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Publications

Preprint Epublish 1 citation

PubMed: 38196596 DOI: 10.1101/2023.12.19.23300265

Longitudinal changes in iron homeostasis in human experimental and clinical malaria.

medRxiv

Authors: Stephen D Woolley, Matthew J Grigg, Louise Marquart, Jeremy Gower, Kim Piera, Arya Sheela Nair, Fiona M Amante, Giri S Rajahram, Timothy William, David M Frazer, Stephan Chalon, James S McCarthy, Nicholas M Anstey, Bridget E Barber

Affiliations

  • Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Clinical Sciences Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
  • Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, United Kingdom.
  • Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
  • Infectious Diseases Society Kota Kinabalu Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Malaysia.
  • School of Public Health, University of Queensland, Brisbane, Australia.
  • Department of Medicine, Queen Elizabeth II Hospital, Kota Kinabalu, Malaysia.
  • Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia.
  • Subang Jaya Medical Centre, Subang Jaya, Malaysia.
  • Medicines for Malaria Venture, Geneva, Switzerland.
  • Victorian Infectious Diseases Institute, Peter Doherty Institute, University of Melbourne, Melbourne, Australia.
  • Infectious Diseases Department, Royal Brisbane and Women's Hospital, Brisbane, Australia.

Abstract

Background

The interaction between iron deficiency and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria.

Methods

We retrieved samples and associated data from 55 participants enrolled in malaria VIS, and 171 malaria patients and 30 healthy controls enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA.

Results

In the VIS, participants' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline iron status (ferritin) was associated with post-treatment increases in liver transaminase levels. In Malaysian malaria patients, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. Hepcidin normalised by day 28; however, ferritin and sTfR both remained elevated 4 weeks following admission.

Conclusion

Our findings demonstrate that parasitaemia is associated with an individual's MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency.

MeSH

Infections, Malaria, Homeostasis, Hepcidins, Ferritins