Equine Herpes Virus (EHV-1 and -4)
The presence of Equine Herpes Virus (EHV) has been brought to the public's attention over the last several years because of outbreaks that have occurred in the pleasure horse, race horse and most recently the sport horse worlds.
Historically, EHV has been important economically in the equine industry because it can cause abortions in mares, early neonatal death in foals, and respiratory disease in young horses. It can also sporadically cause myeloencephalopathy, a kind of neurologic disease, with hind limb weakness, decreased tail and anal tone, and urinary incontinence as the most common neurologic symptoms in the horse. Neurologic disease associated with EHV outbreaks generally occurs soon after abortion storms or after multiple horses with fevers and/or respiratory disease are identified. The classic presentation of an equine herpes virus outbreak is considered to be the identification of a neurologic horse in the presence of an ongoing respiratory disease outbreak, fevers of unknown origin, or abortion. However, recent research has demonstrated that most, if not all, horses have been exposed to herpes virus in the first year of their life, and sporadic shedding of the virus may occur in horses that demonstrate few if any clinical signs of being sick.
Some Basic Facts Regarding Equine Herpes Virus:
| * | EHV1 and EHV4 are considered enzootic (present throughout the equine population), and most horses are thought to have been infected through the respiratory tract in the first year of life. |
| * | The incubation period is 2 to 10 days; in rare instances the incubation period may last as long as 13 days. The incubation period represents the time from exposure to the development of clinical signs. |
| * | Resistance to re-infection by similar strains of the virus occurs after infection, but this resistance is transient and only lasts 3 to 4 months. |
| * | Subsequent infections produce mild disease, although viral shedding from the upper airway does occur. |
| * | The immune system often can not completely eliminate the infection, and therefore the horse may remain latently infected. This may result in recrudescence and shedding of the virus during stressful situations. |
Pathogenesis (How the Disease Develops):
| * | Natural infection occurs through inhalation or ingestion of the virus. |
| * | Transmission may occur from horse to horse contact and by people contacting horses that are shedding the virus and then interacting with other horses. Contaminated bridles, water buckets, and other tack or equipment can move the virus from horse to horse as well. |
| * | The virus rapidly replicates in the cells lining the upper airway, and in young horses the cells of the lungs may be more severely affected. |
| * | The virus also enters cells of the immune system (monocytes), lymph nodes of the upper airway, and possibly the trigeminal ganglion (a group of nerve cells in the head). |
| * | High numbers of virus in the system may allow the virus to leave the monocytes and invade the blood vessels of the central nervous system (brain and spinal cord) or the placenta (in pregnant mares). |
| * | Neurologic disease and abortion are caused by vasculitis (inflammation of blood vessels) that occurs from the virus invading and injuring the cells lining the blood vessels. |
| * | There are neuropathogenic and non-neuropathogenic strains of virus. The neuropathogenic strains are responsible or associated with most, if not all, of the neurologic cases identified. |
| * | The neuropathogenic viral strain is a mutated form that results in more rapid shedding of virus and higher levels of circulating virus (viremia) during infections. |
| * | Newer laboratory techniques have demonstrated that this mutation has been present in outbreaks throughout the world for at least 30 years. |
| * | Historically people have thought that horses previously infected that had high antibody titers may be more prone to the development of neurologic disease; this may or may not be true. |
Symptoms:
Many, if not all, clinical signs associated with herpes are not unique to horses with herpes virus. The most common clinical signs include fever, mild respiratory signs (cough and nasal discharge), and slight edema (swelling) of the lower limbs. These symptoms are associated with many other common problems that horses may encounter. Abortion and neurologic disease can also result from herpes virus infection; these, too, may be caused by other diseases in the horse. The following is a summary of the more common symptoms associated with EHV:
| * | Young horses (1 to 2 years of age) most commonly demonstrate respiratory disease during initial infections. |
| * | Foals can suffer severe respiratory disease and death. |
| * | Older horses may demonstrate few or very subtle symptoms. Many horses will not have a cough, but most horses will have a fever. However, this temperature elevation can be transient and may go unnoticed when rectal temperatures are not routinely measured. |
| * | Pregnant mares may suffer from abortion and therefore are vaccinated frequently during pregnancy. |
| * | Neurologic horses are not generally seen as isolated cases; they are typically identified in the presence of respiratory outbreaks, abortion storms or in barns that have a cluster of horses with elevated rectal temperatures secondary to EHV. |
| * | The most common neurologic signs are decreased tail and anal tone, hind limb weakness, decreased bladder tone, and the inability to urinate normally. However, the specific neurologic signs depend on where the vascular injury occurs. |
Diagnosis:
A presumptive diagnosis can be made by the veterinarian when a neurologic horse is identified in a group of horses that are experiencing fevers of unknown origin, abortions or respiratory disease. However, specific testing is required to confirm the cause.
Virus isolation techniques or serologic testing to identify blood antibody levels (titers) have been used. Virus isolation can be negative if the viral shedding period is missed when nasal swabs are performed. Serologic testing for antibodies requires that it is repeated in 7 to 21 days to demonstrate a 4-fold increase in the antibody levels and therefore an active infection.
Most recently, polymerase chain reaction (PCR) techniques have been developed that can distinguish the neuropathogenic and non-neuropathogenic forms of the virus from nasal swabs or blood samples. PCR has the ability to identify extremely low levels of viral DNA.
Treatment:
Treatment is directed at supportive care for the infected horse. Horses with only fevers may require minimal treatment such as non-steroidal anti-inflammatory agents (Banamine or Phenylbutazone) to control the fever.
| * | Some horses may be treated with anti-viral agents in an attempt to decrease the circulating numbers of virus and decrease the viral shedding. |
| * | The use of other agents such as intravenous DMSO and low-dose aspirin may reduce the degree of vasculitis (inflammation of the blood vessels), blood clot development, and neurologic signs that may develop. |
| * | Neurologic horses require supportive care directed at the area of weakness. The neurologic signs generally stabilize very rapidly, and as long as horses do not become recumbent (unable to stand) there is often complete recovery. |
| * | In order to prevent spread of the virus, it is generally recommended that infected and exposed horses be isolated for 21 days after the fever resolves. |
| * | Discuss a protocol to reduce the risk of herpes virus with your veterinarian. |
| * | Vaccines are very important in reducing the spread of EHV by reducing the viremia and shedding that occur in infected horses. Vaccines offer limited protection to the horse against infection because most horses are infected during their first year of life. |
| * | No vaccine is licensed to protect against the development of neurologic signs. |
| * | Different vaccine types are available, and an educated decision should be made after consultation with your veterinarian. |
| * | Vaccination frequency is best determined by your veterinarian and may differ depending on risk of exposure. Consideration should be given to the horse's own exposure risks from stabling, traveling, competing, and/or handlers, and the similar risks of other horses to which it may be exposed. |
Links:
UC-Davis School of Veterinary Medicine: A general discussion on EHV and testing http://www.vetmed.ucdavis.edu/ceh/topics.htm.
Review Article on the Prevention and Control of Equine Herpes Virus by George P. Allen, PhD at the Gluck Equine Research Center, University of Kentucky.
References:
Wilson WD, Pusterla N. Equine Herpesvirus 1 Myeloencephalopathy. In: Equine Internal Medicine. Eds: Reed SM, Bayly WM, Sellon DC. Saunders Philadelphia 2004, pp 617-628.
Reed SM, Toribio RE. Equine Herpesvirus 1& 4. Vet Clin Equine 20: 631-642, 2004.
The following information was provided by Dr. John Madigan, DVM, PhD. Dr. Madigan is a Professor of Medicine at the University of California-Davis School of Veterinary Medicine.
Diagnostic Testing for EHV-1
Your veterinarian can perform a nasal swab and blood collection and send it to a laboratory where an assay (real-time TaqMan® polymerase chain reaction, PCR) for neurological EHV-1 virus can be performed. Use of other tests may not be as reliable, based on the most recent scientific publications.
The University of California-Davis has two laboratories that are capable of performing diagnostic tests:
California Animal Health and Food Safety Laboratory
Submission forms and shipping requirements
(Click on "Standard Submission Form")
Lucy Whittier Molecular and Diagnostic Core Laboratory
Submission forms and information
Samples for EHV-1 testing should consist of nasal swabs and whole blood samples drawn in EDTA tubes.
The Gluck Equine Research Center in Lexington, Kentucky, is the OIE reference laboratory for EHV-1. Further information regarding EHV-1 can be obtained by clicking here.
Cautionary Note Regarding Diagnostic Testing
The California Animal Health and Food Safety Laboratory (CAHFS) offers two real-time PCR assays (qPCR) for the detection and differentiation of neuropathogenic Equine Herpesvirus-1 from non-neuropathogenic EHV-1. The assays developed by Dr. George Allen at the Gluck Equine Research Center, University of Kentucky, detect viral DNA and distinguish between the two strains by identifying the genetic difference located in the polymerase gene. Dr. Allen's work is described in Equine Veterinary Journal 3:252-257 (2006).
While these real-time PCR results indicate the presence or absence of viral DNA in the specimen tested, they do not predict clinical outcome.
Dr. Allen's work with experimentally infected foals suggests a five-fold higher risk of a horse developing neurological disease when infected with the form of EHV-1 containing the neuropathogenic marker. The real-time PCR testing can be performed on nasal-pharyngeal swabs, EDTA blood (buffy coat), or postmortem tissues. CAHFS will routinely perform both assays for all samples submitted for EHV-1 detection.
The Lucy Whittier Molecular and Diagnostic Core Laboratory also offers routine diagnostic testing for equine viral pathogens using real-time PCR technology.
The Whittier Laboratory offers a well-validated assay, which detects all strains of EHV-1 by targeting the glycoprotein gene. This assay detects the EHV-1 virus but does not differentiate between the various neurogenic strains or the EHV-1 abortion strain, which is considered to be less risk for neurological disease. The sub-differentiation of various strains will be possible in the near future, but until then the molecular detection of EHV-1 by real time PCR should be correlated with clinical presentation (abortion, pneumonia, myeloencephalopathy). For example, a neurological horse with fever and positive PCR has a strain of EHV-1 and should be treated as contagious with all handling guidelines followed.
The PCR assay is performed on either whole blood or nasal secretions in order to document viremia and nasal shedding, respectively.
Research groups have recently identified a region of variation in the genome of different EHV-1 strains that correlates directly with their ability to cause a more virulent form of neurologic disease. Current estimates for the neurogenic strains isolated from exposed horses that have this mutation range from 70 to 94%. In addition, the nonmutant strains of EHV-1 also have historically been implicated as a causative agent for neurological disease.
Currently, molecular assays to differentiate between neurogenic and non-neurogenic strains have been developed and used for research purposes only. While these assays are informative, we believe it is too early to use these types of assays in the diagnostic setting without additional validation. The assay we offer for all strains of EHV-1 will be our standard at this time.
Appropriate use of PCR Testing for EHV-1
Since EHV-1 is considered to be endemic within the horse population, random testing of normal horses for EHV-1 by PCR diagnostics can and likely will detect horses with nonreplicating (dead) viral DNA; latent, low-level, transient carriage of virus; or viral levels that are not sufficient to pose a significant risk for disease transmission. Until more research data regarding the pathogenesis and epidemiology of equine herpesvirus-1 myeloencephalopathy (EHM) is acquired, random testing of horses for the virus may very well result in interference with the free movement of horses and staging of their athletic competitions, which later may be demonstrated to have been unnecessary.
It must be understood that the positive predictive value of any medical diagnostic test is the relationship between those individuals who test positive to the number of those testing positive that actually develop clinically significant disease. Only if that relationship is very close does the diagnostic test have a high positive predictive value.
For example, with equine infectious anemia (EIA), the number of horses testing positive (Coggins test) matches very closely with those that are actively infected and so have clinical significance for transmission of disease. Thus, the Coggins test has a high positive predictive value. By contrast, with equine protozoal myeloencephalitis (EPM), there is a marked difference between the numbers of horses testing positive in the Western Blot test and those who actually exhibit symptoms of the disease. Consequently, it is well accepted that the Western Blot test has a low positive predictive value for EPM.
With our current outbreaks of EHV-1, the interpretation of the positive predictive value of the diagnostic technology employed and the "test result" obtained are problematic at this time. Even given the sophistication of our current molecular testing capabilities, the interpretation of PCR viral detection for EHV-1 should be done only in the context of the presenting clinical signs for disease in the horse being tested.
At this time the significance of a positive PCR in an asymptomatic horse is unknown, regardless of the test being employed or the laboratory performing the test. There is simply not sufficient information yet acquired to justify or recommend control measures or quarantine procedures for horses testing positive for EHV-1 in the absence of clinical signs of disease, unless they have had intimate contact with a known clinical case.
Horses with high fevers and/or clinical signs of coughing or mild nasal discharge, with or without neurologic symptoms, should be tested for EHV-1 by PCR diagnostics if other explanations for these signs of disease are not apparent. Detecting a positive PCR for EHV-1 in these circumstances may warrant some degree of patient isolation and limited movement of exposed horses.