Western equine encephalitis (WEE) is caused by a zoonotic arthropod-borne virus, WEE virus, which belongs to the Togaviridae family and genus Alphavirus. WEE virus is closely related to other arboviral members in the Togaviridae family, namely eastern equine encephalitis and Venezuelan equine encephalitis. Human cases of WEE have occurred in the western and midwestern United States, western Canada, and South America (Guyana, Ecuador, Brazil, Uruguay, and Argentina).

The enzootic cycle of WEE is maintained between passerine birds as the primary reservoirs and the mosquito vector Culex tarsalis. The epizootic transmission to horses and humans is mediated by specific mosquito bridge vectors such as Ochlerotatus melanimon in California, Aedes dorsalis in Utah and New Mexico, and Aedes campestris in New Mexico. Most cases of WEE infection have occurred in summer, from June to September in the United States and a month later in Canada. Similar to Venezuelan equine encephalitis virus, WEE virus can be transmitted through aerosols and so could be used as an agent in bioterrorism.

There has been a significant decline in human cases of WEE since 1988, and no cases have been reported since 2001 according to the US Centers for Disease Control and Prevention (CDC). This decline in incidence is thought to be due to improved mosquito control, a decline in the horse population, and high vaccination rates in horses.

Most human cases of WEE are asymptomatic. In symptomatic patients, a nonspecific febrile syndrome occurs after a 5-10 day incubation period.

Less than 1 in 1000 adult patients develop neuroinvasive encephalitis, but the risk is much higher in children (1:50) and infants (1:1). Typical features of encephalitis are headache, nausea, vomiting, neck stiffness, altered mental status, and seizures. Children and infants tend to have more severe neurologic symptoms.

The overall case fatality rate is estimated to be between 3% and 7% and is especially high in the extremes of age, ie, the young and the very elderly. Among survivors, neurologic sequelae are more common in infants younger than 1 year (sequelae such as intellectual disability, developmental delay) and in elderly patients (sequelae such as parkinsonism, dementia).