Detection of mutant P2 adenosine transporter (TbAT1) gene in Trypanosoma brucei gambiense isolates from northwest Uganda using allele-specific polymerase chain reaction

Trop Med Int Health. 2007 Nov;12(11):1361-8. doi: 10.1111/j.1365-3156.2007.01918.x.

Abstract

Objective: To assess the application of allele-specific PCR (AS-PCR) as a fast, cheap and reliable method for detecting mutant TbAT1 associated with melarsoprol relapse in Trypanosoma brucei gambiense isolates from northwest Uganda.

Methods: A total of 105 trypanosome isolates were analysed using SfaN1 restriction fragment length polymorphism (RFLP) and AS-PCR, the former used as the gold standard. Sensitivity, specificity, positive and negative predictive values of AS-PCR as well as agreement between the tests were determined.

Results: Eleven trypanosome isolates had mutant TbAT1 while 94 exhibited the wild-type TbAT1 genes. There was a highly significant agreement between SfaN1 RFLP and AS-PCR with kappa and intra-class correlation values of 1.0. The sensitivity and specificity of AS-PCR were both 100%, while the positive and negative predictive values were found to be equal to 1.0. Cost and time analyses were performed and AS-PCR was 4.3 times cheaper than SfaN1 RFLP, in addition to the less time required for its execution.

Conclusion: AS-PCR should be the test of choice for screening for mutant TbAT1 in the ever-increasing numbers of field trypanosome isolates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cattle
  • Drug Resistance / genetics*
  • Melarsoprol / pharmacology*
  • Nucleoside Transport Proteins / genetics*
  • Polymerase Chain Reaction / methods*
  • Polymorphism, Restriction Fragment Length
  • Sensitivity and Specificity
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei gambiense / genetics*
  • Trypanosomiasis, African / genetics
  • Uganda

Substances

  • Nucleoside Transport Proteins
  • Trypanocidal Agents
  • adenosine transporter
  • Melarsoprol