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; West 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.

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. One of these includes RNA replicase, which copies the viral RNA to form a double-stranded replicative form, in turn this directs the formation of new virions. Western equine encephalitis is made up of an enveloped virion with a spherical capsid. The capsid has a T=4 icosahedral symmetry made of 240 monomers and measuring approximately 65-70nm in diameter. The envelope contains 80 spikes; each spike is a trimer of E1/E2 proteins.

The genome of western equine encephalitis is monopartite, linear, ssRNA(+), and approximately 11-12 kb. The genome has a methylated nucleotide cap and polyadenylated tail. 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 7-21 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.

• The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
• The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
• On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Causes

• [Disease name] may be caused by either [cause1], [cause2], or [cause3].
• [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for [disease name].

Differentiating [disease name] from other Diseases

• [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

Epidemiology and Demographics

• The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• [Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

Physical Examination

• Patients with [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

• There are no [imaging study] findings associated with [disease name].

• [Imaging study 1] is the imaging modality of choice for [disease name].
• On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
• [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.

• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

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