HORSETALK.CO.NZ — MAY 22, 2013 — The neurological form of equine herpes virus-1 (EHV-1) is a worrying disease for horse owners on several levels.
The death rate among infected horses is concerning enough, but the highly infectious nature of the virus and an apparent marked growth in the number of cases in recent year have scientists working overtime to find a vaccine and medications that will improve survival rates.
Outbreaks are costly for the horse industry. Quarantines and tracing efforts funded by authorities to prevent its spread amount to millions of dollars annually in the United States. Events are canceled to reduce the risk of spread and dozens of competition horses end up confined to their stalls or properties.
On top of that, nearly a third of horses that contract the neurological form die or are euthanized.
Scientists are piecing together the puzzle around a potentially fatal virus that is little different from the standard EHV-1 strain that usually causes little more than a cold.
Researchers at Cornell University in New York have found that a change in just one amino acid is the difference between the milder strain and the life-threatening neurological form, which is sometimes called the mutant or neuropathogenic strain.
Cornell microbiologists discovered that a single amino acid variation in an enzyme that is part of the DNA copying process of EHV-1 creates a different type of EHV-1, which causes the neurological disorders in horses. Both types of EHV-1 can cause abortions.
Although the mutant strain of EHV-1 is most frequently associated with neurological disease, the more common strain, sometimes referred to as the wild-type, has also been known to be associated with such cases.
The researchers postulate that herpes viruses tend to evolve toward strains that produce less disease, so they think that the more virulent neurological strain of EHV-1 is older than the milder type.
The horse herpes virus is closely related to the chickenpox virus in humans.
It lives in horses’ nostrils and is commonly spread by droplets in the air. Horses remain infected for life.
To date, nine EHVs have been identified worldwide.
Three of these — EHV-1, EHV-3, and EHV-4 — pose the most serious health risks for domesticated horses and can have significant economic impacts on the equine industry.
EHV-1 can cause four manifestations of disease in horses, including a neurological form, respiratory disease, abortion, and neonatal death.
EHV-3 causes a venereal disease called equine coital exanthema that affects the external genitalia.
EHV-4 causes a non-fatal upper respiratory tract disease in foals and is uncommonly associated with abortion and rarely with neurologic disease.
The neurologic form of EHV-1 causes what veterinarians call Equine Herpes Virus Myeloencephalopathy (EHM).
Neurological signs appear as a result of damage to blood vessels in the brain and spinal cord associated with EHV infection.
Infection with the milder form, known as the non-neuropathogenic strain, is common. By the age of two, nearly all horses have been infected with EHV-1.
Initial exposure generally occurs in foals from contact with their mothers, usually by respiratory shedding. Scientists are not entirely sure over what distance the virus can spread in this manner under typical horse management and environmental conditions.
It can also be spread indirectly through contact with physical objects contaminated with the virus, such as tack, rugs, water containers, feed buckets, people’s hands and clothing.
The incubation period for the disease may be as little as 24 hours, but is typically 4-6 days. It can be longer.
Respiratory disease caused by EHV-1 is most common in weaned foals and yearlings, often in autumn and winter. Older horses are more likely than younger ones to transmit the virus without showing signs of infection.
Normally, EHV-1 infection takes hold in the upper respiratory tract, causing a mild respiratory disorder. It can, however, infect deeper respiratory tissues and get into the blood stream, giving it a route to the uterus and nervous system, where abortion or neurological disease can result.
Cases of abortion triggered by the disease usually occur without warning, typically late in pregnancy – after eight months. Occasionally, abortion can be triggered as early as four months. EHV abortion can occur from two weeks to several months following infection.
As indicated, the neuropathogenic, or mutant, strain is associated with most of the neurologic cases identified.
The mutation appears to result in more rapid reproduction of the virus, resulting in higher levels of circulating virus in the bloodstream, causing more severe symptoms and leading to abortion and neurological disease.
Scientists have shown through testing that this mutation has been present in outbreaks throughout the world for at least 30 years.
Shedding of both forms of the EHV-1 virus by the respiratory route typically lasts for 7-10 days, but can persist much longer, possibly for three weeks or more. A 28-day isolation period is recommended after diagnosis.
After infection with EHV-1, the virus eventually becomes inactive in the horse’s body, setting up a carrier state that is life-long.
Carrier horses show no external signs of disease when the virus is inactive, or latent. They are capable of shedding virus, with or without clinical disease, particularly at times of stress, for the rest of their lives.
It is this ability to reside as a silent and persistent infection in horses which provides a reservoir of virus for continual transmission.
Authorities acknowledge the growing prevalence of EHV-1, saying it appears to meet the criteria of an emerging disease, in that the neurological form appears to be growing in severity.
The Animal and Plant Health Inspection Service (Aphis) of the US Department of Agriculture points out it is possible that the reporting of EHV-1 cases has increased, rather than an actual increase in the number and severity of cases. However, most researchers appear to agree there has been an increase in the number of cases involving neurological disease triggered by the mutant strain.
Symptoms from the neurological form include a fever, usually before the neurological signs. An affected horse is likely to show poor coordination, urine dribbling, loss of tail tone, hind limb weakness, and may lean against a wall to help maintain balance.
They are likely to be lethargic and may be unable to get up if they lie down.
A veterinarian who suspects the diseases will likely collect a nasal swab and/or take blood for testing.
Care for a horse extends to minimising the effects of the illness, in the hope that the horse will remain well enough to survive the infection. Treatments may include intravenous fluids or anti-inflammatory drugs. Antibiotics may be used to treat a secondary bacterial infection if one develops, but they will have no effect on the herpes infection itself.
Antiviral drugs have been used to treat some cases, but research is not entirely clear on their effectiveness, or what constitutes the ideal time to give them to an infected horse.
In the absence of a vaccine labelled as being able to prevent the neurological form, horse owners must minimise risk by adopting prudent biosecurity measures.
These include rigid quarantining of the sick animal until the risk of transmitting the infection has passed.
Any horse that has aborted or shown signs of fever, respiratory disease, or neurologic disease should be separated from healthy horses.
Ideally, sick horses should be moved into a separate building or paddock on the premises, or be taken to a veterinary hospital with an isolation facility.
Do not share equipment among horses on the property, given that the virus can be spread through contaminated objects such as water and feed buckets, even bridles.
It is important that people in contact with the horses use proper biosecurity measures.
They should wash their hands after handling one horse and before handling another. They should also change their clothes and footwear after working with a sick horse.
Ideally, a person caring for a sick horse should not work with healthy horses.
When this is not practical, healthy horses should be handled first and sick horses last.
Wearing gloves and using disinfectant to sanitize footwear can also help minimize the risk of people spreading the virus between animals.
Evidence indicates that the virus will typically remain capable of infecting a horse for probably less than seven days in most practical field situations, but in ideal conditions may persist for up to 35 days.
Vaccines exist to control the respiratory and abortion manifestations of EHV-1, but are not proven against the neurological form. Researchers are studying several existing vaccines to determine if they may offer some degree of protection against the neurological form, and new vaccines are also being assessed.
Aphis acknowledges that the increase in EHV-1 outbreaks is worrying, because they likely fit the criteria of a disease that is evolving and changing in virulence and behavior.
“In the case of neurologic EHV-1 in the US, the disease appears to be increasing in incidence, mortality and morbidity.
“While there has not been much field research on neurologic EHV-1, mainly due to the sporadic nature of outbreaks, the available data support the theory of disease emergence and are cause for concern.”
In the United States, reports of neurologic EHV-1 outbreaks were sporadic before 2003, with typically none or few outbreaks identified annually.
In 2005, seven outbreaks of neurologic EHV-1 were reported across five states. In 2006, the number of reported outbreaks grew to 11, involving eight states.
Outbreaks have continued to be a worrying problem since.
The number of reported outbreaks in the US has increased, and the numbers infected in an outbreak appear to be much higher than what was seen before 2001.
Beginning with the Ohio outbreak during January 2003 – during which more than 30 per cent of the 138 horses on the premises developed neurologic disease – the progression of the disease in a population, as well as in individual cases, has been seen to be much more rapid than in the past.
This disease behavior was also different to what was seen before 2001 in US outbreaks.
It remains unknown what factors are involved in the emergence and/or maintenance of the viral mutants.
It is also unclear what role the poor immune response to the mutated strain is playing in the outbreaks of recent years.
The factors involved in this emergence are not clear as yet, but several have been suggested. Animal movement appears to be associated with several outbreaks. Movement could result in introduction of the virus to a new population; it is also possible that transport stress plays a role in allowing the disease to express itself or re-emerge from the latent stage.
The role of vaccination is not clearly established. The disease has occurred in well-vaccinated animals. What the attack rate would have been had the population been unvaccinated is unknown. The disease has also occurred in equine populations where no vaccination has occurred.
It is likely that other factors may be playing a role.
Interest in the disease remains high. The economic impact is substantial, not only through horses lost to the disease, but the many costs associated with treatment, quarantines, cancelled events, and the inability of horses to compete.
An Aphis paper entitled Equine Herpesvirus Myeloencephalopathy: Mitigation Experiences, Lessons Learned, and Future Needs, noted that EHV was a focus of presentations at multiple equine industry and veterinary meetings in 2007, illustrating concern within the equine industry related to the disease.
Much remains to be learned about the disease, but clinicians largely agree there is ongoing need for critical evaluation of available literature, vaccine development and further research into the potential effectiveness of exisiting vaccines, and a faster test for detecting the disease that distinguishes between the neurological strain and the non-neurological strain.
They have also identified the need for more information on individual animal risk factors, transmission characteristics, latency studies, and prevention options. More research is also needed into the effectiveness of current treatment options.
A 2009 consensus statement from a panel of the American College of Veterinary Internal Medicine, published in the Journal of Veterinary Internal Medicine in 2009, laid out the challenges ahead.
“Our understanding of the features of EHV-1 is increasing, but there is more to learn before we can best address the challenges that this virus presents.
“In almost every area of this paper we repeatedly encounter limitations of our understanding, that depend principally on our lack of understanding of the pathogenesis of the diseases EHV-1 causes.
“The clear message is that future progress will be dependent on research into viral pathogenesis and epidemiology.”
So, what did they identify as risk factors?
- The presence of both EHV-1 and susceptible horses in the herd.
- The presence of an infected, shedding horse in the herd.
- Season: the majority of EHM outbreaks occur in late autumn, winter, and spring.
- Age is a factor in the development of clinical manifestations of EHM. EHM can occur in horses of all ages, and has been reported in weanlings, both naturally occurring and experimentally induced. However, in a large epidemiological study conducted in The Netherlands, EHM was largely restricted to horses over 3 years of age, and age 4 to 5 years was similarly associated with an increased risk of EHM in a recent large North American outbreak.
- Past exposure produces a limited period of protection from re-infection, of as little as 3 to 6 months, but there are no reports of horses repeatedly affected by EHM, although the rarity of the disease may be a contributing factor. It is rare for mares to suffer from EHV-1-mediated abortion in consecutive pregnancies.
- Pregnancy: Abortion can occur in mares of any age, although it is largely restricted to the last trimester of pregnancy.
- Rectal temperature: Horses with high fever and high fevers occurring several days after the initial onset of fever, are more likely to develop EHM.
- Introduction of horses to a herd is commonly reported before the development of EHV-1 outbreaks, and specifically before EHM outbreaks.
- Breed and sex were identified as risk factors for EHM in 1 epidemiological survey, with ponies and smaller breeds less commonly affected, and females more commonly affected. Geographical region appears to be associated with the development of EHM. For example, the authors found only one published report of this condition in Australia or New Zealand and, anecdotally, there have been only a very small number of cases recorded in those countries.
- Stress factors: Outbreaks of EHV-1 disease are anecdotally associated with stress factors, including weaning, commingling, transportation, and concurrent infections.
- Immunological status has been proposed to have an association with the development of EHM, specifically as a result of vaccination. However, the association between increased use of vaccines and development of EHM described in that study was completely confounded by the fact that vaccination frequency was greatest in older horses, and EHM was strongly associated with greater age. The association of increased age with EHM risk is reported in populations of horses in which vaccination is not practiced.
Professor Peter Timoney, of the Gluck Equine Research Center at the University of Kentucky and chairman of the Infectious Diseases of Horses Committee of the United States Animal Health Association, notes that the mutant strain that causes neurological disease has been identified among isolates of EHV-1 made before 2000.
“As the distribution of this virus mutant becomes more widespread in the equine population, the frequency and severity of outbreaks of EHM is likely to increase further unless measures to control its spread and occurrence of the disease can be developed.”
Based substantially on materials from the Animal and Plant Health Inspection Service of the US Department of Agriculture, and the consensus statement from a panel of the American College of Veterinary Internal Medicine published in the Journal of Veterinary Internal Medicine.
