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Estimating the Hidden Burden of Iron Deficiency Among African Children

30 Pages Posted: 17 May 2019

See all articles by John Muthii Muriuki

John Muthii Muriuki

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; Kenya Medical Research Institute (KEMRI) - Accredited Research Centre

Alexander J. Mentzer

University of Oxford - Wellcome Trust Centre for Human Genetics; University of Oxford - Li Ka Shing Centre for Health Information and Discovery

Emily Webb

London School of Hygiene and Tropical Medicine - Medical Research Council (MRC) Tropical Epidemiology Group

Alireza Morovat

Oxford University Hospitals - Department of Clinical Biochemistry

Wandia Kimita

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme

Francis M. Ndungu

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme

Alex W. Macharia

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme

Rosie J. Crane

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; University of Oxford - Centre for Tropical Medicine and Global Health

James A. Berkley

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; University of Oxford - Centre for Tropical Medicine and Global Health

Swaib A. Lule

University College London - Institute for Global Health; London School of Hygiene & Tropical Medicine; Government of Uganda - Uganda Virus Research Institute (UVRI)

Clare Cutland

University of the Witwatersrand - Faculty of Health Sciences

Sodiomon Sirima

Groupe de Recherche Action en Santé (GRAS); West African Network for Clinical Trials of Antimalarial Drugs (WANECAM); Ministry of Health, Burkina Faso - Centre National de Recherche et de Formation sur le Paludisme (CNRFP)

Amidou Diarra

Groupe de Recherche Action en Santé (GRAS); West African Network for Clinical Trials of Antimalarial Drugs (WANECAM); Ministry of Health, Burkina Faso - Centre National de Recherche et de Formation sur le Paludisme (CNRFP)

Alfred B. Tiono

Groupe de Recherche Action en Santé (GRAS)

Philip Bejon

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; University of Oxford - Centre for Tropical Medicine and Global Health

Shabir A. Madhi

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit

Adrian V. S. Hill

University of Oxford - The Jenner Institute; University of Oxford - Wellcome Trust Centre for Human Genetics; University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Andrew M. Prentice

London School of Hygiene & Tropical Medicine - Medical Research Council Unit The Gambia

Parminder S. Suchdev

Emory University

Alison M. Elliott

London School of Hygiene & Tropical Medicine; Government of Uganda - Uganda Virus Research Institute (UVRI)

Thomas N. Williams

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; University of Oxford - Centre for Tropical Medicine and Global Health; Imperial College London - Department of Medicine

Sarah H. Atkinson

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme; University of Oxford - Centre for Tropical Medicine and Global Health; University of Oxford - Department of Paediatrics

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Abstract

Background: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions.  However, ID may be commonly underestimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria.

Methods: We assayed iron and inflammatory biomarkers in 4,853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, malaria parasitaemia, inflammation, stunting, underweight, and wasting. We defined ID using the WHO ferritin-based definition (ferritin <12µg/L or <30µg/L in children with inflammation (CRP >5mg/L)) and then used regression modelling, correcting for inflammation and malaria, to estimate 'true' prevalence of ID. We further investigated the utility of other iron biomarkers in predicting ID.

Findings: The prevalence of ID was highest at one year of age and in male children. Stunting and underweight were associated with anaemia and iron deficient erythropoiesis. Inflammation and malaria parasitaemia significantly influenced all iron biomarkers, although transferrin saturation was least affected. The WHO definition of ID did not identify 27·0% of Burkinabe, 21·4% of Kenyan, 20·0% of Ugandan, 16·8% of Gambian, and 8·5% of South African children with 'true' iron deficiency. This 'hidden burden' increased with age and with increasing prevalence of inflammation and malaria. We observed similar prevalences of ID using regression modelling and transferrin saturation <11%.
 
Interpretation: The prevalence of ID may be underestimated in African children using the WHO definition because inflammation and malaria obscure the 'true' burden. Transferrin saturation is least affected by inflammation and malaria and may more accurately determine the burden of ID.

Funding Statement: This work was funded by Wellcome (Grant numbers [110255/Z/15/Z to SHA], [202800/Z/16/Z to TNW; 106289/Z/14/Z to AJM; and 064693, 079110, 095778 to AME] and with core awards to the KEMRI-Wellcome Trust Research Programme (203077/Z/16/Z), The Wellcome Centre for Human Genetics (090532/Z/09/Z, 203141) and the Wellcome Sanger Institute (098051, 206194). AJM was also supported by an Oxford University Clinical Academic School Transitional Fellowship and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. JMM was funded through the DELTAS Africa Initiative (DEL-15-003). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The Gambian studies were supported by National Institute of Child Health and Development, Bill and Melinda Gates Foundation, core funding MC-A760-5QX00 to the MRC Unit The Gambia/MRC International Nutrition Group by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. This project also received funding from the European Research Council (ERC) under the European Union’s (Seventh Framework Programme [FP7/2007-2013]) (Grant agreement No 294557 to AVSH).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: Ethical approvals were obtained for Kilifi, Kenya (by the Scientific Ethics Review Unit of the Kenya Medical Research Institute (KEMRI/SERU/CGMR-C/046/3257/2983)); Entebbe, Uganda (locally by the Uganda Virus Research Institute (GC/127/12/07/32) and Uganda National Council for Science and Technology (MV625), and in the UK by the London School of Hygiene and Tropical Medicine (A340) and Oxford Tropical Research (OTR) (39-12, 42-14 and 37-15) Ethics Committees); Banfora, Burkina Faso (by Ministere de la Recherche Scientifique et de l’Innovation in Burkina Faso (2014-12-151) and the OTR Ethics Committees (41-12)); Soweto, South Africa (by the University of Witwatersrand Human Research (M130714) and the OTR Ethics Committees (1042-13 and 42-14)); and West Kiang, The Gambia (by the Gambian Government/Medical Research Council Ethics Committee (874/830)).

Keywords: Iron deficiency; Ferritin; Transferrin saturation; Inflammation; Malaria; Malnutrition; African children

Suggested Citation

Muriuki, John Muthii and Mentzer, Alexander J. and Webb, Emily and Morovat, Alireza and Kimita, Wandia and Ndungu, Francis M. and Macharia, Alex W. and Crane, Rosie J. and Berkley, James A. and Lule, Swaib A. and Cutland, Clare and Sirima, Sodiomon and Diarra, Amidou and Tiono, Alfred B. and Bejon, Philip and Madhi, Shabir A. and Hill, Adrian V. S. and Prentice, Andrew M. and Suchdev, Parminder S. and Elliott, Alison M. and Williams, Thomas N. and Atkinson, Sarah H., Estimating the Hidden Burden of Iron Deficiency Among African Children (May 14, 2019). Available at SSRN: https://ssrn.com/abstract=3388821 or http://dx.doi.org/10.2139/ssrn.3388821

John Muthii Muriuki

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

Kenya Medical Research Institute (KEMRI) - Accredited Research Centre ( email )

Kenya

Alexander J. Mentzer

University of Oxford - Wellcome Trust Centre for Human Genetics

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - Li Ka Shing Centre for Health Information and Discovery ( email )

Oxford, OX3 7FZ
United Kingdom

Emily Webb

London School of Hygiene and Tropical Medicine - Medical Research Council (MRC) Tropical Epidemiology Group ( email )

Keppel Street
London, WC1E 7HT
United Kingdom

Alireza Morovat

Oxford University Hospitals - Department of Clinical Biochemistry ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Wandia Kimita

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

Francis M. Ndungu

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

Alex W. Macharia

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

Rosie J. Crane

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

University of Oxford - Centre for Tropical Medicine and Global Health ( email )

United Kingdom

James A. Berkley

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

University of Oxford - Centre for Tropical Medicine and Global Health ( email )

United Kingdom

Swaib A. Lule

University College London - Institute for Global Health

United Kingdom

London School of Hygiene & Tropical Medicine ( email )

Keppel Street
London, WC1E 7HT
United Kingdom

Government of Uganda - Uganda Virus Research Institute (UVRI) ( email )

Uganda

Clare Cutland

University of the Witwatersrand - Faculty of Health Sciences ( email )

7 York Rd
Parktown, Johannesburg 2193
South Africa

Sodiomon Sirima

Groupe de Recherche Action en Santé (GRAS) ( email )

Ouagadougou
Burkina Faso

West African Network for Clinical Trials of Antimalarial Drugs (WANECAM)

Bamako, 1805
Mali

Ministry of Health, Burkina Faso - Centre National de Recherche et de Formation sur le Paludisme (CNRFP) ( email )

Ouagadougou, BP 2208
Burkina Faso

Amidou Diarra

Groupe de Recherche Action en Santé (GRAS) ( email )

Ouagadougou
Burkina Faso

West African Network for Clinical Trials of Antimalarial Drugs (WANECAM)

Bamako, 1805
Mali

Ministry of Health, Burkina Faso - Centre National de Recherche et de Formation sur le Paludisme (CNRFP)

Ouagadougou, BP 2208
Burkina Faso

Alfred B. Tiono

Groupe de Recherche Action en Santé (GRAS) ( email )

Ouagadougou
Burkina Faso

Philip Bejon

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

University of Oxford - Centre for Tropical Medicine and Global Health ( email )

United Kingdom

Shabir A. Madhi

University of the Witwatersrand - Vaccines and Infectious Diseases Analytics Research Unit ( email )

Adrian V. S. Hill

University of Oxford - The Jenner Institute

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

University of Oxford - Wellcome Trust Centre for Human Genetics ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Andrew M. Prentice

London School of Hygiene & Tropical Medicine - Medical Research Council Unit The Gambia ( email )

Fajara
Gambia

Parminder S. Suchdev

Emory University ( email )

201 Dowman Drive
Atlanta, GA 30322
United States

Alison M. Elliott

London School of Hygiene & Tropical Medicine ( email )

Keppel Street
London, WC1E 7HT
United Kingdom

Government of Uganda - Uganda Virus Research Institute (UVRI) ( email )

Uganda

Thomas N. Williams

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

University of Oxford - Centre for Tropical Medicine and Global Health ( email )

United Kingdom

Imperial College London - Department of Medicine ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Sarah H. Atkinson (Contact Author)

Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme ( email )

Kilifi
Kenya

University of Oxford - Centre for Tropical Medicine and Global Health ( email )

United Kingdom

University of Oxford - Department of Paediatrics ( email )

United Kingdom

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