Resist Resistance
Antibiotic resistance has captured headlines lately, while the issue of drug-resistant parasites has mostly flown under the radar. The time has arrived though, for beef producers to shift toward practices that will delay or prevent the emergence of resistance among cattle parasites.
Even the most effective treatments do not kill every worm, because some worms carry a genetic makeup that allows them to survive treatment. Even if the number of survivors is small, they pass the resistance trait on to their offspring. Within a few generations, resistant parasites dominate the population and treatment with that drug, or class of drug, becomes ineffective.
University of Georgia veterinarian Ray Kaplan studies parasite resistance trends and options for addressing the emerging problem. Drug resistance among nematode worms infecting livestock is not a new phenomenon, he says. Globally, producers of goats, sheep and other small ruminants have battled resistant worms for decades. In some locations, multidrug resistance has left small-ruminant producers with no effective treatments.
The emergence of resistance among worms affecting cattle has, fortunately, been slower, but it is happening. While data is limited, evidence suggests resistance to macrocyclic lactones are emerging in Cooperia, Haemonchus and Ostertagia stomach worm infections. The risk of having no effective anthelmintics is very real, Kaplan says, adding that the best time to address drug resistance is before it reaches significant levels.
Kaplan adds cattle movement in the U.S. facilitates the spread of parasites. “If resistance develops anywhere, it will spread everywhere,” he says.
Limited drug options put additional pressure on ranchers to identify the best control program. Kaplan points out the drugs currently in use for controlling worms in U.S. cattle fall into three chemical classes: benzimidazoles, imidazothiazoles, and macrocyclic lactones. Resistance to one drug can result in resistance across that class, and in some locations, nematode parasites have developed multidrug resistance resulting in “total anthelmintic failure.”
In New Zealand, researchers conducted a prevalence study in 2006 and found multidrug resistant worms, primarily Cooperia species, on 74% of the operations surveyed. Cooperia, Kaplan points out, cause production losses in U.S. cattle herds, but generally do not cause clinical disease.
However, Kaplan says macrocyclic lactone resistance appears to be emerging in Ostertagia ostertagi, also known as the brown stomach worm, which is a more damaging nematode parasite in cattle. In a recent Australian study, three of 20 farms were found to harbor O. ostertagi populations with resistance to all three classes of anthelmintics. “Widespread resistance in O. ostertagi would be a big game changer,” Kaplan says.
Resistance is likely to outpace introduction of new products, Kaplan says. So the best strategy is to preserve the efficacy of existing products through management. He outlines several steps to meet that goal.
1. Manage refugia, or leaving some animals in a herd untreated.
In short, this maintains a population of drug-susceptible parasites. Kaplan says if you treat all the animals in a herd, the only parasites left are those with resistance to the treatment. With a refugia system in place, the majority of worms within the herd or pasture remain susceptible to treatment.
Research results in small ruminants and cattle show ranchers can implement refugia with little to no loss of productivity, while dramatically slowing the development of resistance. Selective treatments greatly reduce the overall parasite burden within the herd or on a pasture, and producers can select some of the healthiest cattle—those least affected by parasites—for the non-treatment group.
In April 2013, the Food and Drug Administration (FDA) released a paper with recommendations for detecting and preventing drug-resistant parasites, with a focus on refugia. e authors list practices they believe contribute to antiparasitic resistance, including treating every animal in the herd and general overuse of antiparasitic drugs. The brochure, titled “Antiparasitic Resistance in Cattle and Small Ruminants in the United States: How to Detect It and What to Do about It,” is available online.
2. Develop drug combinations to achieve efficacy.
The success of refugia as a strategy depends on a high treatment efficacy, or parasite kill rate, among treated cattle. Kaplan says the best way to achieve this is with combination therapy, or simultaneously using two or more anthelmintics from di erent classes.
Kaplan describes the concept behind combination therapy. Even with 99% efficacy for a single drug, the resistance rate increases dramatically within just a few generations of worms. However, using a combination of drugs can have a big impact on survival rates. Say, for example, you have two drugs, each of which will kill 98% of worms when used alone, meaning a 2% survival rate. Drug A kills 98% of the worms in an animal and Drug B kills 98% of the survivors. Using both drugs in combination increases treatment e cacy to 99.96%, or a survival rate of 0.04%, a 50-fold decrease in survival.
There currently are no approved combination dewormers available in the U.S., and existing dewormers cannot be mixed and delivered in a single dose. Until combinations become available, producers, with veterinarian oversight, must administer a separate, full dose of each drug for combination therapy.
Rotating between classes of anthelmintics does little or nothing to slow the development of resistance, Kaplan adds. Each individual treatment leaves enough survivors to establish a resistant population over time. Kaplan acknowledges that combination therapy increases treatment costs, but he believes the long-term benefits will easily pay off.
As for timing, Kaplan says the best parasite-control schedule varies depending on geography and overall management systems on a ranch. However, the optimal times to treat with a single drug on your operation also are the optimal times to use combination therapy.
Refugia and combination therapy work hand-in-hand, Kaplan stresses. Producers should work with their veterinarians to design a parasite control strategy that ts for their individual ranch, using combinations of products that provide a consistently efficacious treatment.
3. Monitor herds for resistance.
One key to addressing resistance in parasite populations is to monitor the efficacy of your control program. Authors of the FDA paper recommend using fecal egg count reduction tests (FECRT), which involve comparing the number of parasite eggs cattle shed before and after a deworming treatment. Your veterinarian can help you design and execute a FECRT. Kaplan suggests running the FECRT in a cowcalf herd about every two years. If the reduction in posttreatment egg counts is less than 95%, or if the reduction is declining over time, resistance is emerging.
4. Non-drug strategies, such as pasture rotations and grazing management can reduce worm populations.
Kaplan also suggests culling heavily infested cattle, as susceptibility to worms is a heritable trait. The authors of the FDA paper on drug resistance recommend additional management steps, such as isolating new livestock and reducing stocking densities.
In 2007, Iowa State University economist John Lawrence estimated the impact from eliminating dewormers across the beef production chain at nearly $190 per head in his paper “Economic Analysis of Pharmaceutical Technologies in Modern Beef Production.”
“We need to think of e ective anthelmintics as valuable, irreplaceable resources,” Kaplan says. “We need to preserve their efficacy as long as possible.”
