| | Etiology and Epidemiology Equine herpesvirus 1 (EHV-1) and equine herpesvirus 4 (EHV-4) comprise two 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 weeks 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 are seen with both virus types. Transmission occurs by direct or indirect contact with infectious nasal secretions, aborted fetuses, placentas, or placental fluids. Clinical Findings 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 biphasic 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. Lesions: 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 develop cell-associated viremia and have a predilection for vascular endothelium, especially the nasal mucosa, lungs, placenta, adrenal, thyroid, and CNS. The neuropathic strain of EHV-1 produces a viremic load 10- to 100-fold higher than that of non-neuropathic strains. 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. Diagnosis 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 neuropathic 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. Treatment 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. Control Immunity after natural infection with either EHV-1 or EHV-4 involves a combination of humoral and cellular immunity. Whereas 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 adult 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 as long as 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 21 days 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. Vaccination (EHV-4 and EHV-1) should begin when foals are 4–6 mo old. A second dose is given 4–6 wk later, and a third dose at 10–12 mo of age. Booster vaccinations may be indicated as often as every 6 mo through maturity (5 yr of age). Vaccination programs against herpesviruses should include all horses that travel to high-risk destinations (racetrack, show grounds) and all other horses on the premises. A high-antigen load, inactivated EHV-1 vaccine is recommended to prevent EHV-1 abortion. Vaccine should be administered during months 3, 5, 7, and 9 of pregnancy. Mares are often vaccinated with inactivated EHV-1/EHV-4 at an interval 4–6 wk before foaling. A modified-live EHV-1 vaccine is available to help prevent respiratory disease caused by EHV-1. Infection by other Herpesviruses Equine herpesvirus 2 (EHV-2) is ubiquitous in respiratory mucosa, conjunctiva, and WBCs of normal horses of all ages. The pathogenic significance remains obscure. It has been suggested that EHV-2 is the cause of herpetic keratoconjunctivitis and inflammatory airway disease in young horses. Equine herpesvirus 3 (EHV-3) is the cause of equine coital exanthema (see Equine Coital Exanthema), a benign, progenital exanthematous disease. Equine gamma herpesvirus 5 (EHV-5) has emerged as the pathogen associated with equine multinodular pulmonary fibrosis (EMPF). The role of EHV-5 in EMPF is unclear (precipitating, causative, incidental). Clinical signs include weight loss, cough, fever (variable), and respiratory difficulty. EMPF is seen primarily in middle-aged horses, although it has been reported in young horses. Physical examination findings include tachycardia, tachypnea, increased respiratory effort (inspiratory), and poor body condition. Wheezes and crackles are often ausculted without a rebreathing procedure. In early cases, EMPF may be mistaken as heaves. In addition to EMPF, EHV-5 has been associated with lymphoproliferative disease and lymphoma. One unusual case report describes a 21-yr-old horse with profound pancytopenia and pulmonary fibrosis; EHV-5 was isolated from the bone marrow of this horse. Diagnostic testing includes routine blood work, thoracic radiographs, and virus-specific PCR testing on pulmonary secretions (bronchoalveolar lavage) or percutaneous lung biopsy sample. CBC reveals neutrophilic leukocytosis with or without hyperfibrinogenemia and anemia. Findings on thoracic radiographics range from a moderate interstitial pattern to a severe reticulonodular pattern. Differential diagnoses of radiographic images include fungal pneumonia and metastatic neoplasia. Fungal pneumonia typically occurs after primary GI disease with neutropenia, and metastatic neoplasia is rare. The most common antemortem diagnostic test is virus-specific PCR of bronchoalveolar lavage fluid. Percutaneous, ultrasound-guided lung biopsy can be performed to confirm the diagnosis and establish a prognosis. The procedure is not without risk in dyspneic horses. Histopathology reveals multifocal granulomas, type II pneumocyte hyperplasia, and intraluminal cellular accumulation. Advanced pulmonary fibrosis indicates a poor prognosis for survival. The prognosis for survival is ~50%. Horses with granulomatous inflammation have been successfully treated with antiviral therapy. Valacyclovir (30 mg/kg, PO, tid) and/or acyclovir (10 mg/kg, IV, in 1 L of isotonic crystalloid fluid as a constant-rate infusion over 1 hr, bid × 2 days) appear promising, although sensitivity of the virus to these medications has not been documented. Doxycycline (5-10 mg/kg, PO, once to twice daily) is administered to combat secondary bacterial infection and for its anti-inflammatory properties. Administration of corticosteroids is controversial, although they are commonly used. Corticosteroids (0.08-0.1 mg/kg, IV, every 24–48 hr) may improve disease outcome through reduction of pulmonary cytokines and inflammatory mediators, but they may also cause immunosuppression, which may enhance viral replication and disease severity. |
