Equine Togaviral Encephalitis

Description

NOTIFIABLE and ZOONOTIC infectious mosquito-borne disease of equidae. The same virus strains can cause serious human disease as well as infecting poultry and other farmed birds including quail, ostriches and emus (ratites). The disease is not directly contagious between horses and man.

Eastern and Western equine encephalomyelitis viruses belong to the genus Alphavirus of the family Togaviridae. These viruses cycle between birds and mosquitoes. The disease occurs sporadically in horses and humans from mid-summer to late autumn. Horses and humans are tangential dead-end hosts. The disease in horses is characterised by fever, anorexia, and severe depression. Eastern equine encephalomyelitis (EEE) virus infection in horses is often fatal, while Western equine encephalomyelitis (WEE) virus can cause a subclinical or mild disease with less than 30% mortality

Viraemia during the acute phase of EEE and WEE. Incubation period of 1-3weeks after experimental infection with EEE or WEE. Incubtion often shorter with EEE. Central nervous system (CNS) replication within a week

Aetiology

see this page for details of the causal pathogen

Epidemiology

Disease associated with EEE, WEE and VEE is largely restricted to the Western Hemisphere, ranging from temperate to desert climates. EEE in the United States is mainly seen in the Southeastern United States but has been detected in all states east of the Mississippi River and some Western states. Large outbreaks of WEE have been described in California and other Western states but the incidence of clinical disease in these areas has experienced a dramatic decrease. The reason for this unknown but may be due to geographical variation in virulence. Equine disease associated with WEE is rare on the Eastern seaboard ofthe United States. VEE virus is a very important human andveterinary pathogen in the Western Hemipshoere that can cause large outbreaks of disease in humans and horses over large geopgrahic areas. VEE has spread into Central America, causing devastating epidemics as far north as Texas. The disease distribution is determined by climatic conditions as well as agricultural practices, such as irrigation, which favour the life cycle and spread of mosquitoes. Transfer is via vector: mostly through mosquito salivary transfer. WEE and VEE may also be transmitted via nasal secretions but this is less likely. Disease amplification occurs during the viraemic phase which lasts until nervous signs develop. Amplification from horses is unlikely with EEE and WEE but occurs with VEE in association with a relatively high viraemia. Ocular and nasal discharges from infected horses cotnain high concentrations of VEE. Zoonotic spread has been noted with VEE but is unlikely for the other two serotypes. Horse to horse spread of EEE is possible. Humans and horses are terminal hosts for WEE. Horses with WEE are sentinels for humans in a given area.

Highlands J virus, antigenically related to WEE virus, has been isolated in eastern USA. Although it is generally believed not to cause disease in mammals, it has been isolated from the brain of a horse dying of encephalitis in Florida (4).WEE virus infection in horses is often observed over a wide geographical area, e.g. sporadic cases over 1000 square miles. EEE virus infections are usually observed in limited geographical areas.

Seasonal Incidence

The diseases occur largely during the height of the vector season. In temperate climates, case numbers peak in June to November. In warm climates, where the vector season is longer, the disease period is prolonged. Global warming may promote more cold climate outbreaks.

Epidemics

Prerequisites for epidemics to occur include adequate and adjacent numbers of reservoir animals, sufficient quantities of virulent virus, infected intermediate hosts, insect vectors and susceptiple horse and human populations. Outbeak prediction has been inaccurate, implyingf that other, unidentified factors may be important.

Pathogenesis

After inoculation into an equine host, viruses multiply in the muscle, enter the lymphatic circulation and localize in lymph nodes. Viral replication occurs in macrophages and neutrophils with subsequent shedding and significant clearance of viral particles. No further clinical signs develop if clearance is successful but neutralizing Abs are still produced. Viral immunological avoidance mechanisms include erythrocyte and leukocyte absorption. After incomplete elimination, residual virus infects endothelial cells and concentrates in highly vascular organs such as the liver and spleen. In these organs, viral replication produces circulating virus. The second viraemic period is typically associated with early clinical signs. CNS infection occurs within 3-5 days.

Signalment

Unvaccinated adult horses and other equids are at risk in areas with suitable vectors. Vaccinated horses can still develop the disease, particularly if they are young or old.

Clinical Signs

The incubation of the disease after infection with the virus is from 1 to 3 weeks. In the initial stage there is fever, which may be accompanied by depression, and loss of appetite, but the reaction may be so mild it goes unnoticed. The virus causing Eastern Equine Encephalomyelitis (EEE) is the most virulent of the three types and the symptoms produced are the most severe, with a case fatality rate of up to 90%. The viraemia (level of virus in the blood) may be so high with this strain that horse to mosquito to horse cycling can occur. The nervous signs, when they appear, are hypersensitivity to sound and touch with periods of excitement and restlessness with apparent blindness. Affected horses may walk blindly into objects or walls. Muscle twitchings may occur in the face and shoulder muscles. A period of severe depression follows. Affected horses stand with their heads hung low and may have a half-chewed mouthful of feed hanging from their lips. The animal appears to be asleep and is unable to hold up his head and often rests it on some solid object. Although VEE does not cause as high a mortality as WEE/EEE, the clinical signs are similar. However, a second generalised infection may be caused by the virus causing fever, depression, colic and diarrhoea.

Worse in unvaccinated animals. Acute signs of EEE and WEE are nonspecific, last up to 5 days and include:

• mild to severe pyrexia
• anorexia
• stiffness

Early signs transient and often missed:

• pyrexia
• mild depression

Disease progression occurs more frequently with EEE than WEE:

• fever may rise and fall sporadically

Cerebral signs often occur a few days post-infection (but can occur at any time. In the acute phase the following may be noted:

• propulsive walking
• depression
• somnolence
• hyperaesthesia
• agression
• excitability
• frenzy in response to sensory stimulation
• conscious proprioceptive deficits

With progression, worsening cerebral cortical and cranial nerve dysfunction may result in:

• head pressing
• propulsive walking
• blindness
• circling
• head tilt
• facial and appendicular muscle fasciculations
• paralysis of pharynx, larynx and tongue
• recumbency for 1-7 days followed by death

VEE may have similar or different clinical presentations to WEE and EEE, which may relate to a persistently hightitre viraemia with VEE and differences in strain pathogenicity:

• pyrexia peaks early and remains high throuhgout the disease course
• mild fever and leukopenia associated experimentally with endemic strains
• severe pyrexia and leukopenia associated with epidemic strains
• diarrhoea, severe depression recumbency and death may precede neurological signs
• neurological signs around 4 days post-infection
• other associated signs: abortion, oral ulceration, pulmonary haemorrhage, epistaxis

• Paralysis of the lips
• Drooping eyelids
• Incoordination

Diagnosis

Presumptive based on clinical signs and epidemiological features. Definitive diagnosis requires serological tests and/or post-mortem examination. Virus isolation can be performed from blood or spinal fluid samples

Laboratory Tests

A combination of complement fixation (CF), haemagglutination inhibition (HAI) and cross-serum neutralization assays supports the acquisition of a positive diagnosis. A 4-fold increase in antibody (Ab) titre in convlescent sera is quoted for diagnosis but this test lacks sensitivity. The presence of viral Abs within 24hours of the initial viraemia typically precedes clinical signs. Ab titre increases sharply then deteriorates over 6 months. Samples taken when clinical signs appear are likely to miss the Ab peak and may thus demonstrate a decreasing titre. A single sample demonstrating an increased titre using HAI, CF and neutralizing Ab can provide a presumptive diagnosis.

Viral-specific IgM to the surface glycoprotein of Venezuelan EEV may be detected by ELISA, from 3 days post-onset of clinical signs up to 21 days post-infection. The ELISA is useful in acute VEE infections where convalescent serum samples are unobtainable. Viral culture may also be useful for acute VEE. Virus may be isolated from the CSF of acutely infected horses. Virus may be found in brain tissue using fluorescent Ab, ELISA and virus isolation.

Maternal-derived Ab may interfere with diagnosis in foals. The serum half-life of colostral Ab in foals is around 20days.

The virus is identified by complement fixation (CF), immunofluorescence, or plaque reduction neutralisation (PRN) tests. EEE and WEE viral RNA may also be detected by reverse-transcription polymerase chain reaction methods

Clinical Pathology

Changes in cerebrospinal fluid (CSF) include increased cellularity (50-400 mononuclear cells per microlitre) and protein concentration (100-200mg/dl)

Post-mortem findings

PRECAUTION: infective viral particles may be present in CNS and other tissues. The brain and spinal cord are typically grossly normal, but vascular congestion and discolouration of the CNS may be seen. Histologically the entire brain is affected by nonseptic mononuclear cell and neutrophilic inflammation. Severe lesions are noted in the cerebral cortex, thalamus and hypothalamus. Mononuclear meningitis, neuronal degeneration, gliosis and perivascular cuffing with mononuclear cell and neutrophilic infiltration are evident. Immunohistochemistry can be diagnostic. Liquefactive necrosis and haemorrhage of the cerebral cortex, atrophy of the pancreatic acinar cells and hyperplasia of the pancreatic duct cells commonly occur with VEE.

IN VEE there may be damage to other organs such as the pancreas, liver and heart.

Gross pathological lesions are rarely observed in horses and, if present, consist only of the congestion of the brain and meninges. Ecchymotic haemorrhages of traumatic origin may be observed. Microscopic lesions are usually found throughout the central nervous system and can be diagnostic. There is widespread evidence of a severe inflammatory response involving the grey matter. Neuronal degeneration with infiltration by polymorphonuclear leukocytes, diffuse and focal gliosis, and perivascular cuffing with lymphocytes and neutrophils are seen. Also observed are neuronophagia and liquefaction of the neuropil. The extent of the lesions depends on the severity of the infection and the duration of the neurological involvement (16). Brain lesions caused by WEE virus infection are focal and have lymphocytic infiltrations. Brain lesions caused by EEE virus infection are more severe and are found throughout the grey matter. They are characterised by a larger number of neutrophils among the inflammatory cells.

Differential diagnosis

• Other togaviral encephalitides
• Trauma
• Hepatic encephalopathy
• Rabies
• Leukoencephalomalacia
• Bacterial meningoencephalitis
• Equine protozoal myeloencephalitis (EPM)
• Verminous encephalomyelitis
• West Nile Virus (WNV) infection
• Toxicosis

Treatment

No effective, specific treatment is available. Supportive management includes:

• NSAIDs (phenylbutazone, flunixin meglumine) to control pyrexia, inflammation and discomfort
• DMSO IV in a 20% solution to control inflamation, provide some analgesia and mild sedation
• Pentobarbital, diazepam IV, phenobarbital PO or phenytoin IV to control convulsions
• Antibiotic therapy in cases with secondary bacterial infection
• Balanced fluid solutions IV or PO as necessary to correct hydration status
• Dietary supplementation (enteral or parenteral if anorexia persists more than 48 hours)
• Laxatives to minimize the risk of impaction
• Protection of areas susceptible to self-induced trauma and provision of deep bedding
• Sling support if the horse is recumbent

Prognosis

Comatose animals rarely survive. Survivors exhibit functional improvement over weeks to months, but complete recovery from neurological deficits is rare. Residual ataxia, depression and abnormal behaviour is often seen with EEE, less commonly with WEE. The mortality rates for neurological equine viral encephalitis are reportedly:

• EEE 75-100%
• WEE 20-50%
• VEE 40-80%

It is generally assumed that infection does not provide protective immunity, however, protection for up to 2 years has been noted.

Control

Vaccination

Vaccinate susceptible horses annually. Vaccinate horses in the face of an outbreak. Vaccinate mares one month prior to foaling. Colostral-derived Ab persists for 6-7 months. Although folas ca be vaccinated at any time, they should be re-vaccinated at 6 months and at one year if they were vaccinated early. Most vaccines are killed (produced in cell culture and inactivated with formalin) and elicit significant increases in Ab titre after 3 days. Protective titres last for 6-8 months. Some cross-protection is seen between the serotypes but not between WEE and EEE. Monovalent, divalent and trivalent vaccines are available but the response to VEE vaccination alone is decreased in horses previously vaccinated against WEE and EEE. Susceptible horses should be vaccinated annually in late spring or several months before the high risk season. Biannual or triannual vaccination is recommended in regions where the mosquito season is prolonged. Vaccination does not interfere with the ELISA assay for VEE. PRECAUTION: human vaccination recommended for vets in endemic areas.

Vector control

Responsible use of insecticides and repellents, elimination of standing water and stable screening will all help to reduce viral transmission. Environmental application of insecticides may be useful in endemic areas or during an outbreak. Horses infected with Venezuelan EEV should be isolated for 3 weeks after complete recovery and such cases are reportable in the United States.

References

Bertone, J.J (2010) Viral Encephalitis in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) Equine Internal Medicine, Third Edition, Saunders, Chapter 12.

Also known as:

Equine viral encephalitis, Equine viral encephalomyelitis Equine viral encephalitides, Equine viral encephalomyelitides Eastern equine encephalitis, Eastern equine encephalomyelitis, EEE Western equine encephalitis, Western equine encephalomyelitis, WEE Venezuelan equine encephalitis, Venezuelan equine encephalomyelitis, VEE