What we know and what we’re learning in light of recent outbreaks

A silent killer lurks deep in the cells of nearly all horses. First infecting very young animals, equine herpesvirus type 1 (EHV-1) can lie dormant for years. It waits patiently in lymphatic and neurologic tissues, never hinting at its presence. Then one day—likely due to a stress event—the virus awakes.

Maybe the horse gets a mild fever or a runny nose. Often, nobody notices any clinical signs whatsoever. But on a microscopic level a war has started. The index horse—the one that sparks an outbreak—starts shedding millions of EHV-1 virus particles through respiratory secretions. With each snort, nasal drip, even breath, he sends pathogens into shared breathing spaces and onto walls, hay, bedding, equipment, and hands, clothes, and boots.

Highly contagious, EHV-1 primarily causes respiratory disease, but it can also trigger abortion and equine ­herpesvirus-1 myeloencephalopathy (EHM)—the neurologic form characterized by ataxia (incoordination), weakness, paralysis, and/or incontinence.

Handlers can limit damage by establishing and enforcing a quarantine on the premises. Sometimes, only a handful of horses get caught up in the outbreak. But other times—especially when reaction time is slow or many horses are housed together—hundreds can be involved.

That’s what happened in the Valencia, Spain, epidemic last year when 18 horses died and more than 200 from dozens of European countries were locked down at the Sunshine Tour competition venue. In the following months cases popped up all over Europe and the U.S.

With each outbreak comes fear, anxiety, management challenges, grief over equine losses, and financial burden. But outbreaks also bring scientific opportunities.

“There’s research being done, and there’s new vaccine technology being developed,” says Gisela Hussey, DVM, MS, PhD, associate professor of pathobiology and diagnostic investigation at the Michigan State University College of Veterinary Medicine, in East Lansing. “So, there’s hope on the horizon.”

In this article we’ll look at what we know about EHV-1, in large part thanks to these recent outbreaks.

Mutations and Variants

Scientists have known for five-plus years that EHV-1 circulates globally as two variants: D752 and N752. Over a decade ago they suggested D752 caused higher viremia levels—more virus, longer, in the bloodstream—and was more likely to cause disease. They also felt it favored neurologic signs, says Nicola Pusterla, DVM, Dipl. ACVIM, professor of equine medicine at the University of California, Davis, School of Veterinary Medicine.

Today scientists know both variants can cause neurologic disease, even if N752 does so less frequently, Pusterla says. They also know that while viremia is a key element to developing EHM, “this is not the whole story.”

Last year his team found a new U.S. variant in Pennsylvania: H752 (first discovered in 2018 in France). It results from a mutation at the same spot as the one that distinguishes the N and D genotypes.

Pusterla says this underlines the importance of accurate testing beyond detecting the two variants. Labs would identify variants more successfully by targeting a universal EHV-1 gene. “So, the question about H752 now is how prevalent is it?” he said. “How many have we missed?”

The findings also highlight the fact that EHV-1 is—fortunately—slow to mutate, says Lutz Goehring, DVM, MS, PhD, Dipl. ACVIM, Warren Wright, Sr.-Lucille Wright Markey Endowed Chair in Equine Infectious Diseases at the University of Kentucky’s Gluck Equine Research Center, in Lexington. “This is the third variation in the polymerase gene detected since we learned about this virus causing neurologic disease in 1966, so that’s a very long period,” he says. “DNA viruses like EHV-1 are very stable, and mutations are rare. It’s a really slow process.”

The Dreaded Neurologic Form

A complex problem with EHV-1 is its ability to slip into and wreak havoc on body systems beyond its primary target. The virus initially attaches to the ­respiratory tract lining and then goes into the lymph nodes and the bloodstream. From there, says Goehring, it can travel into the blood vessels of the uterus, causing abortion, or into the central nervous system, causing EHM, with signs sometimes so severe as to warrant euthanasia.

Animal health officials first declared EHM an emerging disease in the U.S. in 2007 when veterinarians started detecting more cases of fever associated with weakness, ataxia, difficulty urinating and defecating, reduced tail and anal tone, dog-sitting posture, and lying down.

It’s unclear how and why these EHM cases happen, Goehring says. Even so, EHV-1 epidemics have revealed trends, including a greater susceptibility in tall breeds such as Thoroughbreds and Warmbloods and more severe EHM signs in mares and older horses.

To learn more about these trends, Hussey and her colleagues have been studying viral and host factors that might contribute to whether a horse develops EHM. Specifically, they’ve been looking at immune system components that differ between older and younger horses.

“The immune system changes with age, similar to what we see with COVID and older people, who are much more susceptible to severe disease than younger people are,” she says. “Their immune response may be shifted or (not as strong).”

In Valencia, mares made up the majority of horses affected by EHM, says Ana Velloso Alvarez, DVM, PhD, Dipl. ACVS-LA, equine section chief at CEU Cardenal Herrera University’s teaching hospital, which closed its services to the public to focus on horses in the EHV-1 outbreak.

Scientists don’t know why females seem more susceptible than males. But some suspect it might have to do with estrous manipulation.

Improving on a 40-Year-Old Vaccine

The first EHV-1 vaccines were developed in the 1980s. When given at appropriate intervals, vaccines and boosters increase immunity and reduce viremia, Goehring says. While they don’t necessarily stop disease spread and don’t prevent EHM, vaccines can help infected horses fight disease and experience milder clinical signs, says Pusterla.

Despite the benefits, our sources say we are well-overdue for a better vaccine. But producing one is easier said than done, in large part because EHV-1 infection is so complex, says Hussey. “We’re not just talking about a herpesvirus infection that only affects the respiratory tract,” she says. “We’re talking about an infection that very quickly becomes systemic … . This makes it a much more complicated disease with a much more complicated pathogenesis.”

Plus, EHV-1 goes directly to work on the immune system itself, suppressing and modulating immunity, she says. Worse, because it’s capable of taking on a latent, waiting state, it’s adept at evading immunity, she says. “This is a key issue, and I think that’s what makes it so difficult to find or develop vaccines that actually protect horses from this disease.”

Research models also pose a problem, our sources say. Currently, scientists test vaccines on younger horses because these animals haven’t yet been exposed to EHV-1. The older or middle-aged ones, however, are more likely to develop EHM, says Hussey. Focusing on only young research models is “a huge hindrance in developing a vaccine, because that’s not what we’re seeing in the real world,” she says.

Goehring would like to see more research into immunity over time after a vaccination or booster. “Similar to COVID vaccinations, you see there’s this decline … the longer away you are from your last booster,” he says. “If you get a large enough cloud of virus, you’re susceptible again because your remaining immunity is not sufficient to hold up against it.”

A better understanding of vaccine and booster timing could help keep EHV-1 disease, including EHM, more consistently at bay—especially if it can reduce viremia, our sources say.

“The thing about EHM is that viremia is a prerequisite for that neurologic form,” Goehring says. “It’s this delivery of virus away from the respiratory tract lymph nodes into the central nervous system and the spinal cord that makes horses neurologic. If that transport mechanism is blocked, then we will not have EHM.”

Fortunately, because of EHV-1’s slow mutation rate, a good vaccine can remain effective in the industry for years—even decades, Goehring adds. Several groups are churning out new vaccine candidates at record rates. “There’s this energy to produce something more, and we know that with COVID, there are new options out there,” he says.

Lessons From Recent Outbreaks

The Valencia outbreak gave insight into a few of EHV-1’s secrets, Goehring says. It appeared where hundreds of horses were housed together in a new environment after traveling up to three days. Transport and competition stress might have triggered EHV-1 reactivation in one of the nearly 800 horses. A fever might have gone overlooked, and the rows of enclosed stalls allowed the virus to spread quickly.

Horses then left the premises, carrying the virus back to their home countries, where it continued to spread, he says.

People panic during an outbreak. “They want to get their horses home,” Hussey says. “But that’s exactly what you shouldn’t do. You really need to have good biosecurity measures; that’s the No. 1 control measure. Like with COVID, you need to stay put, stay distant.”

Goehring likens latent or dormant EHV-1 infection to a veritable bomb waiting to explode. “You can import that time bomb into your premises,” he says. “It just takes a few days, and then this horse upregulates the virus, and it goes back into his respiratory tract; it replicates, and it sheds into the other horses.”

Some horses shed much more virus than others, even if they have few or no clinical signs. “I think this is one of the most important findings from the last couple of outbreaks,” says Goehring. “These are the so-called Typhoid Marys: They spread a lot of virus through the group, and that challenges the immunity of any horse, but especially the unvaccinated ones or those coming due for a booster. Their immunity just gets ­overrun.”

In a far more preferable scenario, Pusterla and colleagues picked up on EHV-1 in a 31-horse Pennsylvania show barn last year during a routine care visit (TheHorse.com/1108913). The horses appeared healthy and were up to date on their vaccines, but 10 had mild fevers. Broad-panel blood and nasal swab tests found EHV-1 in eight horses. Over the next 35 days, 26 horses developed fever and clinical signs, and almost all tested EHV-1-positive. They received treatment and supportive care, and viremia dropped from 42% to 0% in a week, says Pusterla. All horses recovered, with virus never leaving the premises.

A critical component of curtailing this outbreak was early recognition.

“These were not horses that had their heads on the ground or were spewing nasal discharge,” Pusterla says. “(They)were just looking normal but happened to have elevated rectal temperature.”

The strongest take-home message from that outbreak—aside from finding the H variant—was the often overlooked importance of the thermometer, he says.

“Managers would have been calling the veterinarian a week or 10 days later when they suddenly had three or four horses with neurologic deficits,” says Pusterla. “Everybody wants to look for the magic bullet—this or that test. But taking rectal temperature is still a very powerful tool.”

Microchips including embedded thermometers could be ideal for IDing horses at infection onset, adds Goehring. “A fever doesn’t mean it’s herpes,” he says. “But it definitely shows that something is wrong with the horse that needs investigation.”

He’d also like to see better biosecurity in the competition venues where horses are often stabled overnight in enclosed or tent barns. “Biosecurity has to be ramped up at all events, for sure,” he says. That means regular temperature checks and good surveillance for clinical signs, as well as immediate isolation of febrile horses and their stablemates. It also means good biosecurity upon getting home—­regardless of any findings at the event.

Managers should be on high alert, says Goehring: “If they have returning horses coming back from shows or which are new to the barn, they need a strict quarantine protocol in place. Otherwise, you’re just welcoming in a pathogen that really likes to spread in a group, especially one that’s unprepared.”

Summary

While EHV-1 isn’t new, recent outbreaks have fueled scientific research into it. Researchers are more hopeful than ever about finding ways to mitigate and prevent this disease.