Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation

Filip C. Castberg, Lasse Maretty, Trine Staalsoe, Casper Hempel, Erik Clasen-Linde, Lars Hviid, Jorøgen A. L. Kurtzhals

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Abstract

Background: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial.
Methods: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed.
Results: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores.
Conclusions: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.
Original languageEnglish
Article number34
JournalMalaria Journal
Volume17
Issue number1
Number of pages12
ISSN1475-2875
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • A/J mice
  • FGF23
  • Hepcidin
  • Iron deficiency
  • Malaria
  • Plasmodium chabaudi AS

Cite this

Castberg, Filip C. ; Maretty, Lasse ; Staalsoe, Trine ; Hempel, Casper ; Clasen-Linde, Erik ; Hviid, Lars ; Kurtzhals, Jorøgen A. L. / Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation. In: Malaria Journal. 2018 ; Vol. 17, No. 1.
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title = "Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation",
abstract = "Background: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial.Methods: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed.Results: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores.Conclusions: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.",
keywords = "A/J mice, FGF23, Hepcidin, Iron deficiency, Malaria, Plasmodium chabaudi AS",
author = "Castberg, {Filip C.} and Lasse Maretty and Trine Staalsoe and Casper Hempel and Erik Clasen-Linde and Lars Hviid and Kurtzhals, {Jor{\o}gen A. L.}",
year = "2018",
doi = "10.1186/s12936-018-2186-8",
language = "English",
volume = "17",
journal = "Malaria Journal",
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Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation. / Castberg, Filip C.; Maretty, Lasse; Staalsoe, Trine; Hempel, Casper; Clasen-Linde, Erik; Hviid, Lars; Kurtzhals, Jorøgen A. L.

In: Malaria Journal, Vol. 17, No. 1, 34, 2018.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron deficiency can be reduced by short-term adjunctive iron supplementation

AU - Castberg, Filip C.

AU - Maretty, Lasse

AU - Staalsoe, Trine

AU - Hempel, Casper

AU - Clasen-Linde, Erik

AU - Hviid, Lars

AU - Kurtzhals, Jorøgen A. L.

PY - 2018

Y1 - 2018

N2 - Background: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial.Methods: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed.Results: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores.Conclusions: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.

AB - Background: Iron deficiency is the most widespread nutrient deficiency and an important cause of developmental impairment in children. However, some studies have indicated that iron deficiency can also protect against malaria, which is a leading cause of childhood morbidity and mortality in large parts of the world. This has rendered interventions against iron deficiency in malaria-endemic areas controversial.Methods: The effect of nutritional iron deficiency on the clinical outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of intravenous iron supplementation with ferric carboxymaltose were studied before and after parasite infection. Plasma levels of the iron status markers hepcidin and fibroblast growth factor 23 were measured in animals surviving and succumbing to malaria, and accompanying tissue pathology in the liver and the spleen was assessed.Results: Nutritional iron deficiency was associated with increased mortality from P. chabaudi malaria. This increased mortality could be partially offset by carefully timed, short-duration adjunctive iron supplementation. Moribund animals were characterized by low levels of hepcidin and high levels of fibroblast growth factor 23. All infected mice had extramedullary splenic haematopoiesis, and iron-supplemented mice had visually detectable intracellular iron stores.Conclusions: Blood transfusions are the only currently available means to correct severe anaemia in children with malaria. The potential of carefully timed, short-duration adjunctive iron supplementation as a safe alternative should be considered.

KW - A/J mice

KW - FGF23

KW - Hepcidin

KW - Iron deficiency

KW - Malaria

KW - Plasmodium chabaudi AS

U2 - 10.1186/s12936-018-2186-8

DO - 10.1186/s12936-018-2186-8

M3 - Journal article

VL - 17

JO - Malaria Journal

JF - Malaria Journal

SN - 1475-2875

IS - 1

M1 - 34

ER -