Triclabendazole: new skills to unravel an old(ish) enigma.

Triclabendazole was introduced in the early 1980s for the treatment of Fasciola hepatica infections in livestock. Due to its high activity against immature flukes, it has become established as the principal anti-fluke drug on the market. More recently, triclabendazole has been used to treat human cases of fascioliasis and is now the drug of choice for this infection, too. Resistance to triclabendazole was first reported in 1995 in a field population in Australia and, since that time, resistant populations have been identified in several countries in Europe. Parallel to the spread of resistance has been a sharp increase in the prevalence of fascioliasis, which has been attributed largely to climate changes. Consequently, farmers are faced with an alarming scenario, as none of the other fasciolicides on the market possess such high activity against the damaging immature stages of fluke. The main aim of this review is to assess current understanding of the mechanism of action of triclabendazole against the fluke and the mechanism by which the fluke has become resistant to it. The use of triclabendazole against animal and human infections is summarized and suggestions are given on ways to deal with resistance. Gaps in the knowledge of various aspects of its use are highlighted and this may serve to open up future research areas.