title: An evaluation of the efficacy of compound alpha and triclabendazole against two isolates of Fasciola hepatica.
abstract: Seventy indoor-reared sheep were divided into 10 groups to test the efficacy of the experimental fasciolicide, compound alpha (15mg/kg) against triclabendazole (TCBZ)-resistant and TCBZ-susceptible F. hepatica infections. Activity against the Sligo TCBZ-resistant isolate was tested at three time points post-infection (p.i.): 3 days, 4 weeks and 12 weeks (Groups 1-3, respectively). A parallel trial was carried out using TCBZ (10mg/kg) (Groups 5-7): this provided a direct comparison between the efficacies of the two drugs. Group 4 served as an untreated Sligo control. Groups 8 and 9 were setup to test the efficacy of TCBZ and compound alpha against 12-week-old and 4-week-old TCBZ-susceptible, Cullompton infections, respectively. Group 10 served as an untreated Cullompton control. Sheep were sacrificed at 16 weeks p.i. and efficacies were determined. All remaining flukes were collected and measured, before being processed for whole-mount staining to assess the condition of their reproductive structures (testis, vitellaria, ovary and uterus). A second study was carried out to test the activity of compound alpha (15mg/kg) against mature 12-week-old TCBZ-susceptible F. hepatica infections in sheep. Eighteen sheep were divided into two groups, A and B. Group A was treated and Group B served as an untreated control group. Efficacy was determined by reduction in faecal egg counts. The results showed that, whilst compound alpha was very active against adult TCBZ-susceptible flukes, producing a 100% reduction in faecal egg counts, it only caused a 62.5% reduction in fluke burden against juvenile flukes. Moreover, compound alpha was not effective against any stage of infection with TCBZ-resistant F. hepatica in sheep. Data from the trial also revealed biological differences between the two isolates. Thus, Sligo flukes were smaller in size and produced fewer eggs than the Cullompton flukes and their cysts were less infective to sheep. However, they reached the bile ducts more quickly and their eggs appeared in the faeces >2 weeks earlier.
authors.affiliation: Parasite Proteomics and Therapeutics Research Group, Queen's University Belfast, 97 Lisburn Road, Belfast, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: McConville
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: A
authors.initials: A
authors.lastname: Flanagan
authors.forename: H W J
authors.initials: HW
authors.lastname: Edgar
authors.forename: R E B
authors.initials: RE
authors.lastname: Hanna
authors.forename: M
authors.initials: M
authors.lastname: McCoy
authors.forename: A W
authors.initials: AW
authors.lastname: Gordon
authors.forename: R
authors.initials: R
authors.lastname: Castillo
authors.forename: A
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D005210:Fasciola hepatica / Q000187:drug effects*; D005211:Fascioliasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy* / Q000469:parasitology; D000077682:Triclabendazole
chemical_list: C468032:5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole; D000871:Anthelmintics; D001562:Benzimidazoles; D007093:Imidazoles; D009281:Naphthalenes; D000077682:Triclabendazole