title: Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro.
abstract: In this study, the susceptibility of two isolates of Fasciola hepatica--the Fairhurst and Oberon isolates--to treatment with triclabendazole was investigated, both in vivo and in vitro. The Fairhurst isolate originated in England, but has since been maintained in Australia; the Oberon isolate originated in Australia. Triclabendazole had a very high efficacy against the Fairhurst isolate. In sheep (dose: 10 mg/kg), the efficacy ranged from 78.4% at 2 weeks post-infection to 98.5% at 6 weeks post-infection. In cattle (dose: 12 mg/kg) efficacy was 89% at 2 weeks post-infection and 100% at 12 weeks. In contrast, against the Oberon isolate, triclabendazole had 0% efficacy against 2-week-old flukes in sheep (dose: 10 mg/kg) and 5% against 4-week-old flukes. Surface changes to flukes of the two isolates were assessed by scanning electron microscopy following treatment in vitro for 24 h in triclabendazole sulphoxide (15 and 50 microg/ml). Disruption took the form of blebbing, swelling and furrowing of the tegument and was greater in the Fairhurst than the Oberon isolate. Surface changes generally were more severe in the anterior than posterior region of the fluke and the dorsal surface was also consistently more severely affected than the ventral surface. Disruption was more severe at the higher drug concentration for both isolates. The morphological data is consistent with the efficacy data, which indicates that the Fairhurst isolate of F. hepatica is susceptible to triclabendazole treatment, whilst the Oberon isolate is refractory.
authors.affiliation: Parasite Proteomics and Therapeutics Research Group, School of Biology and Biochemistry, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, BT9 7BL, Belfast, Northern Ireland.
authors.forename: S M
authors.initials: SM
authors.lastname: Walker
authors.forename: B
authors.initials: B
authors.lastname: McKinstry
authors.forename: J C
authors.initials: JC
authors.lastname: Boray
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: A
authors.initials: A
authors.lastname: Trudgett
authors.forename: E M
authors.initials: EM
authors.lastname: Hoey
authors.forename: H
authors.initials: H
authors.lastname: Fletcher
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
mesh_terms: D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D002418:Cattle Diseases / Q000469:parasitology; D005210:Fasciola hepatica / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology / Q000662:veterinary; D005260:Female; D008297:Male; D021261:Parasitic Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D012757:Sheep Diseases / Q000469:parasitology; D013454:Sulfoxides / Q000494:pharmacology* / Q000627:therapeutic use; D000077682:Triclabendazole
chemical_list: D000980:Antiplatyhelmintic Agents; D001562:Benzimidazoles; D013454:Sulfoxides; D000077682:Triclabendazole; C085104:triclabendazole sulfoxide