Difference between revisions of "Western equine encephalitis"

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| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Eastern equine encephalitis]]'''
 
| style="padding: 5px 5px; background: #F5F5F5;" |[[Eastern equine encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by an [[arbovirus|arboviral infection]]; it is less severe than Eastern equine encephalitis. Other findings include [[fever]], [[nausea]], [[headache]], [[vomit]]ing, [[photophobia]], [[seizure]]s, and [[coma]].
 
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| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Venezuelan equine encephalitis]]'''
 
| style="padding: 5px 5px; background: #F5F5F5;" |[[Venezuelan equine encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by an [[arbovirus|arboviral infection]]; complications include severe [[brain]] damage. Other findings include [[fever]], [[nausea]], [[headache]], [[photophobia]], [[seizure]]s, and [[coma]].
 
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| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vector-borne encephalitis]]'''
 
| style="padding: 5px 5px; background: #F5F5F5;" |[[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|West Nile encephalitis}}
 
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| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Viral encephalitis]] '''
 
| style="padding: 5px 5px; background: #F5F5F5;" |[[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|VZV encephalitis}}
 
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| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Encephalopathy]]'''
 
| style="padding: 5px 5px; background: #F5F5F5;" |[[Encephalopathy]] presents with steady [[depression]], generalized [[seizures]]. Generally absent are [[fever]], [[headache]], [[leukocytosis]], and [[pleocytosis]]; [[MRI]] often appears normal.
 
 
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| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
 
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''

Revision as of 14:55, 20 April 2016

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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, 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.[1]

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:[2]

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.[3] 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.[4] 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:[2]

  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:[5][6][7]

Disease Findings
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.
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.[3] In April 2009, the last known Western equine encephalitis fatality occurred in Uruguay.[8] The case-fatality rate of western equine encephalitis is < 5%.[9]

Age

Western equine encephalitis is most commonly observed among children under 4 years of age and adults over 50 years of age.[9]

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:

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:[10][11]

Western Equine Encephalitis Subtype Clinical Presentation Laboratory Findings
Neuroinvasive
Meningitis, encephalitis, acute flaccid paralysis, or other acute signs of central or peripheral neurologic dysfunction, as documented by a physician AND
Absence of a more likely clinical explanation
Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, cerebrospinal fluid (CSF) OR
Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR
Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen OR
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
Fever and chills as reported by the patient or a health care provider AND
Absence of neuroinvasive disease AND
Absence of a more likely clinical explanation
Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, or other body fluid, excluding cerebrospinal fluid OR
Four-fold or greater change in virus-specific quantitative antibody titers in paired sera OR
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:[5][12]

Physical Examination

Common physical examination findings of western equine encephalitis include:[13]

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:[9]

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:[14]

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:[15]

  • 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

References

  1. Meyer KF, Haring CM, Howitt B (1931). "THE ETIOLOGY OF EPIZOOTIC ENCEPHALOMYELITIS OF HORSES IN THE SAN JOAQUIN VALLEY, 1930". Science. 74 (1913): 227–8. doi:10.1126/science.74.1913.227. PMID 17834966.
  2. 2.0 2.1 Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016
  3. 3.0 3.1 WESTERN EQUINE ENCEPHALITIS VIRUS DISEASE. Ohio Department of Health. http://www.odh.ohio.gov/pdf/IDCM/wee.pdf Accessed on March 22, 2016.
  4. Eastern Equine Encephalitis Virus (EEEV). Illinois Department of Public Health (2010) http://www.idph.state.il.us/public/hb/hb_eee.htm Accessed on March 15, 2016.
  5. 5.0 5.1 M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.
  6. Kennedy PG (2004). "Viral encephalitis: causes, differential diagnosis, and management". J Neurol Neurosurg Psychiatry. 75 Suppl 1: i10–5. PMC 1765650. PMID 14978145.
  7. Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016
  8. Delfraro A, Burgueño A, Morel N, González G, García A, Morelli J; et al. (2011). "Fatal human case of Western equine encephalitis, Uruguay". Emerg Infect Dis. 17 (5): 952–4. doi:10.3201/eid1705.101068. PMC 3321764. PMID 21529429.
  9. 9.0 9.1 9.2 The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.
  10. Arboviral Infection: Surveillance Protocol (2016) West Virginia Department of Health and Human Resources: Bureau of Public Health (2016). http://www.dhhr.wv.gov/oeps/disease/Zoonosis/Mosquito/Documents/arbovirus/arbovirus-protocol.pdf Accessed on March 3, 2016
  11. Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 Case Definition. National Notifiable Diseases Surveillance System (NNDSS). Centers for Disease Control (2015). https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ Accessed on March 31, 2016.
  12. Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke. National Institutes of Health (2015). http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_encephalitis_meningitis.htm Accessed on February 9, 2015
  13. Steele KE, Twenhafel NA (2010). "REVIEW PAPER: pathology of animal models of alphavirus encephalitis". Vet Pathol. 47 (5): 790–805. doi:10.1177/0300985810372508. PMID 20551475.
  14. Flavivirus encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/flavivirus-encephalitis Accessed on March 29, 2016.
  15. Eastern Equine Encephalitis (EEE). New York State Department of Public Health (2012). https://www.health.ny.gov/diseases/communicable/eastern_equine_encephalitis/fact_sheet.htm Accessed on March 15, 2016.



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