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What Horse Owners Should Know About EHV-1:


Contents:
                                                                   
     
horse icon    horse 2     horse icon     horse 2     horse icon     horse 2     horse icon



About the Viral Disease

Equine species (horse and donkeys) can be infected by 8 different types of herpesviruses, of these EHV-1 and EHV-4 are the most clinically relevant pathogens (3).  EHV-1 can cause respiratory disease, abortion and neurological disease in horses, and is endemic in horse populations around the world (3, 5).  EHV-1 is similar to EHV-4 in that both viral subtypes can cause respiratory disease, often referred to as rhinopneumonitis, but it is solely EHV-1 that causes abortion, paresis and neonatal foal death (3). In fact, at one point EHV-1 and EHV-4 where thought to be two subtypes of the same virus, namely EHV-1, until recent viral genomic fingerprinting made an official distinction between the two viruses and the diseases they cause (3).  Unfortunately, because of this previous confusion, there is alot of older information that does not make this distinction between EHV-1 and EHV-4. 

EHV-1 strains are grouped according to the type of disease they cause.  For instance, EHV-1 subtype 2 causes respiratory disease, while subtype 1 causes abortion (3).  The following discusses the three forms of disease caused by EHV-1.


Respiratory Disease:

The respiratory form affects mostly younger horses and is the most common manifestation of EHV-1 infection (6).  The respiratory disease caused by EHV-1 is similar but much more severe than that caused by EHV-4 (3).  This rhinopneumonitis, as is it sometimes referred to, develops due to bacterial colonization of the nasal passages (3).  The virus replicates in the upper respiratory tract epithelium and local lymph nodes, before it enters the bloodstream by attaching to leukocytes.  Horses tend to be repeatedly exposed and infected by the virus, but as they age the symptoms of disease become less severe (3)

Clinical signs include the following (3, 5, 6)
  • acute disease
  • fever of 102 - 105 °F (normal temperature range 99.2 - 101.4 °F
  • decreased circulating WBCs
  • mild serous or seromucous nasal discharge
  • cough
  • depression
  • nasal mucosa bright red and congested with blood
  • loss of appetite (anorexia)
  • conjunctivitis may be present
  • ocular discharge
                                                  
 horse 1

In most instances this is a mild illness, however some stressed or otherwise immunocompromised animals may go on to develop a secondary infection, such as a Strep or a Staph bacterial infection, leading to a much more serious and debilitating respiratory disease (5).  This is why it is important to call your veterinarian to assess your horse's situation. 

Diagnosis:

Your veterinarian can diagnose this respiratory viral infection based on clinical signs, serum antibodies to the virus, and virus isolation from nasal swabs (5)

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Abortion:

An EHV-1 infection outbreak can lead to abortion in non-vaccinated pregnant mares, which are sometimes referred to as "abortion storms" when herds of pregnant mares are affected simultaneously (6).
mare and foal
Mechanism of Abortion and Clinical Signs:   (5)

Aborted Fetus
Infected Fetus Born Alive (Perinatal Death):
animated horse                                                                                                                                                                                 
    horse
Diagnosis:
Your veterinarian may partially base his diagnosis on pathological findings in the aborted fetus.  The liver, lung, and lymph nodes of the fetus usually display the characteristic lesions of EHV-1 infection.  These lesions are generally more pronounced in fetuses aborted after the 6th month of gestation.  There may also be some evidence of the viral infection in the placenta.  For a more conclusive diagnosis, viral isolation is usually required and histological findings of inclusion bodies inside cells of the organs primarily affected by the virus (5)

Diagnosis is difficult in these foals that die 2 weeks after birth since the virus is hard to isolate and inclusion bodies are not as easily seen as in the aborted fetus.  Virus isolation, though difficult, is possible from the brain and spinal cord (5).  One way your veterinarian may try to make a more conclusive diagnosis is to test the mare's serum antibody level to EHV-1 by drawing a blood sample and sending it for serological testing.  A high serum antibody level can be indicative of a recent viral infection, and thus may help make the diagnosis.
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Neurological Disease:
The neurological form of EHV-1 infection is the least common manifestation of disease which can be referred to as equine herpesvirus myeloencephalopathy
(6).  This form of EHV-1 is in fact one of the new emerging diseases amongst equids. 

Clinical Signs: 

This disease occurs in mares, stallions and foals, and typically the horses affected are in areas where the respiratory or abortion forms have recently occured
(5).  The presenting signs include a variety of neurologic disorders, including loss of bladder innervation, leading to urinary incontinence and bladder distention, slight ataxia, toe-dragging, floppy tail, inability to defecate, limb weakness, posterior paralysis and incoordination, and even tetraparesis(5, 6).  The cranial nerves which innervate the facial muscles and conduct sensory information are usually unaffected.  Some horses progress to recumbency within 24hrs but do not seem to worsen after this (5, 6).

Diagnosis:
Pathological findings characterisitic of this rare disease form can help your veterinarian reach a diagnosis.  Some of the major gross lesions include congestion of the blood vessels within the central nervous system, hemorrage of the meninges, and focal areas of brain and spinal cord necrosis or tissue death
(5).  This virus affects primarily the small arterial blood vessels servicing the CNS, leading to vessel wall injury and blood clot formation.  The brain and spinal cord tissue fed by these necrotic blood vessels becomes depleted of blood, oxygen and nutrients, and hence also become necrotic.  This is similar to the pathogenesis of disease in the abortion form of viral infection, where the blood vessels servicing the placenta are affected in this way, leading to fetal death (5)

Horses showing neurological signs often have a rise in serum antibody levels to the virus concurrent with clinical signs, thus this may be useful in diagnosis the disease
(5)
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 animated horse                                                                                                                                                                              mare and foal
How, When and Where the Disease is Spread (Epidemiology): 
Equine herpesvirus outbreaks tend to affect primarily equine breeding facilities where there is a large number of horses in contact with one another, and where a large proportion of the equine population are young foals who in general have an immature immune system.  The virus is shed from infected hosts in nasal mucus discharges, which contaminate the environment
(3, 5).  EHV-1 infection then spreads rapidly amongst an equine herd by direct contact, aerosol transmission, and by ingestion of contaminated food or water (5).   During abortion epidemics, infected aborted fetuses may be another potential source of infection (3)

It is believed that the source of infection for the pregnant mares could be the infected weanlings and yearlings from previous breeding season
(5).  EHV-1 infection most likely occur early in life, where lactating mares are in fact the primary source of infection for suckling foals (3).  The foals, who can be infected with EHV-1 as early as 30 days of age, can then transmit the virus to other herd members (3).  Thus once a farm becomes infected, transmission may continue to occur within a herd from breeding season to breeding season without any new introduction of the viral pathogen (5).  Furthermore, reactivation of latent viral infection plays an epidemiological role in the occurence and spread of disease.  Previously infected mares may actually reactivate latent virus during pregnancy leading to subsequent abortion without any new infection occuring, though this has not been proven experimentally (3)Latency complicates the epidemiology of EHV-1, and research continues in this area.

infection cyclr

Outbreaks of the respiratory disease caused by EHV-1 tend to occur during the early winter season affecting primarily weanlings and yearlings on breeding farms and 2 and 3 year olds at race tracks
(5, 6).  These outbreaks are usually mild and unlike true influenza epidemics seen in the spring.

Abortion epidemics seem to occur in non-immune mares exposed to the virus during late fall or early winter when weanlings and yearlings are showing signs of respiratory disease.   At this time, the mares are generally in their 8th month of gestation when they are infected with the virus
(5).  Mares rarely show any symptoms of respiratory disease during the winter respiratory outbreaks or when they abort during late winter or early spring.  Furthermore, the mares tend not to show any rise in virus neutralizing antibody titers during the course of their infection and subsequent abortion (5).  Abortions occur without any warning signs, fetal membranes are expelled with the fetus, and mares generally do not develop any uterine infections or fertility problems thereafter (5).  Most abortions occur in the 9th to 11th month of gestation during the months of January to March.  The incubation period ranges widely, however most mares tend to abort 20 to 90 days post-infection (5)

Natural immunity to the EHV-1 may last 2 to 3 years, thus explaining why "abortion storms" tend to display 3 year cycles
(5).   However, some sources suggest that protection from natural infection may only last 3 to 6 months (1) .  Immunity may not however be solely dependent on serum virus neutralizing antibody titers, since it has been shown that abortion as well as respiratory disease can occur in animals despite high antibody levels, thus other factors may play a role in protection (5)

Latency:                                                                                                                                                               
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Recent research has shown that herpes viruses, namely those belonging to the subfamily Alphaherpesvirinae, are able to establish what is referred to as a latent infection (3).  Latency is an important feature of EHV-1 infection, pathogenesis and epidemiology, allowing the virus to survive and spread within the equine population.  Latency enables virus to reproduce disease and spread to new hosts a long time after the primary infection.  A latent EHV-1 can reside in tissues of the CNS (neuron cell bodies, specifically the trigeminal ganglia) and lymph system (leukocytes, more specifically lymphocytes) without causing any clinical symptoms of disease until the host is immunosuppressed; the virus is then reactivated, causing disease once again (1).  Spontaneous shedding of virus may occur following stressful events such as weaning, castration, relocation and illness (3).  Furthermore, reactivation of latent EHV-1 may be asymptomatic, and thus shedding of virus in nasal mucus may not be accompanied by clinical signs of disease (3).  Latency thus makes detection and elimination of EHV-1 infection and disease quite difficult. 

latency

How Infection causes Disease (Pathogenesis): 

The central lesion caused by equine herpesvirus type 1 responsible for the three types of conditions seen is an infection of endothelial cells, leading to vascular necrosis, thrombus formation and subsequent death to the tissues serviced by these blood vessels (ischemia) (3).  EHV-1 is an intracellular pathogen, requiring transport within macrophages
(5) or leukocytes (3) to travel in the blood and cause a viremia.  More recent research indicates that a leukocyte associated viraemia is more likely, supported by the fact that virus has been isolated from leukocytes (3).  Cell-associated viremia confers protection from the body's immune defenses and allows the virus to spread to endothelial cells lining blood vessels in the CNS and pregnant uterus, depending on the subtype infecting the host, leading to CNS signs or abortion respectively (3).

In order for the virus to cause a viremia and subsequent disease, it must first breach the body's defenses.  An antibody present on mucosal surfaces, IgA, is very important in protecting the nasopharyngeal mucosa of the horse's nasal and upper respiratory tract from viral invasion
(5).  IgA binds to viral antigens present on the surface of the virus, preventing it from penetrating the mucosa and entering the body (5).  Once mucosal surfaces are breached, the body must try to protect itself against the virus by producing other antibodies, such as IgG.  These serum antibodies (present in blood) begin to rise upon viral infection, and they try to neutralize the circulating viral particles (5).  It appears that once the virus has passed the nasalpharynx mucosa, the body must mount both a cellular and humoral response to protect itself from the virus (5).  The cellular response includes phagocytic cells such as macrophages, while the humoral response includes the above mentioned antibodies.  If the combined humoral and cellular immune response is unable to combate and neutralize the majority of viral antigens, then the virus is able to infect host cells, reproduce, and cause disease.      

Once the virus spreads and infects endometrial blood vessels, a vasculitis and subsequent thrombosis develop, leading to ischemic damage of placental tissues and finally abortion of the fetus (3).  In some instances, the virus may actually cross the uteroplacental barrier and cause abortion, or the there may be birth of a live but infected foal that dies a few days afterward (neonatal foal death)
(3).  The majority of abortions occur in the last trimester of pregnancy, but why mares show an increased susceptibility to viral infection at this last stage of gestation is unknown (3).  It has been proposed that perhaps some host factors, such as certain hormones released during pregnancy, may actually activate latently infected leukocytes

viraemia

Some strains of EHV-1 are able to impair the body's immune defenses by causing a leucopenia (decreased WBC count in circulating blood), and thus are termed immunosuppressive
(3).  This impairment of the body's defenses facilitates the virus' dissemination.
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horse running
Prevention and Vaccination: 
Vaccination:

Vaccination is the key to prevention of the respiratory disease of foals and abortions in mares due to EHV-1 infection
(6).  Unfortunately there is no vaccine available for the prevention of the neurological form of EHV-1 infection; some research actually suggests that the vaccine may predispose horses to neurological disease (6).  Currently available inactivated vaccines have reduced the occurence of abortion storms but individual animals remain susceptible to infection and disease (1).  The priority of current research is to develop an effective vaccine that stimulates the appropriate immune responses to confer effective protection from EHV-1 infection and disease (1).

In the past, an attenuated vaccine produced from hamsters was used by intranasal inoculation in mares producing immunity for approximatly 6 months.  However, since the vaccine could produce abortion in a very small percentage of mares, it's use was only recommended in endemic areas (5).  Vaccination was recommended twice per year, once in July and then October (5).  This vaccination program was designed to reduce the shedding by weanlings and yearlings during the winter and thus prevent the mares from being exposed to the virus.  This vaccine prevented the explosive abortion epidemics, however after vaccination horses needed to be isolated for 3 weeks since the vaccine virus was shed for this period of time (5).  As is the problem with many vaccines for EHV-1, it fails to address the impact of latent infection on equine abortion and infection of newborns.  To date the equine industry awaits a highly effective vaccine to be developed (5)
 
The focus of more recent research has been to assess the protective immune mechanisms elicited during a natural EHV-1 infection in order to develop a vaccine that produces the same responses and thus confers immunity (2, 3).  Recent studies have discovered that attenuated live EHV-1 vaccines do not elicit the proper protective immune reactions and thus give incomplete protection from the virus (3).  Most of the commercially available modified live or inactivated vaccines claim only protection from respiratory diseases due to EHV-1 and EHV-4, very few are labelled for protection against EHV-1 mediated abortion (3)One particular vaccine available in Europe must be administered during the 5th, 7th and 9th month of gestation to prevent EHV-1 abortion.  In fact some research shows that even the inactivated vaccines labelled for EHV-1 abortion fail to prevent abortion on subsequent viral challenge following vaccination (2).  Vaccine efficacy is difficult to accurately assess in trial studies because of complicating factors such as latency, previous EHV-1 exposure, age, and prior vaccination histories vary between individuals studied (1).

New research has developed a live vaccine EHV-1 deletion mutant similar to that available for bovine herpesvirus 1 (BHV-1)
(3).  This vaccine protects pregnant mares for up to 6 months after a single intranasal inoculation against EHV-1 respiratory disease, virus shedding in nasal discharges and abortion.  It is further able to protect suckling foals from EHV-1 infection by passage of maternal antibodies to the virus through the milk.  Where other vaccines such as the multidose inactivated vaccines have been unable to protect suckling foals in the past, this deletion mutant vaccine shows new promise in the fight to eliminate EHV-1 (3, 5).  Unfortunately, this vaccine is not yet commercially available. 

The ideal vaccine should prevent early infection of suckling foals as well as latency of infection in pregnant mares.  Suckling foals are considered to be an important reservoir for the transmission of EHV-1, and are thus the target for immunoprophylaxis
(3).  One way suckling foals can be protected from viral infection is through efficient colostral antibody transfer from the vaccinated dam (1).  By protecting foals from infection, and limiting latency from previous infection of dams, the spread of EHV-1 can be reduced and eventually the virus could be eliminated or at least its occurrence reduced within the equine population.  Unfortunately, due to limitations in present research and vaccine efficacy, immunoprophylaxis is not yet possible (3)

Management:
One of the most successful ways to prevent infection is to minimize contact with other horses, and isolate any horse returning home or any new horse brought to your facility, thus limiting potential for the virus to spread to other healthy horses
(6).  The virus can be shed for at least 14 days in various secretions (tears, nasal discharge, abortive fluids), and thus isolation should be for a period of 30 days (6).  Stress can cause previously infected horses to begin shedding the virus again and thus they are also a potential source of infection (6)

Treatment is non-specific, thus veterinarians must rely on supportive care such as IV fluids, bladder catheterization, and a quite low stress environment to manage the disease
(6).  There has however been some success in treatment with a human herpes infection drug, acyclovir (6).  Those horses that do survive, recover over a period of several months.  Those horse that do not progress to recumbency seem to completely recover.  However, once recumbent, treatment becomes more difficult and prognosis worsens, thus many are humanely euthanized.  For those recumbent animals that do survive, recovery is slow and some may not completely return to normal (ie they continue to have some degree of neurological defect) (6)

Commercially Available Vaccines For Control of Equine Abortion:

Vaccine
Manufacturer (market)
Vaccine components and Type
Protection Claim
Duvaxyn EHV-1,4 Fort Dodge (Europe) EHV-1 and EHV-4, inactivated Abortion and respiratory
Pnemabort K +1B Fort Dodge (USA) EHV-1, inactivated Abortion and respiratory disease
Prodigy Intervet (USA) EHV-1, inactivated Abortion


Virus Anatomy:
EHV-1 is a 1inear double stranded DNA viruse belonging to the herpes subfamily Alphaherpesvirinae (3).  It's DNA genome has the ability to code for up to 77 different proteins, whose expression plays a role in the disease produced.  Alphaherpesvirinae viruses characteristically produce a latent infection in sensory neurons, EHV-1 in particular is also able to produce latency in infected leukocytes.  There are 8 types of equine herpes virus that can infect horses, type 1 has been discussed here (3).

herpes virus

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