Literature DB >> 1406879

Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria.

V Gordeuk1, P Thuma, G Brittenham, C McLaren, D Parry, A Backenstose, G Biemba, R Msiska, L Holmes, E McKinley.   

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.

Entities:  

Keywords:  Africa; Africa South Of The Sahara; Data Collection; Demographic Factors; Developing Countries; Diseases; Double-blind Studies; Eastern Africa; English Speaking Africa; Evaluation; Examinations And Diagnoses; Malaria; Parasitic Diseases; Population; Prospective Studies; Research Methodology; Studies; Treatment; Zambia

Mesh:

Substances:

Year:  1992        PMID: 1406879     DOI: 10.1056/NEJM199211193272101

Source DB:  PubMed          Journal:  N Engl J Med        ISSN: 0028-4793            Impact factor:   91.245


  42 in total

1.  In vitro potentiation of antibiotic activities by a catecholate iron chelator against chloroquine-resistant Plasmodium falciparum.

Authors:  Bruno Pradines; Florence Ramiandrasoa; Jean Marc Rolain; Christophe Rogier; Joel Mosnier; William Daries; Thierry Fusai; Gerhard Kunesch; Jacques Le Bras; Daniel Parzy
Journal:  Antimicrob Agents Chemother       Date:  2002-01       Impact factor: 5.191

Review 2.  Diagnosis and management of the neurological complications of falciparum malaria.

Authors:  Saroj K Mishra; Charles R J C Newton
Journal:  Nat Rev Neurol       Date:  2009-04       Impact factor: 42.937

Review 3.  Cerebral malaria.

Authors:  C R Newton; T T Hien; N White
Journal:  J Neurol Neurosurg Psychiatry       Date:  2000-10       Impact factor: 10.154

4.  In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

Authors:  B Pradines; F Ramiandrasoa; L K Basco; L Bricard; G Kunesch; J Le Bras
Journal:  Antimicrob Agents Chemother       Date:  1996-09       Impact factor: 5.191

Review 5.  The Iron age of host-microbe interactions.

Authors:  Miguel P Soares; Günter Weiss
Journal:  EMBO Rep       Date:  2015-10-16       Impact factor: 8.807

Review 6.  Oxidative stress in malaria; implications for prevention and therapy.

Authors:  N S Postma; E C Mommers; W M Eling; J Zuidema
Journal:  Pharm World Sci       Date:  1996-08

Review 7.  Iron metabolism and the innate immune response to infection.

Authors:  Erin E Johnson; Marianne Wessling-Resnick
Journal:  Microbes Infect       Date:  2011-10-20       Impact factor: 2.700

8.  Ferrous iron uptake in Cryptococcus neoformans.

Authors:  E S Jacobson; A P Goodner; K J Nyhus
Journal:  Infect Immun       Date:  1998-09       Impact factor: 3.441

Review 9.  Iron, anaemia, and inflammatory bowel diseases.

Authors:  C Gasche; M C E Lomer; I Cavill; G Weiss
Journal:  Gut       Date:  2004-08       Impact factor: 23.059

10.  Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases.

Authors:  Douglas B Kell
Journal:  BMC Med Genomics       Date:  2009-01-08       Impact factor: 3.063

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