Anthelmintic Resistance in Cattle - an Emerging Problem?16 July 2013
Widely considered to have resistance developed in sheep on many UK farms, Dr David Burden of ADAS explores the possibility of developing Anthelmintic resistance problems in cattle.
Back in 2011, more than 50 per cent of farmers asked at the Dairy Event said there were no anthelmintic resistance problem in cattle, according to Dr Burden.
He says that wide spread use of levamizoles, benzimidazoles and macrocyclic lactones (all Anthelmintic products) means the situation in cattle is not as clear as it is in sheep.
There have been a number of reports of anthelmintic resistance in cattle from South America, Australia and New Zealand (Sutherland and Leathwick, 2011) of which most were to macrocyclic lactones (MLs) such as ivermectin, doramectin, cydectin and moxidectin.
"All that can be done is to slow down the development of resistance in order to extend the useful life of existing anthelmintic products."
Macrocylic lactones have become the predominant class of anthelmintic used in cattle. Most of the cases of resistance reported were in worms of the Cooperia species. The fact that Cooperia is the first species to show resistance is perhaps not surprising as this worm is the least susceptible to MLs. Cooperia is of less clinical significance than some of the other species in cattle such as Ostertagia ostertagi, so the production effects of sub-optimal control of Cooperia might not be obvious and may contribute to the feeling that there is, as yet, no problem.
A number of studies are underway across the UK and Europe to try and establish how much of a problem anthelmintic resistance in cattle really is. Early indications suggest that it is developing in the UK, but for the moment it is at a low level of intensity and distribution and not surprisingly, involves mainly Cooperia species. Judging from the experience in sheep, it can only get worse.
Anthelmintic resistance can be defined as the ability of a parasite to tolerate what would normally be an effective dose of an anthelmintic drug and to pass this ability on to their offspring.
Resistance is not an absolute thing, as ‘resistant’ parasites usually succumb to a higher than normal dose of the same drug. The genes that allow worms to become resistant are thought to pre-exist in susceptible, unselected worm populations. In the absence of anthelmintic, natural selection keeps these genes at a low level.
The continued use of an anthelmintic, however, confers a survival advantage on those carrying the resistant gene. This allows them to reproduce at a higher rate than susceptible worms and thus their frequency within the population increases. Therefore, for all the classes of anthelmintic being used at present, the development of resistance can be considered an inevitable consequence of using the drug. All that can be done is to slow down the development of resistance in order to extend the useful life of existing anthelmintic products.
Wormers within the same class share a similar mode of action so that when resistance develops to one drug, other anthelmintics of the same class will also be less effective. Worms that are resistant to ivermectin, for example, will also be resistant to doramectin, eprinomectin and moxidectin, but not necessarily resistant to a benzimidazole or levamizole class drug. Resistance to each class of drug will develop separately. But resistance to one or more classes of drug can exist in the same strain of worm.
At first glance, checking whether a drug is still effective would seem relatively simple. Either a laboratory test in-vitro could be carried out or cattle could be treated on farm to see if their worms are removed. But as with most things, there are complications.
There is no completely validated and easy to run in-vitro test for resistance to MLs. A test that looks promising is one where the ability of worm larvae to migrate through a small mesh is measured after they have been exposed to various concentrations of drug. It is known as the larval migration inhibition assay and is as fiddly to carry out as the name is clumsy.
With a natural infection, where a few different species of worm are present, the larvae have to be identified, typically by observing them down a microscope. Some species have obvious and unique identifying characteristics but others do not and so the process is inexact as well as laborious. There are now methods for speciation that use the larval worm DNA and these may well become the standard methods in future.
On farm testing for anthelmintic resistance is usually done by carrying out a faecal egg count reduction test (FECRT). In essence, a group of cattle are individually dung sampled and their egg counts measured. Half are then treated and 14 days later the faecal egg counts are repeated.
Comparisons of the egg counts give an indication of drug efficacy. Where efficacy has fallen below 95%, anthelmintic resistance is suspected. The larvae cultured from the eggs before and after treatment are identified to see which species are susceptible or not. Using these methods, it is still difficult to identify anthelmintic resistance on farm in the early stages, when changes to husbandry practice and drug use could alleviate the problem.
Veterinary medicine companies are researching and developing new anthelmintics with novel modes of action. As always, it takes a long time and much effort to bring a new drug to market. The safety and efficacy of any new product has to be painstakingly demonstrated to the regulatory authorities. ADAS has considerable experience of conducting parasite efficacy, safety and residue studies in cattle, and our farm animal health research facilities at Drayton are ideally suited to helping companies in the process of developing new anthelmintics.
In the meantime, there are practical measures that farmers can take to slow the development of anthelmintic resistance and therefore extend the life of the present anthelmintics (see, Control of Worms Sustainably (COWS), a technical manual for veterinarians and farm advisors).