CHAPTER 22 Equine Herpesvirus Infections
Herpesviral infection is most commonly a mild disease of the upper respiratory tract of young and adult horses caused by three related herpesviruses that are widespread throughout the world. Equine herpesvirus 1 (EHV-1) is most commonly diagnosed as a cause of abortion during late pregnancy.
Since the first report of equine herpesviral abortion in 1932,6 EHV-1 and EHV-4 have been widespread in the United States, Canada, Japan, Australia, and Europe. Although horses of all ages are infected, signs of upper respiratory disease are usually observed in young horses. The viruses are highly infectious, and infection originates directly or indirectly from other horses. Transmission occurs by inhalation of infected droplets or by ingestion of food or water contaminated by nasal discharges or aborted fetuses. EHV-1 can survive for 14 to 42 days outside horses.7 Up to 80% of horses in the United States have serologic evidence of exposure to EHV-1 infection. Cattle and donkeys have been reported to be possible reservoirs of the virus, and infection by EHV-1 has been reported in llamas, alpacas, deer, antelope, and gazelle.8
Carriers are necessary for EHV-1 to persist from year to year. Being a typical herpesvirus, infection may persist in a latent state and be reactivated subsequently by various stressors, for example, corticosteroids.9 As immunity to EHV-1 infection is short and transient, horses may be clinically infected a number of times. Cell-mediated immunity is important in the resistance to herpesviruses.
The EHV-1 causes inflammation of the respiratory tract characterized by coughing and nasal discharge. The initial viral infection is most severe, secondary viral infections are less severe, and subsequent infections tend to produce few or no clinical signs. Fatalities in uncomplicated cases are unlikely.
Most outbreaks of abortion are associated with outbreaks of respiratory disease in foals and yearlings several weeks earlier, commonly in the fall and winter. Separation of weanlings and yearlings from pregnant mares is important in the control of EHV-1 abortion. “Storms” of abortions may occur in bands of broodmares, with up to 90% at risk of either aborting or losing their foals during the first day of life. Most herpesviral abortions occur sporadically in a herd, with maiden mares most often affected. Multiple abortions may occur in closed herds or in open herds with additions or transients from other farms or racetracks.10 Multiple abortions are most common on farms where pregnant mares are crowded and where there are additions during the final months of the foaling season. Such conditions produce stress and favor epidemic spread of EHV-1 virus. The prevalence of abortion is higher in mares transported during late pregnancy and in those that have gone through sales. Multiple abortions in all age groups usually indicate a lack of immunity in a closed herd that was recently exposed to the EHV-1 virus by a new addition. Abortion is rare in mares kept in a group with no new mares added after the first trimester of pregnancy.10
As the majority of breeding mares are clinically immune to the respiratory but not to the abortigenic infection, spread of EHV-1 infection occurs commonly in a herd without obvious clinical signs. Although pregnant mares abort 60 days or more after intranasal exposure, most abort within 30 days. Spread of infection within a group of pregnant mares exposed to a mare that aborted from EHV-1 infection depends on the status of their immunity to respiratory tract infection. The most dangerous source of infection to pregnant mares is an infected aborted fetus. Aborting mares do not shed virus from either the respiratory or reproductive tract at the time of abortion.10
Infection with EHV-1 is responsible for at least four distinct syndromes in horses: respiratory, abortigenic, neonatal death, and neurologic.2,7,10,11 EHV-1 is highly contagious, and transmission is by inhalation of infectious aerosols or by direct contact with infectious secretions or contaminated drinking water.6,11 EHV-1 replicates in the epithelial cells of the nasal, pharyngeal, and tonsillar mucosae and then spreads to the regional lymph nodes. That stage is followed by leukocyte-associated viremia and infection of vascular endothelium in a number of organs.6,11,12 From that point, invasion of lungs, endometrium, chorioallantois, fetus, and nervous tissue may occur.11–15 It is surmised that EHV is acquired as a respiratory disease leading to latency and that abortion occurs as an unpredictable sequela to reactivation in a carrier mare.16
Spread of EHV-1 occurs transplacentally to fetuses by infected leukocytes, and abortion occurs within 120 days, with the majority occurring in 7 to 20 days.6,11,15 The longer period may result from persistence of EHV-1 in leukocytes in the endometrium or chorioallantois before it invades the fetus and causes death and abortion. The virus damages the endometrium and the chorioallantois. Local edema occurs at the fetomaternal junction, leading to separation of the chorioallantois from the endometrium and the fetus dies from anoxia; near-term fetuses may be expelled alive but are nonviable. The fetus is usually infected and lesions include massive lymphocytic destruction in the thymus and spleen. Experimental studies have revealed that extensive damage to the endometrium from widespread vasculitis, thrombosis, and ischemia, with replication of EHV-1 in endothelial cells, may occur without evidence of infection in aborted fetuses.15 EHV-1 has been isolated from fetuses aborted by mares with high levels of serum-neutralizing antibodies to EHV-1.17
Abortions usually occur between 7 months of gestation and term, with no maternal illness evident at that time.10 Respiratory disease before abortion may not be observed in mares, as EHV-1 infection may have been mild, subclinical, or latent; latent disease may have been reactivated by stress-induced immunosuppression.6,9,11,16–18
Prenatal infection with EHV-1 without concurrent abortion or respiratory disease has been reported from Australia and resulted in stillbirths or weak, nonviable foals that died within a few hours to 24 hours of birth, and foals apparently normal at birth that developed severe respiratory distress within 18 to 24 hours and died within 24 to 72 hours.19–21 A different prenatal EHV-1 infection resulting in neonatal death in older foals was reported from Kentucky and was characterized by respiratory disease, diarrhea, and weakness during the first weeks of life.22 The foals were normal at birth, were agammaglobulinemic, and survived for a few weeks before succumbing to a variety of secondary bacterial and viral infections.
The pathogenesis of the neurologic form of EHV-1 infection is complex and uncertain. The relationship to reinfection and the microscopic changes in the central nervous system suggest an immune-mediated vasculitis typical of a type III hypersensitivity reaction.11,13,14 Infection is considered to spread to the central nervous system (CNS) through EHV-1-infected leukocytes. Outbreaks of EHV-1 myeloencephalitis appear to be caused by certain strains of EHV-1.13,16 Originally thought to be confined to pregnant mares, the EHV-1 paralytic syndrome has been observed in barren mares, stallions, geldings, and foals.23–25 Experimentally, only pregnant mares in early or midpregnancy, not the last trimester, could be infected.11,13,14,25 The outcome of EHV-1 infection of the spinal cord and brain varied from recovery to permanent locomotor impairment or death.
Severity of EHV-1 respiratory disease is age-related, with acute upper respiratory tract infection occurring mainly in foals, weanlings, and yearlings. After an incubation period of 2 to 20 days, signs include fever (39° to 40.5° C), conjunctivitis, leukopenia (largely neutropenic26), serous to mucopurulent nasal discharge, and cough. The lymph nodes of the throat may be slightly enlarged. The course of illness is usually 2 to 5 days, but the nasal discharge and cough may persist for 1 to 3 weeks.6,7,11,18,26 Inapparent EHV-1 infections are common. Infection in older horses previously infected is mild to subclinical with few or no clinical signs. Secondary bacterial infection may result in pneumonia. Young horses may develop viral pneumonia.