The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep

Smeal, M. G.; Hall, Clifford

doi:10.1111/j.1751-0813.1983.tb02833.x

Cited by 42 publications

(16 citation statements)

References 5 publications

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“…In a separate study on the juvenile fluke, no anterior/posterior variation was observed (Stitt and Fairweather 1993). Smeal and Hall (1983) observed an ascending necrosis in flukes recovered from sheep following treatment with triclabendazole, indicating more posteriorly-induced drug damage. The results of the present study revealed that the dorsal Fig.…”

Section: Discussionmentioning

confidence: 89%

Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro

Walker¹,

McKinstry²,

Boray

et al. 2004

Parasitol Res

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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.

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Section: Discussionmentioning

confidence: 89%

Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro

Walker¹,

McKinstry²,

Boray

et al. 2004

Parasitol Res

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“…In the longest time period in vivo (72 h), damage to one fluke was so severe that a hole had penetrated through its entire body. Such damage has only been observed in specimens of Fasciola gigantica, but not F. hepatica, treated in vitro with the sulphoxide metabolite of triclabendazole (Meaney et al 2002), although more extreme damage in the form of an ascending necrosis has occasionally been described in specimens recovered in vivo (Gusel'nikova 1974;Verheyen et al 1982;Smeal and Hall 1983).…”

Section: Discussionmentioning

confidence: 94%

“…Indeed, it has been suggested that the more posterior damage with these drugs is due to an accumulation of drug in the posterior region of the gut. Furthermore, the concept has been extended to explain the ascending necrosis described for mebendazole, triclabendazole, rafoxanide and bithionol (Gusel'nikova 1974;Verheyen et al 1982;Smeal and Hall 1983).…”

Section: Discussionmentioning

confidence: 98%

Fasciola hepatica : tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax)

McKinstry¹,

Fairweather²,

Brennan³

et al. 2003

Parasitology Research

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Male Sprague-Dawley rats were dosed orally with nitroxynil at a concentration of 40 mg/kg and adult Fasciola hepatica recovered after 24 h, 48 h and 72 h. Surface changes to the flukes were monitored by means of SEM. After the 24 h treatment, extensive swelling and blebbing of the tegument was observed on both surfaces, although the dorsal anterior region was more severely affected than either the posterior dorsal region or entire ventral surface. At high magnification, microvillus-like projections were evident, giving the surface a roughened appearance. After 48 h, the changes evident at 24 h had become more severe and some tegumental loss had occurred in the oral region of the fluke. Surface disruption was particularly evident along the lateral margins of the fluke in this region. In some specimens a single large swelling was present in the dorsal midbody region. The swelling was a more typical feature of flukes recovered. After 72 h, tegumental loss was more widespread, occurring over the oral cone and anterior midbody on the dorsal surface. Overall the dorsal surface was consistently more severely affected than the ventral surface, and the anterior region of the fluke was more disrupted than the posterior region. After 24 h in vitro incubation, the oral cone and midbody exhibited considerable spine loss and swelling. Overall, the dorsal surface was more disrupted than the ventral surface and the anterior region of the fluke was more disrupted than the posterior region. Regional differences in the response of the fluke to nitroxynil will be compared to previously published data with other fasciolicides. The results indicate that the tegument is an important target for nitroxynil action. Disruption of this, the fluke's main line of defence, would allow the drug access to other internal tissues, leading to more widespread damage.

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“…In contrast to this idea, more posteriorly-directed damage has been attributed to the accumulation of the compounds in the posterior region of the gut (Verheyen et al 1982). It has even been suggested that such accumulation would account for the ascending necrosis in liver flukes described for a number of compounds, including mebendazole, triclabendazole, rafoxanide and bithionol (Gusel'nikova 1974;Verheyen et al 1982;Smeal and Hall 1983). So, on the basis of the evidence available to date, it would appear that no clear links can be established between regional variation of drug effects, drug binding data, the chemical classification of the drug, nor the species of host used or developmental stage of the parasite.…”

Section: Discussionmentioning

confidence: 98%

Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

Meaney¹,

Fairweather²,

Brennan³

et al. 2003

Parasitology Research

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The ultrastructural changes in Fasciola hepatica induced by the fasciolicide clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepaticawere dosed orally with clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with clorsulon for 24 h at a concentration of 10 microg/ml. After 24 h in vivo, the young-mature flukes (8 weeks old) showed significant disruption to the tegumental surface, particularly in the anterior mid-body region, where a distinct band of swelling and blebbing was evident. The band began just behind the ventral sucker and ran posteriorly along both margins. The apical cone region of the fluke was characterised by swelling and blebbing of the surface between the spines. Similar changes were evident after 48 h in vivo, but the disruption was more severe and the mid-body band had spread posteriorly. In approximately half of the specimens recovered after 72 h in vivo, widespread disruption had occurred, with sloughing of the apical membrane or the entire syncytium, over almost all of the oral cone and anterior mid-body. For all time periods, the anterior half of the fluke was more severely affected than the posterior half. No differences were seen between the dorsal and ventral surfaces. Old-mature flukes (44 weeks old) showed regionally similar, but more severe and widespread disruption than that seen in the young-mature flukes. The onset of surface changes occurred more quickly in old-mature flukes as well. Eight-week-old flukes which had been incubated for 24 h in vitro showed surprisingly little disruption, but this may be due to the method by which the drug is taken up by the fluke.

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The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep

Cited by 42 publications

References 5 publications

Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro

Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro

Fasciola hepatica : tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax)

Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes

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