The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

Robinson, Mark W.; Lawson, Jill; Trudgett, Alan; Hoey, Elizabeth M.; Fairweather, Ian

doi:10.1007/s00436-003-1003-6

Cited by 97 publications

(93 citation statements)

References 28 publications

(42 reference statements)

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“…The Sligo isolate has been shown to be resistant to the action of TCBZ in vivo Coles and Stafford 2001;McCoy et al 2005) and has been used in a number of in vitro studies (Robinson et al 2002(Robinson et al , 2004Alvarez et al 2005). Four-week-old juvenile flukes were removed from the livers of the rats under sterile conditions in a laminar flow cabinet.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2006

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Juvenile triclabendazole-resistant liver flukes, Fasciola hepatica, were incubated in vitro with 10 microg/ml of the sulphoxide metabolite of the experimental fasciolicide, compound alpha [5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole], for 6 and 18 h. Following treatment, the specimens were examined using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and tubulin immunocytochemistry. The SEM results revealed a posterior-directed disruption comprised predominantly of swelling and blebbing of the tegument; these changes were more severe and extensive after the longer 18-h incubation. Along with swelling of the tegument and blebbing, the TEM results also revealed swelling of the mitochondria and basal infolds. A decrease in the number of both T1 and T2 secretory bodies was observed in the syncytium and cytoplasmic connections after the 18-h treatment. The circular muscle bundles were also disrupted, in that the organisation of the muscle fibres was irregular and the total number of muscle fibres was reduced. The immunocytochemical studies revealed no significant disruption to the distribution of tubulin immunoreactivity within the tegumental syncytium, the cytoplasmic connections or the associated tegumental cells. The results indicate that alpha.SO is capable of disrupting the tegument of 4-week-old triclabendazole-resistant liver flukes, though the morphological changes were not associated with any significant differences in tubulin immunostaining.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2006

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“…The molecular benzimidazole mechanism of resistance has been demonstrated to be the replacement of the amino acid phenylalanine to tyrosine, in the position 200 of the β-tubulin isotype 1 molecule (ROBINSON et al, 2004) but that is not fully accepted because sequences of β-tubulin cDNA from TBZ-susceptible and -resistant flukes may not have differences between their respective primary amino acid sequences (FAIRWEATHER, 2005). The selection of genes that are involved in drug resistance is a concern where sheep is regularly treated with TBZ, especially in farms where cattle share the same pastures.…”

Section: Parasite Resistancementioning

confidence: 99%

Fasciola hepatica: epidemiology, perspectives in the diagnostic and the use of geoprocessing systems for prevalence studies

et al. 2015

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Fasciola hepatica is a parasite that is located in the liver of ruminants with the possibility to infect horses, pigs and humans. The parasite belongs to the Trematoda class, and it is the agent causing the disease called fasciolosis. This disease occurs mainly in temperate regions where climate favors the development of the organism. These conditions must facilitate the development of the intermediate host, the snail of the genus Lymnaea. The infection in domestic animals can lead to decrease in production and control is made by using triclabendazole. Triclabendazole resistance in F. hepatica has been reported worldwide including in Brazil. Another concern is the increase number of human cases with the consumption of contaminated vegetables in regions where sanitation is inadequate together with the presence of infected animals and the absence of efficient control methods. The knowledge of the epidemiology of animal fasciolosis, including their occurrence, distribution and monitoring with techniques such as PCR and ELISA is reaching a new level with the usage of the Geographic Information System. The objective is to use new technologies for early fasciolosis diagnostic, as well as, to develop geoprocessing technics that could allow the determination of its prevalence and the evolution of clinical cases in animals before hand. This review paper provides an overview of F. hepatica, covering the aspects listed above, including original data. Key words: Fasciola hepatica, epidemiology, geographic information system, zoonosis ResumoFasciola hepatica é um parasita que se localiza no fígado de ruminantes, podendo infectar equinos, suínos e humanos. O parasito pertence à classe Trematoda, sendo o agente responsável pela doença denominada fasciolose, que ocorre principalmente em regiões temperadas, com clima favorável para o desenvolvimento do organismo. Tais condições devem auxiliar no desenvolvimento do hospedeiro intermediário, o molusco do gênero Lymnaea. Existe uma crescente preocupação quanto ao número de casos humanos diagnosticados em certas regiões cujo saneamento básico é inadequado, há presença de animais infectados e cultura em consumir hortaliças de áreas contaminadas cruas ou pouco cozidas. O parasitismo em animais domésticos pode levar a uma queda no desempenho animal e seu controle é realizado, principalmente, com o uso do triclabendazole. Entretanto, relatos quanto à resistência do patógeno à este produto vêm sendo descritos, inclusive no Brasil. O conhecimento da epidemiologia da fasciolose animal, incluindo sua ocorrência, distribuição e monitoramento com técnicas laboratoriais como o ELISA e a PCR, estão tendo um novo progresso com a utilização do Sistema de Informação Geográfica. O objetivo de utilizar essas novas tecnologias é diagnosticar a fasciolose mais precocemente, assim como, desenvolver técnicas de geoprocessamento que possam determinar a prevalência e a evolução dos casos em animais. Este artigo aborda recentes avanços no monitoramento da F. hepatica, cobrindo alguns aspectos lista...

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“…The Cullompton isolate was originally derived from an abattoir in Cullompton (Co. Devon, England), and has been shown to be susceptible to the action of TCBZ in vivo and in vitro (Robinson et al 2002(Robinson et al , 2004McCoy et al 2005;Meaney et al 2006Meaney et al , 2007Halferty et al 2008Halferty et al , 2009McConville et al 2009a, b).…”

Section: Animals and Infective Materialsmentioning

confidence: 99%

Surface changes in adult Fasciola hepatica following treatment in vivo with the experimental fasciolicide, compound alpha

et al. 2009

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Sheep infected with the triclabendazole-susceptible Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks postinfection. Adult flukes were recovered from the bile ducts at 24, 48, and 72 h post-treatment (p.t.). Changes to the surface morphology of the flukes were assessed using scanning electron microscopy (SEM). Flukes were still active at 24 h p.t. and displayed limited areas of disruption, which were restricted to the oral cone region. At 48 h p.t., a reduced level of motility was observed in approximately 50% of the flukes recovered. Swelling of the tegument was more widespread and was accompanied by blebbing and partial loss of the tegumental covering of the spines. By 72 h p.t., the reduction in motility was greater, and approximately one quarter of the flukes recovered were inactive. In the majority of the flukes examined, the midbody region was marked by a discoloration of the flukes' tissues. This was seen to be due to the loss of the tegumental syncytium. Sloughing extended into the tail region in some specimens and, in the more badly-affected specimens, the basal lamina was breached to expose the underlying musculature. Elsewhere on the body, the tegument that remained was relatively normal, although areas of swelling and blebbing were present. Overall, the results provided information on the time-scale of changes to the surface morphology of the fluke that underpin the efficacy of compound alpha.

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The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

Cited by 97 publications

References 28 publications

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

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

Fasciola hepatica: epidemiology, perspectives in the diagnostic and the use of geoprocessing systems for prevalence studies

Surface changes in adult Fasciola hepatica following treatment in vivo with the experimental fasciolicide, compound alpha

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