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==Overview==
==Overview==
Japanese encephalitis (JE) virus is the leading cause of [[vaccine]]-preventable [[encephalitis]] in Asia and the western Pacific. For most travelers to Asia, the risk for JE is very low but varies based on destination, duration of travel, season, and activities. JE virus is maintained in a cycle involving mosquitoes and [[vertebrate]] hosts, mainly pigs and wading birds. Humans can be infected when bitten by an infected mosquito. Most human [[infection]]s are [[asymptomatic]] or result in only mild symptoms. However, a small percentage of infected persons develop [[inflammation]] of the brain ([[encephalitis]]), with symptoms including sudden onset of [[headache]], high [[fever]], [[disorientation]], [[coma]], [[tremor]]s and [[convulsion]]s. About 1 in 4 cases are fatal. There is no specific treatment for JE. Patient management focuses on supportive care and management of [[complication]]s. Steps to prevent JE include using personal protective measures to prevent mosquito bites and [[vaccination]].
Japanese encephalitis is a moderate [[infection]] of the [[central nervous system]]. Japanese encephalitis virus is a Group IV positive-sense ssRNA virus within the ''[[Flaviviridae]]'' family of viruses, and the genus ''[[Flavivirus]]''. Japanese encephalitis virus is closely related to [[Yellow fever virus]], [[Dengue virus]], [[West Nile virus]], and [[St. Louis encephalitis|St. Louis encephalitis virus]].<ref name=ViralZoneFlavi> Flavivirus. SIB Swiss Institute of Bioinformatics (2015). http://viralzone.expasy.org/viralzone/all_by_species/24.html Accessed on April 12, 2016</ref> Japanese encephalitis is also known as an [[arbovirus]], or an arthropod-borne virus. Japanese encephalitis virus is usually transmitted via [[mosquito]]s to the human host. Japanese encephalitis must be differentiated from other diseases that cause nondescript symptoms, which include [[fever]], [[headache]], and [[vomiting]]. Prognosis is generally poor. Approximately 20-30% of patients progress to [[mortality]]. Among patients who survive, approximately 50% suffer severe [[neurological]], [[cognitive]], or [[psychological]] deficits.<ref name="pmid22993280">{{cite journal| author=Khandaker G, Zurynski Y, Buttery J, Marshall H, Richmond PC, Dale RC et al.| title=Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric hospitals. | journal=Neurology | year= 2012 | volume= 79 | issue= 14 | pages= 1474-81 | pmid=22993280 | doi=10.1212/WNL.0b013e31826d5ea7 | pmc=PMC4098823 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22993280  }} </ref> The diagnostic method of choice for Japanese encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of Japanese encephalitis include detection of [[IgM]] antibodies in [[serum]] and [[cerebrospinal fluid]], moderate [[leukocytosis]], mild [[anemia]], and [[hyponatremia]]. There is no treatment for Japanese encephalitis; the mainstay of therapy is supportive care.<ref name=NHSUKJapEnceph> Japanese encephalitis. National Health Service United Kingdom (2016). http://www.nhs.uk/Conditions/Japanese-encephalitis/Pages/Introduction.aspx Accessed on April 12, 2016. </ref> There are approximately 15 vaccines available for the prevention of Japanese encephalitis.  


==Historical Perspective==
==Historical Perspective==
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==Classification==
==Classification==
Japanese encephalitis virus is a Group IV positive-sense ssRNA virus within the ''[[Flaviridae]]'' family of viruses, and the genus ''[[Flavivirus]]''. Japanese encephalitis virus is closely related to [[yellow fever virus]], [[dengue virus]], [[west nile virus]], and [[St. Louis encephalitis|St. Louis encephalitis virus]].<ref name=ViralZoneFlavi> Flavivirus. SIB Swiss Institute of Bioinformatics (2015). http://viralzone.expasy.org/viralzone/all_by_species/24.html Accessed on April 12, 2016</ref> Japanese encephalitis is also known as an [[arbovirus]], or an arthropod-borne virus.
Japanese encephalitis virus is a Group IV positive-sense ssRNA virus within the ''[[Flaviviridae]]'' family of viruses, and the genus ''[[Flavivirus]]''. Japanese encephalitis virus is closely related to [[Yellow fever virus]], [[Dengue virus]], [[West Nile virus]], and [[St. Louis encephalitis|St. Louis encephalitis virus]].<ref name=ViralZoneFlavi> Flavivirus. SIB Swiss Institute of Bioinformatics (2015). http://viralzone.expasy.org/viralzone/all_by_species/24.html Accessed on April 12, 2016</ref> Japanese encephalitis is also known as an [[arbovirus]], or an arthropod-borne virus.


==Pathophysiology==
==Pathophysiology==
 
Japanese encephalitis virus is usually transmitted via [[mosquito]]s to the human host. Japanese 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]]. Transmission to humans requires mosquito species capable of creating a "bridge" between infected animals and uninfected humans; this occurs when humans become part of the enzootic cycle. The [[incubation period]] is 5-15 days.<ref name=CDCJaEnceph2> Japanese Encephalitis Symptoms and Treatment. Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. (2015) http://www.cdc.gov/japaneseencephalitis/symptoms/ Accessed on April 12, 2016. </ref> Humans are dead-end hosts for the virus, meaning there is an insufficient amount of Japanese encephalitis virus in the blood stream to infect a mosquito; there is also no evidence of person to person spread.<ref name=WHOJaEncephFact> Japanese encephalitis - Fact sheet No 386. World Health Organization (WHO) (2015) http://www.who.int/mediacentre/factsheets/fs386/en/ Accessed on April 12, 2016</ref>


==Causes==
==Causes==
Japanese encephalitis may be caused by Japanese encephalitis virus. Japanese encephalitis virus is closely related to the [[West Nile virus]], [[Dengue virus]], [[Murray Valley encephalitis virus]], and [[St. Louis encephalitis]] virus.<ref name=ViralZoneFlavi> Flavivirus. SIB Swiss Institute of Bioinformatics (2015). http://viralzone.expasy.org/viralzone/all_by_species/24.html Accessed on April 12, 2016</ref>


==Differentiating Japanese encephalitis from Other Diseases==
==Differentiating Japanese encephalitis from Other Diseases==
Japanese encephalitis must be differentiated from other diseases that cause nondescript symptoms, which include [[fever]], [[headache]], and [[vomiting]], such as [[meningitis]], [[malaria]], and other [[demyelinating disease]]s.<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>


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence of Japanese encephalitis in patients younger than 19 years old is approximately 10-100 per 100,000 individuals worldwide.<ref name="pmid19527110">{{cite journal| author=Kollaritsch H, Paulke-Korinek M, Dubischar-Kastner K| title=IC51 Japanese encephalitis vaccine. | journal=Expert Opin Biol Ther | year= 2009 | volume= 9 | issue= 7 | pages= 921-31 | pmid=19527110 | doi=10.1517/14712590903042282 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19527110  }} </ref> The case-fatality rate of Japanese encephalitis is approximately 20-30% worldwide. Japanese encephalitis more commonly affects individuals younger than 18 years of age. Japanese encephalitis usually affects individuals of the Asian race. Japanese encephalitis is most commonly observed in the summer months within temperate climate zones. Japanese encephalitis is a common disease that tends to affect approximately 30,000 to 70,000 individuals in Asia annually.<ref name=WHOJaEncephFact> Japanese encephalitis - Fact sheet No 386. World Health Organization (WHO) (2015) http://www.who.int/mediacentre/factsheets/fs386/en/ Accessed on April 12, 2016</ref>


==Risk Factors==
==Risk Factors==
The most potent risk factor in the development of Japanese encephalitis is residing in Southeast Asia and Western Pacific regions. Other risk factors include summer season, outdoor recreational activities, and contact with mosquitos, birds, and pigs.<ref name="pmid16943399">{{cite journal| author=Solomon T| title=Control of Japanese encephalitis--within our grasp? | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 9 | pages= 869-71 | pmid=16943399 | doi=10.1056/NEJMp058263 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16943399  }} </ref><ref name=CDCJapEnceph1> Japanese encephalitis - Frequently Asked Questions. CDC Centers for Disease Control and Prevention. (2015) http://www.cdc.gov/japaneseencephalitis/qa/index.html Accessed on April 12, 2016</ref>


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, 50% of patients with Japanese encephalitis may progress to develop severe [[neurological]] deficits, such as [[deafness]], [[hemiparesis]], and [[aphasia]]. Common complications of Japanese encephalitis include [[seizure]]s, [[coma]], and [[spastic paralysis]]. Prognosis is generally poor. Approximately 20-30% of patients progress to [[mortality]]. Among patients who survive, approximately 50% suffer severe [[neurological]], [[cognitive]], or [[psychological]] deficits.<ref name="pmid22993280">{{cite journal| author=Khandaker G, Zurynski Y, Buttery J, Marshall H, Richmond PC, Dale RC et al.| title=Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric hospitals. | journal=Neurology | year= 2012 | volume= 79 | issue= 14 | pages= 1474-81 | pmid=22993280 | doi=10.1212/WNL.0b013e31826d5ea7 | pmc=PMC4098823 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22993280  }} </ref>


==Diagnosis==
==Diagnosis==
===History and Symptoms===
===History and Symptoms===
Less than 1% of people infected with Japanese encephalitis (JE) virus develop clinical illness. Mild [[infection]]s occur without apparent [[symptom]]s other than [[fever]] with [[headache]]. More severe infection is marked by quick onset [[headache]], high [[fever]], [[neck stiffness/pain|neck stiffness]], [[stupor]], [[disorientation]], [[coma]], [[tremors]], occasional [[convulsions]] (especially in [[infant]]s) and [[spastic]] (but rarely [[flaccid]]) [[paralysis]].
Most patients infected with Japanese encephalitis remain [[asymptomatic]]; 1% of infected individuals develop clinical disease. The [[incubation period]] for Japanese encephalitis is usually 5-15 days. Common symptoms of Japanese encephalitis include [[fever]], [[headache]], and [[vomiting]], [[neck stiffness/pain|neck stiffness]], [[stupor]], [[disorientation]], [[coma]], [[tremors]], and [[spastic]] (but rarely [[flaccid]]) [[paralysis]].<ref name=CDCClinical> Japanese Encephalitis, Clinical and Laboratory Evaluation. Centers for Disease Control and Prevention (2015). http://www.cdc.gov/japaneseencephalitis/healthcareproviders/healthcareproviders-clinlabeval.html Accessed on April 14, 2016. </ref><ref name="pmid23235298">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Expanding poliomyelitis and measles surveillance networks to establish surveillance for acute meningitis and encephalitis syndromes--Bangladesh, China, and India, 2006-2008. | journal=MMWR Morb Mortal Wkly Rep | year= 2012 | volume= 61 | issue= 49 | pages= 1008-11 | pmid=23235298 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23235298  }} </ref>
 
===Physical Examination===
===Physical Examination===
Signs of Japanese encephalitis which develop during the [[acute]] encephalitic stage include [[neck rigidity]], [[cachexia]], [[hemiparesis]], [[convulsion]]s and a raised body temperature between 38 and 41 degrees Celsius. The classical description of Japanese encephalitis includes a [[Parkinsonian]] syndrome with masklike [[facies]], [[tremor]], cogwheel rigidity, and [[choreoathetosis|choreoathetoid]] movements. [[Acute]] [[flaccid paralysis]], with clinical and [[pathological]] features similar to those of [[poliomyelitis]], has also been associated with JE.
Patients with Japanese encephalitis are usually ill-appearing. Physical examination of patients with Japanese encephalitis is usually remarkable for [[meningism]], [[fever]], and [[convulsions]]. Signs of Japanese encephalitis which develop during the [[acute]] encephalitic stage include [[neck rigidity]], [[cachexia]], [[hemiparesis]], [[convulsion]]s, and an elevated body temperature between 38-41°C. The classical description of Japanese encephalitis includes a [[Parkinsonian]] syndrome with masklike [[facies]], [[tremor]], cogwheel rigidity, and [[choreoathetosis|choreoathetoid]] movements. [[Acute]] [[flaccid paralysis]], with clinical and [[pathological]] features similar to those of [[poliomyelitis]], has also been associated with Japanese encephalitis.
 
===Laboratory Findings===
===Laboratory Findings===
[[Diagnosis]] of Japanese encephalitis is based on a combination of clinical signs and [[symptom]]s and specialized laboratory tests of [[blood]] or [[cerebrospinal fluid]]. It is diagnosed by detection of [[antibodies]] in [[serum]] and [[CSF]] ([[cerebrospinal fluid]]) by [[IgM]] capture [[ELISA]]. Clinical laboratory findings might include a moderate [[leukocytosis]], mild [[anemia]], and [[hyponatremia]]. Cerebrospinal fluid (CSF) typically has a mild to moderate [[pleocytosis]] with a [[lymphocytic]] predominance, slightly elevated [[protein]], and normal ratio of CSF to [[plasma glucose]]. Because humans have low or undetectable levels of [[viremia]] by the time distinctive clinical symptoms are recognized, virus isolation and [[nucleic acid]] amplification tests are insensitive and should not be used for ruling out a diagnosis of JE.
The diagnostic method of choice for Japanese encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of Japanese encephalitis include detection of [[IgM]] antibodies in [[serum]] and [[cerebrospinal fluid]], moderate [[leukocytosis]], mild [[anemia]], and [[hyponatremia]]. [[Cerebrospinal fluid]] typically has a mild to moderate [[pleocytosis]] with a [[lymphocytic]] predominance, slightly elevated [[protein]], and normal ratio to [[plasma glucose]]. Because humans have low or undetectable levels of [[viremia]] by the time distinctive clinical symptoms are recognized, virus isolation and [[nucleic acid]] amplification tests are insensitive and should not be used for ruling out a diagnosis of Japanese encephalitis.<ref name=CDCJaEnceph3> Japanese Encephalitis Diagnostic Testing. Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. (2015) http://www.cdc.gov/japaneseencephalitis/healthcareproviders/healthcareproviders-diagnostic.html Accessed on April 19, 2016. </ref>
 
===CT===
===CT===
On CT scan, Japanese encephalitis is characterized by symmetric or asymmetric [[bilateral]] [[thalamus|thalamic]] hypodensities, and [[subacute]] or [[chronic]] [[hemorrhagic]] [[lesion]]s.


===MRI===
===MRI===
[[Magnetic resonance imaging]] ([[MRI]]) of the brain is better than [[computed tomography]] ([[CT]]) for detecting Japanese encephalitis virus-associated abnormalities such as changes in the [[thalamus]], [[basal ganglia]], [[midbrain]], [[pons]], and [[medulla]]. Thalamic [[lesions]] are the most commonly described abnormality; although these can be highly [[specificity|specific]] for JE in the appropriate clinical context, they are not a very [[sensitivity (test)|sensitive]] marker of JE.
[[MRI]] is the imaging modality of choice for Japanese encephalitis. On MRI, Japanese encephalitis is characterized by symmetric or asymmetric [[bilateral]] [[thalamus|thalamic]] hypodensities, and [[subacute]] or [[chronic]] [[hemorrhagic]] [[lesion]]s.
===Other Diagnostic Studies===
 
[[EEG]] abnormalities in Japanese encephalitis may include [[theta wave|theta]] and [[delta wave|delta]] [[coma]], burst suppression, [[epileptic|epileptiform]] activity, and occasionally [[alpha wave|alpha]] coma.
===Other Imaging Studies===
On [[EEG]], Japanese encephalitis is characterized by [[theta wave|theta]] and [[delta wave|delta]] [[coma]], burst suppression, [[epileptic|epileptiform]] activity, and occasionally [[alpha wave|alpha]] coma.<ref name=CDCJaEnceph2> Japanese Encephalitis Symptoms and Treatment. Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. (2015) http://www.cdc.gov/japaneseencephalitis/symptoms/ Accessed on April 12, 2016. </ref>


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
No specific treatments have been found to benefit patients with Japanese encephalitis, but [[hospitalization]] for supportive care and close observation is generally required. Treatment is [[symptomatic]]. Rest, fluids, and use of pain relievers and medication to reduce [[fever]] may relieve some [[symptom]]s.
There is no treatment for Japanese encephalitis; the mainstay of therapy is supportive care.<ref name=NHSUKJapEnceph> Japanese encephalitis. National Health Service United Kingdom (2016). http://www.nhs.uk/Conditions/Japanese-encephalitis/Pages/Introduction.aspx Accessed on April 12, 2016. </ref>
 
===Primary Prevention===
===Primary Prevention===
The control of Japanese encephalitis is based essentially on three interventions: mosquito control, avoiding human exposure to mosquitoes and [[immunization]]. Mosquito control has been very difficult to achieve in rural settings and avoidance of exposure is difficult as Culex mosquitoes bite during day time. Immunization is the only effective method for sustainable control. Routine immunization of school-age children is currently in use in Korea, Japan, China, Thailand and Taiwan. The introduction of the JE vaccine into the [[Expanded Program on Immunization (Philippines)|Expanded Program of Immunization]] has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka and China.<ref name="pmid18953721">{{cite journal| author=Tauber E, Dewasthaly S| title=Japanese encephalitis vaccines--needs, flaws and achievements. | journal=Biol Chem | year= 2008 | volume= 389 | issue= 5 | pages= 547-50 | pmid=18953721 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18953721  }} </ref>
Effective measures for the primary prevention of Japanese encephalitis include mosquito population control, avoidance of mosquitos, and [[immunization]]. Mosquito control has been difficult to achieve in rural settings. Avoidance of exposure is also difficult, as ''Culex'' mosquitos are active during day hours. Immunization is the only effective method for sustainable control. Routine immunization of school-age children is currently in use in Korea, Japan, China, Thailand, and Taiwan. The introduction of the Japanese encephalitis vaccine into the [[Expanded Program on Immunization (Philippines)|Expanded Program of Immunization]] has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka, and China.<ref name="pmid18953721">{{cite journal| author=Tauber E, Dewasthaly S| title=Japanese encephalitis vaccines--needs, flaws and achievements. | journal=Biol Chem | year= 2008 | volume= 389 | issue= 5 | pages= 547-50 | pmid=18953721 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18953721  }} </ref>


===Secondary Prevention===
===Secondary Prevention===
There are no secondary preventive measures available for Japanese encephalitis.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
   
   
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Latest revision as of 18:06, 18 September 2017

Japanese encephalitis Microchapters

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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]

Overview

Japanese encephalitis is a moderate infection of the central nervous system. Japanese encephalitis virus is a Group IV positive-sense ssRNA virus within the Flaviviridae family of viruses, and the genus Flavivirus. Japanese encephalitis virus is closely related to Yellow fever virus, Dengue virus, West Nile virus, and St. Louis encephalitis virus.[1] Japanese encephalitis is also known as an arbovirus, or an arthropod-borne virus. Japanese encephalitis virus is usually transmitted via mosquitos to the human host. Japanese encephalitis must be differentiated from other diseases that cause nondescript symptoms, which include fever, headache, and vomiting. Prognosis is generally poor. Approximately 20-30% of patients progress to mortality. Among patients who survive, approximately 50% suffer severe neurological, cognitive, or psychological deficits.[2] The diagnostic method of choice for Japanese encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of Japanese encephalitis include detection of IgM antibodies in serum and cerebrospinal fluid, moderate leukocytosis, mild anemia, and hyponatremia. There is no treatment for Japanese encephalitis; the mainstay of therapy is supportive care.[3] There are approximately 15 vaccines available for the prevention of Japanese encephalitis.

Historical Perspective

Japanese encephalitis was first discovered in 1871 following a large number of recurring outbreaks in the summer months. In 1930, the first vaccine was developed to prevent Japanese encephalitis; today, there are approximately 15 vaccines available.[4]

Classification

Japanese encephalitis virus is a Group IV positive-sense ssRNA virus within the Flaviviridae family of viruses, and the genus Flavivirus. Japanese encephalitis virus is closely related to Yellow fever virus, Dengue virus, West Nile virus, and St. Louis encephalitis virus.[1] Japanese encephalitis is also known as an arbovirus, or an arthropod-borne virus.

Pathophysiology

Japanese encephalitis virus is usually transmitted via mosquitos to the human host. Japanese 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. Transmission to humans requires mosquito species capable of creating a "bridge" between infected animals and uninfected humans; this occurs when humans become part of the enzootic cycle. The incubation period is 5-15 days.[5] Humans are dead-end hosts for the virus, meaning there is an insufficient amount of Japanese encephalitis virus in the blood stream to infect a mosquito; there is also no evidence of person to person spread.[6]

Causes

Japanese encephalitis may be caused by Japanese encephalitis virus. Japanese encephalitis virus is closely related to the West Nile virus, Dengue virus, Murray Valley encephalitis virus, and St. Louis encephalitis virus.[1]

Differentiating Japanese encephalitis from Other Diseases

Japanese encephalitis must be differentiated from other diseases that cause nondescript symptoms, which include fever, headache, and vomiting, such as meningitis, malaria, and other demyelinating diseases.[7][8]

Epidemiology and Demographics

The incidence of Japanese encephalitis in patients younger than 19 years old is approximately 10-100 per 100,000 individuals worldwide.[9] The case-fatality rate of Japanese encephalitis is approximately 20-30% worldwide. Japanese encephalitis more commonly affects individuals younger than 18 years of age. Japanese encephalitis usually affects individuals of the Asian race. Japanese encephalitis is most commonly observed in the summer months within temperate climate zones. Japanese encephalitis is a common disease that tends to affect approximately 30,000 to 70,000 individuals in Asia annually.[6]

Risk Factors

The most potent risk factor in the development of Japanese encephalitis is residing in Southeast Asia and Western Pacific regions. Other risk factors include summer season, outdoor recreational activities, and contact with mosquitos, birds, and pigs.[10][11]

Natural History, Complications, and Prognosis

If left untreated, 50% of patients with Japanese encephalitis may progress to develop severe neurological deficits, such as deafness, hemiparesis, and aphasia. Common complications of Japanese encephalitis include seizures, coma, and spastic paralysis. Prognosis is generally poor. Approximately 20-30% of patients progress to mortality. Among patients who survive, approximately 50% suffer severe neurological, cognitive, or psychological deficits.[2]

Diagnosis

History and Symptoms

Most patients infected with Japanese encephalitis remain asymptomatic; 1% of infected individuals develop clinical disease. The incubation period for Japanese encephalitis is usually 5-15 days. Common symptoms of Japanese encephalitis include fever, headache, and vomiting, neck stiffness, stupor, disorientation, coma, tremors, and spastic (but rarely flaccid) paralysis.[12][13]

Physical Examination

Patients with Japanese encephalitis are usually ill-appearing. Physical examination of patients with Japanese encephalitis is usually remarkable for meningism, fever, and convulsions. Signs of Japanese encephalitis which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions, and an elevated body temperature between 38-41°C. The classical description of Japanese encephalitis includes a Parkinsonian syndrome with masklike facies, tremor, cogwheel rigidity, and choreoathetoid movements. Acute flaccid paralysis, with clinical and pathological features similar to those of poliomyelitis, has also been associated with Japanese encephalitis.

Laboratory Findings

The diagnostic method of choice for Japanese encephalitis is laboratory testing. Laboratory findings consistent with the diagnosis of Japanese encephalitis include detection of IgM antibodies in serum and cerebrospinal fluid, moderate leukocytosis, mild anemia, and hyponatremia. Cerebrospinal fluid typically has a mild to moderate pleocytosis with a lymphocytic predominance, slightly elevated protein, and normal ratio to plasma glucose. Because humans have low or undetectable levels of viremia by the time distinctive clinical symptoms are recognized, virus isolation and nucleic acid amplification tests are insensitive and should not be used for ruling out a diagnosis of Japanese encephalitis.[14]

CT

On CT scan, Japanese encephalitis is characterized by symmetric or asymmetric bilateral thalamic hypodensities, and subacute or chronic hemorrhagic lesions.

MRI

MRI is the imaging modality of choice for Japanese encephalitis. On MRI, Japanese encephalitis is characterized by symmetric or asymmetric bilateral thalamic hypodensities, and subacute or chronic hemorrhagic lesions.

Other Imaging Studies

On EEG, Japanese encephalitis is characterized by theta and delta coma, burst suppression, epileptiform activity, and occasionally alpha coma.[5]

Treatment

Medical Therapy

There is no treatment for Japanese encephalitis; the mainstay of therapy is supportive care.[3]

Primary Prevention

Effective measures for the primary prevention of Japanese encephalitis include mosquito population control, avoidance of mosquitos, and immunization. Mosquito control has been difficult to achieve in rural settings. Avoidance of exposure is also difficult, as Culex mosquitos are active during day hours. Immunization is the only effective method for sustainable control. Routine immunization of school-age children is currently in use in Korea, Japan, China, Thailand, and Taiwan. The introduction of the Japanese encephalitis vaccine into the Expanded Program of Immunization has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka, and China.[15]

Secondary Prevention

There are no secondary preventive measures available for Japanese encephalitis.

References

  1. 1.0 1.1 1.2 Flavivirus. SIB Swiss Institute of Bioinformatics (2015). http://viralzone.expasy.org/viralzone/all_by_species/24.html Accessed on April 12, 2016
  2. 2.0 2.1 Khandaker G, Zurynski Y, Buttery J, Marshall H, Richmond PC, Dale RC; et al. (2012). "Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric hospitals". Neurology. 79 (14): 1474–81. doi:10.1212/WNL.0b013e31826d5ea7. PMC 4098823. PMID 22993280.
  3. 3.0 3.1 Japanese encephalitis. National Health Service United Kingdom (2016). http://www.nhs.uk/Conditions/Japanese-encephalitis/Pages/Introduction.aspx Accessed on April 12, 2016.
  4. Paulke-Korinek M, Kollaritsch H (2008). "Japanese encephalitis and vaccines: past and future prospects". Wien Klin Wochenschr. 120 (19-20 Suppl 4): 15–9. doi:10.1007/s00508-008-1071-9. PMID 19066766.
  5. 5.0 5.1 Japanese Encephalitis Symptoms and Treatment. Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. (2015) http://www.cdc.gov/japaneseencephalitis/symptoms/ Accessed on April 12, 2016.
  6. 6.0 6.1 Japanese encephalitis - Fact sheet No 386. World Health Organization (WHO) (2015) http://www.who.int/mediacentre/factsheets/fs386/en/ Accessed on April 12, 2016
  7. M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.
  8. Kennedy PG (2004). "Viral encephalitis: causes, differential diagnosis, and management". J Neurol Neurosurg Psychiatry. 75 Suppl 1: i10–5. PMC 1765650. PMID 14978145.
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