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Published in: Malaria Journal 1/2014

Open Access 01-12-2014 | Research

The effect of timing of iron supplementation on iron absorption and haemoglobin in post-malaria anaemia: a longitudinal stable isotope study in Malawian toddlers

Authors: Dominik Glinz, Moses Kamiyango, Kamija S Phiri, Francis Munthali, Christophe Zeder, Michael B Zimmermann, Richard F Hurrell, Rita Wegmüller

Published in: Malaria Journal | Issue 1/2014

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Abstract

Background

In sub-Saharan Africa, children with Plasmodium falciparum malaria and anaemia are often given iron supplementation at the time of malaria treatment. Inflammation during and after malaria may decrease iron absorption, thus, absorption might be improved if the start of supplementation is delayed. The study objective was to measure iron absorption from iron supplements started immediately or delayed by two weeks after completion of therapy against uncomplicated P. falciparum malaria.

Methods

Malawian toddlers (n = 48; age 12–24 months) were alternatively assigned to two groups according to their appearance at the health centre: group A was provided iron supplements (30 mg Fe daily) as a FeSO4-containing syrup for eight weeks starting immediately after malarial treatment; group B was given the iron after a two-week delay. Iron absorption from the syrup was measured on the first day of iron supplementation, and after two and eight weeks in both groups. Haemoglobin (Hb), iron status and inflammation were assessed every two weeks. Fractional iron absorption at each time point and cumulative absorption was quantified by measuring erythrocyte incorporation of 57Fe and compared using mixed models.

Results

Comparing group A and B, geometric mean iron absorption did not differ on the first day of supplementation (9.0% vs. 11.4%, P = 0.213) and cumulative iron absorption from the three time points did not differ (6.0% vs. 7.2%, P = 0.124). Hb concentration increased in both groups two weeks after malaria treatment (P < 0.001) and did not differ after eight weeks of supplementation (P = 0.542).

Conclusions

In anaemic toddlers after uncomplicated malaria, a two-week delay in starting iron supplementation did not significantly increase iron absorption or Hb concentration. Iron absorption is sufficiently high in the immediate post-malaria period to warrant supplementation. These findings suggest there is no need to change the current practice of immediate iron supplementation in this setting.

Trial registration

This trial was registered at Pan African Clinical Trials Registry (pactr.​org) as PACTR2010050002141682.
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Literature
1.
go back to reference WHO: Worldwide Prevalence of Anaemia 1993–2005. 2008, Geneva: World Health Organization WHO: Worldwide Prevalence of Anaemia 1993–2005. 2008, Geneva: World Health Organization
2.
go back to reference Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, Regan M, Weatherall D, Chou DP, Eisele TP, Flaxman SR, Pullan RL, Brooker SJ, Murray CJ: A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2013, 123: 615-624.CrossRefPubMed Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, Regan M, Weatherall D, Chou DP, Eisele TP, Flaxman SR, Pullan RL, Brooker SJ, Murray CJ: A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2013, 123: 615-624.CrossRefPubMed
3.
go back to reference Shaw JG, Friedman JF: Iron deficiency anemia: focus on infectious diseases in lesser developed countries. Anemia. 2011, 260380: 1-10.CrossRef Shaw JG, Friedman JF: Iron deficiency anemia: focus on infectious diseases in lesser developed countries. Anemia. 2011, 260380: 1-10.CrossRef
4.
go back to reference Howard CT, McKakpo US, Quakyi IA, Bosompem KM, Addison EA, Sun K, Sullivan D, Semba RD: Relationship of hepcidin with parasitemia and anemia among patients with uncomplicated Plasmodium falciparum malaria in Ghana. Am J Trop Med Hyg. 2007, 77: 623-626.PubMed Howard CT, McKakpo US, Quakyi IA, Bosompem KM, Addison EA, Sun K, Sullivan D, Semba RD: Relationship of hepcidin with parasitemia and anemia among patients with uncomplicated Plasmodium falciparum malaria in Ghana. Am J Trop Med Hyg. 2007, 77: 623-626.PubMed
5.
go back to reference Doherty CP, Cox SE, Fulford AJ, Austin S, Hilmers DC, Abrams SA, Prentice AM: Iron incorporation and post-malaria anaemia. PLoS One. 2008, 3: e2133-10.1371/journal.pone.0002133.PubMedCentralCrossRefPubMed Doherty CP, Cox SE, Fulford AJ, Austin S, Hilmers DC, Abrams SA, Prentice AM: Iron incorporation and post-malaria anaemia. PLoS One. 2008, 3: e2133-10.1371/journal.pone.0002133.PubMedCentralCrossRefPubMed
6.
go back to reference Cercamondi CI, Egli IM, Ahouandjinou E, Dossa R, Zeder C, Salami L, Tjalsma H, Wiegerinck E, Tanno T, Hurrell RF, Hounhouigan J, Zimmermann MB: Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women. Am J Clin Nutr. 2010, 92: 1385-1392. 10.3945/ajcn.2010.30051.PubMedCentralCrossRefPubMed Cercamondi CI, Egli IM, Ahouandjinou E, Dossa R, Zeder C, Salami L, Tjalsma H, Wiegerinck E, Tanno T, Hurrell RF, Hounhouigan J, Zimmermann MB: Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women. Am J Clin Nutr. 2010, 92: 1385-1392. 10.3945/ajcn.2010.30051.PubMedCentralCrossRefPubMed
7.
go back to reference Prentice AM, Ghattas H, Doherty C, Cox SE: Iron metabolism and malaria. Food Nutr Bull. 2007, 28: 524-539. Prentice AM, Ghattas H, Doherty C, Cox SE: Iron metabolism and malaria. Food Nutr Bull. 2007, 28: 524-539.
8.
go back to reference Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I, Cuevas LE, de Haan RJ, Phiri AI, Malange P, Khoka M, Hulshof PJ, van Lieshout L, Beld MG, Teo YY, Rockett KA, Richardson A, Kwiatkowski DP, Molyneux ME, van Hensbroek MB: Severe anemia in Malawian children. N Engl J Med. 2008, 358: 888-899. 10.1056/NEJMoa072727.CrossRefPubMed Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I, Cuevas LE, de Haan RJ, Phiri AI, Malange P, Khoka M, Hulshof PJ, van Lieshout L, Beld MG, Teo YY, Rockett KA, Richardson A, Kwiatkowski DP, Molyneux ME, van Hensbroek MB: Severe anemia in Malawian children. N Engl J Med. 2008, 358: 888-899. 10.1056/NEJMoa072727.CrossRefPubMed
9.
go back to reference WHO: Conclusions and recommendations of the WHO consultations on prevention and control of iron deficiency in infants and young children in malaria endemic areas. Food Nutr Bull. 2007, 28: S621-S627. WHO: Conclusions and recommendations of the WHO consultations on prevention and control of iron deficiency in infants and young children in malaria endemic areas. Food Nutr Bull. 2007, 28: S621-S627.
10.
go back to reference Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S, Othman MK, Kabole FM: Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet. 2006, 367: 133-143. 10.1016/S0140-6736(06)67962-2.CrossRefPubMed Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S, Othman MK, Kabole FM: Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet. 2006, 367: 133-143. 10.1016/S0140-6736(06)67962-2.CrossRefPubMed
11.
go back to reference Zimmermann MB, Troesch B, Biebinger R, Egli I, Zeder C, Hurrell RF: Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin. Am J Clin Nutr. 2009, 90: 1280-1287. 10.3945/ajcn.2009.28129.CrossRefPubMed Zimmermann MB, Troesch B, Biebinger R, Egli I, Zeder C, Hurrell RF: Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin. Am J Clin Nutr. 2009, 90: 1280-1287. 10.3945/ajcn.2009.28129.CrossRefPubMed
12.
go back to reference Troesch B, Egli I, Zeder C, Hurrell RF, Zimmermann MB: Fortification iron as ferrous sulfate plus ascorbic acid Is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women. J Nutr. 2011, 141: 822-827. 10.3945/jn.110.136127.CrossRefPubMed Troesch B, Egli I, Zeder C, Hurrell RF, Zimmermann MB: Fortification iron as ferrous sulfate plus ascorbic acid Is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women. J Nutr. 2011, 141: 822-827. 10.3945/jn.110.136127.CrossRefPubMed
13.
go back to reference WHO: Management of Severe Malaria: A Pratical Handbook. 2012, Geneva: World Health Organization, 3 WHO: Management of Severe Malaria: A Pratical Handbook. 2012, Geneva: World Health Organization, 3
14.
go back to reference Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE: Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr. 2004, 134: 3127-3132.PubMed Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE: Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr. 2004, 134: 3127-3132.PubMed
15.
go back to reference Walczyk T, Davidsson L, Zavaleta N, Hurrell RF: Stable isotope labels as a tool to determine the iron absorption by Peruvian school children from a breakfast meal. Fresenius J Anal Chem. 1997, 359: 445-449. 10.1007/s002160050608.CrossRef Walczyk T, Davidsson L, Zavaleta N, Hurrell RF: Stable isotope labels as a tool to determine the iron absorption by Peruvian school children from a breakfast meal. Fresenius J Anal Chem. 1997, 359: 445-449. 10.1007/s002160050608.CrossRef
16.
go back to reference Linderkamp O, Versmold HT, Riegel KP, Betke K: Estimation and prediction of blood volume in infants and children. Eur J Pediatr. 1977, 125: 227-234. 10.1007/BF00493567.CrossRefPubMed Linderkamp O, Versmold HT, Riegel KP, Betke K: Estimation and prediction of blood volume in infants and children. Eur J Pediatr. 1977, 125: 227-234. 10.1007/BF00493567.CrossRefPubMed
17.
go back to reference Harrington M, Hotz C, Zeder C, Polvo GO, Villalpando S, Zimmermann MB, Walczyk T, Rivera JA, Hurrell RF: A comparison of the bioavailability of ferrous fumarate and ferrous sulfate in non-anemic Mexican women and children consuming a sweetened maize and milk drink. Eur J Clin Nutr. 2011, 65: 20-25. 10.1038/ejcn.2010.185.CrossRefPubMed Harrington M, Hotz C, Zeder C, Polvo GO, Villalpando S, Zimmermann MB, Walczyk T, Rivera JA, Hurrell RF: A comparison of the bioavailability of ferrous fumarate and ferrous sulfate in non-anemic Mexican women and children consuming a sweetened maize and milk drink. Eur J Clin Nutr. 2011, 65: 20-25. 10.1038/ejcn.2010.185.CrossRefPubMed
18.
go back to reference WHO: Diagnosis of Malaria. 1990, Geneva: World Health Organization WHO: Diagnosis of Malaria. 1990, Geneva: World Health Organization
19.
go back to reference Cook JD: Diagnosis and management of iron-deficiency anaemia. Best Pract Res Cl Ha. 2005, 18: 319-332. 10.1016/j.beha.2004.08.022.CrossRef Cook JD: Diagnosis and management of iron-deficiency anaemia. Best Pract Res Cl Ha. 2005, 18: 319-332. 10.1016/j.beha.2004.08.022.CrossRef
20.
go back to reference Hurrell RF, Lynch S, Bothwell T, Cori H, Glahn R, Hertrampf E, Kratky Z, Miller D, Rodenstein M, Streekstra H, Teucher B, Turner E, Yeung CK, Zimmermann MB: Enhancing the absorption of fortification iron. A SUSTAIN Task Force report. Int J Vitam Nutr Res. 2004, 74: 387-401. 10.1024/0300-9831.74.6.387.CrossRefPubMed Hurrell RF, Lynch S, Bothwell T, Cori H, Glahn R, Hertrampf E, Kratky Z, Miller D, Rodenstein M, Streekstra H, Teucher B, Turner E, Yeung CK, Zimmermann MB: Enhancing the absorption of fortification iron. A SUSTAIN Task Force report. Int J Vitam Nutr Res. 2004, 74: 387-401. 10.1024/0300-9831.74.6.387.CrossRefPubMed
21.
22.
go back to reference McDevitt MA, Xie J, Gordeuk V, Bucala R: The anemia of malaria infection: role of inflammatory cytokines. Curr Hematol Rep. 2004, 3: 97-106.PubMed McDevitt MA, Xie J, Gordeuk V, Bucala R: The anemia of malaria infection: role of inflammatory cytokines. Curr Hematol Rep. 2004, 3: 97-106.PubMed
23.
go back to reference Casals-Pascual C, Huang H, Lakhal-Littleton S, Thezenas ML, Kai O, Newton CR, Roberts DJ: Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria. Haematologica. 2012, 97: 1695-1698. 10.3324/haematol.2012.065854.PubMedCentralCrossRefPubMed Casals-Pascual C, Huang H, Lakhal-Littleton S, Thezenas ML, Kai O, Newton CR, Roberts DJ: Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria. Haematologica. 2012, 97: 1695-1698. 10.3324/haematol.2012.065854.PubMedCentralCrossRefPubMed
24.
go back to reference Huang H, Lamikanra AA, Alkaitis MS, Thezenas ML, Ramaprasad A, Moussa E, Roberts DJ, Casals-Pascual C: Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria. PLoS One. 2014, 9: e88408-10.1371/journal.pone.0088408.PubMedCentralCrossRefPubMed Huang H, Lamikanra AA, Alkaitis MS, Thezenas ML, Ramaprasad A, Moussa E, Roberts DJ, Casals-Pascual C: Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria. PLoS One. 2014, 9: e88408-10.1371/journal.pone.0088408.PubMedCentralCrossRefPubMed
25.
go back to reference Skorokhod OA, Caione L, Marrocco T, Migliardi G, Barrera V, Arese P, Piacibello W, Schwarzer E: Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin-generated 4-hydroxynonenal. Blood. 2010, 116: 4328-4337. 10.1182/blood-2010-03-272781.CrossRefPubMed Skorokhod OA, Caione L, Marrocco T, Migliardi G, Barrera V, Arese P, Piacibello W, Schwarzer E: Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin-generated 4-hydroxynonenal. Blood. 2010, 116: 4328-4337. 10.1182/blood-2010-03-272781.CrossRefPubMed
26.
go back to reference van Hensbroek MB, Morris-Jones S, Meisner S, Jaffar S, Bayo L, Dackour R, Phillips C, Greenwood BM: Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria. Trans R Soc Trop Med Hyg. 1995, 89: 672-676. 10.1016/0035-9203(95)90438-7.CrossRefPubMed van Hensbroek MB, Morris-Jones S, Meisner S, Jaffar S, Bayo L, Dackour R, Phillips C, Greenwood BM: Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria. Trans R Soc Trop Med Hyg. 1995, 89: 672-676. 10.1016/0035-9203(95)90438-7.CrossRefPubMed
27.
go back to reference Okebe JU, Yahav D, Shbita R, Paul M: Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2011, 10: CD006589-PubMed Okebe JU, Yahav D, Shbita R, Paul M: Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2011, 10: CD006589-PubMed
28.
go back to reference Hurrell R: Iron and malaria: absorption, efficacy and safety. Int J Vitam Nutr Res. 2010, 80: 279-292. 10.1024/0300-9831/a000035.CrossRefPubMed Hurrell R: Iron and malaria: absorption, efficacy and safety. Int J Vitam Nutr Res. 2010, 80: 279-292. 10.1024/0300-9831/a000035.CrossRefPubMed
29.
go back to reference Zimmermann MB, Chassard C, Rohner F, N’Goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF: The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Côte d’Ivoire. Am J Clin Nutr. 2010, 92: 1406-1415. 10.3945/ajcn.110.004564.CrossRefPubMed Zimmermann MB, Chassard C, Rohner F, N’Goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF: The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Côte d’Ivoire. Am J Clin Nutr. 2010, 92: 1406-1415. 10.3945/ajcn.110.004564.CrossRefPubMed
30.
go back to reference Brunser O, Espinoza J, Araya M, Pacheco I, Cruchet S: Chronic iron intake and diarrhoeal disease in infants. A field study in a less-developed country. Eur J Clin Nutr. 1993, 47: 317-326.PubMed Brunser O, Espinoza J, Araya M, Pacheco I, Cruchet S: Chronic iron intake and diarrhoeal disease in infants. A field study in a less-developed country. Eur J Clin Nutr. 1993, 47: 317-326.PubMed
31.
go back to reference Soofi S, Cousens S, Iqbal SP, Akhund T, Khan J, Ahmed I, Zaidi AK, Bhutta ZA: Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial. Lancet. 2013, 382: 29-40. 10.1016/S0140-6736(13)60437-7.CrossRefPubMed Soofi S, Cousens S, Iqbal SP, Akhund T, Khan J, Ahmed I, Zaidi AK, Bhutta ZA: Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial. Lancet. 2013, 382: 29-40. 10.1016/S0140-6736(13)60437-7.CrossRefPubMed
33.
go back to reference Makanga M, Krudsood S: The clinical efficacy of artemether/lumefantrine (Coartem). Malar J. 2009, 8 Suppl 1: 5-CrossRef Makanga M, Krudsood S: The clinical efficacy of artemether/lumefantrine (Coartem). Malar J. 2009, 8 Suppl 1: 5-CrossRef
Metadata
Title
The effect of timing of iron supplementation on iron absorption and haemoglobin in post-malaria anaemia: a longitudinal stable isotope study in Malawian toddlers
Authors
Dominik Glinz
Moses Kamiyango
Kamija S Phiri
Francis Munthali
Christophe Zeder
Michael B Zimmermann
Richard F Hurrell
Rita Wegmüller
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2014
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-13-397

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