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Genotypic status of the TbAT1/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from northwestern Uganda following melarsoprol withdrawal

By A.J.N. Kazibwe, B. Nerima, H.P. De Koning, P. Mäser, M.P. Barrett and E. Matovu

Abstract

Human African trypanosomiasis (HAT) manifests as a chronic infection caused by <i>Trypanosoma brucei gambiense</i>, or as a more acute form due to <i>T. b. rhodesiense</i>. Both manifestations occur in Uganda and melarsoprol use against the former was jeopardised in the 1990s as reports of reduced efficacy increased to the point where it was dismissed as first-line treatment at some treatment centers. Previous work to elucidate possible mechanisms leading to melarsoprol resistance pointed to a P2 type adenosine transporter known to mediate melarsoprol uptake and previously shown to be mutated in significant numbers of patients not responding to the drug. Our present findings indicate that there is a low prevalence of mutants in foci where melarsoprol relapses are infrequent. In addition we observe that at the Omugo focus where the drug was withdrawn as first line over 6 years ago, the mutant alleles have disappeared, suggesting that drug pressure is responsible for fuelling their spread. Thus constant monitoring for mutants could play a key role in cost-effective HAT management by identifying which foci can still use the less logistically demanding melarsoprol as opposed to the alternative drug eflornithine. What is required now is a simple method for identifying such mutants at the point of care, enabling practitioners to make informed prescriptions at first diagnosis

Publisher: Public Library of Science
Year: 2009
OAI identifier: oai:eprints.gla.ac.uk:41024
Provided by: Enlighten

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