Edited by Dr. Bill Wigle, ADDL Pathologist
A recent outbreak of equine herpesvirus-1 (EHV-1) in the western United States has prompted renewed public interest in this virus. Several horses competing at a Utah horse show became ill and one horse was eventually euthanized due to severe neurologic signs. Cases of EHV-1 infection have since been confirmed in multiple western states. This outbreak has incited concerns regarding increased prevalence and virulence of EHV-1. Due to widespread media coverage, equine practitioners will be faced with an increasing number of questions from concerned horse owners and should be well-versed in the manifestations of EHV-1 and its prevention.
EHV-1 infection results in several distinct clinical syndromes. Young horses less than two years of age develop mild rhinopneumonitis. EHV-1 infection causes late-term abortion in pregnant mares, death of neonatal foals and equine herpesvirus-1 associated myeloencephalopathy (EHM) in adult horses. Animal loss, disruption of training, travel restrictions, event cancellations and facility quarantines all contribute to the profound economic impact of the virus.
Epidemiology
Estimates of EHV-1 seroprevalence in the United States are greater than 60%, although geographic region and testing methodology significantly affect prevalence estimates. Most infected horses are asymptomatic. Transmission occurs in the first months of life primarily via inhalation of aerosolized respiratory secretions. Alternative routes of transmission include direct contact with infected animals or contact with an aborted fetus or placenta.
As with other herpesviruses, latency established in the trigeminal ganglion and lymphoreticular system plays a crucial role in the epidemiology of EHV-1. Subclinical shedding does not appear to occur at significant levels and infection is typically associated with exposure to an animal with clinically apparent disease. Latently infected mares, however, may be able to transmit the virus to their offspring.
EHV-1 infections are associated with late fall, winter and spring. The age of a horse influences the disease presentation. Younger horses are more likely to exhibit mild respiratory disease. Several factors have been associated with development of neurologic manifestations of EHV-1 infection. Older horses, horses with high initial temperatures or those infected with the D752 biovar of EHV-1 are more likely to develop EHM. Protection conferred by prior infection is limited to 3-6 months duration.
Pathogenesis
EHV-1 replicates in the epithelium of the upper respiratory tract, followed by dissemination to local lymph nodes within 24 hours. Virus is shed in nasal secretions for as long as two weeks. Infection of T-lymphocytes and monocytes facilitates systemic distribution and ensures viral protection from humoral immunity. The intracellular localization of virus is consistent with the limited efficacy of vaccination. Viremia appears to be a necessary precursor to development of EHM or abortion. EHV-1 is endotheliotropic and epitheliotropic. Infection is established in CNS endothelial cells and uterine vasculature.
Once established in a tissue, whether in CNS, uterus or lungs, a vasculitis is induced either through viral cytotoxic effects or immune-mediated damage. Inflammation results in thrombo-occlusive necrotizing vasculitis. Ischemic necrosis of the affected tissue is a common sequela. Endometrial arterioles at the base of microcotyledons are affected in cases of abortion. Foals typically die of respiratory failure secondary to placental separation. Spinal cord and brain stem are similarly affected in EHM.
Latency is established in T-lymphocytes and trigeminal ganglia. Periods of stress may be associated with re-activation of the virus. Experimental models of corticosteroid-induced recrudescence have been successful.
Clinical Signs
Herpesvirus rhinopneumonitis in young horses is characterized by biphasic fever, lethargy, anorexia, cough and serous to mucopurulent nasal discharge. Conjunctivitis, lymphadenopathy and distal limb edema are also observed.
EHV-1 induced abortion is associated with sudden fetal loss in the last four months of pregnancy. The fetus is minimally autolyzed. The placenta may be enlarged and edematous or normal.
Indiana’s Animal Disease Diagnostic Laboratory (ADDL) currently offers virus isolation, real time PCR, virus neutralization and fluorescent antibody testing for diagnosis of EHV-1. See their website www.addl.purdue.edu for further information regarding sample submission.
Pathologic Lesions
Lesions associated with EHV-1 infection vary with the age of horse affected and corresponding clinical syndrome. Mild cases of EHV-1 induced myeloencephalopathy are characterized by small, multifocal hemorrhages of the meninges, spinal cord or brain. In more severe cases, larger malacic foci are evident in the brain or white matter of the spinal cord. Histologically, nonsuppurative necrotizing vasculitis and vascular thrombosis are observed. Vessels of the brain stem, spinal cord and meninges are most affected. Edema, hemorrhage and focal malacia are observed adjacent to affected vasculature.
Gross lesions of herpesvirus rhinopneumonitis include serous to suppurative rhinitis and conjunctivitis. Although rare, a necrotizing enterocolitis is also occasionally observed in adult horses with EHV-1 infection. Multifocal hemorrhage and ulceration of the small and large intestinal mucosa are observed grossly. Lesions in neonatal foals include bronchointerstitial pneumonia with intranuclear inclusion bodies along with multifocal necrosis of the spleen, liver and other tissues. The thymus may be reduced in size and edematous. Upon histopathologic examination, loss of cortical cells, subcapsular lymphocytolysis and cellular debris are observed.
Lesions in aborted fetuses are similar to those observed in neonatal foals. In addition, there is generally extensive subcutaneous edema, fluid accumulation within body cavities and severe pulmonary edema. Multifocal necrosis and petechial hemorrhage of the lungs, liver, spleen, kidney and upper respiratory mucosa is also noted. Histologically, eosinophilic intranuclear inclusion bodies are found surrounding areas of necrosis in the different organs. Mononuclear inflammatory cells in the parenchyma surrounding areas of necrosis and edema.
Prevention
Current vaccination and management protocols cannot prevent infection in very young horses, particularly those at large facilities. Although mucosal antibody production may play an important role in attenuation of viral shedding, the efficacy of vaccination in prevention of EHV-1 induced abortion or neurologic disease has not been clearly demonstrated.
Due to the absence of effective vaccination protocols, control of EHV-1 dissemination is of foremost importance. Pregnant mares should be isolated in small groups from other horses on a farm, particularly those animals that are new to the facility. All management stresses (e.g. nutrition, transportation, etc.) should be avoided. Foals should not be simultaneously weaned in large groups. In order to achieve maximal possible immunity, all animals in the facility should be vaccinated. In the event of an outbreak, isolation of affected horses and rigorous diagnostic testing should be pursued.