Tag: Research In Action from the Grayson-Jockey Club Research Foundation

When Debra Ladley first noticed her 18-year-old retired hunter gelding, Jack, was experiencing sudden lameness, she thought what most horse owners do – that there was a hoof abscess brewing.

When Jack's discomfort didn't resolve after a couple of days of anti-inflammatories and no abscess popped from the foot, Ladley called in her horse's care team to dig deeper into the problem.

“It became very clear that it was a bigger issue and then we started intensive, intensive icing,” said Ladley. “Our local vet said as much ice as you can do, that's the best thing, so we iced both of his front feet, although the situation was more acute and required the most attention in the right front.

“We iced him pretty much around the clock during the day and then, up until the night time … half hour on, half hour off, half hour on, all day long. We had two freezers going with as many ice boots as we had collected around the farm.”

Ladley is located in Pennsylvania but her local veterinarian was able to consult remotely with Rood and Riddle Equine Hospital's Dr. Raul Bras, who is part of the clinic's renowned podiatry department. Bras said that icing to address laminitis has become an important tool in the toolbox of veterinarians, farriers, and horse owners.

The confirmation that cold could be used as a laminitis treatment is the result of research funded by the Grayson-Jockey Club Research Foundation in the late 2000s and early 2010s. It's still being studied today as researchers and veterinarians perfect best-practice about how and when to use ice in different situations.

Laminitis has a variety of causes and is a notoriously painful condition that can sometimes prove fatal to horses. It occurs when the tissues that attach the hoof wall to the internal structures of the foot, including the coffin bone, become damaged and inflamed. That attachment occurs through the interlocking of finger-like soft tissue projections on each side, and a disruption to that connection can be catastrophic, and in extreme cases, can result in the fingers separating.

Laminitis has been connected to endocrine, sepsis, and mechanical causes. Horses who have been through a period of stressful illness may experience the disease; it can be brought on by grain overload, or possibly secondary to another injury which requires the horse to offload extra weight onto supporting limbs.

Ladley said in Jack's case, she was stumped about the cause. In hindsight, there had been more rain during that part of the summer and she wondered if that may have changed the sugar composition of his pasture, mimicking a grain overload, but otherwise his routine and health had been unchanged. She also recalled the air quality in Pennsylvania was bad around that time due to Canadian wildfires, and while Jack didn't appear outwardly bothered, she didn't know if the smoke created internal stress.

The key to addressing laminitis is speed. Damage to the lamellar structures is considered by veterinarians to be irreversible, so minimizing that damage is the goal. Cold therapy is most commonly suggested by experts in the same way Ladley knew to use it – at the earliest signs that something is brewing – or preemptively, in cases where horses have gotten into the grain bin or are fighting serious systemic infections.

Bras said that many people believe that cold will prevent laminitis or keep it from worsening because they think it's reducing bloodflow to the tissues in the hoof. That's not quite right.

“The horse has such a complex blood supply anatomy, like the arteriovenous shunts and all those kinds of things, they actually regulate their temperature in their feet,” said Bras. “That's why you see all those horses in Iceland standing on ice and they don't freeze. And that's why you can do cryotherapy as well.

“But the biggest thing about the cryotherapy is actually to decrease or slow down the metabolism in the blood in the hoof capsule.”

Bras said it's the enzymes and inflammatory factors being carried in the blood that are causing the damage, and the cold slows their action down. It probably also provides some anti-inflammatory benefits to make the horse more comfortable. Ice should be applied for at least 72 hours, as constantly as possible – which is tough to do outside a clinic, especially because melted ice has to constantly be refreshed. Ladley said the farm where Jack lives was able to provide him an army of support, with staff from all corners pitching in to keep him on his schedule in that critical timeframe.

At one time veterinarians thought that ice could only be used preventatively, which was tricky since it was impractical to do constant icing on every hospitalized horse who had experienced colic or a fever with the anticipation they could eventually be at elevated risk. Now, vets realize that it's worth doing in the acute stages of the event, too.

Bras says he has also learned more through the years about how to effectively apply the ice. The cold apparatus should go up to the mid-cannon bone for maximum effectiveness, and he's found that using an ice water slurry with the right type of ice boot will actually get the limb colder than straight ice. He also prefers to leave the ice on rather than removing and reapplying, and is not concerned about skin damage for the 72-hour period.

“I tell people you've got to pick your battles,” he said. “I mean of course, it's not the ideal thing for the horse but he's going through laminitis. I'm willing to risk a compromise to insensitive structures and hope to save the internal sensitive structures that provide the blood supply and drive hoof growth.”

Sometimes patients will remain comfortable after the ice is withdrawn at the end of the 72-hour period, but others may become sore. At that point, Bras thinks it's ok to reintroduce the ice in hopes a little more time will beat back those inflammatory mediators. The 72-hour recommendation was based on the way one research study was set up, but Bras says the tricky part about applying academic research to practical cases is you aren't limited to the same time or scale confines the researchers were.

Ice isn't going to be the magic cure long-term, either. Bras wants to follow up that initial period of treatment with a meticulous examination of the foot to check for coffin bone displacement or rotation, followed by corrective shoeing. Then, veterinarians have to try to pinpoint and address the trigger, if there was one, that started the laminitic episode.

“It's a useful finding that gets used a lot but now we're in the stage of perfecting, how to think about it and how to use it,” said Bras.

As for Jack, Ladley hopes the worst is behind him. He's well into a corrective shoeing program together with Ladley's local veterinarian and Bras, who overnighted the first set of supportive shoes to her when Jack's episode began. Ladley suggests that large barns like the one where Jack is stabled have a small freezer on hand to chill ice boots, just in case.

“Obviously we had veterinary support, we had drugs, we had everything else,” said Ladley. “So It wasn't like [the ice] was the only thing we did, but I do think it was a very impactful piece of the puzzle.”

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Placentitis is the sneaky foe of many a breeder or broodmare manager. The condition can arrive with no calling card, or such mild symptoms that they're easily missed. By the time a pregnant mare's caretakers are aware of it, it's often too late to save the foal.

It's been the leading cause of pregnancy loss, especially late pregnancy loss, in horses for years.

Dr. Margo Macpherson, professor emeritus at the University of Florida's College of Veterinary Medicine, has been one of many researchers trying to figure out how to stop it in its tracks.

“I call myself a clinician scientist because I'm a clinician first but I want evidence for the things I'm doing in a clinical setting,” Macpherson said.

Placentitis is the inflammation of a mare's placenta, usually as the result of an infectious agent like a bacteria or a virus. The infection causes inflammation which disrupts the structures that protect a gestating foal. There are various subtypes of placentitis and different sources of the infection, but the risk with all of them is that the suddenly-hostile environment will compromise the foal's growth and eventually stimulate a premature delivery or the death of the foal.

Macpherson said there may be some mild vulvar discharge during the mare's pregnancy that could signal a problem, but sometimes there isn't, or it's so minor that managers may not see it. What they do often report is an early development of the mare's mammary glands, well ahead of the projected foaling date. Sometimes breeders learn the mare had placentitis when the foal is aborted.

Even if they're able to catch onto a case before an abortion happens, Macpherson said veterinarians are often unsuccessful in attempts to reverse the damage from the inflammation.

For many years, the standard treatment was a combination of drugs – an antibiotic to try addressing the infection; altrenogest (known commonly as Regu-Mate) to try to avoid premature foaling, and an anti-inflammatory called pentoxifylline which was believed to reduce inflammation and improve blood flow. The trouble was, Macpherson said there wasn't a lot of evidence about how good pentoxifylline was at accomplishing those goals in placentitis cases, and most clinicians didn't want to keep horses on it long-term.

Paula Quinn, long-time breeder of Thoroughbreds and Warmbloods in Florida, has seen her fair share of placentitis cases and has always been curious about what veterinarians prescribed to her horses and why.

“What I like about a teaching hospital [like University of Florida] is they do a lot of research and they're used to explaining things to people and I have a very curious mind and always want to understand things,” said Quinn. “We had a mare over there that unfortunately developed placentitis and the foal did not live in this particular case, but I was asking about the different medications and protocol.”

This was shortly after the Food and Drug Administration approved firocoxib for use in horses with arthritis in 2016. Quinn knew from her research that firocoxib is a nonsteroidal anti-inflammatory that is targeted in the way it works in a horse's body, moreso than familiar NSAIDs like phenylbutazone or flunixin megalamine. Because firocoxib and other medicines like it target only certain types of inflammatory mediators, they don't cause the same gastrointestinal irritation that less targeted nonsteroidals can. That makes them safer choices for longer-term use.

Quinn had a horse with navicular syndrome who had been on firocoxib for some time with no ill effects. She asked Macpherson – have you considered this new anti-inflammatory for use in placentitis?

It was a new idea to Macpherson, because before then, people really only thought about the drug in terms of arthritis, which is also how it's commonly prescribed in humans. Macpherson designed a study to test out how firocoxib may work in this clinical setting, and got funding from the Grayson-Jockey Club Research Foundation to make it a reality. First, she induced placentitis in two groups of mares and gave firocoxib to one of the groups. Then, she measured the levels of various inflammatory mediators in allantoic and amniotic fluid, and found that treated mares had lower concentrations of inflammatory mediators than those who went untreated.

In her next study, she combined firocoxib with an antibiotic and a double dose of Regu-Mate and gave the combination to a group of pregnant mares with placentitis, as a way to test the typical protocol in the field. The group was small, but she said all of them delivered live foals.

Thanks to her research, many clinicians are already using firocoxib as a part of their placentitis treatment program. The next time Quinn had a mare with placentitis, she was surprised to learn that the medication protocol had changed, and reached out to ask Macpherson – was that because of us?

Quinn and her veterinarian gave their mare the trio of medications that included firocoxib, and the mare produced a healthy foal. At a recent Belgian Warmblood inspection, the horse was rated as a Premium Filly.

“Margo and I were laughing that something I had a part in saved one of my own fillies,” said Quinn. “But she's so generous to give me any credit at all, because the work she's put into this has been amazing.”

Quinn said as a horse owner, it's good to know there's a better treatment out there, but she knows the road to solving the problem of placentitis is a long one.

For Macpherson, the next research focus will involve looking for early warning signs that something is wrong before a mare shows outward symptoms.

“I think a big piece of what we're missing is understanding the pathophysiology of the disease and how we can better diagnose it,” said Macpherson, who noted the University of Kentucky has done great work in this are already. “Probably for me, I have a series of years' worth of samples I've collected under different types of conditions. I'd like to look at those samples to see if we can find any biomarkers that are indicative of impending placentitis so that we can do a better job of initiating those treatments and making those treatments more effective. That's a big piece of it, we find placentitis too late. We find it well into the disease process and then it's hard to catch up.”

In the meantime, it's good to know there's an effective, safe protocol out there that can help in some cases – and it's been embraced broadly in the field.

“People are pretty quick to grab onto those treatments,” Macpherson said. “They want something that works better. Grayson-Jockey Club Research Foundation has been very, very good about supporting research problems that have a clinical impact on horses. They're not just a Thoroughbred-based organization, they're looking after the health and welfare of all horses. We happen to see it a lot in Thoroughbreds because we have an older population of mares who have been breeding a long time, but it's everywhere.”

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Possibly the only thing more unsettling than being a horse owner experiencing an infectious disease outbreak on their farm is to be a veterinarian who experiences one.

That was the case for Dr. Trisha Dowling, professor of veterinary clinical pharmacology at the Western College of Veterinary Medicine in Saskatchewan, Canada. In 2008, Dowling took a horse and a pony off her farm and trailered them to a local lesson barn to use their indoor arena. Neither the horse nor pony encountered any other horses while they were there.

A week later, one of Dowling's horses colicked with unusual symptoms; then the pony fell ill. At first, Dowling thought the pony had contracted rabies and tried to manage the disease unsuccessfully. Two weeks after that, another horse fell ill and this time, she tested the horse for equine herpesvirus (EHV).

“Eventually, six of my horses developed neurological signs,” recalled Dowling. “All survived but one mare remained slightly ataxic for the rest of her life. My youngest horse only developed a fever and a unilateral uveitis. One of my neurological horses developed bilateral uveitis.”

There are a few different strains of EHV, but the most common is EHV-1. It often presents with mild respiratory symptoms and fever, but in some horses it can progress into equine herpes myeloencephalopathy (EHM), which is characterized by neurological symptoms and can quickly turn intense. If a horse develops advanced neurological signs, the disease can prove fatal.

EHV can easily be spread through nasal secretions, and it's unknown how long it can live on shared surfaces or hands.

EHV-1 is a major concern at large events where horses from different populations may be stabled together. Experts believe that most horses have been exposed to the virus at some point in their lives and may spontaneously begin shedding it through their nasal secretions if they're under stress. It may also be true that a small percent of the population could be “super spreaders” who can carry and shed huge amounts of the virus, sometimes without appearing to be ill themselves. This makes the virus very hard to control.

Dowling contacted Dr. Lara Maxwell, professor of physiological sciences at Oklahoma State University. Maxwell has made a study of pharmacology of many equine drugs, as well as their effectiveness against specific diseases. Part of Maxwell's research has dealt with the use of the antiviral valaciclovir against EHV-1, and she suggested Dowling give it a try.

Valaciclovir is the second generation in a closely-related group of drugs that have been tried for EHV-1; acyclovir was its predecessor but had poor bioavailability and had to be given by injection. The oral valaciclovir is easier for laypeople to give, and much more of the drug got to the horse.

“One of my endurance horses was highly rated and I was hoping to make the Canadian Equestrian team for the 2010 World Equestrian Games,” said Dowling. “Dr. Maxwell recommended the treatment with valacyclovir as soon as possible. Basically, I bought all the available supply of the drug in Saskatoon ($4,000 worth) and treated her. She was the only one of my horses that did not develop any signs of EHV even though she tested positive. We did end up as alternates for the team in 2010 – oh, well. But it was worth the cost to me to protect the most valuable of my horses against the clinical signs of EHV.”

Dr. Nicola Pusterla, professor of medicine and epidemiology at the University of California-Davis, said that we now know valaciclovir can be a great weapon against an EHV-1 outbreak like Dowling's – if it's given in the right context. Studies have since shown that if you give it to a horse who's already exhibiting the neurological signs classic of EHM, you probably won't do much to change the outcome of the case. It's also a good protective option if it's given to a horse before they're exposed to EHV-1, but most of the time, horse owners don't know they're taking their horse into a facility where another animal is shedding the virus.

Where it is useful, according to Pusterla, is treating horses who may be showing the earliest signs of illness but for whom neurological symptoms haven't shown up yet – those with fevers and mild lethargy.

“We know that valaciclovir is very potent and repeatedly shown to work best in the early stages of disease,” said Pusterla.

He also thinks it's a good way to slow an outbreak.

“Experimental studies have shown that by the time a horse has a neurological deficit, the use of valaciclovir will not alter the outcome,” he said. “Where I see one of the huge benefits in treating an EHM horse with valaciclovir is the rapid decline of viral shedding and viremia … putting them on a drug which rapidly, in 24 or 48 hours, will significantly reduce the amount of viral shedding and nasal secretion is a tremendous benefit in reducing or preventing environmental contamination or transmission to other horses.”

Pusterla does have concerns that valaciclovir and the third generation of the drug, ganiciclovir, can be overused by panicked horsemen who want to give it to outwardly healthy horses as a way of protecting them. It works for this, for as long as the drug is being actively given, but Pusterla worries it will ultimately create viral resistance to the drug, similarly to the way scientists have noted concerns about a growing bacterial resistance to antimicrobials.

The evolution of veterinary understanding of valaciclovir's use against EHV-1 wouldn't have been possible without years of academic research from Maxwell and her colleagues. Some of those key studies were funded by the Grayson-Jockey Club Research Foundation, which funds research that benefits horses of all breeds. Since its foundation in 1940, the organization has given more than $40 million to underwrite over 426 projects at 45 universities. Grayson-supported research has changed the way owners, farm managers, trainers, and riders of all disciplines manage horses in times of wellness, illness, or injury. Find out more about its current projects here.

In Dowling's case, the drug functioned as it was supposed to – and despite having horses who had lasting deficits from EHM, she hasn't had any more problems on her farm.

“I tested my horses after 'stressful events' such as a colic surgery and after 100-mile endurance rides,” she said. “I was never able to demonstrate any shedding in any of my horses. I brought in naïve horses and they did not become infected. The mare who remained ataxic gave me two nice fillies in the next couple of year.

“We have not had an outbreak around here like the 2008 one (over 100 horses at the [index] barn tested positive and three were euthanized),” Dowling said. “The cost of the drug is what would stop most of the horse owners around here. But if the horse is valuable enough, it seems like a good idea to try to protect them from what can be devastating consequences of EHV infection.”

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