Treatment of Human Late Stage Gambiense Trypanosomiasis with α-Difluoromethylornithine (Eflornithine): Efficacy and Tolerance in 14 Cases in Côte D'Ivoire

Félix Doua Projet de Recherches Cliniques sur la Trypanosomiase, Daloa, Côte d'Ivoire

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Félix Y. Boa Service de Neurologie, CHU de Cocody, Abidjan, Côte d'Ivoire

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Paul J. Schechter Merrell Dow Research Institute, Strasbourg, France, and Cincinnati, Ohio

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Tanoé W. Miézan Projet de Recherches Cliniques sur la Trypanosomiase, Daloa, Côte d'Ivoire

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Didier Diai Secteur de Santé Rurale de Daloa, Côte d'Ivoire

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Singaro R. Sanon Projet de Recherches Cliniques sur la Trypanosomiase, Daloa, Côte d'Ivoire

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Pieter De Raadt Parasitic Disease Programme, World Health Organization, Geneva, Switzerland

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Klaus D. Haegele Merrell Dow Research Institute, Strasbourg, France, and Cincinnati, Ohio

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Albert Sjoerdsma Merrell Dow Research Institute, Strasbourg, France, and Cincinnati, Ohio

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Kangha Konian Direction de la Santé Publique pour le département du Sud, Abidjan, Côte d'Ivoire

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DOI:
https://doi.org/10.4269/ajtmh.1987.37.525
Volume/Issue:
Volume 37: Issue 3
Page(s):
525–533
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α-Difluoromethylornithine (DFMO; eflornithine), an inhibitor of polyamine biosynthesis, was used to treat 14 patients with late stage gambiense sleeping sickness, 12 cases having been previously treated with and considered refractory to melarsoprol. α-Difluoromethylornithine was administered intravenously at a dose of 400 mg/kg/day for 14 days followed by oral treatment, 300 mg/kg/day, for 21–28 days. In all patients treatment was associated with rapid disappearance of trypanosomes from body fluids (in several cases within 24 hr) and decreased cerebospinal fluid white blood cell counts. In all but one patient, who died of a pulmonary infection during treatment, α-difluoromethylornithine produced a dramatic reversal of clinical signs and symptoms of the disease. Determination of drug concentrations in serum and cerebrospinal fluid of 5 patients demonstrated that α-difluoromethylornithine diffuses into the central nervous system with cerebrospinal fluid levels representing up to 51% of corresponding serum concentrations. Diarrhea, abdominal pain, and anemia were the most frequent side effects associated with therapy, but were reversible and did not necessitate discontinuation of treatment. Four patients have been followed for more than 2 years post-treatment without evidence of relapse.

Author Notes

Copyright:
Copyright © 1987 by The American Society of Tropical Medicine and Hygiene 1987
Accepted:
13 May 1987
|
Published Online:
Nov 1987
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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