genotypic status of the tbat1p2 adenosine transporter of trypanosoma brucei gambiense isolates from northwestern uganda following melarsoprol withdrawal基因型状态tbat1p2腺苷运输车的锥虫属brucei gambiense隔离从乌干达西北部美拉胂醇后撤退.pdfVIP

Genotypic Status of the TbAT1/P2 Adenosine Transporter of Trypanosoma brucei gambiense Isolates from Northwestern Uganda following Melarsoprol Withdrawal 1,2 3 1 ¨ 4 1,5 Anne J. N. Kazibwe , Barbara Nerima , Harry P. de Koning , Pascal Maser , Michael P. Barrett , Enock Matovu2* 1 Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom, 2 Faculty of Veterinary Medicine, Makerere University, Kampala, Uganda, 3 National Livestock Resources Research Institute, Tororo, Uganda, 4 Institute of Cell Biology, University of Bern, Bern, Switzerland, 5 Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, Scotland, United Kingdom Abstract Background: The development of arsenical and diamidine resistance in Trypanosoma brucei is associated with loss of drug uptake by the P2 purine transporter as a result of alterations in the corresponding T. brucei adenosine transporter 1 gene (TbAT1). Previously, specific TbAT1 mutant type alleles linked to melarsoprol treatment failure were significantly more prevalent in T. b. gambiense from relapse patients at Omugo health centre in Arua district. Relapse rates of up to 30% prompted a shift from melarsoprol to eflornithine (a-difluoromethylornithine, DFMO) as first-line treatment at this centre. The aim of this study was to determine the status of TbAT1 in recent isolates collected from T. b. gambiense sleeping sickness patients from Arua and Moyo districts in Northwestern Uganda after this shift in first-line drug choice. Methodology and results: Blood and cerebrospinal fluids of consenting patients were