Western equine encephalitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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. Western equine encephalitis is contracted by the bite of an infected mosquito, 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:

Characteristic	Data
Nucleic acid	RNA
Sense	ssRNA(+)
Virion	Enveloped
Capsid	Spherical
Symmetry	Yes; T=4 icosahedral
Capsid monomers	240
Monomer length (diameter)	65-70 nm
Additional envelope information	80 spikes; each spike is a trimer of E1/E2 proteins
Genome shape	Linear
Genome length	11-12 kb
Nucleotide cap	Yes
Polyadenylated tail	Yes
Incubation period	5-10 days

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:

1. Attachment of the viral E glycoprotein to host receptors mediates clathrin-mediated endocytosis of virus into the host cell.
2. Fusion of virus membrane with the host cell membrane. RNA genome is released into the cytoplasm.
3. The positive-sense ssRNA virus is translated into a polyprotein, which is cleaved into non-structural proteins necessary for RNA synthesis (replication and transcription).
4. Replication takes place in cytoplasmic viral factories at the surface of endosomes. A dsRNA genome is synthesized from the genomic ssRNA(+).
5. The dsRNA genome is transcribed thereby providing viral mRNAs (new ssRNA(+) genomes).
6. Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
7. Virus assembly occurs at the endoplasmic reticulum.
8. 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:

Disease	Findings
Eastern equine encephalitis	Eastern equine encephalitis presents with acute inflammation of the brain, caused by an arboviral infection; it is less severe than Eastern equine encephalitis. Other findings include fever, nausea, headache, vomiting, photophobia, seizures, and coma.
Venezuelan equine encephalitis	Venezuelan equine encephalitis presents with acute inflammation of the brain, caused by an arboviral infection; complications include severe brain damage. Other findings include fever, nausea, headache, photophobia, seizures, and coma.
Vector-borne encephalitis	Vector-borne encephalitis presents with acute inflammation of the brain, caused by a bacterial infection; complications include severe brain damage as the inflamed brain pushes against the skull, potentially leading to mortality. See also: Tick-borne encephalitis, California encephalitis virus, La Crosse encephalitis, Japanese encephalitis, and West Nile encephalitis
Viral encephalitis	Viral encephalitis presents with acute inflammation of the brain, caused by a viral infection; complications include severe brain damage as the inflamed brain pushes against the skull, potentially leading to mortality. See also: Herpes simplex encephalitis and VZV encephalitis
Encephalopathy	Encephalopathy presents with steady depression, generalized seizures. Generally absent are fever, headache, leukocytosis, and pleocytosis; MRI often appears normal.
Meningitis	Meningitis presents with headache, altered mental status, and inflammation of the meninges, which may develop in the setting of an infection, physical injury, cancer, or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving inflammation, causing neurologic damage and possible mortality. See also: Bacterial meningitis, Viral meningitis, and Fungal meningitis
Brain abscess	Brain abscess presents with an abscess in the brain caused by the inflammation and accumulation of infected material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head trauma or neurological procedures.
Acute disseminated encephalomyelitis (ADEM)	Acute disseminated encephalomyelitis presents with scattered foci of demyelination and perivenular inflammation; it can cause focal neurological signs and decreased ability to focus.

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:

Western Equine Encephalitis Subtype	Clinical Presentation	Laboratory Findings
Neuroinvasive	Template:Unicode Meningitis, encephalitis, acute flaccid paralysis, or other acute signs of central or peripheral neurologic dysfunction, as documented by a physician AND Template:Unicode Absence of a more likely clinical explanation	Template:Unicode Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, cerebrospinal fluid (CSF) OR Template:Unicode Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR Template:Unicode Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen OR Template:Unicode Virus-specific IgM antibodies in cerebrospinal fluid, with or without a reported pleocytosis, and a negative result for other IgM antibodies in cerebrospinal fluid for arboviruses endemic to the region where exposure occurred
Non-neuroinvasive	Template:Unicode Fever and chills as reported by the patient or a health care provider AND Template:Unicode Absence of neuroinvasive disease AND Template:Unicode Absence of a more likely clinical explanation	Template:Unicode Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, or other body fluid, excluding cerebrospinal fluid OR Template:Unicode Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR Template:Unicode Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen

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

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