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{{SK}} 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 [[mosquito]]s 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]]. [[invasive|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]] [[antibody|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.


'''Synonyms and Related Keywords:''' Mosquito-borne  
==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.<ref name="pmid17834966">{{cite journal| author=Meyer KF, Haring CM, Howitt B| title=THE ETIOLOGY OF EPIZOOTIC ENCEPHALOMYELITIS OF HORSES IN THE SAN JOAQUIN VALLEY, 1930. | journal=Science | year= 1931 | volume= 74 | issue= 1913 | pages= 227-8 | pmid=17834966 | doi=10.1126/science.74.1913.227 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17834966  }} </ref>
==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 [[invasive|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 [[mosquito]]s to the human host. Western equine encephalitis virus contains [[positive-sense ssRNA virus|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:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>
 
{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Characteristic
! style="text-align: center; font-weight: bold;" | Data
|-
| Nucleic acid
| [[RNA]]
|-
| Sense
| [[positive-sense ssRNA virus|ssRNA(+)]]
|-
| Virion
| [[enveloped virus|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
|-
| [[Polyadenylation|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.<ref name=WEEOhioPH> WESTERN EQUINE ENCEPHALITIS VIRUS DISEASE. Ohio Department of Health. http://www.odh.ohio.gov/pdf/IDCM/wee.pdf Accessed on March 22, 2016.</ref> 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.<ref name=EEEVILPubHealth> 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. </ref> 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:<ref name=ViralZoneAlpha> Alphavirus. SIB Swiss Institute of Bioinformatics. http://viralzone.expasy.org/viralzone/all_by_species/625.html Accessed on March 15, 2016 </ref>
 
#Attachment of the viral E [[glycoprotein]] to host receptors mediates [[clathrin|clathrin-mediated]] [[endocytosis]] of virus into the host cell.
#Fusion of [[biological membrane|virus membrane]] with the host [[cell membrane]]. RNA genome is released into the [[cytoplasm]].
#The [[positive-sense ssRNA virus]] is [[translate]]d into a [[polyprotein]], which is cleaved into non-structural proteins necessary for RNA synthesis ([[replication]] and [[transcription]]).
#[[Replication]] takes place in [[cytoplasm]]ic viral factories at the surface of [[endosome]]s. A [[dsRNA]] [[genome]] is synthesized from the genomic ssRNA(+).
#The [[dsRNA]] [[genome]] is [[transcribed]] thereby providing viral [[mRNA]]s (new ssRNA(+) genomes).
#Expression of the subgenomic RNA (sgRNA) gives rise to the structural proteins.
#Virus assembly occurs at the [[endoplasmic reticulum]].
#[[Virion]]s 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:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue=  | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145  }} </ref><ref name=NYDeptofHealth> 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 </ref><ref name="pmid21932127">{{cite journal| author=Eckstein C, Saidha S, Levy M| title=A differential diagnosis of central nervous system demyelination: beyond multiple sclerosis. | journal=J Neurol | year= 2012 | volume= 259 | issue= 5 | pages= 801-16 | pmid=21932127 | doi=10.1007/s00415-011-6240-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932127  }} </ref><ref name="pmid11260760">{{cite journal| author=De Kruijk JR, Twijnstra A, Leffers P| title=Diagnostic criteria and differential diagnosis of mild traumatic brain injury. | journal=Brain Inj | year= 2001 | volume= 15 | issue= 2 | pages= 99-106 | pmid=11260760 | doi=10.1080/026990501458335 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11260760  }} </ref>
 
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+
! style="background: #4479BA; width: 50px;" | {{fontcolor|#FFF|Disease}}
! style="background: #4479BA; width: 100px;" | {{fontcolor|#FFF|Similarities}}
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Differentials}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | Classic triad of [[fever]], [[nuchal rigidity]], and [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Photophobia]], [[phonophobia]], [[rash]] associated with [[meningococcemia]], concomitant [[sinusitis]] or [[otitis]], swelling of the [[fontanelle]] in infants (0-6 months)
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fever]], [[headache]], [[hemiparesis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on the location of the abscess; clinically, [[visual disturbance]] including [[papilledema]], decreased [[sensation]]; on imaging, a [[lesion]] demonstrates both ring enhancement and central restricted diffusion
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Demyelinating disease]]s'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ataxia]], [[lethargy]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Multiple sclerosis]]: clinically, [[nystagmus]], [[internuclear ophthalmoplegia]], [[Lhermitte's sign]]; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”)
[[Acute disseminated encephalomyelitis]]: clinically, [[somnolence]], [[myoclonic]] movements, and [[hemiparesis]]; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Substance abuse]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Tremor]], [[headache]], [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, [[paranoia]], sudden [[panic]], [[anxiety]], [[hallucination]]s
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Electrolyte disturbance]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fatigue]], [[headache]], [[nausea]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on deficient ions; clinically, [[edema]], [[constipation]], [[hallucination]]s; on [[EKG]], abnormalities in [[T wave]], [[P wave]], [[QRS complex]]; possible presentations include [[arrhythmia]], [[dehydration]], [[renal failure]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Stroke]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Ataxia]], [[aphasia]], [[dizziness]]
| style="padding: 5px 5px; background: #F5F5F5;" |Varies depending on classification of stroke; presents with positional [[vertigo]], high [[blood pressure]], [[extremities|extremity]] weakness
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Intracranial hemorrhage]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Headache]], [[coma]], [[dizziness]]
| style="padding: 5px 5px; background: #F5F5F5;" | Lobar [[hemorrhage]], [[numbness]], [[tingling]], [[hypertension]], [[hemorrhagic diathesis]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Trauma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Headache]], [[altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Amnesia]], [[loss of consciousness]], [[dizziness]], [[concussion]], [[contusion]]
|-
|}


==Epidemiology and Demographics==
==Epidemiology and Demographics==
639 confirmed cases in the U.S. since 1964.  
Between 1964-2012, there were 640 confirmed human cases in the United States; the last one was observed in 1999.<ref name=WEEOhioPH> WESTERN EQUINE ENCEPHALITIS VIRUS DISEASE. Ohio Department of Health. http://www.odh.ohio.gov/pdf/IDCM/wee.pdf Accessed on March 22, 2016.</ref> In April 2009, the last known Western equine encephalitis fatality occurred in Uruguay.<ref name="pmid21529429">{{cite journal| author=Delfraro A, Burgueño A, Morel N, González G, García A, Morelli J et al.| title=Fatal human case of Western equine encephalitis, Uruguay. | journal=Emerg Infect Dis | year= 2011 | volume= 17 | issue= 5 | pages= 952-4 | pmid=21529429 | doi=10.3201/eid1705.101068 | pmc=PMC3321764 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21529429  }} </ref> The case-fatality rate of western equine encephalitis is < 5%.<ref name=IDSAEnceph> 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.</ref>


==Risk Factors==  
===Age===
*Epidemic disease that is difficult to predict
Western equine encephalitis is most commonly observed among children under 4 years of age and adults over 50 years of age.<ref name=IDSAEnceph> 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.</ref>
*Residents of endemic areas and visitors
*Persons with outdoor work and recreational activities
*Risk exposure increases as population expands into endemic areas
*Unknown overwintering cycle


==Pathophysiology & Etiology==  
===Race===
Western equine encephalitis virus, member of the family Togaviridae, genus Alphavirus. Closely related to eastern and Venezuelan equine encephalitis viruses.
There is no racial predilection for western equine encephalitis.


===History and Symptoms===  
===Seasonal===
Symptoms range from mild flu-like illness to frank encephalitis, coma and death.
Western equine encephalitis is most commonly observed in the summer months.  


=== Other Diagnostic Studies ===
===Geographic Distribution===
==Risk Stratification and Prognosis==
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.


==Treatment==
==Risk Factors==
*No licensed vaccine for human use
Common risk factors in the development of western equine encephalitis are:
*No effective therapeutic drug
*[[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]], [[tremor]]s, and [[altered mental status]].
 
===Complications===
Complications of western equine encephalitis include:
*[[Seizure]]s
*Loss of basic [[motor skill]]s
*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:<ref name=WVPubHealth> 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 </ref><ref name=CDCCritArboInvasive> 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. </ref>
 
{| class="wikitable"
! style="text-align: center; font-weight: bold;" | Western Equine Encephalitis Subtype
! style="text-align: center; font-weight: bold;" | Clinical Presentation
! style="text-align: center; font-weight: bold;" | Laboratory Findings
|-
| style="font-style: italic;" | Neuroinvasive
|
:{{unicode|☑}} [[Meningitis]], [[encephalitis]], acute flaccid [[paralysis]], or other acute signs of central or peripheral neurologic dysfunction, as documented by a [[physician]] '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{unicode|☑}} Isolation of [[virus]] from, or demonstration of specific viral [[antigen]] or [[nucleic acid in]], [[tissue]], [[blood]], [[cerebrospinal fluid]] (CSF) '''OR'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{unicode|☑}} Virus-specific [[IgM]] antibodies in [[serum]] with confirmatory virus-specific neutralizing antibodies in the same or a later specimen '''OR'''
:{{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
|-
| style="font-style: italic;" | Non-neuroinvasive
|
:{{unicode|☑}} [[Fever]] and [[chills]] as reported by the [[patient]] or a [[health care provider]] '''AND'''
:{{unicode|☑}} Absence of [[invasive|neuroinvasive]] disease '''AND'''
:{{unicode|☑}} Absence of a more likely clinical explanation
|
:{{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'''
:{{unicode|☑}} Four-fold or greater change in virus-specific quantitative antibody [[titer]]s in paired sera '''OR'''
:{{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:<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref><ref name= NINDS> 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 </ref>
*[[Fever]]
*[[Chills]]
*[[Headache]]
*[[Fatigue]]
*[[myalgia|Muscle pain]]
*[[Dizziness]]
*[[Altered mental status]]
===Physical Examination===
Common physical examination findings of western equine encephalitis include:<ref name="pmid20551475">{{cite journal| author=Steele KE, Twenhafel NA| title=REVIEW PAPER: pathology of animal models of alphavirus encephalitis. | journal=Vet Pathol | year= 2010 | volume= 47 | issue= 5 | pages= 790-805 | pmid=20551475 | doi=10.1177/0300985810372508 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20551475  }} </ref>
*[[Fever]]
*[[Ataxia]]
*[[Seizure]]s
*[[Obtundation]]
*[[Myalgia]]
*[[myelitis|Acute flaccid myelitis]]
*[[Lethargy]]
*[[Meningism]]
*[[Photophobia]]
*[[Somnolence]]
*[[Coma]]
*[[Motor neuron]] dysfunction


== Primary Prevention ==
===Laboratory Findings===
*Control measures expensive
The diagnostic method of choice for western equine encephalitis is laboratory testing. The positive presence of [[IgM]] [[antibody|antibodies]] is diagnostic of western equine encephalitis. Other laboratory findings consistent with the diagnosis of western equine encephalitis include:<ref name=IDSAEnceph> 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.</ref>
*Limited financial support of surveillance and prevention
*[[Serologic]] [[cross-reactivity]]
*Persistence of [[IgG]] and neutralizing [[antibody|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:<ref name=EncephGeneralMRI> Flavivirus encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/flavivirus-encephalitis Accessed on March 29, 2016. </ref>
*T2 hyperintensity in the [[basal ganglia]] and [[thalamus]]
*Restricted diffusion in the [[basal ganglia]] and [[thalamus]]
*[[Hemorrhage]] less frequently


== Cost-Effectiveness of Therapy ==  
==Treatment==
*Total case costs range from $21,000 for transiently infected individuals to $3 million for severely infected individuals
===Medical Therapy===
*Insecticide applications can cost as much as $1.4 million depending on the size of area treated
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.  


== Suggested Reading and Key General References ==
===Surgery===
http://www.cdc.gov/ncidod/dvbid/arbor/weefact.htm
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:<ref name=EEENYPubHealth> 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.</ref>
*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


[[Category:DiseaseState]]
==References==
[[Category:Infectious disease]]
{{Reflist|2}}
[[Category:Viruses]]
[[Category:Neurology]]




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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][8][9]

Disease Similarities Differentials
Meningitis Classic triad of fever, nuchal rigidity, and altered mental status Photophobia, phonophobia, rash associated with meningococcemia, concomitant sinusitis or otitis, swelling of the fontanelle in infants (0-6 months)
Brain abscess Fever, headache, hemiparesis Varies depending on the location of the abscess; clinically, visual disturbance including papilledema, decreased sensation; on imaging, a lesion demonstrates both ring enhancement and central restricted diffusion
Demyelinating diseases Ataxia, lethargy Multiple sclerosis: clinically, nystagmus, internuclear ophthalmoplegia, Lhermitte's sign; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”)

Acute disseminated encephalomyelitis: clinically, somnolence, myoclonic movements, and hemiparesis; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders

Substance abuse Tremor, headache, altered mental status Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, paranoia, sudden panic, anxiety, hallucinations
Electrolyte disturbance Fatigue, headache, nausea Varies depending on deficient ions; clinically, edema, constipation, hallucinations; on EKG, abnormalities in T wave, P wave, QRS complex; possible presentations include arrhythmia, dehydration, renal failure
Stroke Ataxia, aphasia, dizziness Varies depending on classification of stroke; presents with positional vertigo, high blood pressure, extremity weakness
Intracranial hemorrhage Headache, coma, dizziness Lobar hemorrhage, numbness, tingling, hypertension, hemorrhagic diathesis
Trauma Headache, altered mental status Amnesia, loss of consciousness, dizziness, concussion, contusion

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.[10] The case-fatality rate of western equine encephalitis is < 5%.[11]

Age

Western equine encephalitis is most commonly observed among children under 4 years of age and adults over 50 years of age.[11]

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:[12][13]

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:[5][14]

Physical Examination

Common physical examination findings of western equine encephalitis include:[15]

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:[11]

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:[16]

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:[17]

  • 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. Eckstein C, Saidha S, Levy M (2012). "A differential diagnosis of central nervous system demyelination: beyond multiple sclerosis". J Neurol. 259 (5): 801–16. doi:10.1007/s00415-011-6240-5. PMID 21932127.
  9. De Kruijk JR, Twijnstra A, Leffers P (2001). "Diagnostic criteria and differential diagnosis of mild traumatic brain injury". Brain Inj. 15 (2): 99–106. doi:10.1080/026990501458335. PMID 11260760.
  10. 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.
  11. 11.0 11.1 11.2 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.
  12. 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
  13. 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.
  14. 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
  15. 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.
  16. Flavivirus encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/flavivirus-encephalitis Accessed on March 29, 2016.
  17. 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.