Parasites: Roads to Resistance
It shouldn't really surprise us: parasites are becoming increasingly resistant to the drugs we use. Parasites simply follow Darwin's law: survival of the fittest. In fact, all biological organisms have this ability to adapt to the environment through evolution. As a result, bacteria are now increasingly resistant to antibiotics, malaria parasites are widely resistant to antimalarials, and insects are now vastly resistant to a number of insecticides. Parasites are no different, and we should all learn the lesson from history.
For 40 years we've treated parasites very intensely, and the results are clear: horses are still exposed to the same species as 40 years ago, and the only major difference is that our drugs are losing their effect. This is worrisome since it remains unknown whether or not new drugs will be introduced to the market, and, if so, when.
How Do Worms Develop Resistance?
In a population of parasites, there will always be worms surviving treatment, regardless of which drug we use. No dewormer is 100% effective. The worms survive because of their genes. Certain genes make them less vulnerable or even fully resistant to treatment.
If horses are treated often and intensely throughout the year, the worms carrying these genes will have a great advantage. They will quickly dominate the population. The resistance genes will be passed to the next generation when the worms are mating, and eventually the genes will build up in the population. At a certain point, the parasite population reaches a critical level of these resistance genes, and we start seeing failure of treatment.
How Long Does it Take for a Population to Become Resistant?
Drug resistance in parasites is slow to evolve. The development depends on a number of factors, such as treatment intensity, the drug's mode of action, the life cycle of the parasite, and probably the age of the horses hosting the parasite.
As a general rule, development of resistance is occurring over decades rather than years or months. As a couple of examples, it took about 20 years before we saw the first reports of ivermectin and pyrantel resistance in equine parasites.
Can Resistant Parasites Become Susceptible Again?
In long-term studies Eugene T. Lyons, PhD, a parasitologist at the University of Kentucky, has clearly shown that even after 20 years with no exposure to the drug, resistant parasites were still resistant. Once we have resistance, there is no way back.
Over the past 50 years the pharmaceutical industry has developed one new drug class per decade on average, but it's been more than 25 years since a new type was introduced to the equine market. In other words, there is a substantial risk that parasite resistance to available drugs is developing quicker than the industry can develop new types with different modes of action.
Do Your Horses Have Resistant Parasites?
The answer is yes, most likely. If you look for resistance, you'll probably find it. But horses can harbor up to 100 different parasites, and not all of these will be resistant to the same drug. In fact, most drugs can still be useful on a farm, but we need to know which parasites we are treating.
The key to good parasite control is regular testing for resistance. Once we know a farm's resistance profile, we can select the right drugs to control the parasite burden. If treatments are carried out without prior testing, most owners will be living with a false sense of security, believing dewormers did the job when, in fact, nothing happened. Although a dewormer syringe is not expensive, it can be a considerable waste of money to use the wrong drug repeatedly.
Meanwhile, we risk building parasite burdens to a level at which horses are at risk for parasitic disease. There are drug formulations to which parasites aren't resistant, and we can use most--or even all--of them effectively if we perform routine testing.
How to Test?
Testing for resistance is simple. All it requires is two fecal samples from each of a number of horses. Take one pre-treatment sample to establish existing parasite egg count, and collect the other sample 10-14 days after deworming, for comparison.
Your vet can calculate the fecal egg reduction for the drug tested, and he/she should know how to interpret the result.
We recommend testing five to 10 horses on each farm, depending on the facility size. Preferably the horses with the highest pre-treatment egg counts should be used for resistance testing. As only one drug can be tested at the time, we recommend starting with the drug that is used the most widely on the farm.
Here are a few rules of thumb for detecting drug-resistant parasites:
- You'll find them in more than one or a few horses, since all horses share the same parasite population;
- The finding should be reproduced. If the drug all of the sudden is working again at a future testing, it was not resistance;
- If the two above criteria are not met, consider other reasons for the reduced effect. Misdosing, wrong storage conditions, and use of drugs after their expiration dates are among the most common reasons.
What Drug Types are Available?
Despite the large variety of drug formulations on the market, there are only a few different modes of action among them:
For nematodes (roundworms; i.e., everything but flatworms, such as tapeworms) the drugs of choice are ben-zimidazoles (fenbendazole and oxibendazole); pyrantel formulations; avermectin/milbemycins (macrocyclic lactones: ivermectin and moxidectin); and piperazine (not available in all countries).
For tapeworms vets suggest using pyrantel (an elevated dose) and praziquantel.
Here are brief accounts of drug resistance reported in parasite groups.
Strongyle Cyathostomins (small strongyles) have been reported widely resistant to benzimidazoles and increasingly resistant to pyrantel formulations. These drugs might still work on individual farms, but test for resistance before using them.
Most recently studies have implied that the first signs of ivermectin and moxidectin resistance are developing in cyathostomins. Although the effects of these drugs are still high in the large majority of equine establishments, it has become important to also regularly test for ivermectin and moxidectin resistance.
The large strongyle parasite group, which includes the bloodworm Strongylus vulgaris, has not been reported as resistant to any of the drug types available.
In some countries piperazine is available for equine treatment. This does not have a satisfactory effect against large strongyles, but it remains an option for cyathostomin treatment. One study has documented piperazine resistance in cyathostomins.
Ascarids The ascarid roundworm Parascaris equorum has been reported as increasingly resistant to ivermectin in recent years. A few reports have also documented moxidectin resistance in these worms.
Ascarids primarily infect foals and yearlings; it's important to know that ivermectin and moxidectin cannot be used effectively without regular testing for resistance.
Very little evidence suggests ascarid resistance to other drug types available, although it's considered biologically feasible. One report has suggested ascarid pyrantel resistance, and no published studies have documented benzimidazole resistance.
If piperazine is available, it can be used for ascarid treatment. It's effective and no studies have documented resistance in this parasite.
Tapeworms Only two drug types are available to treat tapeworms: pyrantel and praziquantel. Currently there are no methods available for detecting drug resistance in equine tapeworms, so we can't tell if resistance is developing.
Drug-resistant parasites are inevitable. It is a logical consequence of treatment. As most of us need to deworm our horses to manage parasites, we cannot avoid resistance completely. What we can influence is the rate at which it develops.
If we can maintain effective drugs for 20 more years instead of five, we'll still have good drugs available for the few horses that get sick from parasitic disease, and there will be time for the industry to develop new drugs to take over when we get resistance.
Leading parasitologists' recommendations for worm control are all based on systematic surveillance of the parasite burdens. We need to know which drugs are working on the premises, and we need to go back and check every year.
We must know whether we are dealing with cyathostomins, ascarids, or both, because it strongly affects our drug choice.
Finally, it becomes useful to know which horses need more intensive treatments and which horses require less. Some horses are able to maintain very low worm burdens with little to no treatment intervention. We can delay development of drug resistance considerably if we do not deworm horses on a treat-all recipe basis, but, rather, based on parasite findings and resistance tests on the farm.
About the Author
Martin Krarup Nielsen, DVM, PhD, Dipl. EVPC, ACVM, is an assistant professor appointment in parasitology at the University of Kentucky's (UK) Maxwell H. Gluck Equine Research Center in Lexington.