Respiratory disease

Respiratory disease caused by EHV-1 and EHV-4 is characterized by a transient elevation of temperature to 38.9–40.0°C, inappetance, nasal discharge, pharyngitis, depression and sometimes limb edema. Affected horses usually give a few coughs but coughing is not a major feature of uncomplicated EHV respiratory disease. There may be slight enlargement of the mandibular and retropharyngeal lymph nodes. Horses frequently suffer from secondary bacterial infections, which prolong the recovery time.

Abortion

Abortion usually occurs without any premonitory signs and the placenta is not retained. The mare’s subsequent fertility is unimpaired.

Foals that are infected in utero but survive to full term are usually abnormal from birth and show signs of acute respiratory distress. Their mucous membranes are often jaundiced. They usually die before 2 wk of age.

Neurologic syndrome

Neurologic signs usually occur 7–10 days after an episode of respiratory disease. At the time when the nervous signs are evident, the horse usually shows no signs of respiratory disease and its body temperature and appetite are normal. Nervous signs vary from mild ataxia followed by complete recovery to fatal paralysis. Early signs may include stiffness, posterior incoordination and urinary incontinence. Uveitis, hypopyon, subcutaneous edema of the hindlimbs, colic, diarrhea, and scrotal edema and prolapse of the penis (q.v.) are sometimes encountered. These may be followed by sternal and then lateral recumbency, dyspnea, convulsions and death. Sudden death with no prior clinical signs has been recorded.

Pulmonary vasculotropic form

Several cases of generalized peracute EHV-1 disease have been reported in young adult horses. Neurologic signs are absent and the main clinical sign is respiratory distress. There is a high mortality rate and affected horses may be found dead.

Coital exanthema

Coital exanthema is manifested by vesicles that become pustular and ulcerate. Scabs develop which persist for 2–3 wk and may leave white scars. Mares develop lesions on the vulva, on the vaginal mucosa and on the perineal skin around the anus. In severe cases the lesions may extend to the hindquarters and hindlimbs. The mare may experience extreme irritation on urinating.

Stallions tend to be less susceptible than mares but lesions may occur on the prepuce and penis resulting in an unwillingness to cover. The lesions usually heal within 2 wk.

Abortion

Our current understanding of the mechanism by which a virus is transported to the fetus is that EHV-1 infected peripheral blood mononuclear cells, predominantly monocytes and T lymphocytes, carry virus to sites of replication such as the endothelium of endometrial blood vessels. Studies using PCR indicate that the virus establishes a latent infection in leukocytes but the factors involved in reactivation of virus and the activation of endothelial cells to facilitate the adhesion of their surface receptors to infected leukocytes need to be elucidated.

It appears that fetal infection is not a prerequisite for EHV-1 induced abortion and a severe infection of the endometrium can result in extensive thrombosis and ischemic infarction (q.v.) which in turn lead to premature placental separation and abortion of a virologically negative fetus. However, this appears to be relatively uncommon and in most cases the virus is transferred across the uteroplacental barrier, the fetal viscera are infected and a fetus with characteristic necrotic lesions and significant virus load is expelled. It has been suggested that it is the endotheliotropism of the virus strain that determines the degree of thrombosis and thus the outcome of virus challenge. However, not all abortigenic isolates are endotheliotropic and it is likely that the outcome of infection is also influenced by host factors.

Neurologic disease

Outbreaks of EHV-1 paralysis are much more uncommon than outbreaks of respiratory disease or abortion and the factors which predispose to their occurrence have not been identified. The occurrence of large abortion storms without concurrent neurologic signs militates against the size of the virus challenge being the predominant factor.

EHV-1 differs from several other herpesviruses in that it does not appear to be primarily neurotropic. The severity of the clinical signs can be correlated to the degeneration of neural tissue but this degeneration is due to hypoxia initiated by vasculitis. Damage to vessel walls leads to a flow of plasma proteins into perivascular sites impeding the exchange of blood and tissue metabolites in adjacent areas. In the central nervous system (CNS) this results in malacia (q.v.). It has been suggested that the condition may be the result of an immunologic process and that inflammatory changes in the CNS may be a reaction to virus antigen and antibody complexes.

Abortion

The most consistent lesions in aborted fetuses and foals that die soon after birth are severe pulmonary edema, petechiation of the mucous membranes, excessive fluid in the pleural and peritoneal cavities, jaundice, splenomegaly and areas of focal necrosis in the liver.

Microscopically, the lesions are bronchiolitis, pneumonitis and necrosis of the spleen and liver. Acidophilic intranuclear inclusion bodies are found in the affected tissues and the presence of EHV antigen may be detected by immunohistochemical methods such as immunofluorescence and immunoperoxidase.

Fetuses aborted prior to the sixth month of gestation are often severely autolyzed. In such cases the classic lesions of EHV-1 abortion may not be present but the intranuclear inclusion bodies will be observed on histologic examination.

Neurologic disease

Gross pathologic findings in horses with the neurologic syndrome are often minimal. There is usually congestion of the mucous membranes and petechial, ecchymotic and hemorrhagic changes are often widespread. Hemorrhage around the spinal nerve roots is a common finding. Foci of malacia in the brain and spinal cord may be visible macroscopically. Intussusception (q.v.) has been observed in foals.

The predominant histopathologic changes are vasculitis and degeneration of nervous tissue. A non-suppurative inflammation of the blood vessels is accompanied by thrombosis and hemorrhage and exudation of plasma into the perivascular tissues. The arteries and arterioles of the CNS are principally affected but vasculitis is sometimes evident elsewhere in the body, for example in the endometrium of pregnant mares, uvea and lungs. Veins are affected less frequently but sometimes more severely.

Axons in the brain and spinal cord are often swollen and dystrophic. Foci of malacia in both gray and white matter, gliosis and neuronal degeneration are the most consistent findings in the CNS.

Respiratory disease

Upper respiratory tract infection caused by EHV must be differentiated from equine rhinovirus, equine influenza virus, equine arteritis virus, bacterial infections and allergic rhinitis (q.v.).

Serologic diagnosis can be made on the basis of a significant rise (4-fold or greater) in antibody titer, which requires the collection of blood samples during the acute stage of the disease and 10–14 days later. The majority of diagnostic laboratories routinely use the complement fixation test (CFT) for the measurement of EHV antibodies. CF antibodies against EHV-1 and EHV-4 tend to reach a peak 10–14 days post infection and usually decline to their original level within 3 mo. Serum neutralizing (SN) antibody titers persist for longer than CF antibodies and are a less reliable indicator of recent exposure.

Because of close antigenic relatedness, infections with EHV-1 and EHV-4 are difficult to differentiate on the basis of serology. A type specific enzyme-linked immunosorbent assay (ELISA) has been used extensively in epidemiologic surveys but it is not quantitative and has not replaced more conventional techniques in the majority of diagnostic laboratories.

Equine herpesviruses are isolated in tissue culture. EHV-1 will grow on a variety of commercially available cell lines such as rabbit kidney cells (RK13) but EHV-4 is more fastidious and with a few exceptions tends to grow only on cells of equine origin. Virus isolates can be typed by immunofluorescence with specific monoclonal antibodies or by PCR. PCR can also be used for rapid virus detection in diagnostic samples and in some laboratories has been shown to be more sensitive than virus isolation. Some caution must be exercised in the interpretation of positive PCR results for blood samples as leukocytes are a site of latency for EHV-1 and EHV-4. The isolation of EHV-1 or EHV-4 from a nasal swab depends on the amount of virus the horse is shedding at the time of sampling. Although virus isolation is sometimes achieved within 24 h, it can take 2 wk or more. PCR can yield a result in less than a day.

Abortion

Diagnosis of EHV abortion is routinely based on post mortem examination of the fetus and on virus isolation. Samples of liver, lung, spleen, adrenal, thymus and kidney from every aborted fetus should be submitted to a virus isolation laboratory for routine screening for EHV. This also applies to the remainder of any fetus that has been partially eaten by predators as the virus can survive for several weeks in a moist environment.

A fetus aborted as a result of EHV infection is usually heavily contaminated with virus. Thus, EHV-1 can often be isolated from positive cases and typed within 48 h. EHV-4 tends to grow more slowly than EHV-1 in tissue culture. Most laboratories passage fetal tissue for at least 1 wk in tissue culture before they declare them negative. PCR is type specific and can be used to detect virus within 2 4 h of receipt of tissue samples.

The recent finding that naturally infected mares can abort virologically negative fetuses poses a problem for both pathologists and virologists and indicates the importance of placental examination.

It is not possible to diagnose EHV abortion by serologic examination. Some mares do not have a significant antibody titer at the time they abort. Alternatively, a mare may have a significant antibody titer due to exposure to virus by vaccination or by a natural infection that did not induce abortion.

EHV infection in neonatal foals can be confirmed by the isolation of virus from a nasal swab or heparinized blood. Serologic examination is not a suitable means of diagnosis.

Neurologic disease

As the nervous signs do not manifest for about 10 days post infection, the majority of horses suffering from EHV neurologic disease have high antibody titers against the virus. Thus, the examination of a single serum sample is often a useful diagnostic aid. Some mares are slow to seroconvert and examination of paired sera is necessary in a minority of cases.

In the case of an outbreak of the neurologic form of the disease, it is usually possible to isolate EHV-1 from the nasal secretions and leukocytes of some of the affected horses. Heparinized blood samples (a minimum of 20 mL per horse) are particularly useful as many horses experience prolonged viremia.

If horses die or are euthanased, a diagnosis can be made by pathologic investigation. EHV-1 antigen may be detected using immunoperoxidase or immunofluorescence techniques and virus can be isolated from the brain or spinal cord.

Coital exanthema

EHV-3 can be isolated from swabs of the ulcerative lesions. The virus usually only grows in cells of equine origin.

Antibodies against EHV-3 can be measured by complement fixation or serum neutralization. Most affected horses have significant antibody titers against the virus.

Respiratory disease

Both killed and live attenuated EHV-1 vaccines were widely used for many years to protect horses against equine herpesvirus respiratory disease, but their use met with only limited success. More recently, vaccines containing both EHV-1 and EHV-4 (e.g. Duvaxyn EHV 1,4 [Fort Dodge Animal Health] and Resequin [Intervet], available in Europe, and Prestige [Intervet] and Equi Guard [Boehringer Ingelheim] available in the USA) have been introduced and although they reduce virus shedding, they do not necessarily offer complete protection against clinical disease. However, regular use of such vaccines at strategic times in a training program (such as prior to or when there is a break in intensive training periods and attendance at race meetings) appears to lessen the effects of virus challenge and decrease the recovery time.

The serologic monitoring of horses on a regular basis serves as a useful aid to the early detection of EHV in a yard. If EHV is detected, it is of the utmost importance to have the virus type determined in a specialist laboratory by PCR or other reliable method.

It is rarely practical or advisable to close a yard with an EHV-4 problem, but it is usually possible to control the disease by careful monitoring of all the horses and identification and isolation of those that are affected. Horses with clinical respiratory disease and those that show signs of depression or inappetance should be isolated from healthy horses and adequately rested before a gradual return to full work. The use of antibiotics, mucolytics and bronchodilators may be indicated in horses with secondary bacterial infection.

Return to work too soon may result in chronic respiratory problems or the reactivation and shedding of latent virus. Because the virus usually spreads quite slowly in a group of horses it is not unusual for some horses from an infected yard to continue to perform well. However, care must be taken not to over-stress subclinically infected animals. Serologic testing will help to identify these horses.

EHV-1 respiratory disease constitutes a greater threat to a training yard than EHV-4. Because of the abortigenic potential of the virus, no horse should be allowed to move from an infected yard to one that contains brood mares. When deciding whether or not to close the yard it should be remembered that EHV-1 can cause paralysis and that there is some evidence to suggest that stressing animals that are incubating the virus may precipitate this condition.

Abortion

A combination of good management and vaccination helps to reduce the threat of EHV abortion. The regular use of a vaccine of proven efficacy, preferably containing both EHV-1 and EHV-4 (e.g. Duvaxyn EHV 1,4 [Fort Dodge]), during each gestation period is recommended. There are many vaccines on the market but only one product, Duvaxyn EHV 1,4, is currently licensed in the EU for use in the prevention of EHV-1 associated abortions. Similarly, only Pneumabort K + 1B (Fort Dodge) and Prodigy (Intervet) have an abortion claim in the USA. A live temperature sensitive EHV-1 vaccine has recently been developed in the UK and the experimental data look promising. This vaccine protected pregnant mares for up to 6 mo after a single intranasal inoculation. In comparison the inactivated vaccines need to be administered at 5, 7 and 9 mo of each gestation.

Properly vaccinated mares rarely abort due to EHV infection unless they are stressed or exposed to a large virus challenge and multiple abortions on studs with a stringent vaccination policy are uncommon. Commercial studs should be advised not to accept unvaccinated pregnant mares or, if this is not possible, to keep them isolated (i.e. in a separate field or barn) from other mares.

Wherever possible, brood mares should not be kept in close proximity to other horses such as racehorses, showjumpers, yearlings and children’s ponies. If mares are kept on mixed premises they should always be handled before other horses. Horses returning from sales, race meetings and competitions should be isolated from the brood mares.

It is important to minimize stress to pregnant mares. There is a risk in transporting heavily pregnant mares over long distances. All pregnant mares, particularly those that have traveled long distances and those from sales yards, should be isolated on arrival at a stud. Horse boxes should be regularly cleaned and disinfected with a product which is active against herpesviruses.

All cases of abortion, stillbirth or foal death within 14 days of birth should be treated as suspect virus abortion. The fetus and the placenta should be submitted to a recognized diagnostic centre for pathologic investigation. The mare should be placed in isolation in case she is shedding virus. If she aborted in a stable, the bedding should be sprayed with disinfectant such as Virkon (Antec International) at a dilution of 1:100 and left for 48 h, after which it can be removed and burned. If she aborted in a field in the company of other mares, these mares should be isolated until further investigation is completed. No horse should be removed from the premises until the possibility of virus abortion has been excluded.

Common Codes of Practice^* exist for the control of contagious equine reproductive diseases in the United Kingdom, Ireland, France, Germany and Italy. It is likely that these Codes will extend to all member states of the European Community in the future.

The correct procedure for the management of herpesvirus abortion is documented in the Code and is applicable to any premises where the owner is concerned to reduce the spread of the disease. The major points in the Code concern the movement of horses from the infected premises. All pregnant mares must remain on the infected stud until they foal. All other horses must remain on the stud until 1 mo after the last abortion. At this time, the infected stud’s own non-pregnant mares, including those that aborted, can visit other studs to be covered subject to the full agreement of the receiving stud. The receiving stud should keep these mares isolated from pregnant mares.

The sampling of horses on infected premises for virus isolation and serologic examination for evidence of exposure to virus will assist a breeder in making decisions about the movement of horses within the stud farm. The cohorts of the mare that aborted should be isolated from other pregnant mares. Pregnant mares should be divided into small groups to minimize the spread of virus. If possible, each pregnant mare should be allotted a separate field or paddock so that if she aborts, her fetus does not serve as a source of virus for other pregnant mares.

Neurologic disease

If the neurologic form of EHV disease is confirmed, no movement should be allowed on or off the infected premises. All horses should be rested immediately as stress exacerbates the condition. In the case of a stud farm, covering should cease and because of the abortigenic potential of the virus, pregnant mares should be divided into small groups and kept on the premises until they have foaled.

The treatment of the neurologic disease is predominantly supportive and with good nursing care the majority of affected horses will recover. Ataxic horses (q.v.) should be stabled with deep bedding. Recumbent horses should be propped up in the sternal position if possible. Horses in lateral recumbency should be rolled frequently. Abdominal slings are useful to decrease muscle damage and the development of decubital ulcers.

Inappetant horses may need to be fed by stomach tube. Manual emptying of the rectum and bladder catheterization may be necessary. Immunosuppressive doses of corticosteroids have been administered during some outbreaks on the basis that this might prevent immune-mediated vasculitis. Neither the efficacy of this therapy nor that of anti-inflammatory drugs (flunixin meglumine, DMSO), vitamin E and aciclovir has been determined. Mildly uncoordinated horses often recover within a few days, but horses that become recumbent usually take much longer and may never recover completely.

The decision to allow movement on and off the premises should only be taken when there is no evidence by serologic examination or by virus isolation that the virus is still circulating. This may take several months.

Coital exanthema

Aciclovir is not licensed for use in horses but is efficacious at the concentrations used in ointments for herpetic ulcers in humans. Antimicrobial ointments may also be applied to the affected areas to control secondary bacterial infection. Covering should cease until the lesions have healed.