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.

Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica

“…The lack of activity of triclabendazole against the Oberon isolate in rats with a standard dose of 10 mg/kg confirms recent findings obtained in sheep; a single 10 mg/kg oral dose of triclabendazole administered to sheep infected with this triclabendazole-resistant strain of F. hepatica showed an efficacy below 5% against 2-and 4-week-old flukes (Walker et al, 2004).…”

Immature triclabendazole-resistant Fasciola hepatica: tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha

“…The posterior focus of disruption caused by alpha.SO has been observed in previous studies involving both adult and juvenile flukes (Rivera et al 2004(Rivera et al , 2005, but conflicts with a separate investigation on adult TCBZ-resistant flukes in which the apical cone and midbody lateral margins were more severely disrupted (McConville et al 2006). In parallel studies on TCBZ.SO, no consistent pattern of disruption has been established for juvenile or adult flukes (Stitt and Fairweather 1993;Meaney et al 2002;Walker et al 2004). A dorsal-ventral difference was evident following the 18-h treatment, with the ventral surface being more severely affected.…”

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

“…On the other hand, triclabendazole was more effective against adult than juvenile F. hepatica flukes in vivo; for instance, at a dosage of 5 mg/kg it achieved worm burden reductions of 56.8 and 12.8% against adult and juvenile flukes, respectively. Although triclabendazole has been well studied against immature and mature F. hepatica in sheep and cattle (2,14,32,38), to our knowledge thorough stage specifity studies of rats have not been carried out to date. This stage specificity appears to arise because of the reduced in vitro sensitivity of the juvenile flukes to the metabolites of triclabendazole, into which the drug is converted rapidly in vivo (10).…”