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

doi:10.1016/j.yexmp.2007.01.009

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

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	104-109
Journal	Experimental and Molecular Pathology
Volume	82
Issue number	2
Early online date	15 Feb 2007
DOIs	https://doi.org/10.1016/j.yexmp.2007.01.009
Publication status	Published - 01 Apr 2007

Keywords

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

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10.1016/j.yexmp.2007.01.009

http://linkinghub.elsevier.com/retrieve/pii/S001448000700010X

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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.",

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T1 - Understanding triclabendazole resistance

AU - Brennan, G. P.

AU - Fairweather, I.

AU - Trudgett, A.

AU - Hoey, E.

AU - ., McCoy

AU - Mcconville, M.

AU - Meaney, M.

AU - Robinson, M.

AU - McFerran, N.

AU - Ryan, L.

AU - Lanusse, C.

AU - Mottier, L.

AU - Alvarez, L.

AU - Solana, H.

AU - Virkel, G.

AU - Brophy, Peter

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PY - 2007/4/1

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N2 - 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.

AB - 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.

KW - triclabendazole

KW - fasciola hepatica

KW - resistance

KW - β-tubulin isotype

KW - molecular modelling

KW - P-glycoprotein

KW - drug metabolism

KW - proteomics

UR - http://hdl.handle.net/2160/36241

U2 - 10.1016/j.yexmp.2007.01.009

DO - 10.1016/j.yexmp.2007.01.009

M3 - Article

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VL - 82

SP - 104

EP - 109

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

IS - 2

ER -

Understanding triclabendazole resistance

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Keywords

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