Will the Worms Win? Part 2: Resistance
Anthelmintic resistance is a growing problem the world over. While we might not see "super worms" ravaging our equine companions, there is a pressing need to update deworming strategies and horse owners' perceptions regarding available deworming tools.
Internal parasite populations develop anthelmintic resistance (resistance to medications capable of expelling or destroying internal parasites, also called dewormers) when recommended doses of dewormers do not kill them as readily as they used to or at all. Populations have developed that are increasingly resistant to the drugs. The issue of anthelmintic resistance has become more publicized and important over the past several years. With no new anthelmintic drugs forthcoming on the market, how does this developing resistance impact horses and their owners?
Will "super worms" develop as a result of this resistance?
The seriousness of this dilemma is obvious to parasitologists around the continent, including Eugene Lyons, PhD, of the Department of Veterinary Science at the University of Kentucky's Gluck Equine Research Center, who has performed extensive research on this topic, and Andrew Peregrine, BVMS, PhD, DVM (Hons) Glasgow, Dipl. EVPC, MRCVS, an associate professor in the Department of Pathobiology at the Ontario Veterinary College in Canada.
"Anthelmintic resistance is only going to get worse over the next decade," says Peregrine.
In part one of this series, we reviewed the "big five" internal parasites of horses and discussed the clinical impact of parasite infections. In this article we'll look at the impact of anthelmintic resistance on the horse industry.
Anthelmintics and Resistance
At first glance there appears to be a vast array of available anthelmintics targeting internal parasites in horses. While the options appear virtually limitless, the reality is that there are only a paltry number of drugs from an even smaller selection of drug classes currently available for deworming horses. The four major drug classes are: macrocyclic lactones (ivermectin, moxidectin); benzimidazoles (fenbendazole, oxibendazole); tetrahydropyrimidines (pyrantel pamoate and pyrantel tartrate); and; prazino-isoquinolines (praziquantel).
The important point here is that not all drug classes are effective against all types of parasites. For example, only two products are effective against tapeworms and only moxidectin is effective against the encysted (hibernating within protective cysts in the lining of the large intestine) small strongyles (at regular doses).
According to Lyons, anthelmintic resistance is a "real and serious dilemma" for the equine industry, considering that several parasites have already developed resistance to one or more of the drug classes.
For example, "Small strongyles are resistant to both of the benzimidazoles (oxibendazole and fenbendazole) and also pyrantel pamoate," explains Lyons.
Concerns regarding ivermectin's efficacy against small strongyles have also been raised. Indeed, the research of Lyons and colleagues in Kentucky has shown that there is an "early return of small strongyle eggs post-ivermectin treatment."
Specifically, researchers have detected strongyle eggs in the feces of treated horses as early as two weeks post-treatment, which means eggs are reappearing more than twice as quickly as when ivermectin was first marketed in the 1980s. Other researchers agree that this is indicative of a genetic change in worm populations, but they suggest that it might be different than resistance.
Development of Resistance
The major reasons for the development of anthelmintic resistance are thought to be overuse and misuse of these products. For example, resistance can develop when:
- Owners deworm horses with the same product year after year;
- Owners administer these same products too frequently throughout the year;
- Owners don't treat horses based on actual weight (many owners underestimate their horse's weight and, therefore, do not administer a large enough dose to kill all the parasites);
- Caretakers do not administer the full dose of anthelmintic (i.e., half the dewormer falls to the ground during administration), resulting in only partial killing of the internal parasites; and
- Owners deworm horses unecessarily at certain times of the year.
The main goal of most horse owners when they administer anthelmintics is to remove internal parasites and maximize the health of their horses. Parasitologists say the main goal should be to prevent contaminating the environment with future generations of parasites that the horses can acquire. Either way, owners should not have "zero tolerance" to worms.
"One important fact that does not seem to be understood by horse owners is that the goal of deworming is not to completely remove all of the parasites, but rather to control the parasite burdens," says Peregrine. "Low parasite burdens can actually be beneficial, as they induce immunity."
So, given the known resistance of multiple parasites to one or more drug classes, what is the best way to control these worms?
Deworming Your Horse
Current deworming schedules vary immensely, ranging from "when I remember" to rotational deworming, targeted deworming, and daily deworming. Since schedules and the pros and cons of the various approaches to chemical deworming have been described elsewhere (article #6064 at TheHorse.com) and were recently discussed in detail during the Strategic Deworming Webinar (available at www.TheHorse.com/Webinar), these schedules will not be reviewed here.
While some owners are not concerned at all about their deworming "schedule," others question whether they have adopted the right schedule and even if they are deworming too frequently. In addition, owners are becoming increasingly aware that blindly deworming their horses, even on a rotational basis, might not be the best approach, since horses are never diagnosed with any specific infection and are, therefore, not treated for the parasites that actually exist in their gastrointestinal systems.
In response to this latter concern, Peregrine and other parasitologists advocate testing for worms at least annually, preferably midway through the grazing season.
"Only a very small number of owners--approximately 2%--have ever actually had a fecal test performed for internal parasites," notes Peregrine.
Another advantage to instituting some form of a targeted deworming program (which includes periodic testing) is economic. According to a 2003 study performed by researchers at North Carolina State University, after using a targeted ivermectin treatment protocol for 30 months, the number of anthelmintic treatments (deemed required and) administered to mares and foals decreased by 77.6% and 55.3%, respectively. Further, they concluded that monies saved on superfluous anthelmintic treatments more than offset the increased costs of designing targeted treatment programs.
Preventing the Super Worm
Resistance to current deworming products has been established, and there are no new products forthcoming on the market. Will the five common internal parasites become more common? Will the 150 less-common parasites become a problem? For example, over the course of the next few years, will veterinarians more frequently diagnose Halicephalobus gingivalis, a free-living nematode (roundworm) capable of infecting horses and humans and causing fatal encephalitis? Not likely.
Tracy Norman, VMD, Dipl. ACVIM, a clinical assistant professor in equine internal medicine at Texas A&M University, suggests that as equine parasites develop resistance to the available anthelmintics, what we will see is a resurgence of parasite-associated disease.
"Unfortunately, this is one of those 'back to the future' sort of scenarios where old problems become new again," she says.
Norman is referring to the types of diseases that equine practitioners used to see prior to the introduction of ivermectin. Thus, we are likely to see an increase in the number of horses with protein-losing enteropathy (intestinal inflammation) and diarrhea related to cyathostomiasis (i.e., massive infestation of small strongyles), a greater number of roundworm impactions in young horses, and more clinical signs related to roundworm infections (e.g., respiratory signs and increased liver enzymes secondary to larval migration) in young horses.
She suggests, "The development of resistance of large strongyles, if and when it occurs, is likely to have the biggest industry impact. Migrating larvae irritate the lining of blood vessels, which can lead to thrombosis (clots) in the blood supply to the intestines, which was once a major cause of fatal colic in horses. Aberrant migration of larvae can cause the formation of clots that can cause a myriad of problems, from unrelenting lameness, to weakness, to neurological disease."
As pharmaceutical companies continue to look for new chemical treatments, researchers are seeking alternate ways to use existing products. For example, netobimin is a pro-benzimidazole anthelmintic used in ruminants. Preliminary studies in horses have shown netobimin is absorbed, metabolized, and can decrease the number of strongyle eggs per gram of feces up to 10 weeks post-administration. Some researchers say its efficacy against a population of small strongyles already resistant to fenbendazole or oxibendazole would likely be very short-lived. However, it might be effective against other parasites, but generally fenbendazoles and oxibendazoles still are as well.
While researchers need to perform additional safety studies on netobimin before they are willing to recommend this product for use in horses, this work highlights the fact that all currently available anthelmintics (not just those available for horses) should be re-evaluated.
Parasitologists say that since netobimin is not approved for use in the United States for cattle, it could be five to six years before it would hit the market if a company began working on the approval process.
As an adjunct to chemical dewormers, veterinarians should recommend increased attention to improving management practices. Such techniques include pasture rotation, manure removal and management, elevated feeding (off the ground), and routine cleaning of the barn. These techniques, of course, require elbow grease and can be costly to initiate.
From a holistic standpoint, there are proponents of a chemical-free approach to managing internal parasites intended to eliminate concerns surrounding anthelmintic resistance. These individuals say that in conjunction with proper nutrition and management practices, the use of various herbs can completely eliminate the need for chemical anthelmintics. As with many alternative or complementary therapies in veterinary medicine, the caveat is that safety and efficacy of these products have not been demonstrated via controlled clinical trials. Thus, the clinical significance of herbal preparations for deworming horses remains unclear.
Experts strongly recommend consulting your veterinarian about controlling parasites. Deworming is no longer a simple do-it-yourself procedure, but a complex, multifaceted issue with serious health consequences for your equine companions.
About the Author
Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.
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