Western equine encephalitis
Synonyms and keywords: WEE; WEEV; West equine encephalitis;

# Overview
Western equine encephalitis is a mild to moderate infection of the central nervous system. Western equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the Togaviridae family of viruses, and the genus Alphavirus. Western equine encephalitis is closely related to eastern equine encephalitis virus and Venezuelan equine encephalitis virus. Western equine encephalitis virus is usually transmitted via mosquitos to the human host, primarily Culiseta melanura and Culex tarsalis. Western equine encephalitis virus must be differentiated from other diseases that cause fever, headache, seizures, and altered mental status. Western equine encephalitis was last observed in humans in the United States in 1999. Prognosis for western equine encephalitis is generally good; western equine encephalitis is considered more mild than eastern equine encephalitis. Neuroinvasive vs non-neuroinvasive western equine encephalitis can be differentiated based on both clinical and laboratory findings. The diagnostic method of choice for western equine encephalitis is laboratory testing. The positive presence of IgM antibodies is diagnostic of western equine encephalitis. There is no treatment for western equine encephalitis; the mainstay of therapy is supportive care. There are currently no human vaccines available for western equine encephalitis.

# Historical Perspective
Western equine encephalitis was first identified by Karl Friedrich Meyer, an American scientist of Swiss origin, in 1930 following an epizootic outbreak in horses in the San Joaquin Valley in California.

# Classification
Western equine encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Western equine encephalitis may also be classified according to neuroinvasiveness of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive. Western equine encephalitis belongs to the Group IV positive-sense ssRNA virus within the Togaviridae family of viruses, and the genus Alphavirus. Western equine encephalitis is closely related to eastern equine encephalitis virus and Venezuelan equine encephalitis virus. Western equine encephalitis is known as an arbovirus, or an arthropod-borne virus.

# Pathophysiology
Western equine encephalitis virus is usually transmitted via mosquitos to the human host. Western equine encephalitis virus contains positive-sense viral RNA; this RNA has its genome directly utilized as if it were mRNA, producing a single protein which is modified by host and viral proteins to form the various proteins needed for replication. The following table is a summary of the western equine encephalitis virus:
Western equine encephalitis is contracted by the bite of an infected mosquito, primarily Culiseta melanura and Culex tarsalis. The virus is maintained in a cycle between either of the mosquitos and avian hosts in freshwater hardwood swamps. Neither are an important vector of western equine virus to humans because both feed almost exclusively on birds. Transmission to humans requires mosquito species capable of creating a "bridge" between infected birds and uninfected mammals, such as some Aedes, Coquillettidia, and other Culex species. The incubation period is 5-10 days. Humans and horses are dead-end hosts for the virus, meaning there is an insufficient amount of western equine encephalitis virus in the blood stream to infect a mosquito. Many cases in horses are fatal. There is no known transmission between horses and humans. Recent studies have demonstrated other equine, such as mules and donkeys, and other animals, such as pigs, reptiles, amphibians, and rodents, can be infected.
Western equine encephalitis virus is transmitted in the following pattern:
- Attachment of the viral E glycoprotein to host receptors mediates clathrin-mediated endocytosis of virus into the host cell.
- Fusion of virus membrane with the host cell membrane. RNA genome is released into the cytoplasm.
- The positive-sense ssRNA virus is translated into a polyprotein, which is cleaved into non-structural proteins necessary for RNA synthesis (replication and transcription).
- Replication takes place in cytoplasmic viral factories at the surface of endosomes. A dsRNA genome is synthesized from the genomic ssRNA(+).
- The dsRNA genome is transcribed thereby providing viral mRNAs (new ssRNA(+) genomes).
- Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
- Virus assembly occurs at the endoplasmic reticulum.
- Virions bud at the endoplasmic reticulum, are transported to the Golgi apparatus, and then exit the cell via the secretory pathway.

# Causes
Western equine encephalitis may be caused by western equine encephalitis virus.

# Differentiating Western equine encephalitis from Other Diseases
Western equine encephalitis virus must be differentiated from other diseases that cause fever, headache, seizures, and altered mental status, such as:

# Epidemiology and Demographics
Between 1964-2012, there were 640 confirmed human cases in the United States; the last one was observed in 1999. In April 2009, the last known Western equine encephalitis fatality occurred in Uruguay. The case-fatality rate of western equine encephalitis is < 5%.

## Age
Western equine encephalitis is most commonly observed among children under 4 years of age and adults over 50 years of age.

## Race
There is no racial predilection for western equine encephalitis.

## Seasonal
Western equine encephalitis is most commonly observed in the summer months.

## Geographic Distribution
Western equine encephalitis virus has been observed in North, Central, and South America; most cases have been reported from the Great Plains and Western regions of the United States.

# Risk Factors
Common risk factors in the development of western equine encephalitis are:
- Age
- Immunosuppression
- Residing or visiting woodland areas
- Mosquito contact
- Bird contact
- Horse contact
- Summer season
- Outdoor recreational activities

# Natural History, Complications and Prognosis

## Natural History
If left untreated, approximately 10% patients with western equine encephalitis may progress to develop a febrile prodrome followed by meningismus, weakness, tremors, and altered mental status.

## Complications
Complications of western equine encephalitis include:
- Seizures
- Loss of basic motor skills
- Loss of coordination
- Meningitis

## Prognosis
Prognosis for western equine encephalitis is generally good; western equine encephalitis is considered more mild than eastern equine encephalitis.

# Diagnosis

## Diagnostic criteria
Neuroinvasive vs non-neuroinvasive western equine encephalitis can be differentiated based on both clinical and laboratory findings. These include:

## History and Symptoms
If possible, a detailed and thorough history from the patient is necessary. Common symptoms of western equine encephalitis include:
- Fever
- Chills
- Headache
- Fatigue
- Muscle pain
- Dizziness
- Altered mental status

## Physical Examination
Common physical examination findings of western equine encephalitis include:
- Fever
- Ataxia
- Seizures
- Obtundation
- Myalgia
- Acute flaccid myelitis
- Lethargy
- Meningism
- Photophobia
- Somnolence
- Coma
- Motor neuron dysfunction

## Laboratory Findings
The diagnostic method of choice for western equine encephalitis is laboratory testing. The positive presence of IgM antibodies is diagnostic of western equine encephalitis. Other laboratory findings consistent with the diagnosis of western equine encephalitis include:
- Serologic cross-reactivity
- Persistence of IgG and neutralizing antibodies
- Confirmation of arboviral-specific neutralizing antibodies in enzyme linked immunosorbent assay (ELISA)
- In cerebrospinal fluid:
Pleocytosis
Increased protein levels
Normal to slightly elevated glucose levels
- Pleocytosis
- Increased protein levels
- Normal to slightly elevated glucose levels

## Imaging Findings
There are no imaging findings specifically associated with western equine encephalitis. MRI is the modality of choice to evaluate all types of encephalitis. Although the pattern of involvement varies, in general, sites of involvement include:
- T2 hyperintensity in the basal ganglia and thalamus
- Restricted diffusion in the basal ganglia and thalamus
- Hemorrhage less frequently

# Treatment

## Medical Therapy
There is no treatment for western equine encephalitis; the mainstay of therapy is supportive care. Because supportive care is the only treatment for western equine encephalitis, physicians often do not request the tests required to specifically identify the western equine encephalitis virus.

## Surgery
Surgical intervention is not recommended for the management of western equine encephalitis.

## Prevention
There is no human vaccine for western equine encephalitis. There is a western equine encephalitis vaccine available for horses. In consultation with a veterinarian, vaccinate your horse(s) against the virus. Primary prevention strategies for western equine encephalitis include:
- Removal of standing water
- Screens on doors and windows
- When outdoors, wearing:
Insect repellent containing DEET
Long sleeves, pants; tucking in pants into high socks
- Insect repellent containing DEET
- Long sleeves, pants; tucking in pants into high socks