title: Understanding triclabendazole resistance.
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.
authors.affiliation: Queen's University of Belfast, Belfast, N. Ireland. g.brennan@qub.ac.uk
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
authors.forename: A
authors.initials: A
authors.lastname: Trudgett
authors.forename: E
authors.initials: E
authors.lastname: Hoey
authors.lastname: McCoy
authors.forename: M
authors.initials: M
authors.lastname: McConville
authors.forename: M
authors.initials: M
authors.lastname: Meaney
authors.forename: M
authors.initials: M
authors.lastname: Robinson
authors.forename: N
authors.initials: N
authors.lastname: McFerran
authors.forename: L
authors.initials: L
authors.lastname: Ryan
authors.forename: C
authors.initials: C
authors.lastname: Lanusse
authors.forename: L
authors.initials: L
authors.lastname: Mottier
authors.forename: L
authors.initials: L
authors.lastname: Alvarez
authors.forename: H
authors.initials: H
authors.lastname: Solana
authors.forename: G
authors.initials: G
authors.lastname: Virkel
authors.forename: P M
authors.initials: PM
authors.lastname: Brophy
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D005210:Fasciola hepatica / Q000187:drug effects* / Q000235:genetics; D005211:Fascioliasis / Q000188:drug therapy* / Q000662:veterinary*; D015801:Helminth Proteins / Q000378:metabolism; D006801:Humans; D040901:Proteomics; D000077682:Triclabendazole
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; D015801:Helminth Proteins; D000077682:Triclabendazole