The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

Elliott, Timothy; Spithill, Terry W.

doi:10.1016/j.molbiopara.2014.11.006

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…In vitro screening of AR is used for some gastrointestinal nematodes, but its application is limited for liver flukes. No reliable molecular markers for TCBZ resistance have so far been reported ( Elliott and Spithill, 2014 , Hodgkinson et al., 2013 ). However, in parallel with larval in vitro testing in nematodes, the Fasciola egg hatch test (FEHT) has been developed to diagnose susceptibility of F. hepatica eggs to ABZ ( Alvarez et al., 2009 , Canevari et al., 2014 , Robles-Perez et al., 2014 ) and TCBZ ( Fairweather et al., 2012 , Robles-Perez et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test

Novobilský

Solis

Skarin

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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Anthelmintic resistance (AR) to Fasciola hepatica is emerging worldwide. Recently, AR to the adulticide compound albendazole (ABZ) was shown in Argentina and Spain. In Sweden, ABZ treatment failure against F. hepatica was first reported in sheep in 2012. The present study tested the efficacy of ABZ and triclabendazole (TCBZ) in sheep naturally infected with F. hepatica using a combination of three different diagnostic methods: faecal egg counts (FEC), coproantigen ELISA (cELISA) and Fasciola egg hatch test (FEHT). Two deworming trials, in November 2014 and January 2015, were performed on two sheep farms (farms A and B) in south-western Sweden. Except ABZ in November, treatment with ABZ or TCBZ achieved sufficient efficacy (97–100%) against adult F. hepatica on farm A. In contrast, ABZ treatment failed in the sheep flock on farm B, despite low initial faecal egg output. On farm B, ABZ efficacy based on FEC was 67% (95% CI: 35–84) and four of eight ewes tested were coproantigen-positive 21 days post-treatment. Ovicidal activity of ABZ against Fasciola eggs in isolates from both farms and one additional bovine isolate were tested by FEHT to exclude the presence of juvenile flukes and other factors such as dosing failure and poor quality of drug product. Irrespective of drug trial, data from FEHT showed significantly lower ovicidal activity of ABZ for the ovine farm B isolate than for the isolate from farm A. This confirms that the low efficacy of ABZ in sheep flock B was associated with ABZ resistance. Overall, the usefulness of three complementary methods for detection of ABZ resistance in the field was demonstrated.

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Section: Introductionmentioning

confidence: 99%

Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test

Novobilský

Solis

Skarin

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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“…This highlights that drug resistance studies on highly heterogeneous populations need to distinguish between the impact of standing genetic variation and that of genetic mutations responsible for conferring resistance traits. It is worth noting that a mutation in a PGP gene in a small number of TCBZ-resistant liver fluke in Northern Ireland [ 41 ] was not detected in a larger number of drug resistant fluke in Australia [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones

et al. 2018

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BackgroundFasciola hepatica is of worldwide significance, impacting on the health, welfare and productivity of livestock and regarded by WHO as a re-emerging zoonosis. Triclabendazole (TCBZ), the drug of choice for controlling acute fasciolosis in livestock, is also the drug used to treat human infections. However TCBZ-resistance is now considered a major threat to the effective control of F. hepatica. It has yet to be demonstrated whether F. hepatica undergoes a genetic clonal expansion in the snail intermediate host, Galba truncatula, and to what extent amplification of genotypes within the snail facilitates accumulation of drug resistant parasites. Little is known about genotypic and phenotypic variation within and between F. hepatica isolates.ResultsSix clonal isolates of F. hepatica (3× triclabendazole-resistant, TCBZ-R and 3× triclabendazole-susceptible, TCBZ-S) were generated. Snails infected with one miracidium started to shed cercariae 42–56 days post-infection and shed repeatedly up to a maximum of 11 times. A maximum of 884 cercariae were shed by one clonally-infected snail (FhLivS1) at a single time point, with > 3000 clonal metacercariae shed over its lifetime. Following experimental infection all 12 sheep were FEC positive at the time of TCBZ treatment. Sheep infected with one of three putative TCBZ-S clones and treated with TCBZ had no parasites in the liver at post-mortem, whilst sheep each infected with putative TCBZ-R isolates had 35–165 adult fluke at post-mortem, despite TCBZ treatment. All six untreated control animals had between 15–127 parasites. A single multi-locus genotype was reported for every fluke from each of the six clonal isolates. Adult F. hepatica showed considerable variation in weight, ranging from 20–280 mg, with variation in weight evident within and amongst clonal isolates.ConclusionsA genetic clonal expansion occurs within G. truncatula, highlighting the potential for amplification of drug resistant genotypes of F. hepatica. Variation in the weight of parasites within and between clonal isolates and when comparing isolates that are either susceptible or resistant to TCBZ represent inherent variation in liver fluke and cannot be attributed to their resistance or susceptibility traits.

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“…Diversos estudios han tratado de estudiar el mecanismo de resistencia de Fasciola al TCBZ pero ninguno ha logrado aun aclarar el mecanismo preciso. En el pasado se había mostrado que un polimorfismo único de nucleótido (A T687G) en el gen de la glicoproteína-P del parasito era el responsable de la resistencia al TCBZ, pero esto no fue corroborado en otro estudio en Australia [20] , por lo tanto esta hipótesis fue rechazada. Se sabe que la resistencia de los nematodos a las drogas de la familia benzimidazole está ligada a una substitución de un aminoácido (phenilalanina a tirosina) en la posición 200 de la molécula Beta-tubulina, pero en Fasciola no se ha encontrado tal hallazgo a pesar que la tubulina estaba intacta en aquellos parásitos resistentes al TCBZ a comparación de los no resistentes, estos Triclabendazole en fasciolosis humana Terashima A & Marcos LA últimos tenían la tubulina destruida por acción del TCBZ [21] .…”

Section: Discussionunclassified

Fracaso de dosis única de triclabendazole para el tratamiento de fasciolosis humana

Terashima¹,

Marcos²

2016

Acta Med Peru

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La fasciolosis humana es prevalente en zonas ganaderas del Perú. La única droga efectiva para tratar a la infección por Fasciola hepatica en la práctica clínica es el triclabendazole (TCBZ). Sin embargo, se ha reportado recientemente resistencia de la F. hepatica al TCBZ en Perú tanto en humanos como en animales. Este problema ya se sospechaba anteriormente en vista que una dosis única de triclabendazole no curaba (eliminación de huevos de Fasciola en heces) en algunos pacientes. Aquí reportamos 11 de 12 casos humanos infectados por F. hepatica que no respondieron a dosis única de TCBZ 10 mg/kg vía oral. En vista de estos resultados observados en la práctica clínica, recomendamos considerar por lo menos dos dosis de TCBZ para los infectados. Creemos que el tratamiento de fasciolosis se ha convertido en un problema emergente desde el punto de vista farmacológico. Se necesitan nuevos regímenes de terapia o drogas contra F. hepática.

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The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

Cited by 17 publications

References 21 publications

Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test

Assessment of flukicide efficacy against Fasciola hepatica in sheep in Sweden in the absence of a standardised test

Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones

Fracaso de dosis única de triclabendazole para el tratamiento de fasciolosis humana

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