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Published in: BMC Medicine 1/2020

01-12-2020 | Malaria | Research article

Estimating the burden of iron deficiency among African children

Authors: John Muthii Muriuki, Alexander J. Mentzer, Emily L. Webb, Alireza Morovat, Wandia Kimita, Francis M. Ndungu, Alex W. Macharia, Rosie J. Crane, James A. Berkley, Swaib A. Lule, Clare Cutland, Sodiomon B. Sirima, Amidou Diarra, Alfred B. Tiono, Philip Bejon, Shabir A. Madhi, Adrian V. S. Hill, Andrew M. Prentice, Parminder S. Suchdev, Alison M. Elliott, Thomas N. Williams, Sarah H. Atkinson

Published in: BMC Medicine | Issue 1/2020

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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 incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children.

Methods

We assayed iron and inflammatory biomarkers in 4853 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, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard.

Results

The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard.

Conclusions

The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.
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Literature
1.
go back to reference Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood J. 2014;123:615–25.CrossRef Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood J. 2014;123:615–25.CrossRef
2.
go back to reference GBD-2016-Disease-and-Injury-Incidence-and-Prevalence-Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211–59.CrossRef GBD-2016-Disease-and-Injury-Incidence-and-Prevalence-Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211–59.CrossRef
3.
go back to reference Mccann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr. 2007;85:931–45.CrossRef Mccann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr. 2007;85:931–45.CrossRef
4.
go back to reference Suchdev PS, Williams AM, Mei Z, Flores-ayala R, Pasricha S, Rogers LM. Assessment of iron status in settings of inflammation : challenges and potential approaches. Am J Clin Nutr. 2017;106:1626–33.CrossRef Suchdev PS, Williams AM, Mei Z, Flores-ayala R, Pasricha S, Rogers LM. Assessment of iron status in settings of inflammation : challenges and potential approaches. Am J Clin Nutr. 2017;106:1626–33.CrossRef
5.
go back to reference Northrop-Clewes CA. Interpreting indicators of iron status during an acute phase response--lessons from malaria and human immunodeficiency virus. Ann Clin Biochem. 2008;45:18–32.CrossRef Northrop-Clewes CA. Interpreting indicators of iron status during an acute phase response--lessons from malaria and human immunodeficiency virus. Ann Clin Biochem. 2008;45:18–32.CrossRef
6.
go back to reference Phiri KS, Calis JCJ, Kachala D, Borgstein E, Waluza J, Bates I, et al. Improved method for assessing iron stores in the bone marrow. J Clin Pathol. 2009;62:685–9.CrossRef Phiri KS, Calis JCJ, Kachala D, Borgstein E, Waluza J, Bates I, et al. Improved method for assessing iron stores in the bone marrow. J Clin Pathol. 2009;62:685–9.CrossRef
8.
go back to reference World Health Organization and Centers for Disease Control (CDC). Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzer. 2007. World Health Organization and Centers for Disease Control (CDC). Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level, Geneva, Switzer. 2007.
9.
go back to reference Feelders RA, Vreugdenhil G, Eggermont AMM, Kuiper-Kramer PA, van Eijk HG, Swaak AJG. Regulation of iron metabolism in the acute-phase response : interferon gamma and tumour necrosis factor alpha induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients. Eur J Clin Investig. 1998;28:520–7.CrossRef Feelders RA, Vreugdenhil G, Eggermont AMM, Kuiper-Kramer PA, van Eijk HG, Swaak AJG. Regulation of iron metabolism in the acute-phase response : interferon gamma and tumour necrosis factor alpha induce hypoferraemia, ferritin production and a decrease in circulating transferrin receptors in cancer patients. Eur J Clin Investig. 1998;28:520–7.CrossRef
10.
go back to reference Namaste SML, Rohner F, Huang J, Bhushan NL, Flores-ayala R, Kupka R, et al. Adjusting ferritin concentrations for inflammation : Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia ( BRINDA ) project. Am J Clin Nutr. 2017;106(Suppl):359S–71S.PubMedPubMedCentral Namaste SML, Rohner F, Huang J, Bhushan NL, Flores-ayala R, Kupka R, et al. Adjusting ferritin concentrations for inflammation : Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia ( BRINDA ) project. Am J Clin Nutr. 2017;106(Suppl):359S–71S.PubMedPubMedCentral
11.
go back to reference Mast AE, Blinder MA, Gronowski AM, Chumley C, Scott MG. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem. 1998;44:45–51.CrossRef Mast AE, Blinder MA, Gronowski AM, Chumley C, Scott MG. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem. 1998;44:45–51.CrossRef
12.
go back to reference Menendez C, Quinto LL, Kahigwa E, Alvarez L, Fernandez R, Gimenez N, et al. Effect of malaria on soluble transferrin receptor levels in Tanzanian infants. Am J Trop Med Hyg. 2001;65:138–42.CrossRef Menendez C, Quinto LL, Kahigwa E, Alvarez L, Fernandez R, Gimenez N, et al. Effect of malaria on soluble transferrin receptor levels in Tanzanian infants. Am J Trop Med Hyg. 2001;65:138–42.CrossRef
13.
go back to reference Verhoef H, West CE, Ndeto P, Burema J, Beguin Y, Kok FJ. Serum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria. Am J Clin Nutr. 2001;74:767–75.CrossRef Verhoef H, West CE, Ndeto P, Burema J, Beguin Y, Kok FJ. Serum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria. Am J Clin Nutr. 2001;74:767–75.CrossRef
14.
go back to reference Rohner F, Namaste SM, Larson LM, Addo OY, Mei Z, Suchdev PS, et al. Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106:372S–82S.PubMedPubMedCentral Rohner F, Namaste SM, Larson LM, Addo OY, Mei Z, Suchdev PS, et al. Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106:372S–82S.PubMedPubMedCentral
15.
go back to reference Foote EM, Sullivan KM, Ruth LJ, Oremo J, Sadumah I, Williams TN, et al. Determinants of Anemia among Preschool Children in Rural , Western Kenya. Am J Trop Med Hyg. 2013;88:757–64.CrossRef Foote EM, Sullivan KM, Ruth LJ, Oremo J, Sadumah I, Williams TN, et al. Determinants of Anemia among Preschool Children in Rural , Western Kenya. Am J Trop Med Hyg. 2013;88:757–64.CrossRef
16.
go back to reference Namaste SML, Aaron GJ, Varadhan R, Peerson JM, Suchdev PS. Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106(Suppl 1):333–47. Namaste SML, Aaron GJ, Varadhan R, Peerson JM, Suchdev PS. Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2017;106(Suppl 1):333–47.
17.
go back to reference Bejon P, Williams TN, Liljander A, Noor AM, Wambua J, Marsh K. Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya. PLoS Med. 2010;7:e1000304.CrossRef Bejon P, Williams TN, Liljander A, Noor AM, Wambua J, Marsh K. Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya. PLoS Med. 2010;7:e1000304.CrossRef
18.
go back to reference Elliott AM, Kizza M, Quigley MA, Ndibazza J, Nampijja M, Muhangi L, et al. The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood. Clin Trials. 2007;4:42–57.CrossRef Elliott AM, Kizza M, Quigley MA, Ndibazza J, Nampijja M, Muhangi L, et al. The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood. Clin Trials. 2007;4:42–57.CrossRef
19.
go back to reference Tiono AB, Nebie I, Anagnostou N, Coulibaly AS, Bowyer G, Lam E, et al. First field efficacy trial of the ChAd63 MVA ME- TRAP vectored malaria vaccine candidate in 5–17 months old infants and children. PLoS One. 2018;13:e0208328.CrossRef Tiono AB, Nebie I, Anagnostou N, Coulibaly AS, Bowyer G, Lam E, et al. First field efficacy trial of the ChAd63 MVA ME- TRAP vectored malaria vaccine candidate in 5–17 months old infants and children. PLoS One. 2018;13:e0208328.CrossRef
20.
go back to reference Nunes MC, Cutland CL, Jones S, Hugo A, Madimabe R, Simões EAF, et al. Duration of infant protection against influenza illness conferred by maternal immunization. JAMA Pediatr. 2016;170:840.CrossRef Nunes MC, Cutland CL, Jones S, Hugo A, Madimabe R, Simões EAF, et al. Duration of infant protection against influenza illness conferred by maternal immunization. JAMA Pediatr. 2016;170:840.CrossRef
21.
go back to reference Atkinson SH, Rockett K, Sirugo G, Bejon PA, Fulford A, O’Connell MA, et al. Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype. PLoS Med. 2006;3:652–8.CrossRef Atkinson SH, Rockett K, Sirugo G, Bejon PA, Fulford A, O’Connell MA, et al. Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype. PLoS Med. 2006;3:652–8.CrossRef
22.
go back to reference Wray K, Allen A, Evans E, Fisher C, Premawardhena A, Perera L, et al. Hepcidin detects iron deficiency in Sri Lankan adolescents with a high burden of hemoglobinopathy: A diagnostic test accuracy study. Am J Hematol. 2017;92:196–203.CrossRef Wray K, Allen A, Evans E, Fisher C, Premawardhena A, Perera L, et al. Hepcidin detects iron deficiency in Sri Lankan adolescents with a high burden of hemoglobinopathy: A diagnostic test accuracy study. Am J Hematol. 2017;92:196–203.CrossRef
24.
go back to reference Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003;101:3359–64.CrossRef Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003;101:3359–64.CrossRef
25.
go back to reference Phiri KS, Calis JCJ, Siyasiya A, Bates I, Brabin B, van Hensbroek MB. New cut-off values for ferritin and soluble transferrin receptor for the assessment of iron deficiency in children in a high infection pressure area. J Clin Pathol. 2009;62:1103–6.CrossRef Phiri KS, Calis JCJ, Siyasiya A, Bates I, Brabin B, van Hensbroek MB. New cut-off values for ferritin and soluble transferrin receptor for the assessment of iron deficiency in children in a high infection pressure area. J Clin Pathol. 2009;62:1103–6.CrossRef
26.
go back to reference Yamanishi H, Iyama S, Yamaguchi Y, Kanakura Y, Iwatani Y. Total iron-binding capacity calculated from serum transferrin concentration or serum iron concentration and unsaturated iron-binding capacity. Clin Chem. 2003;49:175–8.CrossRef Yamanishi H, Iyama S, Yamaguchi Y, Kanakura Y, Iwatani Y. Total iron-binding capacity calculated from serum transferrin concentration or serum iron concentration and unsaturated iron-binding capacity. Clin Chem. 2003;49:175–8.CrossRef
27.
go back to reference World Health Organization. Iron deficiency anaemia: assessment, prevention, and control. A Guide for Programme Managers. 2001. World Health Organization. Iron deficiency anaemia: assessment, prevention, and control. A Guide for Programme Managers. 2001.
29.
30.
go back to reference Snow RW, Sartorius B, Kyalo D, Maina J, Amratia P, Mundia CW, et al. The prevalence of Plasmodium falciparum in sub-Saharan Africa since 1900. Nature. 2017;550:515–8.CrossRef Snow RW, Sartorius B, Kyalo D, Maina J, Amratia P, Mundia CW, et al. The prevalence of Plasmodium falciparum in sub-Saharan Africa since 1900. Nature. 2017;550:515–8.CrossRef
31.
go back to reference Ziegler EE, Nelson SE, Jeter JM. Iron stores of breastfed infants during the first year of life. Nutrients. 2014;6:2023–34.CrossRef Ziegler EE, Nelson SE, Jeter JM. Iron stores of breastfed infants during the first year of life. Nutrients. 2014;6:2023–34.CrossRef
32.
go back to reference Tamura T, Hou J, Goldenberg RL, Johnston KE, Cliver SP. Gender difference in cord serum ferritin concentrations. Biol Neonate. 1999;75:343–9.CrossRef Tamura T, Hou J, Goldenberg RL, Johnston KE, Cliver SP. Gender difference in cord serum ferritin concentrations. Biol Neonate. 1999;75:343–9.CrossRef
33.
go back to reference Domellof M, Lonnerdal B, Dewey KG, Cohen RJ, Rivera L, Hernell O. Sex Differences in Iron Status During Infancy. Pediatrics. 2002;110:545–52.CrossRef Domellof M, Lonnerdal B, Dewey KG, Cohen RJ, Rivera L, Hernell O. Sex Differences in Iron Status During Infancy. Pediatrics. 2002;110:545–52.CrossRef
34.
go back to reference Jaeggi T, Moretti D, Kvalsvig J, Holding PA, Tjalsma H, Kortman GAM, et al. Iron status and systemic inflammation, but not gut inflammation, strongly predict gender-specific concentrations of serum hepcidin in infants in rural Kenya. PLoS One. 2013;8:1–8.CrossRef Jaeggi T, Moretti D, Kvalsvig J, Holding PA, Tjalsma H, Kortman GAM, et al. Iron status and systemic inflammation, but not gut inflammation, strongly predict gender-specific concentrations of serum hepcidin in infants in rural Kenya. PLoS One. 2013;8:1–8.CrossRef
35.
go back to reference Pediatrics I. Anemia and undernutrition among preschool children in Uttar Pradesh. India Indian Pediatr. 2003;40:985–90. Pediatrics I. Anemia and undernutrition among preschool children in Uttar Pradesh. India Indian Pediatr. 2003;40:985–90.
36.
go back to reference Büyükkaragöz B, Akgun NA, Bulus AD, Aydogdu SD, Bal C. Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition? Arch Argent Pediatr. 2017;115:125–32.PubMed Büyükkaragöz B, Akgun NA, Bulus AD, Aydogdu SD, Bal C. Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition? Arch Argent Pediatr. 2017;115:125–32.PubMed
37.
go back to reference Sumarmi S, Puspitasari N, Handajani R, Wirjatmadi B. Underweight as a risk factor for iron depletion and iron-deficient erythropoiesis among young women in rural areas of East Java, Indonesia. Mal J Nutr. 2016;22(2):219–32. Sumarmi S, Puspitasari N, Handajani R, Wirjatmadi B. Underweight as a risk factor for iron depletion and iron-deficient erythropoiesis among young women in rural areas of East Java, Indonesia. Mal J Nutr. 2016;22(2):219–32.
38.
go back to reference Aguilar R, Moraleda C, Quintó L, Renom M, Mussacate L, Macete E, et al. Challenges in the diagnosis of iron deficiency in children exposed to high prevalence of infections. PLoS One. 2012;7:3–9. Aguilar R, Moraleda C, Quintó L, Renom M, Mussacate L, Macete E, et al. Challenges in the diagnosis of iron deficiency in children exposed to high prevalence of infections. PLoS One. 2012;7:3–9.
39.
go back to reference Righetti AA, Wegmul̈ler R, Glinz D, Ouattara M, Adiossan LG, N’Goran EK, et al. Effects of inflammation and Plasmodium falciparum infection on soluble transferrin receptor and plasma ferritin concentration in different age groups: A prospective longitudinal study in Côte d’Ivoire. Am J Clin Nutr 2013;97:1364–1374.CrossRef Righetti AA, Wegmul̈ler R, Glinz D, Ouattara M, Adiossan LG, N’Goran EK, et al. Effects of inflammation and Plasmodium falciparum infection on soluble transferrin receptor and plasma ferritin concentration in different age groups: A prospective longitudinal study in Côte d’Ivoire. Am J Clin Nutr 2013;97:1364–1374.CrossRef
40.
go back to reference Wessells KR, Hess SY. Asymptomatic malaria infection affects the interpretation of biomarkers of iron and vitamin a status , even after adjusting for systemic inflammation , but does not affect plasma zinc concentrations among young children in Burkina Faso 1–3. J Nutr. 2014;144:2050–8.CrossRef Wessells KR, Hess SY. Asymptomatic malaria infection affects the interpretation of biomarkers of iron and vitamin a status , even after adjusting for systemic inflammation , but does not affect plasma zinc concentrations among young children in Burkina Faso 1–3. J Nutr. 2014;144:2050–8.CrossRef
Metadata
Title
Estimating the burden of iron deficiency among African children
Authors
John Muthii Muriuki
Alexander J. Mentzer
Emily L. Webb
Alireza Morovat
Wandia Kimita
Francis M. Ndungu
Alex W. Macharia
Rosie J. Crane
James A. Berkley
Swaib A. Lule
Clare Cutland
Sodiomon B. Sirima
Amidou Diarra
Alfred B. Tiono
Philip Bejon
Shabir A. Madhi
Adrian V. S. Hill
Andrew M. Prentice
Parminder S. Suchdev
Alison M. Elliott
Thomas N. Williams
Sarah H. Atkinson
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2020
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-020-1502-7

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