VET CLINIC
In association with
Mark Andrews, BVM&S CertEP MRCVS, of
Equine Science Update
we are pleased to provide the latest Equine Veterinary Information
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ANTHELMINTIC RESISTANCE
The growing importance of anthelmintic resistance in cyathostomes (small red worms) poses a threat to the health and welfare of horses of all types. Anthelmintic resistance is a common cause of failure in worm control programs.
Cyathostomes (also known as small strongyles or small redworms) are the most important internal parasite of horses. They often cause sub-clinical impairment of intestinal function, which may lead to poor performance, weight loss or failure to thrive. They may cause overt disease with diarrhoea, severe weight loss and oedema. They are also the worms that are most likely to develop resistance to anthelmintics.
Resistance of large strongyles to anthelmintics has not been clearly demonstrated.
How can we detect anthelmintic resistance?
There are several measures which have been used in the laboratory to investigate the phenomenon of anthelmintic resistance. Among the most useful are:
Faecal worm egg count reduction test. Faecal worm egg counts (FWECs) are carried out before, and 10 - 14 days after, treatment with anthelmintic. Resistance is detected when the second worm egg count is not at least 90% lower than the first count. This is probably the most useful practical measure of anthelmintic resistance.
The egg reappearance period (ERP) is defined as the time for FWEC to return to 20% or more of the pre-treatment value. Often the development of resistance is preceded by a reduction in ERP. For example, when the benzimidazoles were introduced in the 1960s, they had an ERP of between 6 and 8 weeks. Now the ERP is often only 4 weeks.
To which wormers do worms develop resistance?
Three main classes of anthelmintics (wormers) are used to control cyathostomes:
- benzimidazoles (including fenbendazole, oxfendazole, mebendazole)
-
pyrantel group (tetrahydropyramidines), and
-
avermectin/milbemycins (ivermectin and moxidectin).
All were effective when they were first introduced. However, resistance to the benzimidazole group has been widely reported, and resistance to pyrantel has been recorded in USA and Europe. So far, there have been no reports of resistance to ivermectin or moxidectin.
Resistance to the benzimidazole group of anthelmintics is found throughout the world. Cross resistance usually occurs between individual anthelmintics within the group. One possible exception used to be oxibendazole, which was effective against worms resistant to other members of the benzimidazole group. It is less likely to be effective against resistant worms now.
Fenbendazole resistance was found to be widespread in the south of England in the early 1990`s. Recent investigations in Yorkshire(1) , have shown that a significant number of horses are infected with anthelmintic resistant worms. Of particular concern is the finding that a five-day course of treatment with fenbendazole did not overcome resistance. (Previous work had suggested that fenbendazole (at a dose of 7.5mg/kg for 5 days) was effective against inhibited mucosal cyathostome larvae, even when resistant adult cyathostomes were present.)
Benzimidazole resistance seems to develop in stages:
Individual worms are still susceptible to higher doses of the drug. In this case giving a 5-day course of fenbendazole may overcome the resistance.
Increased level of resistance - the worms are no longer susceptible even to repeated doses, as in the animals in this study.
The fact that newer wormers such as ivermectin and moxidectin are currently very effective should not lull us into a false sense of security. The benzimidazoles were once very effective. The potential for cyathostomes to develop resistance to other wormers is ever present. One study in America compared a herd of horses that was regularly wormed with a feral herd which had never previously been treated with anthelmintics. They found that some of the worms in the feral herd were tolerant to low concentrations of ivermectin despite never being previously exposed to this class of anthelmintic.(4)
The ERP for ivermectin was 9-10 weeks when it was first introduced in the 1980s. Recent research(3) , found that the ERP has fallen to 6 weeks. This reduction in ERP may be the first sign that cyathostomes are developing resistance to ivermectin. It is probably only at matter of time before cyathostomes start to develop resistance to the drug.
Moxidectin has a persistent action and is effective against mucosal stages of the cyathostomes. Some people have suggested that as the worms are exposed to it for a long time they may be more likely to develop resistance. On the other hand, if the persistence of the drug allows it to be used less frequently selection pressure would be released.
How long does anthelmintic resistance last?
Once resistance develops to benzimidazole drugs it may be many years before worms revert to being susceptible. In one study, worms were still resistant to benzimidazole anthelmintics, even though the drugs had not been used for 24 - 38 months.
What can be done to reduce the risk of resistance developing?
The development of anthelmintic resistant cyathostomes has been encouraged by an extensive reliance on the use of drugs. Strategies to reduce the development of resistance should be used where possible to prolong the useful life of current wormers.
In order to reduce pasture contamination and reduce selection for drug resistance the following measures have been recommended:
Responsible use of anthelmintics:
Appropriately timed treatments: There is nothing to be gained from worming a horse when it is not necessary. If good pasture management practices are observed it may be possible to reduce the amount of anthelmintic used. Faecal worm egg counts can be used to determine when worming is due. The correct dose of anthelmintic for the weight of the horse should be used.
Periodic testing of drug efficacy: In particular fenbendazole should not be used as a single dose anthelmintic without previously demonstrating its efficacy. According to Chandler(1) , resistance to fenbendazole is so widespread now that this anthelmintic should be avoided in prophylactic dosing regimes, unless faecal egg count reduction tests prove that the drug is still effective. A five-day course of fenbendazole should be reserved for the treatment of clinically affected animals or those animals at higher risk of developing cyathostomiasis.
Rotating anthelmintics: There is conflicting evidence on the value of alternating or rotating anthelmintics. It used to be thought that frequently rotating anthelmintics every few months helped slow the development of resistance. However, there is little evidence to support that view, and frequent rotation may even accelerate the development of multiple resistance, as each generation of worms is exposed to several different classes of drug. (Multiple resistance has been reported in sheep). Current advice is to rotate anthelmintics in a slow rotation every 1 or 2 years - so that each generation is exposed to only one class of drug.
Sound pasture management:
Collection of faeces: Research carried out in Newmarket showed that twice weekly collection of faeces resulted in better parasite control than that achieved using anthelmintics.
Pasture harrowing: If this is done in hot dry weather it will break up the faecal pats and expose the larvae to death by dehydration. If done in wet weather it will only serve to spread viable larvae over a wider area.
Break from grazing: This will allow larvae to die out. But in cool damp conditions larvae may survive at least six months. Leaving pasture de-stocked for a month or two is likely to do more harm than good.
Mixed grazing with cattle or sheep: The value of this has been questioned because cows initially graze the upper layers of vegetation, where few horses worm larvae live. This could result in a concentration of larvae on the remaining grass. However, grazing pasture with cows for the first six months of the year would allow any horse larvae that had survived the winter in the pasture to die out.
A new method of worm control currently under study involves nematode-trapping fungi. The fungus Duddingtonia flagrans has been shown to trap the free-living stages of roundworm ("nematode") parasites, such as cyathostomes. It grows rapidly in fresh faeces and its chlamydospores (resistant spores) are able to survive the passage through the gastro-intestinal tract of the horse. These fungal spores have no effect on the animal and only germinate once passed in the faeces where they develop into nematode-trapping fungal nets. Fernandez and others(2) showed that, on average, pasture surrounding faecal pats containing Duddingtonia flagrans had 94.8% fewer larvae. They concluded that the use of nematode-trapping fungi against free-living larvae stages of horse strongyles represents a potentially useful method in equine parasite control.
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REFERENCES
1. Efficacy of a five-day course of fenbendazole in benzimidazole- resistant cyathostomes.
K.J. Chandler, M.C.Collins, S.Love.
Veterinary Record (2000) 147, 661-662
http://www.equinescienceupdate.co.uk/widesprd.htm
2. A new isolate of the nematodophagous fungus Duddingstonia flagrans as biological control agent against free-living larvae of horse strongyles.
A Silvina Fernandez, E Henningsen, M Larsen, P Nansen, J Gronvold,
J. Sondergaard.
Equine Veterinary Journal (1999) 31 (6) 488-491.
http://www.equinescienceupdate.co.uk/worm4.htm
3. Prevalence and clinical implications of anthelmintic resistance in cyathostomes of horses.
Jaime L Tarigo-Martinie, Amy R Wyatt, Ray M Kaplan
JAVMA (2001) 218 (12) 1957-1960
http://www.equinescienceupdate.co.uk/worms3.htm
4. Parasite diversity and anthelmintic resistance in two herd of horses.
Young KE, Garza V, Snowden K, Dobson RJ, Powell D, Craig TM.,
Veterinary Parasitology 1999 85; 205-214
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