Understanding triclabendazole resistance

G. P. Brennan, I. Fairweather, A. Trudgett, E. Hoey, McCoy ., M. Mcconville, M. Meaney, M. Robinson, N. McFerran, L. Ryan, C. Lanusse, L. Mottier, L. Alvarez, H. Solana, G. Virkel, Peter Brophy

Research output: Contribution to journalArticlepeer-review

186 Citations (SciVal)

Abstract

Triclabendazole (TCBZ) has been the drug of choice to treat liver fluke infections in livestock for > 20 years, due to its high activity against both adult and juvenile flukes. More recently, it has been used successfully to treat human cases of fascioliasis. Resistance to TCBZ first appeared in the field in Australia in the mid-1990s. Since then, resistance has been reported from a number of countries throughout Europe: Ireland, Scotland, Wales, Spain and The Netherlands. The heavy reliance on a single drug puts treatment strategies for fascioliasis at risk. Should resistance develop further, the prospect is an alarming one. This review will present an overview of progress in understanding the mechanism of resistance to TCBZ, examining possible changes in the target molecule, in drug influx/efflux mechanisms and in the metabolism of TCBZ by the fluke. The review will also consider ways to deal with resistance, covering drug-oriented options such as: the use of alternative drugs, drug combinations and the search for new compounds.
Original languageEnglish
Pages (from-to)104-109
JournalExperimental and Molecular Pathology
Volume82
Issue number2
Early online date15 Feb 2007
DOIs
Publication statusPublished - 01 Apr 2007

Keywords

  • triclabendazole
  • fasciola hepatica
  • resistance
  • β-tubulin isotype
  • molecular modelling
  • P-glycoprotein
  • drug metabolism
  • proteomics

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