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Genotypic and phenotypic characterization of Trypanosoma brucei gambiense isolates from Ibba, South Sudan, an area of high melarsoprol treatment failure rate

Maina, Naomi and Maina, Kagira Joseph and Mäser, Pascal and Brun, Reto. (2007) Genotypic and phenotypic characterization of Trypanosoma brucei gambiense isolates from Ibba, South Sudan, an area of high melarsoprol treatment failure rate. Acta tropica : Zeitschrift für Tropenwissenschaften und Tropenmedizin = revue des sciences tropicales et de médecine tropicale = review of tropical science and tropical medicine, Vol. 104, H. 2-3. S. 84-90.

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Official URL: http://edoc.unibas.ch/dok/A6124428

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Abstract

Resistance of trypanosomes to melarsoprol is ascribed to reduced uptake of the drug via the P2 nucleoside transporter. The aim of this study was to look for evidence of drug resistance in Trypanosoma brucei gambiense isolates from sleeping sickness patients in Ibba, South Sudan, an area of high melarsoprol failure rate. Eighteen T. b. gambiense stocks were phenotypically and only 10 strains genotypically characterized. In vitro, all isolates were sensitive to melarsoprol, melarsen oxide, and diminazene. Infected mice were cured with a 4 day treatment of 2.5mg/kg bwt melarsoprol, confirming that the isolates were sensitive. The gene that codes for the P2 transporter, TbATI, was amplified by PCR and sequenced. The sequences were almost identical to the TbAT1(sensitive) reference, except for one point mutation, C1384T resulting in the amino acid change proline-462 to serine. None of the described TbAT1(resistant)-type mutations were detected. In a T. b. gambiense sleeping sickness focus where melarsoprol had to be abandoned due to the high incidence of treatment failures, no evidence for drug resistant trypanosomes or for TbAT1(resistant)-type alleles of the P2 transporter could be found. These findings indicate that factors other than drug resistance contribute to melarsoprol treatment failures.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Mäser, Pascal and Brun, Reto
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Elsevier Science Publ.
ISSN:0001-706X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:23
Deposited On:24 May 2013 09:19

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