Progress, but No Victory, in Battle Against EHV-1

Recent EHV-1 (Equine herpesvirus 1) outbreaks have again focused attention on this nasty disease.

* On Nov. 3, 2016, a horse at the Los Angeles Equestrian Center in California developed a fever and his barn was quarantined. On Nov. 9 he tested positive for EHV-1. In the days that followed 15 cases were confirmed and one horse was euthanized. That quarantine was recently lifted—after 2 1/2 months.

* A 2-year-old filly at Fair Grounds Race Course & Slots in New Orleans was euthanized and three barns on the premises quarantined in an outbreak that began Dec. 26. Those horses were all tested, with temperatures monitored twice daily. Three more horses tested positive Jan. 10, after testing negative three days earlier. New cases start the mandatory two-week quarantine again; a quarantine is not lifted until affected horses are no longer shedding the virus and there are no new cases.

^ On Jan. 21 in Lexington a horse tested positive at Keeneland, where two barns have been quarantined and all of those horses are being tested and monitored. There also were positives at Turfway Park and a training center in the state. Kentucky has placed restrictions on racehorses coming from Louisiana.

WHY THE CONCERN?

There are several types of equine herpesviruses, and some are more damaging than others. EHV-1 can cause respiratory illness, abortion in pregnant mares, congenital infection (birth of weak foals), and sometimes a more severe (potentially fatal) illness involving the nervous system. This form is called EHM, equine herpesvirus myeloencephalopathy.

Historically the neurologic form has been rare, but recent years have seen an increase in EHM cases and outbreaks in North America, as well as in other parts of the world, at racetracks, and in horses attending other events—congregating from various areas.

Dr. Gillian Perkins, of Cornell University in New York, said equine herpesvirus is common in horses. Most horses are carriers.

“They are usually infected early in life; the virus becomes latent, hiding in the body, and undetectable,” she said. “It may recur or break out again and become active during periods of stress but we can’t always determine why it comes out of latency.”

WHY IS IT A CHALLENGE TO CONTAIN?

Dr. Josie Traub-Dargatz of Colorado State University, said herpesviruses have many ways to avoid the immune system. They can hide in white blood cells/lymph nodes and remain untouched by the body’s usual response to infection.

“We don’t currently have a vaccine or a biosecurity method to prevent initial infection of young horses,” she said. “None of our vaccines can keep foals from getting infected in a herd environment. They may get it from their dam if she is shedding this virus out of her nose. Some shedders are perfectly healthy, normal-appearing horses, and you wouldn’t know they are carrying and shedding the virus.

“None of our vaccines can prevent reactivation of the virus or completely prevent infection,” she continued. “Most horses are exposed and infected at a young age. The virus continues to live in the body, in a form the body does not recognize as foreign. If the virus becomes active again, it can be shed through the nose—to expose other horses.”

The shedding horse may develop signs of disease at that time, but may not.

“It is difficult to control this disease when we don’t have a vaccine or biosecurity method to prevent the initial infection or to prevent reactivation and shedding,” Traub-Dargatz said. “We need to work toward reducing the severity of clinical disease if it occurs, reduce the shedding, and try to reduce exposure of horses to a shedding horse.

“We don’t have a good way to detect the silent shedder—the horse with no signs of illness—but many outbreaks begin with a clinical case. Recognizing the first horse that has signs of disease, and finding out it is shedding (diagnostic testing), and then trying to reduce exposure of other horses to that horse is our best containment method at this time.”

Test results may take a day or two, so actions need to be taken before that to prevent possible exposure of other horses while we wait for results.

The virus can sometimes be spread in other ways and not just direct horse-to-horse contact. It could be carried from one horse to another by people handling the infected horse and then touching another horse.

Dr. Nicola Pusterla at the University of California Davis has sampled clothing, hands, tack, equipment, etc. after people have been caring for an EHV-1 case and detected DNA of the virus on those surfaces.

The virus particles can be spread through the air, depending on humidity, air temperature and environment. “In a barn with fans blowing air from one end to the other, if the virus-shedding horse is on the intake end of the fan, this would blow the virus farther than it could go on still air,” Traub-Dargatz explained.

WHAT WE LEARN FROM OUTBREAKS

“EHV-1 crops up every year,” Perkins said. “It is reported more often, possibly because it has become a reportable disease in many states, so they can keep track of it and contain it by closing down barns and facilities, using quarantine to halt the spread. If our diagnostic lab at Cornell gets a sample that tests positive for equine herpesvirus, the lab informs the state. In addition, media coverage is quick to report it; there are news items in equine publications and e-mail alerts.”

Today horsepeople quickly know where and when the disease shows up; there is more awareness among horse owners about EHV-1 than in earlier years.

“When it cropped up in Ogden, Utah, at the National Cutting Horse Association Western National Championship show in 2011, people didn’t know much about EHV-1,” Perkins said. “Some horses got sick toward the end of the show, but everybody took their horses home (to multiple states), and some unknowingly took the disease with them. After this incident, many horseshow and racetrack facilities developed biosecurity measures and a plan to deal with this disease if something like this happens.”

“In 2008 we interviewed veterinarians to create a report, focusing on lessons learned at that point,” Traub-Dargatz said. “We recommend that facilities have a place to move infected horses—away from the rest—as quickly as possible, and a plan for where they would put a neurologic horse to isolate it and provide veterinary care and treatment. It’s also important to limit how many people are going in and out of the area since every contact is a potential risk. Well-meaning people may not do the right thing when they leave the stall or barn. Also, make sure everyone on the containment team understands what needs to be done.”

In the first day or two it is important to have enough people asking where these horses went, making phone calls, making sure they don’t come into contact with other horses, and getting quarantines in place as quickly as possible.

Outbreaks have taught us more about how to help keep the virus from spreading.

“It involves basic biosecurity,” said Pusterla. “Outbreaks like the one at Ogden cannot be prevented. When you bring more than 400 horses under the same roof from all over the country, with minimal biosecurity protocols, it is just a matter of when and where this disease will strike. We are seeing more outbreaks because events are getting bigger; more people are bringing horses from various regions.

“What we have learned from earlier outbreaks includes what not to do—learning from our mistakes,” he continued. “We have increased awareness about biosecurity and factors that could predispose horses to developing neurological disease. If we apply this information, it will help. The problem is that people become complacent again—until the next outbreak happens.

“After these outbreaks we realize the vaccines currently available are not optimal,” Pusterla said. “We need new technology and new vaccines. So far, there is no vaccine labeled for the prevention of neurological disease, and the vaccines for preventing EHV-1 respiratory disease or abortion are simply aids; they will not prevent these 100%.”

GENETIC DIFFERENCES IN THE VIRUS

Numerous strains of EHV-1 (equine herpesvirus 1) exist in nature. A number of studies show that neurologic disease is more frequently associated with EHV-1 strains of a certain mutant genotype rather than the “wild” type of this virus, but one survey has shown that 14% of all neurologic cases of the disease were associated with the “wild” strains.

Researchers are trying to learn more about the different genetic types. Dr. Udeni Balasuriya (professor of virology, Maxwell H. Gluck Equine Research Center, University of Kentucky) is investigating genetic diversity among EHV-1 isolates from outbreaks of neurologic disease. With enough samples he can identify and compare viruses.

“I don’t believe that a single mutation is the sole determinant of neurologic disease in horses,” Balasuriya said. “Studies have shown that in outbreaks there can be both genetic types.”

We know that a certain percentage of neurologic cases are associated with the “wild” type.

The laboratory at Gluck has also isolated EHV-1 of the neuropathologic type (some of which contain additional mutations) from horses that did not develop neurologic signs. The goal of this study is to clarify the relationship between neurologic disease and genetically specific strains of EHV-1, and determine whether additional mutations in the virus’ genes influence development of neurologic disease.

Balasuriya’s study aims to clarify the relationship between the genetic type of the virus and the frequency and severity of neurologic disease in horses, and identify additional mutations that could be involved.

“This information is needed to enable us to design improved diagnostic assays, vaccines, and medications (for treating horses with the neurologic form of the disease) in the future,” Balasuriya said.

CURRENT RESEARCH

“Several groups are looking at anti-viral medications,” Perkins said. “These medications are still not proven to make a difference once the horse is neurologic. Primary treatment for a horse with EHV-1 is supportive. This involves rest, keeping the horse hydrated, using Banamine to reduce pain, fever and inflammation. The research investigating various antiviral drugs may help guide future treatment.

“A lot of the work we did on equine EHV-1 a few years ago looked at the neurologic form of the virus,” she said. “There is a diagnostic test that can differentiate between the neurologic and the non-neurologic (wild) form, looking at genetic makeup of the virus. We know both forms of the virus can cause neurologic disease, however, so it is important to take biosecurity precautions no matter which virus is found. A lot of emphasis has been put on dangers of the neurologic strain, but people need to remember that the non-neurologic strain is also dangerous and can sometimes cause neurologic disease as well."

Pusterla noted different genotypes have different genetic makeup.

“Researchers determined the entire genome sequence of two different prototype strains,” he said. “One strain was associated with neurological disease, causing EHM. They also sequenced the entire genome of an EHV-1 strain associated with respiratory disease and abortion. They found a small percentage of area of divergence within the genome of these two EHV-1 viruses relevant to the virulence of these viruses, but it’s not black and white.”

There is a gray area in which neurologic disease can be caused by either genotype.

“EHV-1 can cause a variety of clinical diseases such as rhinopneumonitis, neonatal death, abortion, and EHM,” Pusterla said. “The most common disease form is a self-limiting disease of the upper respiratory tract (rhinopneumonitis). The other disease forms are less frequent but have greater impact for the infected animals.”

People need to understand that it’s not just about the virus when it comes to disease. It also depends on the environment and the host horse (age, gender, breed, stress factors, etc.).

“This is a multi-factorial disease; there is variable susceptibility among the population,” Pusterla explained.

“In recent years there has been an impression that we are dealing with a more powerful, mutant of EHV-1 with larger outbreaks. In reality, the less pathogenic one originated from the more pathogenic older virus.”

A virus that kills the host is less likely to continue transmitting in the host population. A virus is better off to co-exist with the host. The less virulent one has a selective advantage and is widespread and dormant in the lymph nodes and certain nerves.

“When we screen horses, we find that the majority are infected with N752 (which is less damaging), and the minority are infected with D752,” he said. “This is good news and explains why most of the outbreaks are self-limiting and not associated with neurological disease. The disease form following infection with EHV-1 is difficult to predict, however, based on genotype only.”

Research goals are for development of a new vaccine for EHV-1 and evaluation of efficacy of current vaccines against EHM. Horsepeople are hoping for a vaccine that would prevent latency of EHV-1 and the neurologic form.