In the deep reaches of Star Trek’s space live the Borg, an alien race whose major claim to fame is the line, “Resistance is futile”.
In our own parallel universe, horse parasites would strongly disagree. They have not lived for millions of years without learning a trick or two, and building resistance to the limited arsenal of worming drugs used by horse owners is one of them.
Mankind’s fight against equine parasites centers around a plot riddled with twists and dead-ends. It brings us to the present day, where it is now widely acknowledged that resistance is a growing problem, new drugs to combat parasites are not waiting in the wings, and the calendar-based drenching programs that have dominated for decades have been superseded by a needs-based worming regime.
The days of blood letting to supposedly control parasites are thankfully long behind us. Even, a century ago, in the early 1900s, worming strategies had turned to dosing horses with chemical agents. Horses were regularly being drenched with either carbon disulfide or carbon tetrachloride.
Both killed parasites but, like so many drenches that had gone before, both proved toxic. Another worming agent from the time included tobacco. It was given internally for parasites, and a plug of tobacco in the bottom was considered effective against pinworms.
The first dewormer of the modern era, phenothiazine, arrived in the 1940s. It was effective against strongyles, but toxicity remained a concern. It was popular for a good 20 years, but scientists began to notice growing worm resistance to the chemical. Resistance to phenothiazine was first recorded in the late 1950s.
But by this time horse owners had a choice. They could use piperazine, said to be effective against several parasites. Unfortunately, large strongyles were not among them.
Later, organophosphates were used but were very toxic – and not just for horses.
In combination, some of these early wormers proved quite effective and allowed lower doses, which was better for horses.
One of the biggest breakthroughs was in the 1960s and 70s when the benzimidazoles came on the scene. They were highly effective against a wide range of parasites and the dose needed was so low that they were considered very safe.
Thiabendazole led the way and brought deworming to the masses. Before then, drenches were largely given by veterinarians. The benzimidazole family had a good margin of safety and could be sold over-the-counter in easy-to-use pastes.
Other members of the family quickly followed: cambendazole, oxfendazole, fenbendazole, oxibendazole and mebendazole. Some are still used today.
Sadly, it was only a matter of time before the resistance problem came to the fore again. Scientists had already seen worm resistance in phenothiazine, and the benzimidazole family was to be no exception. Their effectiveness began to decline.
The modern-day drenching arsenal, more formally known as anthelmintics, are available under an array of brand names, but what is ultimately important is the active ingredient – or ingredients.
There are, in fact, still only a comparatively modest number of drench families available to us. Each has its strengths and weaknesses.
Most work by paralysing the parasite. This generally has one of two effects. Some will let go their grip on the gut and pass out of the animal. If this isn’t the case, the paralysed parasite will be unable to feed, runs out of energy, and dies.
Parasites have no fat reserves so if they are unable to feed they quickly die.
It is important to realize that the drenches at our disposal today do not have equal effectiveness. Some target only certain larval stages of some parasites and may not even be able to kill some at all.
The stars in the line-up are the so-called macrocyclic lactones, which include ivermectin and moxidectin. They are highly effective against gut parasites and also deliver a killer blow to lice and other skin-based parasites. Parasite control would be much trickier without them.
The benzimidazoles, made up of fenbendazole, oxfendazole and oxibendazole, are effective agents but tend to be at their best in courses delivered over several days.
The tetrahydropyrimidines comprise pyrantel pamoate and pyrantel tartrate. They are fast-acting but kill only adult parasites, meaning worm populations recover rather more quickly than other drenches, given that the maturing larvae survive the dosing.
Piperazine is not commonly used in horses these days and would normally be administered by a vet using a tube into the horse’s stomach. In some part of the world it may be available to be administered as a feed supplement.
The last drenching agent is praziquantel, an important player because it is the only agent effective against tapeworms. It is normally sold as part of a combination drench with ivermectin or moxidectin.
But the real star among these drenches is ivermectin. It arrived in the early 1980s and was effective to an almost unbelievable extent. It quickly became a market leader.
For a time, it seemed parasites were not developing resistance to ivermectin, but it was not to be. Resistance may not have been as quick to develop against ivermectin as it was against other deworming agents, but develop it did, although perhaps not to the same extent as other drench families.
Moxidectin is broad spectrum like ivermectin, but, crucially, proved effective against small strongyles in their encysted larval stage.
But today, all drenches have fallen victim – at least in part – to worm resistance.
Perhaps scientists will develop new drenches in the fight against parasites. Perhaps these drenches will work on parasites in a way that reduces or even eliminates the development of resistance.
But it would be dangerous for the horse community to assume that something bigger or better is just around the corner.
Prudent horse owners need to work with the cards they have been dealt and, today, that comprises a quite limited range of deworming chemicals with a range of properties.
Many horse owners are worried about the effects these agents have on their animals, and turn to natural remedies. Do they work?
Parasitologist Martin Nielsen, who joined the Gluck Equine Research Center at the University of Kentucky in 2011 as an assistant professor, has spoken many times to groups of horse owners on parasite control, and the question of natural dewormers often arises.
Nielsen is upbeat on the subject, but his views are tempered by the hundreds of papers he has read on parasite control, a significant number of which were devoted to testing potential agents – many of them naturally sourced – in the quest to control parasites.
He is well aware of the wide interest among horse owners in natural dewormers.
“I share their interest,” he told Horsetalk. “As a scientist in the field, I realise that we need alternatives.”
Ultimately, new compounds need to be found to replace the current families of chemicals used for worm control, he says.
Nielsen is entirely open to the possibly such compounds may be the likes of natural plant extracts. Indeed, many have shown promise in the control of parasites.
However, Nielsen is quick to point out that there is a huge jump from a natural substance – indeed, any substance – that shows an ability to kill parasites and producing a marketable, safe and proven product.
“There is actually quite a bit of work being done, with all sorts of plant extracts, fungal extracts, even fruit extracts,” Nielsen says.
“There is a lot of them that do contain some kind of compound, chemical substance, that do actually kill parasites, or reduce burdens.”
So, why has the scientific community and manufacturers of dewormers not embraced these natural compounds with a demonstrated ability to kill parasites?
Nielsen says there are several reasons. First, there is a question of overall effectiveness. Some of these compounds will kill parasites, but not in sufficient numbers to be commercially viable. Others may work on some parasites, but leave others untouched.
Some, he says, require daily dosing to be effective, which raises practical issues. There is also the issue of toxicity. An active compound may be in a plant extract, but it is still a chemical and may be toxic to the horse.
Herbal products present another set of problems, he explains.
Nielsen says research has shown that the concentration of active ingredients in plant material can be highly variable. In terms of any medication or treatment, providing the active ingredient in a uniform measure is the first step toward ensuring an animal receives the correct dose.
“A drug formulation ensures we know the concentration. We know what it is so we can dose correctly.”
Ivermectin, he points out, is a dewormer derived from the naturally occurring fungus, Streptomyces avermitilis.
Nielsen says because natural products with a known anti-parasitic effect have fallen short on key parameters, most have not been subjected to the same degree of scientific testing found in the scientifically proven drugs.
For proven compounds, scientists know their effectiveness, the recommended dosing rate, the margin of safety in dosing, the range of parasites against which they are effective, their side-effects have been documented, and they are all sold in precisely measured quantities to ensure those giving a horse a dose give the right amounts. Extensive trials have been conducted to measure their effects, if any, on everything from body temperature, respiration rate and bowel function, to liver and blood chemistry, and a raft of other biomarkers.
So, how do other agents, such as plants or plant extracts touted as natural wormers, compare in terms of scientific assessment?
Even agents that have shown some worm-killing effect but have shortcomings – either related to toxicity, the range of parasites they kill, or the dosing regimen required to get any effect – are unlikely to have been tested further scientifically, at least in terms of their potential as a parasite control agent.
He encourages horse owners to look for evidence of effectiveness.
He cites the example of garlic. “A lot of people like to claim that garlic is able to kill parasites. They smell it and taste it, and figure ‘it has got to do something’.
“There is not much evidence, if any, to support that.”
Also, the picture around worming agents can be clouded by regulations that vary between countries.
In some countries, only products licensed as scientifically proven to be effective in parasite control can be sold as such. In others, products with an ability to control parasites can be prescribed only by veterinarians.
Some products touted as wormers may be licensed as feed additives, and marketed as tonics to support gut health.
Nielsen says, by way of example, he has found three scientific papers that look at homeopathic remedies for worm control. The results, he said, were contradictory.
He said he realised some people strongly believed in the healing effects of homeopathic remedies. “I want to remain open to the possibility of something like that to be useful, but I have a strong problem understanding how it can work, but maybe that is because I am a scientist.”
Nielsen believes the issue of natural wormers is often viewed in black or white.
“The truth is somewhere in between,” he suggests. “We still need dewormers. But we need to use them in a different way to how we did before. We have learnt from history.”
Earlier worming strategies, such as regular six-weekly dosing without assessing the need through fecal egg counts, have contributed to the growing problem of drug resistance among parasites.
Horse owners are able to minimize worm problems through the likes of picking up manure and smart use of rotational grazing.
But chemical measures are needed to control worm burdens, especially so in animals with a tendency to high egg counts.
“The answer is not to turn away from the drugs completely.“
Drug resistance is inevitable against worming agents, he says, natural or otherwise.
“When we get new drugs – new licensed drugs for horse parasites – we don’t want to go back to the old regime. We need to use it more intelligently.”
Nielsen suggests anyone adhering to any natural parasite control program should test its effectiveness with a standard fecal egg count reduction test (FECRT), which involves assessing the worm burden on the day of dosing through a fecal egg count, and then re-testing the animal 14 days later.
Be careful, he suggests, as evidence around potential toxicity in horses may be scant.
Many other questions arise over compounds that have not been scientifically evaluated, he says. What, for example, is the supposed active ingredient? What is the recommended dose rate? How does it work in killing parasites? Does it survive the acid conditions in the stomach? What sort of safety margin does the product have?
Nielsen is confident there is another agent out there that will ultimately provide horse owners with a new arsenal to fight parasites – and it may very well be a plant extract or a compound from a fungus.
“There is something out there. I really believe it,” he says, but he stresses that it is a long journey from having a simple substance showing some effectiveness in killing nematodes in a laboratory to having a drug that horse owners and veterinarians can rely upon.
Nielsen believes the horse industry is at last waking up to the very real problems around parasite resistance, and are wanting to know more.
“We cannot rely blindly on drugs,” he says.
“We have trusted the drugs a bit too much.”
The answer, he says, is monitoring parasite burdens, using management practices, such as pasture rotation and picking up manure, to help break the life cycles of parasites, and using proven anti-parasitic drugs to control worm burdens when egg counts show the need.
Interested in equine parasite control? Check out our worming series.