Dewormer resistance came as no surprise to parasitologists, Ray Kaplan says, but it did shatter some long-held illusions in the beef industry. "This was a problem in sheep long before it became a problem in cattle," says the professor of parasitology in the University of Georgia's College of Veterinary Medicine. "That created this illusion that it would never be a problem for beef producers, and there were a lot of people with their heads in the sand. But parasitologists knew it was coming."
Anthelmintics used by U.S. cattle producers to control parasitic nematodes currently include benzimidazoles (the "white dewormers" with brand names including Safe-Guard, Panacur, Valbazen and Synanthic), macrocyclic lactones (brand names including Eprinex, LongRange, Ivomec, Dectomax and Cydectin) and levamisole (brand names including Levasol, Tramisole and Prohibit). They are available as injections, oral applications or spray/pour-ons. Kaplan says the relative low cost of these products, along with their proven effectiveness against internal parasites, has led to overuse in the cattle industry and hence increased case reports of resistance in nematode parasites.
"Studies performed by my laboratory on a number of cow/calf farms in Georgia and on stocker cattle purchased at various stockyards in the southern region suggest that macrocyclic lactone (ML) resistance in cattle is both common and widespread," he reports. He adds they have not tested a farm in the past five years that did not have ML-resistant Cooperia spp (the most common intestinal parasitic roundworm infecting calves). The exception to that, he says, was one organic operation with a long history of no anthelmintic use.
Kaplan notes resistance is most common in both Cooperia spp and Haemonchus spp (barber's pole worm), and it's far from being just a U.S. problem. A study in New Zealand reported ivermectin resistance was evident on 92% of cattle farms, and resistance to both ivermectin and albendazole was evident on 74% of farms. The problem is also common in Argentina, Australia and Brazil.
The only way to know whether parasites are resistant in a herd is through the use of fecal egg count (FEC) reduction tests. Douglas Ensley, professional services veterinarian with Boehringer Ingelheim (BI), out of Athens, Georgia, says producers need to have 90% or better FEC reduction on tests. He adds FEC tests they have looked at recently are indeed indicating resistance in some areas, especially the South.
"I do believe dewormer resistance is real, and it's growing," he says. "It is so important today for producers using dewormers to work with their veterinarians to first test for resistance in their herds and then to create a program to manage against it."
Ensley believes the cattle industry is dealing with resistance now, in large part, because it became so common to use pour-on dewormers for fly control.
"We've tended to use these products twice a year, year in and year out. When we started turning to the pour-ons for fly, or even lice, control, use became more frequent. We were only killing the susceptible populations and allowing resistance to build in the gene pool to the dewormers we have," he explains.
While traditional thinking has been that it's not possible to reverse resistance once it occurs, Ensley says scientists now believe that may not be true.
"In some herds, we now believe you can dilute the number of resistant parasites by bringing in new animals, for example. It's also important to time the use of dewormers to maximize effectiveness and think about grazing and pasture management that will help control the problem. Also, try to avoid using these products for external controls. Focus on the internal."
Parasitologist Kaplan says the good news when it comes to how the cattle industry can address dewormer resistance is that a lot has already been learned in sheep that will be applicable.
"Yes, sheep are different, but the facts are the facts when it comes to resistance; and we can take what we know and apply it in the best way possible to address the issue," Kaplan says.
Of all the things today's sheep producers do to reduce resistant worm populations in their flocks, two tactics offer the most hope to cattle producers, Kaplan believes. They are combination treatments and refuge populations.
Combining two classes of anthelmintics and administering them together is a proven way of reducing the number of surviving internal parasites. It's an approach that is so successful that, in some countries, including Australia and New Zealand, few anthelmintics are sold as single active-ingredient products now. Most contain three, four or even five different anthelmintic classes. Kaplan notes they have more classes available than U.S. producers. By combining drugs, efficacy of the treatment increases, and that efficacy is broad spectrum. Resistance is species and drug specific, so achieving higher efficacy equals fewer resistant survivors.
"If two drugs, each with 90% efficacy, are used in rotation, then each time cattle are treated, 10% of the worms would survive," he says. "In contrast, if the two drugs are used in combination, then the efficacy would be 99%. This then yields 10 times fewer resistant survivors."
Combining anthelmintics is not as simple as mixing two products together and applying them. Kaplan stresses different groups of dewormers are not chemically compatible, and they can't be mixed together in the same syringe. To achieve a combination treatment, producers need to administer products separately, one immediately after the other -- and at the full, recommended dose. If withdrawal times are a concern, use the longest one.
FEC reduction tests are important prior to this step, as they will determine which drugs are going to be most effective. In the U.S., Kaplan says producers will combine a macrocyclic lactone with either benzimidazole or levamisole. Admittedly, this will add to treatment costs, but the parasitologist notes this obstacle could be reduced if animal pharmaceutical companies sold combination products in the U.S. as they do overseas. He stresses the time for combination treatments is not after resistance has become a big problem. The earlier, the better.
"Absolutely do not wait till you have a train wreck. If you use combinations when the drugs are still highly effective … there will be a dramatic change in the evolution of drug resistance in the worm populations on your farm," says the parasitologist.
CLASSROOM TO FARM
One of Kaplan's former students, Tyson Strickland, is now a practicing veterinarian and is helping spread use of the combination dewormer treatment program in his area of Winterville, Georgia.
"I like the combination therapy for a couple of reasons," he explains. "You're administering dewormers with different routes and mechanisms for killing parasites. The research that's been done shows where resistant parasites are exposed to two different mechanisms of action, they can't handle it, and treatment success goes up dramatically. Not only does it work well in resistant populations, but it minimizes development of resistance."
Strickland, whose practice primarily serves producers with cattle, small ruminants and show pigs, admits it can be challenging to convince producers to add a second dewormer at time of treatment. "It's been a mixed response. It's easier to convince producers who had problems with parasites (some to the point of death loss) to try this. They can more easily see the value of a quality deworming program."
Parasitologist Kaplan says creating a refuge population within the herd goes hand in hand with a combination dewormer plan. It may seem counterintuitive, but he stresses not deworming the best 10% of the herd will benefit the overall operation. This helps add to the population of worms susceptible to anthelmintics.
BI's Ensley says this refuge population-management idea is gaining ground. "Some parasitologists will say don't deworm adult cows at all, but I'm not sure about that," he adds. "I'm especially concerned that could be an issue in the South. I'd rather look at a 10% refuge population, where I take those cows that are in really good condition and don't deworm them."
Kaplan says drug-susceptible refugia dilute out resistant worms that survive treatment in the 90%. This helps maintain a predominantly drug-susceptible worm population. He adds production loss in the 10% is likely to be small because they were in the upper quartile of animals before treatment, and their growth was likely not heavily impaired by parasites. Without refugia, producers won't see the necessary dilution of resistant survivors, leading to multiple-resistant worm types that can no longer be controlled.
FUTURE FOR DEWORMERS
What does the future for anthelmintics look like in the cattle industry? Both Kaplan and Ensley believe there is still time for producers, and the industry, to write a positive ending.
"No new classes of anthelmintic have been introduced for use in cattle since ivermectin in 1981 -- 36 years ago," Kaplan says. "Currently, there are no new anthelmintic prospects in the late-phase pipeline, thus we are left in a situation where it could be a long while before a new anthelmintic class is sold in the U.S. for cattle. This makes it important that the efficacy of currently available products be protected as much as is reasonably possible."
Strickland's veterinary practice, just started last year, puts him in a position to experience firsthand the challenges going forward.
"I really believe that those producers who work with their herd veterinarians to develop a solid deworming program and a strategy for the future will see benefits. Those operations won't just survive but will thrive. Effective dewormers benefit the animals, but they are also critical to the bottom line of the operation. It all ties together. The right deworming strategy will pay for itself again and again."
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