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Chemotherapy against human African trypanosomiasis: Is there a road to success?

Published online by Cambridge University Press:  20 October 2010

CHRISTIAN BURRI
CHRISTIAN BURRI*
Affiliation:
Swiss Tropical and Public Health Institute, Department of Medicines Research, Basel, Switzerland; University of Basel, Basel, Switzerland
*
*Corresponding author: Christian Burri, MPharm. Ph.D., Head, Department of Medicines Research, Swiss Tropical & Public Health Institute, Socinstrasse 57, P.O. Box, CH-4002 Basel, Switzerland. Tel: +41 61 225 26 61. Fax: +41 61 225 26 78. E-mail: Christian.Burri@unibas.ch
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Summary

For over fifty years, human African trypanosomiasis (HAT, sleeping sickness) has been treated with suramin, pentamidine and the very toxic organo-arsenical melarsoprol that was the only drug available for effective treatment of the second stage of the disease. Recently there have been significant efforts using molecular and biochemical approaches to drug design, including high-throughput screening, but the number of lead compounds with promising activity against T. brucei spp. and an acceptable toxicity index has remained astonishingly small. Clinical research continues to be difficult due to the economic constraints and the complexity of trials on a low prevalence disease in remote and impoverished African regions. Despite those limitations the situation for the patients is improving thanks to the combination of a number of critical factors. By the late 1990s the disease had reached epidemic levels that triggered political support. WHO would sign a donation agreement with the manufacturers for all drugs to treat HAT. A result of this agreement was that eflornithine which is much safer than melarsoprol became available and widely used by non-governmental organizations. The Impamel I and II programmes demonstrated that against all odds the conduct of clinical trials on HAT was feasible. This allowed the initiation of trials on combination therapies which eventually resulted in the nifurtimox-eflornithine combination treatment (NECT). This combination is currently being introduced as first line treatment, and there is even the prospect of having a new compound, fexinidazole, in the development pipeline. This review summarizes the key information about the existing drugs and gives a comprehensive summary about the recent and currently ongoing efforts towards new drugs.

Keywords

Human African trypanosomiasissleeping sicknesstreatmentdrugspentamidinesuraminmelarsoproleflornithineNECTpafuramidine maleateDB289fexinidazole
Type
Research Article
Information
Parasitology , Volume 137 , Special Issue 14: African trypanosomiasis: New insights for disease control , December 2010 , pp. 1987 - 1994
Copyright
Copyright © Cambridge University Press 2010

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