Equine viral arteritis is an acute, contagious, viral disease of equids caused by equine arteritis virus (EAV). It is characterized by fever, depression, anorexia, leukopenia, dependent edema (especially of the lower hind extremities, scrotum, and prepuce in the stallion), conjunctivitis, supra- or periorbital edema, nasal discharge, abortion, and infrequently, illness and death in young foals.
Etiology and Pathogenesis
EAV is a small, enveloped RNA virus and the prototype virus of the genus, family Arteriviridae, order Nidovirales. It is one of the 3 most important equine viral respiratory pathogens. The virus is not resistant outside the body and survival at or above 37°C is short-lived. In contrast, EAV can maintain infectivity in tissue or fluid specimens for extended periods at storage temperatures equal to or below freezing. It can remain viable in frozen semen for many years.
Although only one serotype of EAV has so far been identified, the prototype Bucyrus strain, genomic and antigenic variation does exist among temporally and geographically different isolates. Variability in pathogenicity also occurs among viral strains, with some capable of causing severe signs of disease while others only induce a fever.
Following inhalation exposure, EAV invades the respiratory epithelium and multiplies in both bronchial and alveolar macrophages. These transport the virus to the regional lymph nodes, where it undergoes a further cycle of replication before being released into the bloodstream. The cell-associated viremia that follows ensures dissemination of EAV throughout the body. By day 6–8 the virus localizes in the vascular endothelium and medial myocytes of the smaller blood vessels, especially the arterioles, and causes a panvasculitis. It can also be found in the epithelium of certain tissues, particularly the adrenals, seminiferous tubules, thyroid, and liver. Vascular lesions include endothelial swelling and degeneration, neutrophil infiltration, and necrosis of the tunica media of affected vessels. These lesions give rise to edema and hemorrhage, which are believed to result from activation of proinflammatory cytokines. Maximal vascular injury occurs by about day 10, after which lesions begin to resolve.
Based on experimental infection of pregnant mares with the experimentally derived highly virulent Bucyrus strain of EAV, abortion is believed to result from a myometritis that gives rise to impairment of the placental circulation and death of the fetus. However, this may not represent the pathogenesis of abortion in naturally acquired cases of EAV infection, which has yet to be determined.
With the exception of certain infected stallions that become carriers of the virus, EAV is no longer detectable in tissues and body fluids beyond day 28 after primary infection. Stallions that remain persistently infected, on the other hand, harbor the virus in certain accessory sex glands, especially the ampulla of the vas deferens, where it can remain for many years. Some carrier stallions may shed EAV from their reproductive tracts even after a prolonged period.
Epidemiology and Transmission
While the natural and experimental host range of EAV is restricted principally to equids, there are limited data to suggest the virus can also infect alpacas and llamas. There is no evidence that EAV is transmissible to humans. Based on serologic surveys and reported outbreaks of equine viral arteritis, EAV is present in equine populations in many countries worldwide, with the notable exceptions of Japan and Iceland. The prevalence of infection varies widely both between countries and among breeds in the same country. It is frequently highest in Standardbreds and Warmbloods. Despite the widespread global distribution of EAV, laboratory-confirmed outbreaks of equine viral arteritis are relatively uncommon. This situation appears to be changing in more recent years with an increase in the number of verified occurrences of the disease being reported. A major factor contributing to this change is the continued growth in the volume of international trade in horses and equine semen.
The epidemiology of equine viral arteritis involves virus-, host-, and environment-related factors, including variability in pathogenicity among naturally occurring strains of the virus, modes of transmission, occurrence of the carrier state in the stallion, and the nature of acquired immunity to infection. Outbreaks of equine viral arteritis are most often linked to the movement of infected animals or the shipment of virus-contaminated semen. Frequently, viral transmission occurs with minimal if any detectable clinical signs in acutely infected equids.
Transmission of EAV can occur by respiratory, venereal, and congenital routes or by indirect means. Spread by the respiratory route is the principal mode of dissemination of the virus during the acute phase of infection. It is primarily responsible for transmission of EAV among naive equids kept in close contact (eg, at racetracks, shows, sales, veterinary hospitals, and under conditions of intensive management on breeding farms). EAV can also be transmitted venereally by the acutely infected mare and by the acutely or chronically infected stallion. Mares can be readily infected by the venereal route following breeding to a carrier stallion either by live cover or artificial insemination with fresh-cooled or cryo-preserved semen. There is evidence that EAV can be spread through embryo transfer. Spread of infection can also occur through indirect contact with virus-contaminated fomites (eg, breeding shed equipment, shanks, or twitches) or on the hands or apparel of animal handlers.
The carrier state has been confirmed in sexually mature intact males, specifically post-pubertal colts and stallions, but not in mares, geldings, sexually immature colts, or fillies. Establishment and persistence of EAV in the reproductive tract of stallions is testosterone-dependent. The carrier stallion is the natural reservoir of EAV and is responsible for its dissemination and persistence. Frequency of the carrier state can vary from <10% to >70%. Persistently infected stallions shed EAV constantly in the sperm-rich fraction of the semen, but not in any other secretions or excretions. Duration of the carrier state can range from weeks to many years. Spontaneous clearance of persistent EAV infection occurs in a variable percentage of stallions, with no evidence of subsequent reversion to a shedding state. Existence of the carrier state does not appear to impair the fertility of infected stallions nor otherwise adversely affect their clinical condition. Carrier stallions also serve as the principal means whereby genetic diversification of the virus can occur.
Compared to other equine respiratory viruses, EAV stimulates a stronger, longer-lasting immunity that is protective against development of clinical disease and establishment of the carrier state in the stallion. High levels of neutralizing antibodies that can persist for at least 2–3 yr can be stimulated by natural exposure to the virus and by vaccination.
Exposure to EAV may result in clinical or asymptomatic infection, depending on the relative pathogenicity of the virus strain involved, viral dose, age and physical condition of the animal, and various environmental factors. The majority of cases of primary infection are asymptomatic. The onset of the acute phase of EAV infection, whether associated with clinical signs of illness or not, is preceded by an incubation period of 3–14 days, which varies mainly with the route of exposure. Clinical signs can differ in range and severity between disease outbreaks and between affected individuals in the same outbreak. Any combination of the following may be seen: fever of 2–9 days' duration, leukopenia, depression, anorexia, limb edema (especially of the lower hindlimbs), and edema of the scrotum and prepuce. Less frequently encountered signs include conjunctivitis, lacrimation and photophobia, periorbital or supraorbital edema, rhinitis and nasal discharge, edema of the ventral body wall (including the mammary glands of mares), an urticarial-type skin reaction that is often localized to the sides of the face, neck, or over the pectoral region (although it can be generalized), stiffness of gait, dyspnea, petechiation of mucous membranes, diarrhea, icterus, and ataxia.
Strains of EAV can cause abortion throughout much of pregnancy (3 mo to over 10 mo). Abortion may occur late in the acute phase or early in the convalescent phase of the infection, with or without prior clinical signs of equine viral arteritis. In natural outbreaks, abortion rates can vary from <10% to as high as 60%. There is no evidence confirming that mares bred with EAV-infective semen will abort later in gestation. Mares that abort from the virus are already pregnant at time of exposure; this occurs primarily by the respiratory route through direct proximity with an acutely infected animal. Abortion takes place 1–4 wk later. Mares exposed very late in gestation may not abort but give birth to a foal congenitally infected with the virus. Mares that abort from EAV infection have not been proved to be less fertile.
Stallions with equine viral arteritis may undergo a period of short-term subfertility. This has been observed in individuals that develop a high and prolonged fever and extensive scrotal edema. Affected stallions can show reduced libido associated with decreases in sperm motility, sperm concentration, and percentage of morphologically normal sperm. The changes in semen quality are believed to result from increased intratesticular temperature and not from the direct effect of EAV on spermatogenesis and testicular function. Semen changes can last for 14–16 wk before returning to normal. No longterm adverse effects on fertility have been observed in fully recovered stallions.
The frequency and severity of clinical illness associated with EAV infection tend to be greater in very young, old, or debilitated individuals. Regardless of severity of clinical signs, affected horses invariably make complete recoveries, even in the absence of symptomatic treatment. Mortality in older horses is very rarely encountered in natural outbreaks. It can occur, however, in young foals up to a few months of age that succumb from a fulminating pneumonia or pneumoenteritis.
The gross and microscopic lesions in fatal cases of equine viral arteritis reflect the extensive and considerable vascular damage caused by the virus; these descriptions are primarily based on experimental infection with the highly pathogenic Bucyrus strain of EAV. The most significant gross findings include edema, congestion, and hemorrhages, especially in the subcutis of the limbs and abdomen; excess peritoneal, pleural, and pericardial fluid; and edema and hemorrhage of the intra-abdominal and thoracic lymph nodes and of the small and large intestine, especially the cecum and colon. Pulmonary edema, emphysema and interstitial pneumonia, enteritis, and infarcts in the spleen have been reported in naturally acquired fatal cases of the disease in foals.
Aborted fetuses are often partly autolyzed. Gross lesions are usually absent; if present, they are limited to an excess of fluid in body cavities and a variable degree of interlobular pulmonary edema. The vascular damage and immune-mediated lesions observed in older animals are seldom found in infected fetuses.
The characteristic microscopic lesion seen in cases of EAV infection is a vasculitis, involving primarily smaller arterioles and venules. Histologically, changes can range from vascular and perivascular edema, with occasional lymphocytic infiltration and endothelial cell hypertrophy in mild cases, to fibrinoid necrosis of the tunica media, extensive lymphocytic infiltration, necrosis and loss of endothelium, and thrombus formation in severe cases. Microscopic lesions are frequently not observed in cases of abortion. If present, vasculitis has been observed in the placenta and the brain, liver, spleen, and lungs of the fetus.
Fatal cases of EAV infection in young foals are characterized by interlobular edema, congestion and mononuclear cell infiltration in the lungs, lymphoid depletion and hemorrhage in lymphoreticular tissues. Focal hemorrhages and necrosis of the intestinal mucosa have been described where there is an associated enteritis.
Clinical signs of equine viral arteritis can mimic the signs of a range of other respiratory and nonrespiratory equine diseases. Accordingly, laboratory confirmation is essential in establishing the diagnosis. Equine influenza, equine rhinopneumonitis, infection with equine rhinitis A and B viruses or equine adenoviruses, and purpura hemorrhagica are among the more common equine diseases that clinically resemble equine viral arteritis. The latter must also be differentiated from equine infectious anemia, toxicosis caused by hoary alyssum (Berteroa incana), and allergy-induced urticaria. Several foreign diseases that should be considered in a differential diagnosis for equine viral arteritis include Getah virus infection, dourine, and African horse sickness (see African Horse Sickness).
Abortion caused by EAV must be differentiated from that due to equine herpesvirus 1 or 4. A helpful but not confirmatory distinguishing feature is that mares that abort from EAV may display prior clinical evidence of equine viral arteritis, whereas mares seldom exhibit any premonitory clinical signs in the case of equine herpesvirus abortion. Furthermore, EAV-infected fetuses are often somewhat autolyzed at time of expulsion and very frequently are devoid of any gross lesions. In contrast, herpesvirus-infected fetuses are invariably fresh and usually display characteristic gross and microscopic lesions.
Laboratory confirmation of a provisional clinical diagnosis of equine viral arteritis should be pursued without delay in suspected outbreaks. This can be based on virus isolation, detection of viral nucleic acid or antigen, or demonstration of a recent humoral antibody response by testing paired (acute and convalescent) sera collected 3–4 wk apart.
Appropriate samples for virus isolation and/or detection of viral nucleic acid by reverse transcriptase-PCR include nasopharyngeal swabs or washings and unclotted (citrated or EDTA) blood samples. To optimize the chances of isolation or detection, samples should be collected as early as possible after the onset of clinical signs or suspicion of EAV infection. After collection, swabs should be transferred directly to a viral transport medium and shipped refrigerated or frozen in an insulated container via an overnight delivery service to a laboratory competent to test for this infection. Unclotted blood samples should be transported refrigerated but not frozen.
In suspect cases of EAV-related abortion, virus detection should be attempted from placental tissues and fluids and from fetal lung, liver, lymphorecticular tissues (especially thymus), and peritoneal or pleural fluid. Chorioallantoic membrane and fetal lung are the tissues of choice for recovery of virus. When EAV is suspected in deaths of young foals or older horses, a wide range of tissue specimens, especially the lymphatic glands in the thoracic and abdominal cavities and related organs, should be collected and submitted for laboratory examination, including histologic and immunohistochemical testing.
Detection of the carrier state in a stallion is based on initial confirmation of the individual's seropositive status. In the absence of a certified history of vaccination, stallions with a serum neutralizing antibody titer ≥1:4 should be considered potential carriers of the virus until proven otherwise, based on an absence of detectable EAV in their semen. Confirmation of the carrier state is based on demonstration of virus in a semen sample containing the sperm-rich fraction of the ejaculate either by isolation of virus or its detection by reverse transcriptase-PCR. It can also be accomplished by test breeding a putative carrier stallion to 2 seronegative mares and checking these for seroconversion 28 days after breeding.
Of the serologic assays evaluated for detection of antibodies to EAV, the complement-enhanced virus neutralization test continues to be the most reliable for the diagnosis of acute EAV infection and for seroprevalence studies. A few ELISA tests have been developed that offer comparable but not equivalent sensitivity and specificity. None of the available tests can differentiate antibody titers resulting from natural infection from those due to vaccination.
Treatment, Prevention, and Control
There is no specific antiviral treatment currently available for equine viral arteritis. Because virtually all naturally affected horses recover completely, symptomatic treatment (eg, antipyretic, anti-inflammatory, and diuretic drugs) is indicated only in severe cases. Symptomatic treatment of stallions with a high or prolonged fever and significant scrotal and preputial edema can reduce the likelihood of short-term subfertility. Good nursing care and a gradual return to normal activity are indicated. There is no effective treatment for equine viral arteritis-related cases of pneumonia or pneumoenteritis in foals. While there is some evidence that temporary down-regulation of circulating testosterone by GnRH immunization or through the use of a GnRH antagonist promotes clearance of EAV from the reproductive tract of carrier stallions, neither strategy has yet been adequately validated.
Equine viral arteritis is a manageable and preventable disease that can be controlled by sound management practices together with a targeted vaccination program. Only one commercial vaccine, a modified live virus product, is currently available in North America. The vaccine protects against development of equine viral arteritis and establishment of the carrier state in the stallion. While the vaccine is safe and immunogenic for stallions and nonpregnant mares, the manufacturers do not recommend its use in pregnant mares, especially in the final 2 mo of gestation, or in foals <6 wk of age, unless under circumstances of high risk of exposure to natural infection. Minimizing or eliminating direct or indirect contact of unprotected horses with infected animals or with virus-infected semen is critical to the success of any prevention program.
The primary focus of current control programs is to restrict the spread of EAV in breeding populations and reduce the risk of outbreaks of virus-related abortion, death in young foals, and establishment of the carrier state in stallions and postpubertal colts. Although EAV has occasionally been responsible for extensive outbreaks of disease at racetracks, shows, sales, and veterinary hospitals, these have been so sporadic that no specific control programs have been developed to prevent such occurrences.
Effective control programs are predicated on observance of sound management practices similar to those recommended for other respiratory infections. These include segregation of pregnant mares, identification or carrier stallions, annual immunization of noncarrier breeding stallion populations, and vaccination of colts at 6–12 mo of age to minimize the risk of them becoming carriers. Carrier stallions should be managed separately and bred only to naturally seropositive mares or mares vaccinated against equine viral arteritis. Because fresh-cooled or frozen semen can be a significant source of EAV, it should be tested by a reputable laboratory to ensure its safety, especially if imported. When breeding a mare artificially with virus-infected semen, the same precautions apply as if breeding by live cover to a carrier stallion.
In the event of a suspected outbreak of equine viral arteritis, appropriate veterinary authorities should be promptly notified, affected and in-contact horses isolated, and restrictions immediately imposed on movement of horses onto and off the affected premises. Laboratory confirmation of the diagnosis should be established as soon as possible. Breeding activity should be suspended on breeding farms to minimize further spread of the infection. Stalls and equipment that might have come in contact with infected animals should be thoroughly sanitized. Vaccination of the at-risk equine population on a premises should be seriously considered as a means of restricting further transmission of EAV and bringing an outbreak more rapidly under control. Movement restrictions should not be lifted until at least 3 wk after the last clinical case of equine viral arteritis or laboratory-confirmed case of EAV infection.
Last full review/revision March 2012 by Peter J. Timoney, MVB, MS, PhD, FRCVS