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Cited by 69Helminth infection and controlVeterinary Pharmacology and AnesthesiaMollusks and Parasites Studies

A novel approach for combining the use of in vitro and in vivo data to measure and detect emerging moxidectin resistance in gastrointestinal nematodes of goats

Kaplan, R.M., Vidyashankar, A.N., Howell, S.B., Neiss, J.M., Williamson, L.H., Terrill, T.H.·2007·International Journal for Parasitology
DOI 10.1016/j.ijpara.2007.01.001
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Abstract

Ivermectin and moxidectin are closely related avermectin/milbemycin anthelmintics and available data suggest that side resistance occurs with these two drugs. However, moxidectin remains effective against many species of ivermectin-resistant worms due to its higher potency. The larval development assay (LDA) is routinely used to diagnose ivermectin resistance in Haemonchus contortus but laboratory diagnosis of moxidectin resistance is hampered by the lack of any validated in vitro tests. The objective of this study was to measure the relative susceptibility/resistance of H. contortus to moxidectin on goat farms in Georgia, and to validate the DrenchRite LDA for detecting resistance to moxidectin. Fecal egg count reduction tests (FECRT) were performed at five different moxidectin dose levels and DrenchRite LDAs were performed in duplicate on nine meat goat farms in Georgia, USA. To improve our ability to make inferences on the relative levels of resistance between farms, FECRT data were first analysed using a linear mixed model, and then Tukey's sequential trend test was used to evaluate the trend in response across dose levels. LDA data were analysed using log-dose logit-response and probit models. Using these statistical results, we were able to rank the nine farms from the least to the most resistant, and to develop a set of criteria for interpreting DrenchRite LDA results so that this assay can be used to diagnose both clinically apparent moxidectin resistance, as well as sub-clinical emerging resistance. These results suggest that our novel approach for examining these types of data provides a method for obtaining an increased amount of information, thus permitting a more sensitive detection of resistance. Based on results of the LDA, moxidectin-resistant farms had resistance ratios, compared with an ivermectin-sensitive farm, ranging from 32 to 128, and had resistance ratios of 6-24 compared with an ivermectin-resistant/moxidectin naive farm. Moxidectin resistance was diagnosed both in Haemonchus and Trichostrongylus on almost half of the farms tested, despite this drug only being used on these farms for 2-3 years.

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Crossref · 10.1016/j.ijpara.2007.01.001

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  • The LDA is a commonly used in vitro bioassay for detecting resistance to multiple different classes of anthelmintics in gastrointestinal nematode parasites of sheep and goats.

    “The LDA is a commonly used in vitro bioassay used for detecting resistance to multiple different classes of anthelmintics in gastrointestinal (GI) nematode parasites of sheep and goats [42, 60, 61].”

    From Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? (2019) · cites this paper as [61]

  • A study investigating the emergence of moxidectin resistance in H. contortus found that a farm naïve to moxidectin but with ivermectin resistance had an LDA resistance ratio of 5.3, whereas farms with resistance to moxidectin had resistance ratios of 32-128, which is 6-24-fold higher.

    “A study investigating the emergence of moxidectin resistance in H. contortus found that a farm naïve to moxidectin but with ivermectin resistance had an LDA resistance ratio of 5.3, whereas farms with resistance to moxidectin had resistance ratios of 32–128, which is 6–24-fold higher [61].”

    From Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? (2019) · cites this paper as [61]

  • In H. contortus, ivermectin-resistant worms that are naïve to moxidectin are typically killed at very high efficacy following administration of moxidectin; however, once moxidectin is used regularly in an ivermectin-resistant population, resistance to moxidectin can develop rapidly.

    “In H. contortus, ivermectin-resistant worms that are naïve to moxidectin are typically killed at very high efficacy following administration of moxidectin [65, 66]; however, once moxidectin is used regularly in an ivermectin-resistant population, resistance to moxidectin can develop rapidly [61].”

    From Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? (2019) · cites this paper as [61]

  • The IC50 and corresponding resistance ratio measured in A. caninum for both macrocyclic-resistant and -susceptible isolates were fairly comparable to those previously reported for H. contortus.

    “The IC50 and corresponding resistance ratio we measured in A. caninum for both macrocyclic-resistant and -susceptible isolates were fairly comparable to those previously reported for H. contortus [61].”

    From Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? (2019) · cites this paper as [61]

  • The disparity in these findings is consistent with the rapid evolution of moxidectin resistance when moxidectin is used against ivermectin-resistant worms.

    “The disparity in these findings is consistent with the rapid evolution of moxidectin resistance when moxidectin is used against ivermectin resistant worms [61].”

    From Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? (2019) · cites this paper as [61]

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Authors
Kaplan, R. M., Vidyashankar, A. N., Howell, S. B., Neiss, J. M., Williamson, L. H., & Terrill, T. H.
Affiliations
  • University of Georgia (US)
  • Cornell University (US)
  • Fort Valley State University (US)
Corresponding author
Kaplan, R.M.
ORCID
Venue
International Journal for Parasitology
Publisher
Elsevier BV
Published
2007-06
Volume
37
Issue
7
Pages
795-804
ISSN
0020-7519 (ISSN-L)
DOI
10.1016/j.ijpara.2007.01.001
OpenAlex
W2124623523
Cited by
69
References
32
Citations by year
2026: 1 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 3
FWCI
5.23
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • International Journal for Parasitology (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Department of Agriculture
Topics
  • Health Sciences › Veterinary › Small Animals › Helminth infection and control
  • Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
  • Life Sciences › Agricultural and Biological Sciences › Insect Science › Mollusks and Parasites Studies
Keywords
ivermectin resistance, Haemonchus contortus, Trichostrongylus, gastrointestinal nematodes, goats, larval development assay, faecal egg count reduction test, resistance ratio, linear mixed models, probit model, dose-response relationship
MeSH terms
Animals, Anthelmintics, Data Interpretation, Statistical, Dose-Response Relationship, Drug, Drug Resistance, Feces, Gastrointestinal Diseases, Goats, Haemonchiasis, Haemonchus, Larva, Parasite Egg Count, Goat Diseases, Macrolides

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