Neurologic Equine Herpesvirus Q&A

It isn't just our imagination--we have been hearing about more neurologic equine herpesvirus outbreaks in the past several years than we were aware of previously. The current outbreaks in Kentucky and Maryland bring the disease back to the forefront, and there are many questions that horse owners, trainers, and even veterinarians have about the illness in its current state.

The University of Kentucky's Gluck Equine Research Center has the only Office International des Epizooties (OIE, or World Organization for Animal Health) reference laboratory for equine herpesvirus in the Western hemisphere. Thus, samples from most of the outbreaks are sent here so George Allen, PhD, professor in veterinary science at Gluck and head of that laboratory, can type these viruses and know which strains are circulating. Yesterday (Jan. 10) The Horse interviewed Allen, David Powell, BVSc, FRCVS, professor in veterinary science, and Peter Timoney, FRCVS, PhD head of the Gluck Center, on the basics of neurologic EHV-1, characteristics of the current outbreaks, and what we've learned about preventing the illness and controlling its spread.

Q: With all of the different herpesvirus outbreaks over the past few years, there is a lot of confusion and fear among horse owners because they don't understand it. What would you like horse owners to understand and what do you think the horse owning population needs to know about herpesvirus in general and neurologic herpesvirus?

A: Allen--I think the most significant thing is there seems to be an increase in the occurrence of disease caused by these neuropathogenic strains of herpesvirus. This particular disease is one that's especially of concern because it has the potential for causing devastating outbreaks and for shutting down much of the industry, especially the racing industry.

Powell-- It's only within recent years that it seems there's been an increase in the incidence of this neurological form, which came into prominence with the outbreak in northern Ohio at the beginning of 2003. Since then, we've identified outbreaks of this neurological form occurring throughout the United States in different breeds and in different areas. In 2003, we examined material from five different outbreaks in five states (the initial outbreak in Ohio at Findlay University, cases in Kentucky at Turfway, Virginia, Oregon, and a racetrack in Pennsylvania) of the neurological, whereas in 2004 we saw just one or two (Maryland and Michigan). We saw in 2005 an increase--six outbreaks reported in Kentucky, Maryland, Michigan, Pennsylvania, and New York.

I think it's also interesting to observe that overseas, there's been an apparent increase in the incidence of this particular manifestation, particularly in Europe. England is where it has been primarily reported in Europe.

Allen--Previous to 2003, the most number of outbreaks that we were aware of in all those preceding years was on average one outbreak per year.

Q: Are the current outbreaks at Turfway, in Henderson, and at Pimlico caused by a strain that is distinctly different from others seen recently (as in Findlay, Churchill, Maryland, Pennsylvania, and others)? Or all they all the same thing?

A: Allen--All isolates of EHV-1 recovered from neurologic outbreaks share a common mutation, so they're the same genetic strain, but different from the strains of EHV-1 that cause only respiratory disease and abortion. There are other minor strain differences (between EHV-1 isolates), but none of those are associated with any known difference in clinical disease except for the specific ones that we've discovered and talked about (the neurologic strains).

Q: When does this mutation happen? Is it a regular herpesvirus, per se, that gets into the horse and mutates there, then the horse spreads it as a mutated virus, or did the virus mutate once and that mutated strain is what's spreading?

A: Allen--That's the question we wish we knew we had the answers to, but you just identified the two possibilities, either there's a reservoir of horses that carry this mutant herpesvirus and that latent virus is periodically reactivating and spreading to other horses, or it may be that each new outbreak of this disease is a result of an independent and new mutation event. And we just don't know the answer to that. A mutation of the wild type regular strain into the paralytic strain, that mutation event may be occurring in multiple cases--each case giving rise to another outbreak.

Q: It has been said that these horses have higher titers of EHV in their blood than in past outbreaks. Are you finding this in all herpes cases or just specific outbreaks? What do these higher titers mean?

A: Allen--The higher titers is referring to the viral load that's present in the circulating blood of these horses--it's called viremia--it's virus that's present within the lymphocytes (white blood cells) of the horse. It's those lymphocytes that carry the virus to the central nervous system. So, horses that are infected with these neuropathogenic strains have higher numbers of virus-containing lymphocytes that are constantly bombarding the central nervous system, so there's an increased risk of infection of the CNS because of that.

Timoney--There are three characteristics of the response of the horse to these neuropathogenic strains. (The viremia) occurs earlier, it reaches a higher peak, and it lasts longer (he refers to a figure that ran with an update in Equine Disease Quarterly).

Q: Please describe the clinical signs in the current outbreaks.

A: Powell--The initial feature is the animal developing quite a high fever, and one of the new features of this manifestation is that they very quickly become ataxic (incoordinated) or paralyzed in the hind legs, usually they display incontinence, and the feature is the very rapid progression of the disease to the extent that a number of animals have become recumbent and unfortunately have been euthanized within two, three, or four days. And this is something that hasn't been observed before--the progression of the disease has previously been much slower than that. 

Q: When you say previously, does that mean before the 2003 outbreaks, or before the current ones?

A: Powell--I would say that prior to the Findlay outbreak, there was a pattern of disease that was somewhat different, and subsequent to the Findlay outbreak we've seen a much more rapid progression of clinical signs in the horses.

Q: What is the incubation period of the illness in the current outbreaks?

A: Allen--It's during that febrile phase that the horse is most infectious, most contagious, to others. And then, anywhere from six to 12 days later is when the neurologic signs set in.

Q: Are these horses displaying respiratory signs?

A: Allen--The majority of the horses that get this don't show any respiratory signs, and those that do show only a mild nasal discharge.

Powell--One might add that in situations where pregnant mares have been exposed, those mares have usually aborted.

Q: It has been said that the virus can spread 35 feet in the air. Where did that figure come from, and is it possible that in the outbreaks we've seen recently, that it can spread farther?

A: Allen--I don't know where that figure came from either. We do know that it gets spread from one end of the barn to the other end in quite a rapid time period. Part of that spread is from horse-to-horse-to-horse, it just runs down that aisle of stalls.

Q: Does it spread this way through touching noses, or from picking up the virus particles in the air?

A: Allen--It can be either of those. Primarily it's airborne infection.

Timoney--Clearly there is a potential for aerosol transmission, i.e. infective viral particles are in the air that's exhaled by an infected horse and then inhaled by a susceptible animal. However, within barns, there's always the potential for horse handlers to transfer the infection by indirect means. They may come along and put a shank on a horse…they don't give a second thought if the horse looks normal…there may be a total absence of any respiratory signs. Then they'll go down the stall row and handle some other horses. It's part of their daily routine. You can't exclude or say definitively that contagion couldn't be transmitted indirectly through a person's hands or other objects, if they put their hands around the nostril area of an asymptomatically infected horse and then proceed and handle other healthy horses.

Q: What are your vaccination recommendations when EHV is detected at a facility?

A: Allen--You are asking all the hard ones that there are no hard answers to.

Powell--As far as the respiratory and the abortion form of the disease in concern, we think vaccination is very helpful, although it certainly doesn't prevent individual animals from succumbing to cases of abortion.

As far as policy on vaccination for the neurological form of the disease, historically it was recommended that during an outbreak it was unwise to vaccinate the in-contact animals because some thought that there might be an immune-stimulated/mediated reaction. But I think the most recent work that Dr. Allen has undertaken indicates that might not be the case and that we're dealing with some more virulent strain of the virus. So I think in terms of neurological form of the disease, we may have to rethink our philosophy on vaccination, but because of the rapidity of the disease in terms of the manifestation of clinical signs, it's unlikely that vaccination of immediate animals in contact is going to have any great benefit, and as it has already been said, the virus is probably spread to those animals within a relatively short period of time. So, I think the bottom line is in the context of these neurological cases, we may have to rethink our philosophy on vaccination and how we approach the problem, in terms of whether we're looking to develop new vaccines or whether we change the routine.

Timoney--Getting to the core of it, there has been one report that would suggest that the modified live virus vaccine against herpes 1 has some efficacy against the neurologic form of the disease.

Allen--What that study really  showed was that the vaccine was efficacious in minimizing the non-neurological clinical signs-- fever and virus shedding--but it was not a study that provided firm evidence that  the vaccine prevented the neurological manifestations. In fact, in our own studies here recently, we found that the horses that are most likely to develop the neurologic signs following EHV-1 infection are those that show no fever at all. So that study, in my view, is not as strong in making the claim for vaccine efficacy against EHV-1 neurological disease  as those investigators have stated.

In terms of preventing infection, I think vaccination is still a recommended activity. But in terms of vaccinating already exposed horses, it's still an open question.

Q: What is the length of quarantine you recommend? Is it still the 21 days after the last fever resolves?

A: Allen--As far as I know that's still the quarantine that the state veterinarian's office is sticking to and they found it to be effective.

Q: People have said horses are being moved off the grounds at Turfway in the barns that aren't under quarantine. How do we know that one or more of these healthy-appearing horses isn't carrying the virus back to naïve horses at home?

A: Allen--I would say that it's essential for the racing industry to be able to move their horses and if movement is curtailed, then racing is going to be shut down. So there has to be some happy medium of restricting movement in those horses that are likely to have been exposed vs. those that are not so likely to have been exposed. But there's still the chance that there may be one or two in that latter group that has been exposed, but that's one of the risks that has to be taken to keep the racing going.

Powell--The risks can be mitigated by checking the horses before they are moved, particularly the temperature records. I think in the outbreaks that have occurred, this has been a very effective tool for identifying possible animals--it's not perfect (fever might persist only for a short period and can be missed even if temperatures are taken every 24 hours), but it's an excellent and very simple tool to apply without having to resort to any laboratory procedures. I think it is a simple procedure that only takes a short period of time, and it can be done by any personnel at the farm or at the racetrack.

Timoney--If we completely close down movement, you're essentially going to undermine confidence in the industry and it will likely result in significant economic loss. What the state veterinarian is doing is essentially carrying out risk assessment and trying to mitigate the risk factors and yet allow for controlled movement to occur. You can't have a zero risk situation. Through the work that Dr. Allen and others have done, we know that this particular group of viruses has the ability to establish latency in a very high percentage of exposed and infected animals, so there is a carrier reservoir out there. It's analogous to herpes simplex virus infection in man. What do you do? Do you restrict every one that develops cold sores from consorting with those that are not affected? 

We must bear in mind that a lot of these procedures have been implemented in the past, namely the period of quarantine or restricted movement. They've been found to work in curtailing spread of the disease. There is a historical background that we can draw upon and say, "Look, we're not plucking intervals of times or procedures out of thin air."

Q: Why are these outbreaks seemingly spotty, they disappear, and then they pop up again? What can we learn from this in preventing outbreaks?

A: Timoney--You could ask that question of many, many infectious diseases. We don't know when they're likely to occur, all we do know is they will recur, and our ardent hope is that we minimize the number of animals that express clinical signs of whatever disease it is, whether its respiratory disease , whether it's abortion, whether it's whatever. But we're not at a point where we can say with any degree of certainty or assurance that we're not going to continue to see sporadic occurrences and outbreaks of this or other diseases.  Hopefully, any such outbreaks will involve minimal numbers of clinically affected animals.

Allen--One factor that's probably involved is stress. It's been shown that astronauts that go into orbit almost invariably show serologic evidence of reactivation of latent herpesviruses. Any stress situations could be a factor in those spotty episodes that are seen and I think minimalization of stress should be one of the management goals. Again, stress is part of the activities of a horse's life--a performing horse or a breeding horse.

Q: Currently, how long does it take for a diagnostic test to come back?

A: Allen--If you send it to me, it takes three days. If you send it to the diagnostic lab, they have a 24-hour turnaround time.

Q: I understand there might be a need for a high-speed PCR. Do you think that is something the diagnostic center should have?

A: Allen--Yes, a high-thoroughput (PCR)

Q: What other entities can test for EHV?

A: Allen--Most state animal disease labs have the capability to test for EHV.

Q: Any closing remarks?

A: Timoney--People need to realize that the neurologic form of this disease has existed and has occurred for a significant number of years, long before the Findlay occurrence, and in some instances with major economic consequences for the industry…not just in North America, but in Western Europe. What we're talking about here as a clinical pathologic syndrome is not unique. What Dr. Allen and his colleague (researcher Nick Davis-Poynter, PhD, head of infectious diseases at the Animal Health Trust in England) have been able to demonstrate is there is a scientific basis (the mutation) for the behavior of equine herpesvirus in situations where it's associated with neurologic disease, which is a terrific advance.

Powell--From a research point of view, (the current state of equine herpesvirus) emphasizes how important it is to be studying a problem over a long term and not suddenly jumping from one situation to the next. Dr. Allen has spent his career (25 years) working on equine herpesvirus and following the manifestations of the virus in its genetic and clinical sense. A great deal of what we know now and some of this new information would not necessarily have arisen unless that long-term commitment to research on the problem had been undertaken.

About the Author

Stephanie L. Church, Editor-in-Chief

Stephanie L. Church, Editor-in-Chief, received a B.A. in Journalism and Equestrian Studies from Averett College in Danville, Virginia. A Pony Club and 4-H graduate, her background is in eventing, and she is schooling her recently retired Thoroughbred racehorse, Happy, toward a career in that discipline. She also enjoys traveling, photography, cycling, and cooking in her free time.

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