title: Fasciola hepatica: morphological effects of a combination of triclabendazole and clorsulon against mature fluke.
abstract: A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength clorsulon, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 microg/ml), clorsulon (5 microg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.
authors.affiliation: Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK.
authors.forename: M
authors.initials: M
authors.lastname: Meaney
authors.forename: J
authors.initials: J
authors.lastname: Allister
authors.forename: B
authors.initials: B
authors.lastname: McKinstry
authors.forename: K
authors.initials: K
authors.lastname: McLaughlin
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: A B
authors.initials: AB
authors.lastname: Forbes
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; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005210:Fasciola hepatica / Q000166:cytology* / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D013424:Sulfanilamides / Q000494:pharmacology* / Q000627:therapeutic use; D000077682:Triclabendazole
chemical_list: D000980:Antiplatyhelmintic Agents; D001562:Benzimidazoles; D013424:Sulfanilamides; D000077682:Triclabendazole; C015675:clorsulon