Worms’ adaptation a critical problem

Dr. Ray M. Kaplan said anthelmintic resistance is reaching critical levels in small ruminants.

Anthelmintic resistance also is a severe problem in horses, second in severity only to the problem in goats and sheep, Dr. Kaplan said. And resistance is an often unidentified yet increasing problem in cattle.

“There has been a kind of idea in the cattle industry that resistance is not a problem there, and that’s no longer true,” he said.

Dr. Kaplan is a professor in the Department of Infectious Diseases at the University of Georgia College of Veterinary Medicine, where his laboratory researches primarily drug resistance in parasites. He wrote in a May 2012 scientific article that the rapid increase in prevalence and magnitude of anthelmintic resistance worldwide has followed “excessive and irrational” anthelmintic use, and resistance development almost certainly will outpace development of new drug classes (Vet Parasitol 2012;186:70-78).

Joan M. Burke, PhD, a research animal scientist with the Agricultural Research Service in the Department of Agriculture, said most sheep and goat farms in the Eastern U.S. have parasites resistant to one or two—if not all three—approved classes of dewormers. The problem is the worst for goats, which are not as well-adapted as sheep or other livestock to grazing on pastures rather than ranges and have been more frequently treated for parasites, she said.

Dr. Kaplan noted that parasites have been susceptible to moxidectin, despite being resistant to other drugs in its class—the macrocyclic lactones—but that parasites on farms are increasingly found to have resistance to moxidectin as well.

Dr. Burke said Haemonchus contortus, a blood-sucking worm that can kill small ruminants, is the most problematic parasite and is present in most states.

“It doesn’t always predominate, but if warm, humid conditions exist, even in dry states where they irrigate, it could be a problem,” Dr. Burke said. “If there are worms, and producers are following the old recommendations of ‘deworm often,’ that’s when anthelmintic resistance quickly develops and becomes a problem.”

Anthelmintic resistance has become widespread among parasites of ruminants and horses, and a mix of biological and management factors are selecting for that resistance, according to a report published in March by the Food and Drug Administration. That report summarized a series of lectures, including one Dr. Kaplan delivered during a meeting one year earlier.

Like Dr. Kaplan and Dr. Burke, the report noted that resistance is particularly common in small ruminants.

“Since 2003, antiparasitic resistance in small ruminants has been well-documented and widespread in the U.S., with most resistance in the southeastern states,” the report states. “Often, the parasites are resistant to multiple classes of antiparasitic drugs.”

In fact, the USDA report “Sheep and Lamb Nonpredator Death Loss in the United States, 2009” states that, while internal parasites caused about 8 percent of all U.S. sheep deaths not connected with predation during 2009, they caused about 23 percent of such deaths in the Southeastern states and Hawaii, which were included in the same category for the report. Internal parasites also caused 13 percent of such deaths in the Northeastern region.

Anthelmintic resistance can vary with the species of parasite, breed of infected animal, environmental source of the parasite, drugs used for treatment, region where the animals are raised, and even the types of animals of the same species on a single farm, according to Dr. Thomas Craig, a professor at Texas A&M University College of Veterinary Medicine & Biomedical Sciences. For example, a farm’s foals can carry different parasites than its mares and yearlings, and the parasites affecting the foals can be resistant to a drug that is effective in the other animals.

Detecting resistance

Dr. William P. Shulaw, a professor and extension veterinarian for The Ohio State University College of Veterinary Medicine, first saw evidence of anthelmintic resistance in Ohio sheep flocks during the early and mid-1990s, when he and a parasitologist colleague documented levamisole and albendazole resistance among endoparasites. He gradually saw resistance to most types of anthelmintics, and he has since 2007 worked on projects designed to teach people how to reduce resistance development through selective deworming, grazing strategies, and providing particular plants as feed.

“We find resistance to be pretty common when we look for it,” Dr. Shulaw said. “And our educational efforts have focused on trying to help people understand how resistance develops and modern strategies for either reducing the impact of resistance or wisely using chemicals that still work for them.”

In small ruminants, H contortus will exsanguinate sheep or goats from within, providing obvious proof of anthelmintic failures, Dr. Kaplan said. But treatment failures are harder to detect among, for example, strongyles in horses and Cooperia in cattle, since both have low pathogenicity.

Most anthelmintics given to horses are unneeded, since the animals typically will remain healthy unless infected with high numbers of parasites, Dr. Kaplan said. He previously wrote that the substances often are given to improve performance.

But a steer with high numbers of Cooperia could be up to 60 pounds lighter than another given effective parasite control, even though both will look healthy on casual observation, he said.

The FDA report notes that benzimidazole resistance is high among strongyles found in horses throughout the U.S., and a study of Southern horse farms found about half had parasites resistant to pyrantel. Ivermectin resistance also may be increasing among roundworms and pinworms of horses.

The report also notes that data collected in 2009 confirmed resistance, mainly to macrocyclic lactones, was found in cattle parasites in the Southeast and West, and resistance among Cooperia species was increasing.

Frequent treatment with anthelmintics, treatment of entire herds, use of long-acting drugs, and use of anthelmintics without veterinarian oversight all have increased selection for resistant parasites, particularly when entire herds are treated or when animals are given inadequate doses, the FDA report states. Deworming after a harsh winter or dry summer also can select for resistance, as parasites inside the animals will be exposed to anthelmintics at a time when environmental conditions reduced the population of unexposed parasites on the ground.

Changing practices

Dr. Burke said farms using anthelmintics need to treat only some of their animals and leave a population of worms not exposed to anthelmintics. Those unexposed worms will dilute the population of resistant worms, slowing resistance development.

Typically, about a third of a flock or herd needs dewormers, Dr. Burke said. Citing recommendations from the American Consortium for Small Ruminant Parasite Control, she also recommended culling from that third to improve the herd’s or flock’s natural resistance to parasites.

At Texas A&M’s research farm, some parasites have proved to be resistant to all federally approved anthelmintics, Dr. Craig said. He and others who care for livestock on the farm have used combinations of multiple anthelmintic products to combat the parasites, and they have decided in recent years that it may be unwise to simultaneously treat all animals with products that have residual effects. Instead, treatment has focused on the animals that are sick or at greater risk.

Examining the mucous membrane color—ranging from pink to white—in the eyes of individual animals has been effective in helping determine a sheep's or goat’s stage of anemia and the need for treatment, Dr. Craig said. He said parasites in animals are like wealth in humans: “A few have a lot.”

Reserving treatment for animals that need it helps maintain anthelmintics’ remaining effectiveness longer, Dr. Craig said.

The easiest option following a treatment failure often is to combine drugs for an additive effect, Dr. Kaplan said. But, when such combinations are used to kill resistant populations in the absence of management changes, he expects rapid selection for multidrug-resistant parasites.

Dr. Kaplan described modern deworming drugs as an amazing “chemical crutch.” Fixation on anthelmintic use has led to neglect of management and husbandry methods to reduce parasite populations in animals, he said.

For example, about 90 percent of infective-stage parasite larvae found in the environment are in the bottom 4 inches of grass, and reducing overstocking in pastures can reduce risk, he said. Rotating multiple species of livestock among pastures also can greatly reduce parasite loads, since most of the important livestock parasites are not shared among horses, cattle, and small ruminants.

Such rotation is unlikely on large-scale commercial farms, Dr. Kaplan said, but it has been adopted as a strategy on organic farms that raise animals.

In his May 2012 article, Dr. Kaplan wrote that most farms need less-intensive parasite treatment programs and should use anthelmintics as part of a broader worm-control program, with fecal egg count surveillance and resistance testing to ensure only effective anthelmintics are used.

Dr. Kaplan said lack of concern and awareness about anthelmintic resistance has hurt efforts to gain funding for research that could improve understanding of the mechanisms of resistance and help create laboratory-based diagnostic tests for parasites of horses and cattle. Funding from federal and private sources is not keeping pace with need, he said.

The lack of awareness extends to veterinarians, according to the FDA meeting report.

“Veterinarians seem poorly informed about the current level of antiparasitic resistance in the U.S., particularly in cattle,” the report states.“