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

Abstract Background Fasciola 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...

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Main Authors: Jane E. Hodgkinson, Krystyna Cwiklinski, Nicola Beesley, Catherine Hartley, Katherine Allen, Diana J. L. Williams
Format: Article
Language:English
Published: BMC 2018-06-01
Series:Parasites & Vectors
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13071-018-2952-z
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author Jane E. Hodgkinson
Krystyna Cwiklinski
Nicola Beesley
Catherine Hartley
Katherine Allen
Diana J. L. Williams
author_facet Jane E. Hodgkinson
Krystyna Cwiklinski
Nicola Beesley
Catherine Hartley
Katherine Allen
Diana J. L. Williams
author_sort Jane E. Hodgkinson
collection DOAJ
description Abstract Background Fasciola 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. Results Six 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. Conclusions A 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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spelling doaj.art-1a769a4a64d1424281e71a728f29bc582022-12-21T17:44:06ZengBMCParasites & Vectors1756-33052018-06-011111910.1186/s13071-018-2952-zClonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clonesJane E. Hodgkinson0Krystyna Cwiklinski1Nicola Beesley2Catherine Hartley3Katherine Allen4Diana J. L. Williams5Veterinary Parasitology, Dept Infection Biology, Institute of Infection and Global Health, University of LiverpoolVeterinary Parasitology, Dept Infection Biology, Institute of Infection and Global Health, University of LiverpoolVeterinary Parasitology, Dept Infection Biology, Institute of Infection and Global Health, University of LiverpoolVeterinary Parasitology, Dept Infection Biology, Institute of Infection and Global Health, University of LiverpoolVeterinary Parasitology, Dept Infection Biology, Institute of Infection and Global Health, University of LiverpoolVeterinary Parasitology, Dept Infection Biology, Institute of Infection and Global Health, University of LiverpoolAbstract Background Fasciola 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. Results Six 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. Conclusions A 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.http://link.springer.com/article/10.1186/s13071-018-2952-zFasciola hepaticaGalba truncatulaTriclabendazole resistanceClonal isolateIsolate variation
spellingShingle Jane E. Hodgkinson
Krystyna Cwiklinski
Nicola Beesley
Catherine Hartley
Katherine Allen
Diana J. L. Williams
Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones
Parasites & Vectors
Fasciola hepatica
Galba truncatula
Triclabendazole resistance
Clonal isolate
Isolate variation
title Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones
title_full Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones
title_fullStr Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones
title_full_unstemmed Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones
title_short Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones
title_sort clonal amplification of fasciola hepatica in galba truncatula within and between isolate variation of triclabendazole susceptible and resistant clones
topic Fasciola hepatica
Galba truncatula
Triclabendazole resistance
Clonal isolate
Isolate variation
url http://link.springer.com/article/10.1186/s13071-018-2952-z
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