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International journal for parasitology. Drugs and drug resistance2024; 27; 100576; doi: 10.1016/j.ijpddr.2024.100576

Quantitative DNA metabarcoding reveals species composition of a macrocyclic lactone and pyrantel resistant cyathostomin population in the UK.

Abstract: Cyathostomins are the most abundant equid endoparasites globally. There are approximately fifty cyathostomin species and, whilst they occupy distinct niches within the large intestine, they are generally considered to share similar characteristics in terms of pathogenicity and response to drug treatment. There are three classes of anthelmintic licensed in the UK to treat cyathostomins (benzimidazoles, tetrahydropyrimidines and macrocyclic lactones) and cases of resistance have been documented for all classes. Previously, faecal egg count reduction tests (FECRT) on four UK Thoroughbred studs revealed multidrug resistant cyathostomins on one stud (A), with evidence of resistance to the macrocyclic lactones (MLs) ivermectin (IVM) and moxidectin (MOX), and to pyrantel (PYR). The remaining three studs (B-D) lacked resistance to IVM and MOX but had a shortened egg reappearance period post treatment. To determine whether specific species could be associated with the observed resistance and shortened egg reappearance period, strongyle eggs collected from between six and 15 individual horses per stud were copro-cultured to third larval stage (L3), before and after anthelmintic treatment, over a three-year timeframe (2021-2023). Quantitative DNA metabarcoding of the ITS-2 region was carried out on all samples. On stud A, single but differing species were found to be responsible for ML and pyrantel resistance in yearlings, Cyathostomum catinatum and Cylicocyclus nassatus, respectively. On studs B-D, with shortened egg reappearance periods, species composition remained largely unchanged post treatment. This study is the first to quantitatively profile cyathostomin species composition pre- and post-treatment in a multidrug resistant population in the UK, revealing that resistance in cyathostomins was species specific. This raises the question of whether these species may be responsible for ML and PYR resistance more widely and indicates that anthelmintic resistance in cyathostomins may not be a multi-species phenomenon.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Publication Date: 2024-12-22 PubMed ID: 39778419PubMed Central: PMC11762968DOI: 10.1016/j.ijpddr.2024.100576Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research investigates the species composition of cyathostomin parasites in UK horses that show resistance to common anthelmintic drugs, specifically macrocyclic lactones and pyrantel.
  • Using DNA metabarcoding, the study identifies which specific parasite species are linked to drug resistance, revealing species-specific resistance rather than a generalized multi-species phenomenon.

Background

  • Cyathostomins are the most common internal parasites of horses worldwide, with around 50 known species.
  • Although these species occupy slightly different niches in the horse’s large intestine, they are generally assumed to have similar impacts on health and response to treatments.
  • In the UK, three classes of anthelmintics (anti-parasitic drugs)—benzimidazoles, tetrahydropyrimidines, and macrocyclic lactones—are licensed to treat cyathostomin infections.
  • Cases of parasite resistance (i.e., the parasites surviving treatment) to all these drug classes have been documented.

Previous Observations

  • Faecal egg count reduction tests (FECRT) on four UK Thoroughbred studs indicated multi-drug resistance in one stud (A), including resistance to macrocyclic lactones (ivermectin and moxidectin) and to pyrantel.
  • The other three studs (B-D) did not show resistance to macrocyclic lactones but exhibited a shortened egg reappearance period after treatment, indicating faster return of parasite eggs in feces.

Research Aim and Approach

  • The researchers aimed to determine whether specific cyathostomin species were associated with the observed drug resistance and shortened egg reappearance.
  • They collected strongyle eggs from 6 to 15 individual horses per stud over a three-year period (2021-2023).
  • Eggs were cultured to the third larval stage (L3) both before and after treatment with anthelmintics.
  • Quantitative DNA metabarcoding targeting the ITS-2 region of parasite DNA was conducted on all samples to identify and quantify species composition.

Key Findings

  • On stud A, which had multidrug resistance, two different species were implicated in drug resistance:
    • Cyathostomum catinatum was linked to macrocyclic lactone resistance.
    • Cylicocyclus nassatus was linked to pyrantel resistance.
  • The other studs (B-D), which had a shortened egg reappearance period but no full resistance, showed little change in species composition after treatment.
  • This indicates that drug resistance in cyathostomins can be specific to particular species rather than affecting multiple species equally.

Significance and Implications

  • This study is the first to quantitatively observe species-level changes in cyathostomin populations in response to anthelmintic treatment in a multidrug resistant setting in the UK.
  • Identifying species-specific resistance patterns suggests that some cyathostomin species may be primarily responsible for resistance to specific drugs like macrocyclic lactones and pyrantel.
  • This finding challenges the assumption that resistance in cyathostomins is a general characteristic across species.
  • Understanding which species are resistant can help in developing more targeted parasite control strategies and could influence future drug development and usage protocols.
  • Further research may explore whether these findings apply to cyathostomin populations beyond the studied studs and regions.

Cite This Article

APA
Bull KE, Hodgkinson J, Allen K, Poissant J, Peachey LE. (2024). Quantitative DNA metabarcoding reveals species composition of a macrocyclic lactone and pyrantel resistant cyathostomin population in the UK. Int J Parasitol Drugs Drug Resist, 27, 100576. https://doi.org/10.1016/j.ijpddr.2024.100576

Publication

International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
NlmUniqueID: 101576715
Country: Netherlands
Language: English
Volume: 27
Pages: 100576
PII: 100576

Researcher Affiliations

Bull, K E
  • Bristol Veterinary School, University of Bristol, Bristol, BS40 5DU, UK. Electronic address: katie.bull@bristol.ac.uk.
Hodgkinson, J
  • Department of Infection and Microbiome, Institute of Infection, Veterinary and Ecological Sciences, Leahurst Campus, University of Liverpool, Neston, CH64 7TE, UK.
Allen, K
  • Bristol Veterinary School, University of Bristol, Bristol, BS40 5DU, UK.
Poissant, J
  • Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada.
Peachey, L E
  • Bristol Veterinary School, University of Bristol, Bristol, BS40 5DU, UK.

MeSH Terms

  • Animals
  • Horses
  • Anthelmintics / pharmacology
  • Pyrantel / pharmacology
  • Strongyloidea / drug effects
  • Strongyloidea / genetics
  • Strongyloidea / classification
  • United Kingdom / epidemiology
  • Feces / parasitology
  • Parasite Egg Count
  • DNA Barcoding, Taxonomic
  • Drug Resistance / genetics
  • Lactones / pharmacology
  • Strongyle Infections, Equine / parasitology
  • Strongyle Infections, Equine / drug therapy
  • Ivermectin / pharmacology
  • Horse Diseases / parasitology
  • Horse Diseases / drug therapy
  • Macrolides

Conflict of Interest Statement

Declaration of competing interest None.

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Citations

This article has been cited 5 times.
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