Green; Crystal D. Karakochuk; Parminder S. Suchdev; Philip Bejon; Patrick E. Duffy; George Davey Smith; Alison M. Elliott; Thomas N. Williams; Sarah H. Atkinson

doi:10.1038/s41591-021-01238-4

Malaria is a cause of iron deficiency in African children

John Muthii Muriuki
, Alexander J. Mentzer
, Ruth Mitchell
, Emily L. Webb
, Anthony O. Etyang
, Catherine Kyobutungi
, Alireza Morovat
, Wandia Kimita
, Francis M. Ndungu
, Alex W. Macharia
, Caroline J. Ngetsa
, Johnstone Makale
, Swaib A. Lule
, Solomon K. Musani
, Laura M. Raffield
, Clare L. Cutland
, Sodiomon B. Sirima
, Amidou Diarra
, Alfred B. Tiono
, Michal Fried

Moses Gwamaka, Seth Adu-Afarwuah, James P. Wirth, Rita Wegmüller, Shabir A. Madhi, Robert W. Snow, Adrian V.S. Hill, Kirk A. Rockett, Manjinder S. Sandhu, Dominic P. Kwiatkowski, Andrew M. Prentice, Kendra A. Byrd, Alex Ndjebayi, Christine P. Stewart, Reina Engle-Stone, Tim J. Green, Crystal D. Karakochuk, Parminder S. Suchdev, Philip Bejon, Patrick E. Duffy, George Davey Smith, Alison M. Elliott, Thomas N. Williams, Sarah H. Atkinson

Department of Nutrition And Food Science

Wellcome Trust Research Laboratories Nairobi
Open University of Kenya
Nuffield Department of Medicine
Bristol Medical School
London School of Hygiene & Tropical Medicine
African Population and Health Research Center
Oxford University Hospitals NHS Foundation Trust
University of Mississippi
University of North Carolina at Chapel Hill
University of the Witwatersrand
06 BP 10248
US Department of Health and Human Services
Seattle Biomedical Research Institute
Muheza Designated District Hospital
University of Dar es Salaam
GroundWork
University of Oxford
Wellcome Sanger Institute
WorldFish
Helen Keller International
University of California at Davis
South Australian Health and Medical Research Institute
Adelaide University
University of British Columbia
Emory University School of Medicine
Imperial College London

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

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%.

Original language	English
Pages (from-to)	653-658
Number of pages	6
Journal	Nature Medicine
Volume	27
Issue number	4
DOIs	https://doi.org/10.1038/s41591-021-01238-4
Publication status	Published - Apr 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41591-021-01238-4

Cite this

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., ... Atkinson, S. H. (2021). Malaria is a cause of iron deficiency in African children. Nature Medicine, 27(4), 653-658. https://doi.org/10.1038/s41591-021-01238-4

@article{58cb49fbec164169a17312ca3334644d,

title = "Malaria is a cause of iron deficiency in African children",

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\%.",

author = "Muriuki, \{John Muthii\} and Mentzer, \{Alexander J.\} and Ruth Mitchell and Webb, \{Emily L.\} and Etyang, \{Anthony O.\} and Catherine Kyobutungi and Alireza Morovat and Wandia Kimita and Ndungu, \{Francis M.\} and Macharia, \{Alex W.\} and Ngetsa, \{Caroline J.\} and Johnstone Makale and Lule, \{Swaib A.\} and Musani, \{Solomon K.\} and Raffield, \{Laura M.\} and Cutland, \{Clare L.\} and Sirima, \{Sodiomon B.\} and Amidou Diarra and Tiono, \{Alfred B.\} and Michal Fried and Moses Gwamaka and Seth Adu-Afarwuah and Wirth, \{James P.\} and Rita Wegm{\"u}ller and Madhi, \{Shabir A.\} and Snow, \{Robert W.\} and Hill, \{Adrian V.S.\} and Rockett, \{Kirk A.\} and Sandhu, \{Manjinder S.\} and Kwiatkowski, \{Dominic P.\} and Prentice, \{Andrew M.\} and Byrd, \{Kendra A.\} and Alex Ndjebayi and Stewart, \{Christine P.\} and Reina Engle-Stone and Green, \{Tim J.\} and Karakochuk, \{Crystal D.\} and Suchdev, \{Parminder S.\} and Philip Bejon and Duffy, \{Patrick E.\} and \{Davey Smith\}, George and Elliott, \{Alison M.\} and Williams, \{Thomas N.\} and Atkinson, \{Sarah H.\}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2021",

month = apr,

doi = "10.1038/s41591-021-01238-4",

language = "English",

volume = "27",

pages = "653--658",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "4",

}

Muriuki, JM, Mentzer, AJ, Mitchell, R, Webb, EL, Etyang, AO, Kyobutungi, C, Morovat, A, Kimita, W, Ndungu, FM, Macharia, AW, Ngetsa, CJ, Makale, J, Lule, SA, Musani, SK, Raffield, LM, Cutland, CL, Sirima, SB, Diarra, A, Tiono, AB, Fried, M, Gwamaka, M, Adu-Afarwuah, S, Wirth, JP, Wegmüller, R, Madhi, SA, Snow, RW, Hill, AVS, Rockett, KA, Sandhu, MS, Kwiatkowski, DP, Prentice, AM, Byrd, KA, Ndjebayi, A, Stewart, CP, Engle-Stone, R, Green, TJ, Karakochuk, CD, Suchdev, PS, Bejon, P, Duffy, PE, Davey Smith, G, Elliott, AM, Williams, TN & Atkinson, SH 2021, 'Malaria is a cause of iron deficiency in African children', Nature Medicine, vol. 27, no. 4, pp. 653-658. https://doi.org/10.1038/s41591-021-01238-4

TY - JOUR

T1 - Malaria is a cause of iron deficiency in African children

AU - Muriuki, John Muthii

AU - Mentzer, Alexander J.

AU - Mitchell, Ruth

AU - Webb, Emily L.

AU - Etyang, Anthony O.

AU - Kyobutungi, Catherine

AU - Morovat, Alireza

AU - Kimita, Wandia

AU - Ndungu, Francis M.

AU - Macharia, Alex W.

AU - Ngetsa, Caroline J.

AU - Makale, Johnstone

AU - Lule, Swaib A.

AU - Musani, Solomon K.

AU - Raffield, Laura M.

AU - Cutland, Clare L.

AU - Sirima, Sodiomon B.

AU - Diarra, Amidou

AU - Tiono, Alfred B.

AU - Fried, Michal

AU - Gwamaka, Moses

AU - Adu-Afarwuah, Seth

AU - Wirth, James P.

AU - Wegmüller, Rita

AU - Madhi, Shabir A.

AU - Snow, Robert W.

AU - Hill, Adrian V.S.

AU - Rockett, Kirk A.

AU - Sandhu, Manjinder S.

AU - Kwiatkowski, Dominic P.

AU - Prentice, Andrew M.

AU - Byrd, Kendra A.

AU - Ndjebayi, Alex

AU - Stewart, Christine P.

AU - Engle-Stone, Reina

AU - Green, Tim J.

AU - Karakochuk, Crystal D.

AU - Suchdev, Parminder S.

AU - Bejon, Philip

AU - Duffy, Patrick E.

AU - Davey Smith, George

AU - Elliott, Alison M.

AU - Williams, Thomas N.

AU - Atkinson, Sarah H.

PY - 2021/4

Y1 - 2021/4

N2 - 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%.

AB - 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%.

UR - https://www.scopus.com/pages/publications/85101198218

U2 - 10.1038/s41591-021-01238-4

DO - 10.1038/s41591-021-01238-4

M3 - Article

C2 - 33619371

AN - SCOPUS:85101198218

SN - 1078-8956

VL - 27

SP - 653

EP - 658

JO - Nature Medicine

JF - Nature Medicine

IS - 4

ER -

Malaria is a cause of iron deficiency in African children

Abstract

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