Etiology and Epidemiology
Equine herpesvirus 1 (EHV-1) and equine herpesvirus 4 (EHV-4) comprise 2 antigenically distinct groups of viruses previously referred to as subtypes 1 and 2 of EHV-1. Both viruses are ubiquitous in horse populations worldwide and produce an acute febrile respiratory disease upon primary infection, characterized by rhinopharyngitis and tracheobronchitis. Outbreaks of respiratory disease occur annually among foals in areas with concentrated horse populations. Most of these outbreaks in weanlings are caused by strains of EHV-4. The age, seasonal, and geographic distributions vary and are determined by immune status and horse population. In individual horses, the outcome of exposure is determined by viral strain, immune status, pregnancy status, and possibly age. Infection of pregnant mares with EHV-4 rarely results in abortion.
Mares may abort several week to months after clinical or subclinical infection with EHV-1. The neurologic form of EHV-1 has demonstrated increasing morbidity and mortality in the documented outbreaks since 2000, and appears to be evolving in virulence and behavior. Therefore, the USDA has designated neuropathic EHV-1 as a potentially emerging disease. The natural reservoir of both EHV-1 and EHV-4 is the horse. Latent infections and carrier states occur with both virus types. Transmission occurs by direct or indirect contact with infectious nasal secretions, aborted fetuses, placentas, or placental fluids.
The incubation period of EHV is 2–10 days. Susceptible horses develop fever of 102–107°F (38.9–41.7°C), neutropenia and lymphopenia, serous nasal discharge, malaise, pharyngitis, cough, inappetence, and/or submandibular or retropharyngeal lymphadenopathy. Horses infected with EHV-1 strains often develop a diphasic fever, with cell-associated viremia coinciding with the second temperature peak. Secondary bacterial infections are common and manifest with mucopurulent nasal exudate and pulmonary disease. The infection is mild or inapparent in horses immunologically sensitized to the virus.
Mares that abort after EHV-1 infection seldom display premonitory signs. Abortions occur 2–12 wk after infection, usually between months 7 and 11 of gestation. Aborted fetuses are fresh or minimally autolyzed, and the placenta is expelled shortly after abortion. There is no evidence of damage to the mare's reproductive tract, and subsequent conception is unimpaired. Mares exposed late in gestation may not abort, but give birth to live foals with fulminating viral pneumonitis. Such foals are susceptible to secondary bacterial infections and usually die within hours or days.
Outbreaks with specific strains of EHV-1 infection result in neurologic disease (see Diseases of the Spinal Column and Cord). Clinical signs vary from mild incoordination and posterior paresis to severe posterior paralysis with recumbency, loss of bladder and tail function, and loss of skin sensation in the perineal and inguinal areas. In exceptional cases, the paralysis may progress to quadriplegia and death. Prognosis depends on severity of signs and the period of recumbency.
The pathogenetic mechanisms of EHV-1 and EHV-4 differ significantly. EHV-4 infection is restricted to respiratory tract epithelium and associated lymph nodes; EHV-1 strains have a predilection for vascular endothelium, especially the nasal mucosa, lungs, adrenal, thyroid, and CNS. EHV-1 gains access to peripheral tissues via cell-associated viremia, which may manifest as abortion or neurologic disease.
Gross lesions of viral rhinopneumonitis are hyperemia and ulceration of the respiratory epithelium, and multiple, tiny, plum-colored foci in the lungs. Histologically, there is evidence of inflammation, necrosis, and intranuclear inclusions in the respiratory epithelium and germinal centers of the associated lymph nodes. Lung lesions are characterized by neutrophilic infiltration of the terminal bronchioles, peribronchiolar and perivascular mononuclear cell infiltration, and serofibrinous exudate in the alveoli.
Typical lesions in EHV-1 abortion include interlobular lung edema and pleural fluid; multifocal areas of hepatic necrosis; petechiation of the myocardium, adrenal gland, and spleen; and thymic necrosis. Intranuclear inclusions are found in lung, liver, adrenal, and lymphoreticular tissues.
Horses with EHV-1-associated neurologic disease may have no gross lesions, or only minimal evidence of hemorrhage in the meninges, brain, and spinal cord parenchyma. Histologically, lesions are discrete and comprise vasculitis with endothelial cell damage and perivascular cuffing, thrombus formation and hemorrhage, and in advanced cases, areas of malacia. Lesions may occur at any level of the brain or spinal cord.
Equine viral rhinopneumonitis is difficult to clinically differentiate from equine influenza (see Equine Influenza), equine viral arteritis (see Equine Viral Arteritis), or other equine respiratory infections solely on the basis of clinical signs. Definitive diagnosis is determined by PCR or virus isolation from samples obtained via nasopharyngeal swab and citrated blood sample (buffy coat) early in the course of the infection.
In cases of suspected EHV-1 abortion, definitive diagnosis is based on PCR, virus isolation, and characteristic gross and microscopic lesions in the aborted fetus. Lung, liver, adrenal, and lymphoreticular tissues are productive sources of virus. Serologic testing of mares after abortion has little diagnostic value. Diagnosis of neuropathic EHV-1 is determined by real-time PCR on samples obtained from nasal secretions, CSF, or neural tissue to detect the specific strain of EHV-1. A presumptive diagnosis can be based on clinical signs and CSF analysis (xanthochromia, albuminocytologic dissociation). Necropsy reveals characteristic perivascular cuffing and hemorrhage in the CNS.
There is no specific treatment for EHV infection. Rest and nursing care are indicated to minimize secondary bacterial complications. Antipyretics are recommended for horses with a fever >104°F (40°C). Antibiotic therapy is instituted upon suspicion of secondary bacterial infection evidenced by purulent nasal discharge or pulmonary disease. Most foals infected prenatally with EHV-1 die shortly after birth despite intensive nursing and antimicrobial medication. If horses with neuropathic EHV-1 remain ambulatory or are recumbent for only 2–3 days, the prognosis is usually favorable. Valacyclovir (30 mg/kg, PO, bid) has shown promise in the treatment of affected horses and in prophylaxis during EHV-1 outbreaks. Intensive nursing care is necessary to avoid pulmonary congestion, pneumonia, ruptured bladder, or bowel atony. Recovery may be complete, but a small percentage of cases have neurologic sequelae.
Immunity after natural infection with either EHV-1 or EHV-4 involves a combination of humoral and cellular immunity. While little cross-protection occurs between virus types after primary infection of immunologically naive foals, significant cross-protection develops in horses after repeated infections with a particular virus type. Most horses are latently infected with EHV-1 and EHV-4. The infection remains dormant for most of the horse's life, although stress or immunosuppression may result in recrudescence of disease and shedding of infectious virus. Immunity to reinfection of the respiratory tract may persist for up to 3 mo, but multiple infections result in a level of immunity that prevents clinical signs of respiratory disease. Diminished resistance in pregnant mares allows cell-associated viremia, which may result in transplacental infection of the fetus.
For prevention and control of EHV-4- and EHV-1-related diseases, management practices that reduce viral spread are recommended. New horses (or those returning from other premises) should be isolated for 3–4 wk before commingling with resident horses, especially pregnant mares. Management-related stress-inducing circumstances should be avoided to prevent recrudescence of latent virus. Pregnant mares should be maintained in a group away from the weanlings, yearlings, and horses out of training. In an outbreak of respiratory disease or abortion, affected horses should be isolated and appropriate measures taken for disinfection of contaminated premises. No horse should leave the premises for 3 wk after recovery of the last clinical case.
Parenterally administered modified live vaccines are licensed in some countries but banned in others. A high-antigen load, inactivated EHV-1 vaccine is recommended to prevent EHV-1 abortion. Vaccine should be administered during mo 3, 5, 7, and 9 of pregnancy. Antigenic variation within each virus type means that available vaccines do not cover all strains to which horses can be exposed. Vaccination (EHV-4 and EHV-1) should begin when foals are 4–6 mo old and, depending on the vaccine used, a second and third dose given at 4- to 6-wk intervals. Booster vaccinations may be indicated as often as every 6 mo through maturity. Vaccination programs against herpesviruses should include all horses on the premises.
Infection by other Herpesviruses
Equine herpesvirus 2 (EHV-2) is ubiquitous in respiratory mucosa, conjunctiva, and WBC of normal horses of all ages. The pathogenic significance remains obscure. It has been suggested that EHV-2 is the cause of herpetic keratoconjunctivitis. Equine herpesvirus 3 (EHV-3) is the cause of equine coital exanthema (see Equine Coital Exanthema), a benign, progenital exanthematous disease.
Last full review/revision March 2012 by Bonnie R. Rush, DVM, MS, DACVIM