Evidence map›Paper›PMID 36701396›Full record

ArticlePLoS pathogens2023

A major locus confers triclabendazole resistance in Fasciola hepatica and shows dominant inheritance.

Nicola J Beesley, Krystyna Cwiklinski, Katherine Allen, Rebecca C Hoyle, Terry W Spithill, E James La Course, Diana J L Williams, Steve Paterson, Jane E Hodgkinson

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A practical miracidial motility assay for assessing Fasciola hepatica sensitivity to compounds in vitro.International journal for parasitology. Drugs and drug resistance · 2026
    Article
  5. Triclabendazole and Other Fasciolicides: Resistance ofAnimals : an open access journal from MDPI · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Genetic diversity and host-symbiont cophylogenetic analysis ofCurrent research in parasitology & vector-borne diseases · 2026
    Article
  11. Article
  12. Structural Insights and Calcium-Switching Mechanism ofInternational journal of molecular sciences · 2025
    Article
  13. Design of a Multi-Epitope Vaccine Based onInternational journal of molecular sciences · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Nicola J BeesleyVeterinary Parasitology, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0003-0557-1833
Krystyna CwiklinskiVeterinary Parasitology, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Katherine AllenVeterinary Parasitology, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Rebecca C HoyleVeterinary Parasitology, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Terry W SpithillDepartment of Animal, Plant and Soil Sciences and Centre for AgriBioscience, La Trobe University, Bundoora, Australia.
E James La CourseLiverpool School of Tropical Medicine, Liverpool, United Kingdom.
Diana J L WilliamsVeterinary Parasitology, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Steve PatersonCentre for Genomic Research, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Jane E HodgkinsonVeterinary Parasitology, Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
University of Liverpool · GBLa Trobe University · AULiverpool School of Tropical Medicine · GB

Funding

Biotechnology and Biological Sciences Research Council BB/1002480/1Biotechnology and Biological Sciences Research Council BB/P001912/1
6 · The paper itself

Abstract

Fasciola hepatica infection is responsible for substantial economic losses in livestock worldwide and poses a threat to human health in endemic areas. The mainstay of control in livestock and the only drug licenced for use in humans is triclabendazole (TCBZ). TCBZ resistance has been reported on every continent and threatens effective control of fasciolosis in many parts of the world. To date, understanding the genetic mechanisms underlying TCBZ resistance has been limited to studies of candidate genes, based on assumptions of their role in drug action. Taking an alternative approach, we combined a genetic cross with whole-genome sequencing to localise a ~3.2Mbp locus within the 1.2Gbp F. hepatica genome that confers TCBZ resistance. We validated this locus independently using bulk segregant analysis of F. hepatica populations and showed that it is the target of drug selection in the field. We genotyped individual parasites and tracked segregation and reassortment of SNPs to show that TCBZ resistance exhibits Mendelian inheritance and is conferred by a dominant allele. We defined gene content within this locus to pinpoint genes involved in membrane transport, (e.g. ATP-binding cassette family B, ABCB1), transmembrane signalling and signal transduction (e.g. GTP-Ras-adenylyl cyclase and EGF-like protein), DNA/RNA binding and transcriptional regulation (e.g. SANT/Myb-like DNA-binding domain protein) and drug storage and sequestration (e.g. fatty acid binding protein, FABP) as prime candidates for conferring TCBZ resistance. This study constitutes the first experimental cross and genome-wide approach for any heritable trait in F. hepatica and is key to understanding the evolution of drug resistance in Fasciola spp. to inform deployment of efficacious anthelmintic treatments in the field.

Indexed as

AnthelminticsFasciola hepaticaFascioliasisAnimalsBenzimidazolesDrug ResistanceHumansTriclabendazoleAnthelminticsBenzimidazolesTriclabendazole

Identifiers

PMID36701396
PMCPMC9904461
OpenAlexW4318141857

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.