Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria

Sarah E. Cusick, Robert O. Opoka, Andrew S. Ssemata, Michael K. Georgieff, Chandy John

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. Objectives: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment. Design: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 mmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. Results: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 mmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 μg/L (95% CI: 84.2, 121.0 μg/L) compared with 152.9 μg/L (128.8, 181.6 μg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P <0.011]. Conclusions: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration.

Original languageEnglish (US)
Pages (from-to)919-925
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Volume103
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Antimalarials
Malaria
Iron
Cerebral Malaria
Anemia
Therapeutics
Hepcidins
Ferritins
Heme
Hemoglobins
Inflammation
Uganda
Standard of Care

Keywords

  • Hepcidin
  • Inflammation
  • Iron
  • Malaria
  • Timing of iron supplementation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria. / Cusick, Sarah E.; Opoka, Robert O.; Ssemata, Andrew S.; Georgieff, Michael K.; John, Chandy.

In: American Journal of Clinical Nutrition, Vol. 103, No. 3, 01.03.2016, p. 919-925.

Research output: Contribution to journalArticle

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abstract = "Background: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. Objectives: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment. Design: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 mmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. Results: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 mmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 μg/L (95{\%} CI: 84.2, 121.0 μg/L) compared with 152.9 μg/L (128.8, 181.6 μg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P <0.011]. Conclusions: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration.",
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T1 - Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria

AU - Cusick, Sarah E.

AU - Opoka, Robert O.

AU - Ssemata, Andrew S.

AU - Georgieff, Michael K.

AU - John, Chandy

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N2 - Background: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. Objectives: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment. Design: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 mmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. Results: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 mmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 μg/L (95% CI: 84.2, 121.0 μg/L) compared with 152.9 μg/L (128.8, 181.6 μg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P <0.011]. Conclusions: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration.

AB - Background: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. Objectives: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment. Design: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 mmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. Results: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 mmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 μg/L (95% CI: 84.2, 121.0 μg/L) compared with 152.9 μg/L (128.8, 181.6 μg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P <0.011]. Conclusions: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration.

KW - Hepcidin

KW - Inflammation

KW - Iron

KW - Malaria

KW - Timing of iron supplementation

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