Equine herpesvirus has been on the minds of many horse people over the past few years. Outbreaks have popped up all over the United States, from Ohio to California and Florida to Connecticut, proving it is a significant and widespread problem. Perhaps the most alarming development is the number of outbreaks of equine herpesvirus-1 (EHV-1) manifesting neurological signs. Everyone is talking about this often deadly neurologic form, and several researchers have been trying to do something about it.
Overview of Herpesvirus
The two most common forms of equine herpesvirus circulating in our horse populations that cause consistent clinical signs and are regularly diagnosed by veterinarians are EHV-1 and EHV-4; both are known to cause respiratory disease.
EHV-4 generally only presents as a respiratory problem. We mainly see it in younger animals. Although older animals will test positive for the virus, natural immunity developed upon initial exposure usually prevents any significant clinical signs.
EHV-1 is a bit more challenging to manage, as it can cause several negative effects, including respiratory disease, abortion, stillbirth, and neurologic disease.
The EHV-1 virus is found circulating in horses latently (not causing clinical signs) in the majority of the equine population worldwide. Basically, most horses already are infected, and outbreaks occur when something happens to the horse that causes the level of virus in the body to increase to a level where clinical signs are apparent. Stress can cause this, as well as exposure to an animal that has a clinical level of infection or is shedding the disease without clinical signs.
The disease can be caused by exposure to an incoming horse or by a resident horse that is latently infected and has been stimulated by environmental stressors, such as transportation, herd dynamics, and environmental stressors. It is transmitted by direct or indirect contact with infectious nasal discharge (this includes airborne droplets), aborted fetuses, placentas, or placental fluids.
EHV-1 has an incubation period of three to seven days, meaning that signs of the disease generally show up three to seven days after the horse is exposed. Horses with EHV can remain infectious for up to 21 days post-infection.
The clinical signs of respiratory EHV-1 infection are similar to those you see in a case of influenza. They include fever, nasal discharge, possible cough, malaise, pharyngitis, swollen glands, and inappetance (the horse is off feed). Abortions can occur from nine to 120 days post-infection or reactivation of the virus. An aborted fetus appears normal, but the fetus and/or placenta and its fluids are full of virus. It is very common for horses with EHV to get a secondary bacterial infection since they are immunosuppressed, with bacteria such as Streptococcus zooepidemicus.
A global collaborative effort led to the discovery that a mutation within a single EHV-1 gene is associated with a higher risk of neurologic signs. The research groups were led by four scientists: the late George Allen, PhD, University of Kentucky Gluck Equine Research Center; Nicholas Davis Poynter, PhD, formerly of the Animal Health Trust in Newmarket, U.K., and now at Sir Albert Sakzewski Virus Research Centre in Queensland, Australia; Arianna Loregian, PhD, University of Padova, Italy; and Klaus Osterrieder, DVM, DVM Habilitation (equivalent to PhD), Cornell University and the Free University Berlin Institute of Virology.
Initially, detailed detective work compared variable gene sequences for a large panel of isolates and determined that a specific change in one of the genes was much more likely to occur in isolates from neurologic outbreaks. Subsequently, direct evidence that the "neurologic mutation" resulted in altered disease potential was obtained. Convincingly, Osterrieder's lab was able to take a non-neurologic equine herpesvirus isolate and genetically alter it to become the neurologic form and back again. Strains carrying the "neurologic mutation" are a very real threat.
Clinical signs for neurologic EHV-1 generally begin with a high fever followed by a six- to 10-day period of apparent recovery before the onset of fever and neurologic signs. Horses might not have evidence of typical respiratory signs. Some horses develop small hemorrhage areas on the mucous membranes and show edema (fluid swelling) in the limbs or abdomen.
Neurologic signs begin to develop when the virus reaches the lymphatic system and works its way through the circulatory system. There the virus causes damage to the blood vessels and cell death.
Neurologic signs vary, but the most common are hind limb weakness and ataxia (incoordination), which can progress to the point affected horses are unable to get up. Poor tail tone, urine leakage, and poor anal tone are signs that paralytic EHV-1 might be imminent. Horses that show instability or ataxia, but remain able to get up and down, have a good prognosis. Those that progress to recumbency for more than two days have a very poor prognosis.
Older horses are at a greater risk for the neurologic form of the disease.
Several diagnostic options are available to identify EHV-1 and EHV-4. Veterinarians can submit a nasal swab or wash or whole blood to their local diagnostic laboratory for culture. Several labs are now running a much more specific PCR (polymerase chain reaction) test that identifies live or dead virus at the DNA level. Some labs even offer a specific PCR that can identify the neurologic form of the disease.
The advent of PCR has helped labs accurately diagnose the disease. This has allowed clinicians to get ahead of the curve in managing outbreaks, as the test will show virus before clinical signs appear.
Nicola Pusterla, DVM, PhD, Dipl. ACVIM, an assistant professor in the Department of Medicine and Epidemiology at the University of California, Davis, is working on a new test to measure mRNA, which would allow the labs to distinguish active live infection from nonactive latent virus.
Current treatment for EHV is mostly palliative care, such as administration of fluids, anti-inflammatory medications, and making the horse comfortable.
There is some research in progress on a human antiviral medication called valacyclovir by Lara Maxwell, DVM, PhD, assistant professor of physiological sciences at Oklahoma State University.
"The results are encouraging on the clinical side of things," Maxwell says of the nearly complete Grayson-Jockey Club Research Foundation-funded study. "We are now conducting laboratory studies to corroborate the live animal (clinical) data." Although she was cautious in her statements, the clinical data indicated the drug was effective in reducing signs of infection.
One of the major problems researchers have faced in the study of equine herpesvirus, especially the neurologic form, is successfully reproducing the neurologic signs seen in a natural outbreak in a research setting. Maxwell used a model that was developed by Allen at the Gluck Center that used older mares as test subjects. Maxwell is happy to report, "Dr. George Allen's model worked well. Our data corroborated his findings, and I think it will be a great model for further research."
Maxwell has accessed expertise from sources at Oklahoma State as well as in Kentucky to ensure the study was done well. It was possible that results might be presented at the Havemeyer workshop on EHV in the fall of this year.
Maxwell noted that in the field valacyclovir has been used in some recent outbreaks, including one in Saskatoon, Canada. Anecdotal data from these outbreaks suggests it will be a valuable tool for treating all forms of this disease.
An immunomodulator product on the market, Zylexis (inactivated parapox ovis virus), has been shown safe and effective in reducing the severity and duration of clinical signs of EHV-1 and EHV-4 respiratory infections. It has been used in Germany for several years and became available in the United States in 2006.
The best defense for any infectious disease is a combination of practicing disease prevention strategies around the barn and keeping vaccinations current. The American Association of Equine Practitioners released its recommended vaccination guidelines earlier this year.
Minimize disease risks by making sure horses have adequate ventilation in the barn; a closed-up barn that isn't kept clean can be a breeding ground for bacteria and viruses. (See more on barn ventilation on page 26.)
Shared tack and water sources offer an easy way for horses to swap bacteria and viruses. A stringent disinfection plan will go far in reducing the incidence of disease. Respiratory diseases spread rapidly where lots of horses congregate, so splitting horses on a farm into multiple fields is a great strategy. Vets advise owners to quarantine new horses for two to three weeks. If a new horse is carrying an infectious disease, clinical signs should show up within that time. Keep pregnant mares away from incoming horse traffic or new additions to the resident population.
Research will be critical to understanding the disease better, and there are several studies under way. Paul Lunn, BVSc, PhD, MRCVS, Dipl. ACVIM, department head and professor of equine medicine in Colorado State University's Department of Clinical Sciences, and Osterrieder are examining the immunology of equine herpesvirus through a USDA-funded grant.
"Herpesviruses are masters of disguise," says Osterrieder. "They coevolve with their hosts and try to develop a commensal relationship (whereby one organism benefits from the other without damaging or benefiting it). In doing this they have developed techniques to avoid immune detection. We want to try to identify the molecular and biological mechanisms the virus is using (to hide) and integrate those techniques into our vaccines."
Vaccine development is an ongoing area of study as well. Osterrieder feels strongly that modified live vaccines are far superior to the existing killed vaccines for prevention. "That might change as we learn more, but for now, it is the best known technology out there," says Osterrieder.
He is working on a variety of vaccine options, including turning the actual equine herpesvirus into a vector for vaccination against other diseases (i.e., flu, strangles). The initial lab work is being accomplished quickly due to new technologies available. The biggest limiting factor is finding necessary funding to test these constructs.
A disease such as EHV is a challenge for researchers and drug companies. It is difficult to reproduce and has great variability in how severely it affects each horse. More research is needed to help vets and owners fight EHV, especially with the emergence of the neurologic strain, which is incapacitating and killing horses.
From a clinical and management perspective, Fairfield Bain, DVM, Dipl. ACVIM, ACVP, ACVECC, of Littleton Large Animal Clinic in Colorado, says, "The recent outbreaks of herpes have created a higher level of awareness of issues of biosecurity among the veterinary profession and within the horse industry."
As researchers discover more about how herpesviruses affect the immune system and how we can protect horses against them, the results could change how horses are managed. "Over time, some of this might change how we move and mix horses from different locations," Bain says.
About the Author
Liza Holland is a freelance writer and voice talent based in Lexington, Ky.
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