Encephalitis is defined as an acute inflammation of the brain parenchyma, often with secondary meningeal involvement. Although some bacterial, fungal, and autoimmune disorders are capable of causing encephalitis, most cases are secondary to viruses. The incidence is 1 case per 200,000 population in the United States, with herpes simplex virus being the most prominent cause and arboviruses accounting for 10% (occasionally 50% during epidemic years) of cases. (See Epidemiology.)
Western equine encephalitis (WEE) is spread primarily by the vector mosquito Culex tarsalis. Other mosquitoes (eg, Aedes species) and, occasionally, small, wild mammals also have been known to spread the virus. C tarsalis is a mosquito that often is found on the West Coast of the United States and that prefers warm, moist environments. In these locations, cycles of wild bird and mosquito interactions and infectivity allow the virus to remain endemic. No cases of bird transmission of the disease have been reported, making mosquitoes the primary vector and birds simply reservoirs. Epidemic outbreaks in the equine or pheasant population often precede human epidemics of WEE. (See Pathophysiology and Etiology.)
WEE is a summertime infection found in the Western United States, and it is more common in rural areas. (See Epidemiology.)
WEE belongs to the genus Alphavirus, in the family Togaviridae. Togaviridae also encompasses Eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE). These alphaviruses are spherical and have a diameter of 60-65 nm. The outer layer consists of a glycoprotein shell with protruding glycoprotein spikes, beneath which lies the lipid bilayer. The nucleocapsid core contains the single-stranded ribonucleic acid (RNA) genome. [1, 2]
Of the alphaviruses, EEE virus most closely resembles WEE and may have been a genetic predecessor of WEE. The completed nucleotide sequence for WEE revealed an 11,508-nucleotide organism with an 84% concordance of protein similarity with EEE.  Additional cross-genetic research has revealed that the virus is an amalgamation of the EEE and Sindbis virus.
Further genetic research has differentiated the potential virulence of particular strains of WEE. Of 3 epizootic strains and 5 enzootic strains, researchers found that the enzootic strains were neither neurovirulent nor neuroinvasive but that the epizootic forms were virulent. Epizootic forms are believed to arise from nonpathogenic strains (eg, AG80-646), which are consistently maintained in enzootic cycles, allowing an opportunity for further screening of vectors with potential precursors of the virulent WEE strains. 
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The primary complications other than death in WEE are variable levels of central nervous system (CNS) impairment. Numerous factors, including location and specific inflammatory cell response, may determine the resulting impairment.
Demyelination is a known byproduct of this disease, and it can be detected radiologically. Often, these areas heal quite well unless overlying fibrosis or cell death occurs.
Additional complications include mental retardation, behavioral changes, paralysis, permanent focal neurologic deficits, seizure disorders, cerebellar damage, and choreoathetosis. Cases of Parkinson syndrome have been reported in adults after WEE infection. (See History and Physical Examination.)
WEE can be reported electronically to a CDC-run site called ArboNet, which assists states in tracking mosquito-borne viruses.
Pathophysiology and Etiology
The WEE virus is a neurotropic alphavirus, which causes encephalitis and viral symptoms without an associated rash. The disease is usually subclinical and may mimic many viral and inflammatory syndromes.
Diffuse CNS involvement characterizes WEE in its more severe stages. Much of the damage is mediated by the large number of immunologically active cells that enter the brain parenchyma and perivascular areas. Focal necrosis is often found in the striatum, globus pallidus, cerebral cortex, thalamus, pons, and meninges. Neutrophils and macrophages may infiltrate the brain parenchyma and may cause neuronal destruction, neuronophagia, focal necrosis, and spotty demyelination. Vascular inflammation with endothelial proliferation, small vessel thrombosis, and perivascular cuffing may also occur. Cell death by apoptosis occurs primarily in the glial and inflammatory cells. Gross inspection during autopsy reveals edema, leptomeningeal vascular congestion, hemorrhage, and encephalomalacia. In infants or children who die of the disease, diffuse atrophy, particularly of the cortex, may be present.
The virus is transmitted from the mosquito into subcutaneous and cutaneous tissue of the host. It cannot be transmitted via the aerosol route. The virus can also be transferred transplacentally. In the fetus, infection often results in massive cerebral necrosis and death. Infection via contaminated blood transfusions is unlikely because the level of viremia in the donor is extremely low.
The infected individual usually develops a general viral prodrome with fevers, chills, weakness, headache, or myalgias. Viral replication in nonneural tissues, most often adjacent or lymphoid tissue, marks this period.
The virus binds to specific tissue receptors, undergoes endocytosis, and begins an RNA-dependent synthesis of RNA and protein. If the inoculum is high enough, a subsequent viremia develops, with eventual translocation to the CNS via cerebral capillary endothelial cells. The exact mechanism of this is not known but is believed to be secondary to vascular infiltration because factors that increase vascular permeability often facilitate neuroinvasion. Cell-to-cell spread in the CNS occurs via neighboring dendrites and axons.
The initial symptoms may progress rapidly to CNS symptoms of mental confusion, somnolence, coma, and death in 1-2 days, or they may resolve without sequelae.
During epidemics, a significant percentage of the population seroconverts, but the case-infection ratio is low in human adults (1:1000) and high in infants (1:1). Most infected individuals rarely experience severe CNS manifestations, and most infections are subclinical. An inverse ratio has been found between age and clinical CNS manifestations, including seizures and other sequelae.
Although no individual risk factors exist except for age, behavioral risk factors exist. Behavioral risk factors primarily include outdoor activities during peak mosquito activity, most often in rural areas.
Occurrence in the United States
Western equine encephalitis (WEE) often is found in states west of the Mississippi River, west of the Rocky Mountains, and in the corresponding Canadian provinces. The virus tends to have a sporadic or a consistent infectivity, based on the community. Sporadic cases have occurred in the Sacramento Valley, Calif, but infection is consistent in the nearby Imperial Valley, Calif. Additionally, local strains rarely extend into neighboring environments.
A study of WEE from 4 different regions of northern California revealed that the strains have evolved independently, with little movement between regions. However, in southern California, the virus tends to circulate more freely secondary to the movement of birds and mosquitoes. Most notably, WEE is able to survive a wintering effect and to reappear in a similar region because of an ability to survive in the immature Aedes larva and diapausing eggs. The summer bird– C tarsalis cycle that is then responsible for most infections is secondary to viral amplification during the spring.
WEE is most common between April and September, with peaks in July and August, which likely is due to the peak vector population during these periods.
Although weather plays an important role in the spread of WEE, geographic epidemiology has indicated vector spread via wind distribution is unlikely; thus, epidemic origins are difficult to judge. Warmth is an important factor in the promulgation of the virus, because it facilitates an alteration in the transmission rate such that a drop in temperature of a few degrees can differentiate between a 10-month and an 8-month transmission season. Heavy rainfalls or prominently snowy seasons also can increase the vector population.  An increase in global temperature may increase the duration of infectivity in the future.
The annual incidence of the virus varies greatly because of the presence of endemic and epidemic forms. The number of cases tends to increase during epidemic years, the worst of which occurred in the western United States and Canadian plains in 1941 and resulted in 300,000 cases of encephalitis in mules and horses and 3336 cases in humans. Because of the geographic and vector similarities between St. Louis encephalitis and WEE, epidemic outbreaks of both frequently overlap.
With the moderate prevalence of WEE in some California communities, neutralizing antibodies originally were believed to be widespread in this population. However, only a low percentage (>1%) of people with these antibodies has been discovered. This finding may be explained by the low rates of contact between infectious mosquitoes and humans.
A subtype of WEE in Argentina is a likely endemic reservoir in South America. Aedes albofasciatus, a neotropical flood mosquito, is the primary vector in this region. The mosquito is relatively ubiquitous and tends to have varied bursts of epidemic growth based on larval concentration factors and weather factors.
Sex- and age-related demographics
WEE has been found, based on cumulative cases, to be more common in males than in females, a situation that is believed to be secondary to frequent occupational exposure of rural land workers.
WEE is most common among infants because of the high case-infection ratio (1:1). Adults are often targets of the vector, but they have a very low infectivity rate (1:1000). However, older adults tend to develop more severe disease. Infants and children younger than 4 years also develop more severe disease and are more likely to develop CNS manifestations of infection with the virus.
Patients infected with Western equine encephalitis (WEE) who do not develop neurologic signs or symptoms have an excellent prognosis.
Patients with mild neurologic symptoms often rapidly recover.
Once adults recover, they often have very few residual effects.
Children who develop neurologic symptoms have a poorer prognosis.
In addition, patients who develop seizures are more likely to develop a subsequent lifetime seizure disorder.
Reported neurologic sequelae include developmental delay, motor impairments (pyramidal and extrapyramidal), and residual behavioral problems.
The case-fatality rates vary for adults and children. The fatality rate is 3-4%, in stark contrast to EEE, which has a 50-70% mortality rate.
The morbidity of such illnesses is higher in infants than in adults. Infected children have a 30% chance of developing neurologic sequelae, including retardation, seizures, spasticity, or behavioral disorders. The infectivity rate is 1:1000 in adults, 1:58 in children aged 1-4 years, and 1:1 in infants younger than 1 year.
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