Taking the fight to equine parasites

March 2, 2009

by Neil Clarkson


Martin Krarup Nielsen ©: Jan B. Jensen

Martin Krarup Nielsen has a close group of acquaintances that most of us have little desire to meet. He'll happily introduce you to Strongylus vulgaris or Parascaris equorum, but you'll find yourself staring into a microscope.

The 36-year-old Danish-born scientist spends his working days probing the inner-most habits of equine parasites.

Parasites don't make for ideal dinner-party conversation, but Nielsen finds a ready audience among horse owners who realise that controlling the 150 or so parasites capable of infecting horses is crucial to the long-term wellbeing of their animals.

Parasites pose a growing set of challenges for veterinary science across all domestic livestock. Since his days at veterinary college in Denmark, Nielsen's career has been on a path that now sees him studying important issues surrounding parasite management.

Today, he finds himself working in the United States researching the most dangerous of all equine worms, Strongylus vulgaris.

He is probing many of the key issues taxing parasite experts, including the growing problem of resistance and the best use of drenches.

"It had to be parasites," Nielsen said of his choice of research. "Parasites are very exciting, fascinating," he says in a tone that acknowledges not all horse owners may share his view.

Parasites may not capture the public imagination like space research, but they do present real scientific challenges. Parasites are a highly adaptable group of creatures with widely varying life cycles. Our current methods of control are far from perfect and the difficulties they pose through growing resistance remain significant.

Parasite research has ebbed and flowed over the decades. It enjoyed a higher profile in the 60s, 70s and early 80s when developing new and more effective drenches was seen as important for the livestock industry.

Ironically, one of finest discoveries from that period has played no small part in reducing the amount of parasite research in recent years. The emergence of ivermectin in 1983 revolutionised the drenching of all domestic livestock.

"Ivermectin is an exceptional drug," says Nielsen. "There has not been a new drug family since," he adds, pointing out that moxidectin, which appeared in the 1990s, is actually another member of the same family of macrocyclic lactones.

"Ivermectin has been a great success. It is very broad spectrum, very reliable, safe. It took 20 years before there were any signs of resistance at all in ascarids."

Signs have only recently emerged that strongyles may now be developing resistance to ivermectin, with researchers noticing eggs reappearing quicker in dung samples tested after drenching.

"It's still a very good drug," he says, but he warns that the clock is ticking.

Nielsen completed his veterinary degree at The Royal Veterinary and Agricultural University in Denmark.

Renowned parasitologist Dr Peter Nansen was based there. "There was a lot of interesting parasite research going on there," he explains. It was easy to get involved in parasite projects and it was that work that sparked his interest in the field.

He completed his doctorate at the University of Copenhagen, researching parasite infections in horses and focusing on diagnosis, surveillance and control.

Nielsen has worked as a veterinarian and rides. His wife is an equestrian journalist.

He knows only too well the practical issues horse owners face in worm control.

When he got a job as a large-animal veterinarian not long after qualifying, it seemed his reputation was already being established.

"My boss said, 'you're that worm guy'," recalls Nielsen. He was asked to develop a worm programme for local horse-owning clients.

"I got some good experience in the field," he says. He realised that there were good and bad habits surrounding worm management practices, and he became determined to dig deeper into the problems in search of solutions.

He understands the importance of worm management strategies being practical for horse owners. "Even now, I still give a lot of talks to riding clubs and associations."

He finds the feedback valuable and always approaches it from the point of view of what a horse owner needs to know to make the right choices in managing parasites.

Some, for example, are relieved to know that, while picking up paddock dung is a dull chore, it's an important parasite management strategy.

While the parasite control efforts of horse owners usually centre on scooping dung and regularly administering drenches, Nielsen is embroiled in a rather closer working relationship.

"After I got my PhD I felt I had only just got started in research, and that I would like the opportunity to do some more."

He said there were several scientific grants available for post-graduate research, but it was usually difficult to get any for horses. He convinced a scientific committee that the really bad parasite on the equine block, Strongylus vulgaris, more commonly called the blood worm, was worthy of research funding.

His project has taken him to the United States, where he now finds himself at the University of Kentucky's Gluck Equine Center, where he is continuing his work.

Nielsen's US research has enabled him to discuss and collaborate on work with scientists such as Eugene Lyons and Ray Kaplan - men who are as close as you are ever likely to get to household names in the field of parasitology.

Gluck provides a resource for Nielsen that he is unlikely to find anywhere else. The university farm runs two herds of horses for parasite research. One of the herds has not been drenched for parasites for 30 years. The animals, he notes, are perfectly healthy.

Nielsen said he decided to focus his current research on the blood worm for several reasons. While it is considered a dangerous parasite - it can cause damage to a horse's internal organs during the migratory part of its life cycle - it has also been paid relatively little research attention in the last 20 years.

"It was a main concern in the 60s, 70s and the first part of the 80s, but then got out of the picture," he says. "It's a very pathogenic parasite but people tend to have forgotten about it."

It is the parasite most likely to cause the death of a horse.

There is a need, he says, to learn more about the prevalence and control of blood worms, as well as finding new ways to identify infections.

Important questions remain unanswered. Nielsen hopes his research will go some way toward answering them, with the hope of new and sustainable strategies for parasite control.

Nielsen has already developed a reliable Polymerase Chain Reaction (PCR) test that can detect DNA from blood worms in the dung of horses.

The next challenge, he says, is to develop a reliable blood test capable of detecting the DNA in a horse's bloodstream, enabling infections to be detected earlier, during the migratory phases.

"We have had our ups and downs," he says of his work so far on the blood test. "It's been problematic. The larvae are not circulating in the bloodstream. They park and just sit there." The amount of DNA available to be found will be tiny - that shed by the parasite as it moults from one stage to another. It therefore requires a highly sensitive test.

The more sensitive a test becomes, the greater the risk of contamination and the chances of a false-positive result.

He points out that once mature blood worms are laying eggs in the horse's gut, they have already completed their damaging migration around internal organs, among them the liver and arteries. Early detection and treatment means that damage can be minimised.

Nielsen comes from a nation that has taken what many other countries would consider to be a bold stand on drench availability.

In 1999, Denmark banned over-the-counter sales of drenches and reclassified them as a prescription-only medication available through veterinarians.

The law change has altered the way Danish horse owners manage parasites in their animals, he says.

A survey in 1996 showed that Danes were typical of horse owners elsewhere in the world where drenches were available over-the-counter, typically drenching five or six times a year.

Now, Danish horse owners typically get faecal egg counts done on their horses twice a year and drench according to the severity of the worm burden. "There has been a major change," he says. "The picture has been changed dramatically."

Sweden followed suit by tightening controls in 2007 and the Netherlands followed a year later. Nielsen says he was recently in France, where drenches remain freely available. He was talking with French equine veterinarians about the Danish experiences.

"They said, 'We just can't see this here ... you can never get horse owners to submit faecal samples'. And I said, 'well, that is what is happening in Denmark'.

"In the US, I don't think we can expect a change in legislation, but there is actually a change in attitude among horse owners and vets."

In Kentucky, he has noticed more veterinary practices encouraging horse owners to get faecal egg counts done before deciding to drench.

He says the issue of drench resistance will not go away, and is already a serious enough problem in equine parasites. "We know from the sheep industry that the end product is a superworm - worms not affected by any of the drugs available.

"The good part of the story is that horses tolerate parasites pretty well as long as the burdens don't get too high. The big issue is to prevent the build-up.

"Horse co-evolved with these parasites for millions of years. It's as natural to have parasites as it is to have bacteria.

"People don't like the thought of parasites. They're disgusting to look at, I admit that. But as long as the burden doesn't get too high, they are not a serious danger."

There is even evidence that parasites stimulate the same part of the immune system that swings into gear during an allergic reaction. Some evidence suggests some parasites can assist the host in coping with certain allergies, although more research is needed.

Nielsen says it is important that the horse industry uses the limited number of available drenches with care to ensure any resistance builds slowly.

No new drench family has emerged since ivermectin. He is aware of only one new drench currently under testing, in cattle and sheep. Even if testing proves satisfactory, a new drench could be five years from being commercially available.

Twenty-five years is a long time between drenches, he points out.

"If we do get a new drench, I hope we have learnt a lesson from history and don't just resort to blanket treatment on a regular basis year-round. We should try to do something more sustainable; adopt a more sustainable treatment strategy than the ones we have used for the last 40 years." There is a risk that we may have to wait another 25 years for the next-generation drug.

Nielsen says research is still needed in some quite fundamental areas of parasite control. For one, there needs to be a long-term evaluation of treatment schedules.

Researchers don't actually know the long-term effects of many commonly recommended parasite treatment schedules, he says. "We don't know what happens longer term. Do we still get the control we want? With some recommendations, the hard evidence is not really there supporting them."

There is even debate over the right cut-off levels in faecal egg counts. "This is not based on any kind of science," he says.

The second part of Nielsen's current research project will involve the use of computer modeling in a bid to predict the longer-term outcomes of some treatment regimes, based on data gathered during the first part of his project.

Crunching the numbers will not be easy. "It quickly becomes extremely complicated to look at, trying to deal with all these statistics."

At the time of writing, he was due to visit Anand Vidyashankar at Cornell University, who has experience in statistical modeling around parasites.

Nielsen counts himself as fortunate to have received Danish government funding to undertake equine parasite research.

"There is not a lot of research being done in the field. There are very few people like Dr Lyons and Dr Kaplan around working with horses."

Put simply, the world is not awash with equine parasite experts exploring future avenues of parasite control. "It's surprising how little we know," confesses Nielsen.

It's a problem Nielsen is working to rectify.