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Effect of Iron Chelation Therapy on Recovery from Deep Coma in Children with Cerebral Malaria

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Gordeuk, Victor, Thuma, Philip, Brittenham, Gary, McLaren, Christine, Parry, Dean, Backenstose, Anita, Biemba, Godfrey, Msiska, Roland +5 more·1992·New England Journal of Medicine
DOI 10.1056/nejm199211193272101
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Abstract

BACKGROUND: Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy. METHODS: To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis. RESULTS: The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52). CONCLUSIONS: Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.

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  • Children suffering from cerebral malaria benefited from the addition of the iron chelator desferrioxamine to a standard anti-malaria treatment, as reflected by faster recurrence from coma and clearance of plasmodia, although this did not translate into a survival benefit.

    “Along this line children suffering from cerebral malaria benefited from the addition of the iron chelator desferrioxamine to a standard anti-malaria treatment, as reflected by faster recurrence from coma and clearance of plasmodia, although this did not translate into a survival benefit (Gordeuk et al., 1992; Mabeza et al., 1999), although anti-plasmodial innate immune responses were positively”

    From Iron at the interface of immunity and infection (2014) · cites this paper as Gordeuk et al., 1992

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  • Plasmodium falciparum requires considerable iron for growth, and lowering available iron provides a promising route to antimalarials.

    “the malarial parasite Plasmodium falciparum requires considerable iron for growth, and there is evidence that lowering the amount of available iron provides a promising route to antimalarials (e.g. [1478-1494]”

    From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1481]

  • Systemic Fe chelation by desferrioxamine can improve the clinical course of malaria, without providing an overt survival benefit.

    “Systemic Fe chelation by desferrioxamine can improve the clinical course of malaria, without, however, providing an overt survival benefit [236].”

    From The Iron age of host–microbe interactions (2015) · cites this paper as [236]

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Research works printed but not linked: 2

  1. [5]5. The malaria situation in 1976. WHO Chron 1978;32:9-17.
  2. [24]24. Ambrosio G, Zweier JL, Jacobus WE, Weisfeldt ML, Flaherty JT. Improv s o a o monn administration of deferoxamine at the time of reflow: the role of iron in the pathogenesis of reperfusion injury. Circulation 1987;76:906-15.

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Authors
Gordeuk, V., Thuma, P., Brittenham, G., McLaren, C., Parry, D., Backenstose, A., Biemba, G., Msiska, R., Holmes, L., McKinley, E., Vargas, L., Gilkeson, R., & Poltera, A. A.
Affiliations
  • MetroHealth Medical Center (US)
  • Pennsylvania State University (US)
  • Minnesota State University Moorhead (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1992-11-19
Volume
327
Issue
21
Pages
1473-1477
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199211193272101
OpenAlex
W1983646126
Cited by
210
References
23
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2018: 3 · 2016: 1 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 6
FWCI
19.69
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl042814-05)
  • U.S. Food and Drug Administration (FD-R-000657-01)
  • National Heart, Lung, and Blood Institute (R01 HL42814-02)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
cerebral malaria, iron chelation, deferoxamine, deep coma, consciousness recovery, Plasmodium falciparum, quinine, sulfadoxine-pyrimethamine, parasite clearance, mortality, children
MeSH terms
Child, Preschool, Coma, Consciousness, Deferoxamine, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Pyrimethamine, Quinine, Sulfadoxine, Time Factors, Proportional Hazards Models, Malaria, Cerebral

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