Triple anthelmintic resistance on a French Thoroughbred stud farm

Well, here it is. A well conducted study finding that a population of horses is resistant to the main three anthelminic drugs currently used. It speaks strongly to the need to immediately begin aggressive deworming programs, perhaps as described in our Overview and Schedule Topics and listed as the Parasitologist Recommendation.
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The first report of triple anthelmintic resistance on a French Thoroughbred stud farm
Int J Parasitol Drugs Drug Resist. 2024 Feb 23:24:100528. doi: 10.1016/j.ijpddr.2024.100528. Online ahead of print.
Authors
Aurélie Merlin 1 , Nicolas Larcher 2 , José-Carlos Vallé-Casuso 2
Affiliations

1 Anses, Laboratory for Animal Health in Normandy, Physiopathology and Epidemiology of Equine Diseases Unit, 14430 Goustranville, France; Mixed Technological Unit “Equine Health and Welfare – Organisation and Traceability of the Equine Industry” (UMT SABOT), France. Electronic address: aurelie.merlin@anses.fr.
2 Anses, Laboratory for Animal Health in Normandy, Physiopathology and Epidemiology of Equine Diseases Unit, 14430 Goustranville, France; Mixed Technological Unit “Equine Health and Welfare – Organisation and Traceability of the Equine Industry” (UMT SABOT), France.

PMID: 38422764
DOI: 10.1016/j.ijpddr.2024.100528

Abstract

This study assessed the anthelmintic resistance in strongylid nematodes against commonly used anthelmintic (AH) drugs in a French galloping racehorse stud farm from March to December 2023. Faecal egg count reduction tests (FECRTs) were conducted in three different groups of Thoroughbred yearlings (a group of 6 males, a group of 13 females and a group of 8 females and 3 males) following the new World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. The efficacy of fenbendazole was tested in two groups once during the monitoring period (in March), the efficacy of ivermectin in 3 groups twice (in March-April and in November-December) and the efficacy of pyrantel in one group once (in May-June). For each FECRT, the 90% confidence interval of the percentage faecal egg count reduction was calculated using the hybrid Frequentist/Bayesian analysis method. The resistance in strongylids was observed to fenbendazole, pyrantel and ivermectin in all the groups in which these drugs were tested. The number of animals in each group was sufficient to reach ≥80% power for the resistance test. The results highlight the first case of triple AH resistance in strongylids in France. Further studies involving more farms and equids are required to assess the prevalence of AH resistance in France and refine recommendations for owners.

Keywords: Anthelmintic resistance; Faecal egg count reduction test; Horses; Strongylids.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Furthe excerpted from the paper:

3. Results and discussion
During the monitoring period (March–December 2023), the year-
lings received four different AH treatments (Fig. 1): i) a FBZ treatment in
early March, ii) an IVM treatment at the end of March, iii) a PYR
treatment at the end of May and iv) an IVM treatment at the end of
November. In this farm, the animals also received an IVM treatment in
January 2023. The frequency of AH treatment use per year was higher
than that reported in a previous French study with managers/keepers of
animals ≤2 years old susceptible to AH resistance (5 versus 1–3 AH
treatments per year; Merlin et al., 2023).
Using the mean pre-treatment FECs obtained in each group of
yearlings of more than five animals, the power calculation showed that
these groups obtained the required number of horses to reach ≥80%
power for the outcome: positive evidence of resistance should the effi-
cacy be reduced (Tables 1 and 2).
The efficacy of FBZ was first tested in a group of males (n = 6) and in
a group of females (n = 12, the 13th female was excluded because it had
to stay in the stable for a few days for an orthopaedic problem) (Fig. 1).
Before FBZ treatment, all males could be classified as “high shedders” as
they shedded >500 EPG according to the AAEP guideline (AAEP –
American Association of Equine Practitioners, 2019). In the group of
females, 58% of animals (7/12) could be considered as “high shedders”
and the minimum FEC for “low shedders” was 150 EPG. Fourteen days
post-treatment, all the horses in both groups continued to shed strong-
ylid eggs. The FECs increased between pre- and post-treatment in 4/6
males and 8/12 females. According to the new WAAVP guidelines, the
resistance to FBZ against strongylids was identified in both groups
(Table 1). This result is consistent with previous studies from around the
world, including France, which reported widespread and
well-established resistance patterns in strongylids against this molecule
(Nielsen, 2022). Indeed, confirmed resistance for FBZ was observed in
92–100% of the tested groups according to the previous French studies
(Traversa et al., 2012; Geurden et al., 2013; Sall´e et al., 2017).
As the treatment with FBZ did not reduce egg excretion by the ani-
mals (same high mean pre and post-treatment FEC; Table 1), an IVM-
based treatment was administered 21 days after the previous FBZ
treatment to avoid any impact on the health and growth of the yearlings
(Fig. 1). As the interval between the two treatments was short, it is
possible that the subpopulation of parasites within the animals may have
undergone drug selection. Despite a possible persistence of FBZ activity
on the worm population (which nevertheless seems minor given the
results), the efficacy of IVM was tested in the same group of males and
females. However, the size of the group of females was reduced (from 13
to 6 animals) due to the sale of animals or the end of breeding contract
(Fig. 1).
Before IVM treatment, 100% of males (6/6) and 83% of females (5/
6) could still be considered as “high shedders” (Table 2). The low
shedder female exhibited a pre-treatment FEC of 220 EPG. Fourteen
days post-treatment, all the animals in both groups continued to shed
strongylid eggs. The FECRT conducted in these two groups revealed the
IVM resistance in both (Table 2).
Next, the efficacy of the PYR was tested in the group of males with at
least six individuals (Fig. 1 and Table 1). The interval between IVM and
PYR treatments was around two months (56 days). Before PYR treat-
ment, 5/6 animals were high shedders. The low shedder male exhibited
a FEC of 165 EPG. Fourteen days post-treatment, 5/6 males continued to
shed strongylid eggs. Resistance to PYR was discovered in the group of
males (Table 1). This result is consistent with the fact that the PYR
resistance has increasingly emerged between and within countries over
the past couple of decades (Nielsen, 2022). In earlier French studies
dating back five to ten years, confirmed resistance for PYR was found in
up to 23% of the groups tested (Traversa et al., 2012; Geurden et al.,
2013; Sall´e et al., 2017). It is therefore, not surprising to observe PYR
resistance in our recruited farm; this resistance is probably now more
widespread within the country and deserves to be studied.
Finally, the efficacy of IVM was again tested in a group of females
and males (n = 11; Fig. 1). Resistance to IVM in strongylids being un-
common, the confirmation of a reduced efficacy with several tests is
strongly recommended by Kaplan et al. (2023) before declaring that IVM
resistance is present in a farm. An interval of approximately six months
was left between the PYR and the IVM treatments. This period minimizes
the impact of the PYR treatment on the worm infrapopulation and
ensure that it is representative of the overall worm population on the
farm. Before treatment, 6/11 horses could be considered as high shed-
ders. The minimum FEC in low shedders was 105 EPG. Fourteen days
post-treatment, 10/11 of the horses continued to shed strongylid eggs.
IVM resistance was also demonstrated in this group at this time of year
(Table 1).
In Thoroughbreds, the intensive breeding practices, frequent AH International Journal for Parasitology: Drugs and Drug Resistance 24 (2024) 100528
4treatments and frequent movements between countries for raising and
training young horses, but also for racing, sales, stallion visiting and
breeding (i.e., natural cover) expose this population to the risk of AH
resistance emerging and spreading resistant worms. The resistance to
ML (IVM and/or MOX) in strongylids has already been reported in
Thoroughbred stud farms importing horses from other countries, such as
Ireland and the UK (Nielsen et al., 2020; Abbas et al., 2021; Bull et al.,
2023).
The Thoroughbred horseracing industry is an essential sector of
Ireland and the UK economy. The two countries complement each other;
Ireland is the European leader in Thoroughbred production in terms of
births (producing almost half of all Thoroughbred horses in Europe), and
the UK trains the third highest proportion of top-ranked flat Thor-
oughbreds behind only the USA and Australia (Teagasc, 2022; IFHA –
International Federation for Horseracing Authorities, 2023). With this
structuring of the Thoroughbred sector, European or international reg-
ulations should be implemented to impose a quarantine procedure for all
equids coming from foreign countries to limit the spread of ML resistant
strongylids. This quarantine procedure could include FECRT with tar-
geted AH molecules whose effectiveness in the structure has been
proven.

To conclude, this study provides the first evidence of triple resistance
to all three licenced classes of AH, and more specifically to three of the
four molecules available: FBZ, PYR and IVM. MOX is not currently used
on yearlings on this farm, so it remains the last line of defence against
strongylids. These results made the owner of the farm aware of the state
of the situation, and since the beginning of 2024, he has wanted to
continue with regular coproscopic analysis and, in partnership with his
veterinarian, to start implementing a strategy of targeted selective
treatment on high shedders. Further field studies involving more farms
and horses are required to assess the prevalence of PYR and ML resis-
tance in France. In parallel, the setting up of a European or worldwide
network to monitor resistance, in particular, in this at-risk population,
the galloping racehorses, could make it possible to inform owners of the
risk of importing multi-resistant parasites and to offer them recom-
mendations and to impose instructions on them.
Authors’ contributions
AM supervised and conducted this study. AM and NL performed the
faecal egg counts. AM and JCV carried out the data analysis. All the
authors critically revised the article and approved the final version
before submission.
Funding sources
This work was supported by the French Agency for Food, Environ-
mental and Occupational Health & Safety (Anses).
Declaration of competing interest
The authors declare no conflicts of interest concerning the research,
authorship, publication of this article and/or financial and personal
relationships that could inappropriately influence this work.
Conflicts of interest
The authors declare no conflicts of interest with respect to the International Journal for Parasitology: Drugs and Drug Resistance 24 (2024) 100528
5research, authorship, publication of this article and/or financial and
personal relationships that could inappropriately influence this work.
Acknowledgments
The authors are very grateful to the owner of the farm, Felix Lep-
eudry, and his veterinarian, Xavier d’Ablon for agreeing to participate to
this study and for their collaboration on the collection of faecal samples