A Tale of 2 Treatments: Aspirin and Acyclovir During an EHV-1 Outbreak

By Paul Basilio

Equine Herpesvirus-1 (EHV-1) is endemic to the North American horse population, with more than 80% of horses exposed to the virus by age 2. However, few treatments have been evaluated during naturally occurring outbreaks.

Susannah S. Lewis, DVM, PhD, of the Rainland Farm Equine Clinic in Woodinville, Wash., recently experienced such an outbreak firsthand. She spoke about the effect of antiviral and anticoagulant treatment at a 60-horse boarding and training farm at the 65th Annual AAEP Convention in Denver.

The index case underwent a respiratory panel for 5 common respiratory pathogens via nasal swab PCR. Results were positive for EHV-1 G2254, which is known as the neurotropic strain due to the higher rate of neurologic disease. This strain is also known to cause abortion, but luckily there were no pregnant mares on the farm at the time, she said.

Neurotropic strain

“Our index case had a fever at day 0, and then it progressed,” Dr. Lewis said. “It was a weekend and there was a shipping delay, so we didn’t get the results back from the nasal PCR swab until day 6. At that point, the horse had recovered.”

EHV-1 G2254 typically causes fever and mild respiratory signs. The main worry was the neurologic complications that usually arise.

“Equine herpes myeloencephalitis [EHM] is due to a vasculitis,” Dr. Lewis explained. “There’s inflammation in the blood vessels, which triggers the coagulation cascade, which leads to microthrombi forming in the spinal cord. That leads to ischemic injury and neurologic signs.”

Flaccid paralysis typically starts at the back of the horse and moves forward. Clients were instructed to take the horse’s temperature twice daily, and to be on the lookout for loose, floppy tails.

“All of our neurologic cases had some grade of hind limb ataxia, and we had a number that lost control of their urinary sphincter,” she said. “You need to pass a catheter to allow the bladder to void.”

Ataxia can progress to all limbs and result in recumbency, and severe cases can have flaccid paralysis of the respiratory muscles. These are typically the horses that cannot be saved, she said.

On the first day that temperatures were collected following isolation of the pathogen, there were 7 horses with new fevers. With 8 horses shedding virus at that point, the farm knew they were in for the long haul.

As the outbreak progressed, they had 44 fevers total. The average fever duration was 3 to 4 days, and the last fever was noted on day 27. There was about a 4½ day average delay between the onset of first fever and the onset of neurologic signs. A total of 12 horses had neurologic signs, and 7 of those were euthanized.

“Our last neurologic case was on day 28,” Dr. Lewis said. It took 42 days from the last fever until the end of the state quarantine, which lasted 67 days, Dr. Lewis told The Modern Equine Vet. “The state quarantine started on day 6 when we had our first positive result, and temperatures were taken twice daily throughout. It was a treasure drove of data.”

The Study

In 33 of the horses with EHV-1 infection, valacyclovir 27 mg/kg PO 3 times daily was administered for 2 days, followed by 18 mg/kg PO twice daily for 10 days.

Treatment was initiated within 3 days of the fever starting in 12 horses, and at more than 3 days after initial fever in 11 horses. Ten asymptomatic horses were given the drug, and 21 febrile horses did not receive it.

“All of our horses were also treated with dexamethasone,” Dr. Lewis said. “I know it’s controversial because we’re giving steroids in the face of an infection. But we really never saw a horse improve until it was given dexamethasone.

“After that, we got a little more aggressive and talked to some other internists for different takes on it,” she said. “We ended up giving dexamethasone to all of the horses, in addition to flunixin twice daily plus supportive care, such as vitamin E, urinary catheterization, and management for the down horses.”

Results showed that valacyclovir did not affect the duration or magnitude of the fever—how long they had fever or how high the fever was—regardless of when treatment was initiated. It also did not affect the number of cases that progressed to EHM.

“Our clinical impression, however, was that when we started valacyclovir on a large number of horses, we saw a decrease in the number of new fevers,” Dr. Lewis added. “It's possible…that it reduces viral shedding enough that it inhibits the spread of the disease—not so much for the horse you’re giving it to, but for the horses around it. But we didn't have enough data to analyze that accurately.”

Of the 12 horses with EHM, 8 were recumbent at 1 stage, and 5 survived overall. Two of the survivors had also been recumbent. While previous research has shown that older age was linked with a greater risk of EHM, the outbreak at this farm did not show that pattern. Nor was there a significant association between EHM and length or severity of fever.

Aspirin has not previously been reported for use in EHV-1, but it is used in other vasculitis conditions. “We figured we had a vasculitis, and we know we have the activated coagulation cascades, and aspirin was something that was orally bioavailable and we could readily buy,” she explained.

Aspirin did significantly decrease the proportion of EHM cases that were euthanized. Eight horses that had EHM were not given aspirin. Six of those horses became recumbent, and 7 were euthanized.

“Of the 4 cases that were given aspirin, 2 became recumbent and none were euthanized.” she said. “The odds of being euthanized were 45 times higher if the horse was not given aspirin than in the horses that were.”

She noted that the n of this study was small and there was a temporal selection bias. Once the decision was made to give aspirin, all of the EHM horses were given it.

“I cross my fingers that this is going to be a fruitful area of future study, and that we can optimize these compounds in how we can use them to best manage a difficult disease,” she said. “In addition to implementation of effective farm biosecurity, it can help the course of the outbreak.”