Logo Information und Hilfe

Demystifying Neurologic Herpes EHV-1

by: Equine Disease Quarterly April 16 2007 Article # 9378


Our attention has recently been captured by reports of numerous outbreaks of equine herpesvirus-1 (EHV-1) neurologic disease at racetracks, show venues, clinics, and boarding stables across the country. Questions about the neuropathogenic herpesvirus are the buzz of the industry. The intent here is to address several misconceptions about neurologic herpes in response to questions most frequently put to investigators at the Maxwell H. Gluck Equine Research Center.
The neuropathogenic strain of EHV-1 is not a "business-as-usual" equine herpesvirus. Although only a single, tiny mutation within its genome has been revealed by comparative DNA sequence analysis, that small genetic change has huge consequences for the virus's behavior in the horse. The fateful mutation has turned the microbe into one with enhanced replicative powers and as a consequence increased pathogenic potential. The mutant (neuropathogenic) strain of EHV-1 replicates to very high levels--tenfold higher than the wild type strain--in the upper respiratory tract, blood leukocytes, and vascular endothelium of the infected horse. Its pathogenic hallmark is a shift toward more severe morbidity and greater mortality. This is the result of ischemic damage to the horse's central nervous system ignited by a widespread and intense inflammation of virus-infected, blood vessel endothelium.
Because of its replication-facilitated increase in the level of nasal shedding, the mutant EHV-1 strain has also acquired the ability to spread more efficiently, another essential feature of epidemic strains of viruses. Other than its exaggerated replicative capacity, however, no additional attributes distinguish the mutant strain of EHV-1 from its wild-type parent. The two genetic strains of EHV-1 exhibit no known differences in their antigenic composition, susceptibility to disinfectants, or tropism for nervous tissue of the horse.
The horse has no hiding place from neurologic EHV-1! Circulating within the world's horse population at least since the time of its first isolation in 1966, neuropathogenic strains comprise 15% of the current biological reservoir of latent EHV-1. The mutation event has occurred on multiple occasions and in each of the six evolutionary branches of the virus. Recent surveillance studies at the University of Kentucky Livestock Disease Diagnostic Center indicate that approximately 6% of today's horses are latently infected with a neuropathic genotype of EHV-1. With such compelling statistics, it is apparent that there is no justification for culling or quarantining latent carriers of the mutant herpesvirus or for any differential treatment of survivors of EHV-1 neurologic disease.
More worrisome is that vaccination, the cornerstone for prevention of infectious diseases, offers little assistance for controlling outbreaks of neurologic EHV-1. Limited scientific evidence exists that any currently marketed vaccine for EHV-1 will provide significant protection against the neurologic manifestation of infection. None of the licensed products carries a label claim for efficacy in preventing central nervous system disease from infection by EHV-1. Efforts at further vaccine development for the disease are conceptually behind, and much catching up is required. Without an efficacious vaccine, an epidemic of EHV-1 paralytic disease could be a scary and potentially devastating scenario.
Furthermore, the most effective strategy for curtailing the spread of the neurologic herpesvirus and blunting its epidemic mortality--keeping horses minimally stressed and physically segregated--does not fit well into the densely populated, heavily intermingling, high-stress environments of racetracks, show events, training centers, or boarding/riding stables. And, finally, efforts at pharmaceutical intervention via antiviral treatment of neurologic herpes have shown little immediate promise. The unsettling consequence of such a triad of management failures (ineffective segregation, vaccination, and antiviral therapy) is that there is currently no foolproof method for either prevention or treatment of neurologic EHV-1, and its threat for disruption of large equestrian events is therefore likely to continue.
The only remaining weapon in our arsenal against infectious diseases is containment and elimination of the viral infection at its point of origin by the practices of isolation, quarantine, and testing. This containment effort will be facilitated by a recent, novel test procedure for rapid identification of horses infected with the neuropathogenic strain of EHV-1. However, random application of the PCR diagnostic procedure to test for the presence of neuropathogenic EHV-1 DNA in the blood of asymptomatic horses not associated with an ongoing disease outbreak represents an inappropriate use of the procedure. The precise interpretation of positive test results in such instances would not be possible due to issues of latency, silent reactivation, residual dead virus, vaccination, etc.
Overall, the prevailing situation with neurologic EHV-1 highlights the importance for all facilities in which large numbers of horses of diverse origin congregate for purposes of shows, racing, training, sales, etc., to have established and well-rehearsed plans as well as the necessary physical facilities for
1. defining the requirements for entry of horses into the facility,
2. temporary isolation of new arrivals during an observation period,
3. rapid infectious disease control responses in the face of an EHV-1 neurologic outbreak.
Useful information on the establishment of such contingency plans can be found at the following Web sites (pdf files):
Contact: Dr. George Allen, 859/257-4757, gallen@uky.edu, Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky.

This is an excerpt from Equine Disease Quarterly , funded by underwriters at Lloyd's, London, brokers, and their Kentucky agents.

Prof. Osterrieder 2005 in einem Zeitungsbericht über die vermutete Mutation:

Cornell Research on Herpesvirus Vaccines
by: Kimberly S. Herbert, Editor
May 2005 Article # 5810

A presentation on recent research into herpesvirus type 1 (EHV-1) vaccines was given by Klaus Osterrieder, DVM, DVM Habilitation (a German equivalent to a PhD), associate professor of virology in the College of Veterinary Medicine at Cornell the evening of March 26 in Lexington, Ky. His discussion was on EHV-1, Thoughts About the Virus, the Disease, and Ways of Prevention. Osterrieder asked the question of his audience: Why do a pedestrian vaccination study using a vaccine that has been around since the 1960s? His answer: Because there was Findlay and because we appear to see the neurological disease more often. An outbreak of neurologic EHV-1 at the University of Findlay in Ohio in early 2004 was discussed at a meeting in Italy that Osterrieder attended. At that meeting, researchers from The Ohio State University discussed the outbreak, including detailing the severity and type of neurologic signs based on how the horses had been vaccinated.

Osterrieder, who also studies herpesviruses in other species, understands that modified live vaccines work well against this virus. The Ohio numbers suggested that the few horses vaccinated with the modified live vaccine (Rhinomune) were protected or had less severe clinical signs than horses vaccinated with killed vaccines. The Ohio researchers also noted that horses vaccinated with killed vaccines multiple times were more likely to have more severe clinical signs. He hypothesized that maybe we are vaccinating horses too often against EHV-1, and possibly we are using the wrong vaccine.

Osterrieder used virus from the Findlay outbreak to challenge horses in a vaccination trial earlier this year. He took 15 horses, stressed them with shipping, and they did not develop herpesvirus viremia. Satisfied he would not have horses develop disease they were carrying (reactivation), he vaccinated five with the modified live vaccine (Rhinomune), five with a killed virus vaccine, and used five as controls. He vaccinated horses on Days 21 and 55 of the study, then exposed them to the Findlay EHV-1 virus through aeorsolization with a face mask four weeks later. Osterrieder and his colleagues recorded temperature, respiratory and heart rates, and took daily nasal swabs for 14 days after the challenge. They also took blood samples for testing viral and antibody levels.

He said after the challenge, physical parameters showed some animals in the group vaccinated with the killed vaccine increased considerably, indicating to him that replication of the virus was going on in the horses. He said there was also indication of viral replication in the animals vaccinated with the modified live vaccine, but antibody titers went down after 14 days, while antibody titers in the other groups stayed high. He noted that the day after the challenge, for example, rectal temperatures showed a spike in fever in all groups. However, on the second, third and seventh there was a statistical difference between the horses vaccinated with the modified live vaccine and the other two groups.

He also said that he could repeatedly isolate virus from nasal secretions from horses vaccinated with the killed virus or the control group, but only had one virus isolation from one horse on one day from the group vaccinated with the modified live virus vaccine. "There was much less nasal shedding with the modified live vaccine," Osterrieder said. He reminded the group that he and his colleagues didn't know which horses had been vaccinated with what at the time of the experiment. He said that there was reduced tail tone and reduced anal tone in some animals (controls or vaccinated with the killed vaccine). "Two horses, one in the control group and one in the inactivated (killed vaccine) group showed signs of subtle ataxia (incoordination) on circling," he noted. "They couldn’t step over themselves (faulty proprioception, or knowing where the feet are being placed), and they would show weakness in hind limbs if they were circled hard." In other parameters, the heart rates in the controls were consistently higher than in the vaccinated groups after challenge, but it wasn't statistically significant. The respiratory rates were very high the first couple of days following challenge horses in the modified live vaccinated group "did better" than the other horses. What have we learned and what needs to be done? asked Osterrieder. "In my opinion, we should rely more on modified live vaccines," he said. "Don't be afraid of them." He added that while we probably will not be able to protect against all EHV-1 infection, we can combat it. "This is not a perfect vaccine," he said. "We still have a lot of work to do.

We need to answer the question of whether the viruses mutate during reactivation or whether there truly are there two different types of viruses out there? "Immunity against EHV-1 is relatively short-lived," he added. "However, the choice of the right vaccine will determine sustained success. Even after natural infection the horse's immune system can't counteract all the tricks the virus has, so we need to build a vaccine to outsmart the tricks the virus has. "The only way to prevent this disease is through reasonable vaccination," he reminded.

Osterrieder said there is no problem in distinguishing between "wild" type EHV-1 and that use in a modified live vaccine. And to his knowledge, there have been no major problems caused by modified live vaccines. He referred to two studies that were done in Germany some 10-15 years ago. A question from the audience asked if he would recommend using the modified live vaccine in the face of an outbreak. Osterrieder said all the vaccines on the market are labeled for prophylaxis against EHV-1. "In my opinion, the best you can do is vaccinate with a modified live vaccine. In the end the vet and the horse owner have to make the decision whether they want to apply the vaccine in such a situation. It has been used in the face of an outbreak in Europe, and anecdotally the ones vaccinated with the modified live didn’t get sick." Another question from the audience stated: If you had a horse in Kentucky, what would you do to protect it? "I would go for a modified live virus vaccine," Osterrieder said. "What about a pregnant mare?" asked another audience member. "It has been proven safe and its labeled for use in pregnant mares," Osterrieder said. "It has been used in Europe more than it has here. Given it is the same virus (used to make the vaccine), again I would go for the modified live vaccine."

Another question asked in outbreaks with high numbers of animals affected, why does it happen? Is it a more potent virus or are the animals more susceptible? "That's the million dollar question," said Osterrieder. "There seems to be an abortion-only and an abortion plus neurologic type that needs to be corroborated. To be naive is bad, but to vaccinate too often is apparently not advisable!" This presentation was sponsored by Pfizer, the pharmaceutical company who manufacturers Rhinomune, the only approved modified live vaccine for prevention of EHV-1. Pfizer, among other groups, had given Osterrieder an unconditional grant for study of herpesviruses and protection against them in horses. (Ende)


aktualisiert 6.5.07


Über uns | Datenschutz | Impressum | Sitemap| © 2007 C. Schmedt