Equine Herpes virus: questions and answers Hal Schott, DVM, PhD, DACVIM Department of Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, MI 48824 What diseases equine herpes viruses cause? There are four herpes viruses that can cause disease in horses. Equine herpes virus 1 (EHV-1) causes respiratory disease, abortion, and occasionally neurological disease. Equine herpes virus 2 (EHV-2) is a relatively innocuous virus that has been implicated in outbreaks of mild rhinitis (nasal inflammation) and conjunctivitis (inflammation of the pink tissues around the eye). Equine herpes virus 3 (EHV-3) is the venereal form of the virus and causes lesions in breeding stallions and mares. Equine herpes virus 4 (EHV-4) also causes respiratory disease and, less commonly, abortion. What herpes viruses are most important in young racehorses? EHV-1 and EHV-4 are the herpes viruses of greatest concern in young performance horses. Both most commonly cause rhinopneumonitis, a combination of signs of both upper and lower respiratory tract disease, including fever, mild depression, decreased appetite, watery nasal discharge, and development of a cough later in the course of disease. It is important to emphasize that these clinical signs are not specific for EHV-1 or EHV-4 because infection with equine influenza virus or a number of other viruses can cause identical clinical signs of disease. EHV-1 occasionally also results in outbreaks of neurological disease, usually 1-4 weeks after initial signs of rhinopneumonitis. What is the difference between EHV-1 and EHV-4? In the past, these two herpes viruses were classified as subtypes of EHV-1 but subsequent studies of their genetic makeup showed enough differences to classify them as different herpes viruses. Practically, the most important difference between EHV-1 and EHV-4 is the degree to which they invade the horse’s body beyond the respiratory tract. EHV-4 infections are mostly limited to the respiratory tract although they can occasionally extend further and, rarely, infect the placenta and developing fetus in pregnant mares and lead to abortion. EHV-1 also primarily affects the respiratory tract but is accompanied by a greater degree of viremia, circulation of virus particles through the bloodstream, than with infection with EHV-4. This greater viremia allows EHV-1 to be more invasive to other tissues, including the placenta (leading to abortion or birth of a weak foal) and the central nervous system (causing neurological disease in some affected horses). How do herpes viruses differ from other viruses? Herpes viruses are somewhat unique in that they are among a few types of viruses that result in lifelong infection of the host. The saying “herpes is forever” is often used to emphasize this point. However, despite persistence of the infection, clinical signs of rhinopneumonitis are only transient. As the affected patient recovers, herpes viruses become latent. In other words, they persist by hiding out in certain lymphoid tissues and ganglia of the nervous system. With stressful events or the normal immunosuppression that accompanies pregnancy, herpes viruses can recrudesce or become reactivated. This can lead to another round of viremia and the potential for placental and fetal infection in the pregnant mare. Despite reactivation of the herpes virus, clinical signs of respiratory disease in adult mares are largely absent. This is because most horses are infected with EHV-1 and EHV-4 in the first year or two of life. These initial infections cause typical signs of viral respiratory disease, including fever, mild depression, nasal discharge, and coughing. However, once a horse has had two or three bouts of rhinopneumonitis, subsequent infection with a similar strain of EHV-1 or EHV-4 or recrudescence of a latent EHV-1 or EHV-4 rarely produces clinical signs. However, affected horses are actively shedding the virus during this time and can be a source of infection to other horses. How common is infection with EHV-1 and EHV-4? Infection with EHV-1 and EHV-4 is widespread in young horses, especially those that travel frequently and intermingle with other young horses. It has been estimated that 50-75% of horses that are 2-years-old or less have likely been infected at least once with EHV-1 and/or EHV-4. Thus, infection with these two viruses is one of the most common causes of respiratory disease in weanlings through young racehorses. How are EHV-1 and EHV-4 spread between horses? Both EHV-1 and EHV-4 are most commonly spread between horses by aerosol transmission from an infected horse to surrounding naïve horses. There are large numbers of infective viral particles in each drop of nasal secretions from an infected horse but, more important than direct contact between horses, is dissemination of virus in clouds of aerosol vapor from a coughing horse. The latter aerosol cloud can potentially travel 50 to 100 feet from the nose of an infected horse to its surrounding neighbors. Although of less important in respiratory disease outbreaks with coughing horses, transfer of virus on animal caretakers’ hands and clothing, as well as on inanimate objects such as shared grooming and feeding utensils, can also be important in transmitting disease, especially between groups of horses housed a barn or more away from coughing horses. It cannot be overemphasized that simple preventive measures including hand washing and limiting traffic flow (of people and horses) and use of shared equipment can dramatically reduce the potential for spread of disease in potential outbreaks. How long do horses shed EHV-1 and EHV-4? Most horses that are infected with these viruses will shed the virus from the onset of clinical signs (or even a day or two before) to between 1-2 weeks after clinical signs have resolved. This results in a typical viral shedding period of 1-3 weeks, depending on the severity of the infection and clinical signs. However, it is important to recognize that horses that are not sick can also shed the virus for one to two weeks when they are experiencing a subclinical infection (infection without clinical signs) or a recrudescence of a latent infection. Because the majority of horses infected with EHV-1 or EHV-4 only shed virus for 1-2 weeks following cessation of clinical signs, a 21-day quarantine period, following recovery of the last clinical case, has commonly been used during outbreaks of neurological disease. Although this is generally considered an appropriate period of quarantine, it is important to recognize that not all outbreaks are the same and that an occasional horse could actually shed virus for a longer period of time. How are EHV-1 and EHV-4 infections diagnosed? The first requirement for diagnosis of EHV-1 or EHV-4 as a cause of respiratory disease is the presence of clinical signs of rhinopneumonitis. The clinical signs of disease usually develop between 3 and 7 days (incubation period) after exposure to an infected horse. Duration of clinical signs of disease may be as short as 1-2 days or can last as long as 1-2 weeks. Typically, affected horses can recover without any treatment although phenylbutazone or BanamineTM is often given to horses with high fevers. Increased concern, and further evaluation and treatment by a veterinarian, is warranted if fever lasts longer than a couple of days or returns after a few days as these more severe cases may be complicated by a secondary bacterial pneumonia (typically due to proliferation of Streptococcal spp. bacteria in the lungs). To document that EHV-1 or EHV-4, rather than equine influenza or another virus, as the cause of disease, several tests can be pursued. Classically, swabs of the nasopharynx (back of the throat) and buffy coat samples (portion of a centrifuged blood sample rich in white blood cells) were used in an attempt to infect thin layers of healthy cells grown in Petri dishes. This test is referred to as cell culture and has the advantage of recovering live virus from infected horses. However, cell culture techniques are somewhat labor intense and require presence of an ongoing source of living cells for cell culture by the testing laboratory. More importantly, cell culture requires 7-10 days to complete and has a relatively low sensitivity to detect infection. This means that a number of infected horses that may have only low numbers of live virus circulating in blood or being shed onto the nasopharyngeal swab may not be detected with this test (false negative results). Measuring the amount (or titer) of antibodies in blood samples has been another traditional test to determine which virus may be causing clinical signs of respiratory diseases. An increase in the antibody titer from the onset of disease (acute sample) through the recovery period (convalescent sample collected 10-14 days later) provides evidence that the virus was the cause of clinical disease. The major problem with this test is that the answer is not available until long after the horse has already recovered from the infection. Thus, this type of testing, termed viral serology, is rarely pursued because it will have little benefit for treating the individual horse. Viral serology is of greater use in documenting the cause of outbreaks of viral respiratory disease in groups of horses with the goal of implementing or modifying preventive medicine programs in an attempt to decrease the risk of similar disease outbreaks in the future. What is PCR testing for EHV-1 and EHV-4? Recently, a new test based on the polymerase chain reaction (PCR) has been introduced for the diagnosis of a number of infectious diseases of horses. The test is also performed on the buffy coat of centrifuged blood samples or on nasopharyngeal swabs for detection of EHV-1 and EHV-4. PCR testing amplifies, or makes a large number of copies, specific portions of the genetic material of the infectious agent. After enough copies are made, the genetic material can then be detected. The advantages of PCR testing are that results can be obtained within 48-72 hours of sample submission and the test results can distinguish between EHV-1 and EHV-4. The disadvantage is that the test does not discriminate between genetic material from dead or live viruses that may be recovered from the patient. Although the test is more sensitive at detecting EHV-1 and EHV-4 than cell culture, no test is ever 100%. Thus, false negative test results can be obtained from horses that may be shedding only small amounts of virus or that may shed the virus intermittently. Further, at present PCR testing does not distinguish between strains of viruses, especially strains of EHV-1 that may cause abortion or neurological disease. What do some strains of EHV-1 have the potential to cause neurological disease? This is one of those $64,000 questions. There has been concern over the past few years that outbreaks of EHV-1 associated neurological disease (a.k.a. herpes virus myelitis) are on the increase. Whether this is true or not is uncertain but what is clear is that the publicity of these outbreaks has been more widespread and that more than one of the outbreaks has involved large numbers of horses. Preliminary information from analysis of EHV-1 strains collected from several of these recent outbreaks of EHV-1 associated neurological disease suggests that the EHV-1 strains causing neurological disease may have a mutation that allows more rapid proliferation of the virus in the host. In addition to a greater level of viremia, these EHV-1 strains appear to preferentially attack endothelial cells, cells lining blood vessels, in the central nervous system. It is important to emphasize that these are preliminary research findings and more information is needed before we can better understand why certain strains of EHV-1 may be predisposed for attacking the spinal cord. How is a diagnosis of EHV-1 myelitis definitively established? The presence of neurological disease is clearly a requisite for diagnosis of EHV-1 myelitis. However, because there are other more common causes of neurological disease in young horses, including cervical spinal cord compression (Wobbler syndrome) and equine protozoal myelitis, additional diagnostic test results are necessary to confirm the diagnsosis. Currently, PCR testing is being used as the supporting test for initial diagnosis of EHV-1 myelitis in affected horses. As mentioned above, this test is not always 100% but detection of positive PCR results from a nasopharyngeal swab or blood sample collected from a horse with neurological disease should be considered adequate to establish the diagnosis in a suspected patient and for implementation of control policies. The most definitive diagnostic test is a necropsy examination during which the spinal tissue can be examined microscopically. Unfortunately, that test can only be performed in horses that fail to survive. Is neurological disease due to EHV-1 infection invariably fatal? No. Typically, the majority of horses suffering from EHV-1 myelitis recover over a period of several weeks. However, there may be mild to moderate neurological deficits that can persist for months to years following onset of disease. Thus, the prognosis for affected horses is usually guarded and substantial nursing care may be required during the first few weeks of disease. The prognosis is generally poorer for horses that become recumbent and unable to rise and the cost of saving these more severely affected horses increases substantially. Are horses with EHV-1 associated myelitis contagious? Until a couple of years ago, horses afflicted with equine herpes virus myelitis were not thought to shed the virus or be of contagious risk to their neighbors. However, experience in recent outbreaks has shown that horses with neurological disease can shed EHV-1 and do pose a risk to other horses. However, because horses with neurological disease are rarely coughing, caretakers and inanimate objects become a more important factor in transferring virus from horses with neurological disease to other horses. Do currently available EHV-1 vaccines protect against the neurological form of EHV-1? Again, this is a question for which there is no definite answer. However, the consensus opinion at present is that currently available vaccines are not protective against the neurological form of EHV-1. If it is true that the strains of EHV-1 that produce neurological disease have a similar mutation that allows them to proliferate more rapidly than the more common strains, it makes sense that such viruses could overpower any defenses induced by vaccination. What should we learn from the recent series of EHV-1 associated neurological disease at Northville Downs? It is important to realize that although the recent apparent outbreak of EHV-1 myelitis at Northville Downs was devastating for the affected horses, the problem could have been much more serious. Although communication and dissemination of information by all parties involved can always be improved and quarantines can be more strictly followed and monitored, responses in this outbreak appear to have been largely effective in stopping a problem that could have affected many more horses and had a much more detrimental effect on Michigan’s Standardbred racing industry. But it is not necessarily time for a pat on the back for all parties involved. Rather, it is time to plan for potential future problems and to develop response policies that all parties involved can agree upon before another potentially serious disease outbreak is faced. Whether we are traveling on an airplane or attending a major public event, concerns about security are on the increase. The racing industry of Michigan is no exception. If we step back and think about it, racetracks are not much different than equine airports. A large number of potentially susceptible horses are brought together nearly every race day and it is somewhat surprising that disease outbreaks are not a bigger problem. At the least, it should be our common goal to recognize the risks facing the industry and to progressively focus increased attention on biosecurity. It is clear that going to a racetrack will never be 100% safe for a young horse in terms of exposure to contagious disease, just as traveling on an airplane will never be 100% safe. However, simple steps including making sure that horses are appropriately identified and housed where they are supposed to be is of obvious importance. Similarly, when problems arise, quarantines will need to be implemented in a timely manner and all aspects of the quarantine clearly followed by all personnel involved. Appropriate recognition of diseases early in the course of an outbreak and institution of appropriate response measures will ultimately lead to a healthier horse population and industry as a whole.