Fasciolicides: Efficacy, actions, resistance and its management

The modes of action of fasciolicides are described. Closantel and other sal icylanilides interfere with energy metabolism by uncoupling oxidative phosp horylation in the fluke. Other fasciolicides are believed to have a metabol ic action-halogenated phenols (via uncoupling) and clorsulon (via inhibitio n of glycolysis)-but direct evidence is lacking. Benzimidazoles (in particu lar, riclabendazole) bind to fluke tubulin and disrupt microtubule-based pr ocesses. Diamphenethide inhibits protein synthesis in the fluke. Other pote ntial drug actions may contribute to overall drug efficacy. In particular, a number of fasciolicides-salicylanilides, phenols, diamphenethide-induce a rapid paralysis of the fluke, so their action may have a neuromuscular bas is, although the actions remain ill-defined. Resistance to salicylanilides and triclabendazole has been detected in the field, although drug resistanc e does not appear to be a major problem yet. Strategies to minimize the dev elopment of resistance include the use of synergistic drug combinations, to gether with the design of integrated management programmes and the search f or alternatives to drugs, in particular, vaccines. (C) 1999 Harcourt Publis hers Ltd.