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

Maina, Naomi; Maina, Kagira Joseph; Mäser, Pascal; 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, 104(2-3), pp. 84-90. Basel: Elsevier 10.1016/j.actatropica.2007.07.007

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	08 Faculty of Science > Department of Biology > Institute of Cell Biology
UniBE Contributor:	Mäser, Pascal
ISSN:	0001-706X
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:57
Last Modified:	05 Dec 2022 14:17
Publisher DOI:	10.1016/j.actatropica.2007.07.007
Web of Science ID:	000251094700002
URI:	https://boris.unibe.ch/id/eprint/24699 (FactScience: 52838)