Japanese encephalitis overview: Difference between revisions
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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 (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]]. | ||
==Causes== | |||
The causative agent, Japanese encephalitis virus is an [[enveloped virus]] of the [[genus]] [[flavivirus]]; it is closely related to the [[West Nile virus]], [[Murray Valley encephalitis virus]] and [[St. Louis encephalitis]] virus. All members in the serogroup have avian [[vertebrate]] [[host (biology)|hosts]] and are [[vector]]ed by Culex spp mosquitoes. JEV has also occasionally been recovered from Aedes spp mosquitoes. The virus is a 40-50 nm [[enveloped virus|enveloped]], [[Positive-sense ssRNA virus|positive-sense single stranded RNA]] virus, with an isometric 30 nm [[nucleocapsid]] core. The envelope is spiked with a mature [[membrane protein|membrane]] (M) protein and a [[glycosylated]] envelope (E) protein which is stabilized by disulfide bonds and comprises three domains (I, II and III) involved in [[antigen]]ic properties, [[cell receptor]] binding and penetration of the [[virion]] into the host-cell. [[Positive-sense ssRNA virus|Positive-sense single stranded RNA]] [[genome]] is packaged in the [[capsid]], formed by the capsid protein. The outer [[envelope (biology)|envelope]] is formed by envelope (E) protein and is the protective [[antigen]]. It aids in entry of the virus to the inside of the cell. The 10,976 [[base pair|bases]] long single-stranded viral [[RNA]] encodes an uninterrupted [[open reading frame]] that is [[translation|translated]] into a [[protein precursor|polyprotein precursor]] eventually processed into capsid (C) pre-M and E [[Structural Classification of Proteins|structural proteins]] and into seven non-structural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is produced as secretory form also. NS3 is a putative [[helicase]], and NS5 is the viral [[polymerase]]. It has been noted that the Japanese encephalitis virus (JEV) infects the [[lumen]] of the [[endoplasmic reticulum]] (ER) and rapidly accumulates substantial amounts of viral proteins for the JEV. | |||
==Diagnosis== | ==Diagnosis== | ||
===Symptoms=== | ===History and Symptoms=== | ||
Mild | 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]]. | ||
===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. | |||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Diagnosis is based on a combination of clinical signs and | [[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. | ||
===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. | |||
===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. | |||
==Treatment== | |||
===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. | |||
===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>. | |||
===Future or Investigational Therapies=== | |||
There are a number of new [[vaccine]]s under development. The mouse-brain derived vaccine is likely to be replaced by a [[cell culture]] derived vaccine that is both safer and cheaper to produce. China licensed a live [[attenuated virus|attenuated]] vaccine in 1988 and more than 200 million [[dose]]s have been given; this vaccine is available in Nepal, Sri Lanka, South Korea and India. There is also a new [[chimera (virus)|chimeric]] vaccine based on the [[yellow fever]] 17D vaccine that is currently under development<ref name="Solomon">{{cite journal | volume=355 | pages=869-871 | year=2006 | issue=9 | title=Control of Japanese Encephalitis—within our grasp? | author=Tom Solomon | url=http://content.nejm.org/cgi/content/full/355/9/869 }}</ref>. | |||
Initative for Vaccine Research (IVR) monitors and advises on research related to the design of optimal strategies for [[immunization]], including the selection of age groups for catch-up and the definition of at-risk [[population]]s, and the impact of [[vaccination]]. The duration of protection and booster needs, and well as [[immunization]] of special target groups, also require further analysis. Regulatory guidelines for production, quality control and evaluation of novel live, chimeric vaccines are in preparation. | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 23:59, 30 December 2012
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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 infections 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, tremors and convulsions. About 1 in 4 cases are fatal. There is no specific treatment for JE. Patient management focuses on supportive care and management of complications. Steps to prevent JE include using personal protective measures to prevent mosquito bites and vaccination.
Causes
The causative agent, Japanese encephalitis virus is an enveloped virus of the genus flavivirus; it is closely related to the West Nile virus, Murray Valley encephalitis virus and St. Louis encephalitis virus. All members in the serogroup have avian vertebrate hosts and are vectored by Culex spp mosquitoes. JEV has also occasionally been recovered from Aedes spp mosquitoes. The virus is a 40-50 nm enveloped, positive-sense single stranded RNA virus, with an isometric 30 nm nucleocapsid core. The envelope is spiked with a mature membrane (M) protein and a glycosylated envelope (E) protein which is stabilized by disulfide bonds and comprises three domains (I, II and III) involved in antigenic properties, cell receptor binding and penetration of the virion into the host-cell. Positive-sense single stranded RNA genome is packaged in the capsid, formed by the capsid protein. The outer envelope is formed by envelope (E) protein and is the protective antigen. It aids in entry of the virus to the inside of the cell. The 10,976 bases long single-stranded viral RNA encodes an uninterrupted open reading frame that is translated into a polyprotein precursor eventually processed into capsid (C) pre-M and E structural proteins and into seven non-structural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is produced as secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that the Japanese encephalitis virus (JEV) infects the lumen of the endoplasmic reticulum (ER) and rapidly accumulates substantial amounts of viral proteins for the JEV.
Diagnosis
History and Symptoms
Less than 1% of people infected with Japanese encephalitis (JE) virus develop clinical illness. Mild infections occur without apparent symptoms other than fever with headache. More severe infection is marked by quick onset headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, occasional convulsions (especially in infants) and spastic (but rarely flaccid) paralysis.
Physical Examination
Signs of Japanese encephalitis which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions 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 choreoathetoid movements. Acute flaccid paralysis, with clinical and pathological features similar to those of poliomyelitis, has also been associated with JE.
Laboratory Findings
Diagnosis of Japanese encephalitis is based on a combination of clinical signs and symptoms 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.
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 specific for JE in the appropriate clinical context, they are not a very sensitive marker of JE.
Other Diagnostic Studies
EEG abnormalities in Japanese encephalitis may include theta and delta coma, burst suppression, epileptiform activity, and occasionally alpha coma.
Treatment
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 symptoms.
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 of Immunization has helped curb the disease in countries like Thailand, Vietnam, Sri Lanka and China[1].
Future or Investigational Therapies
There are a number of new vaccines under development. The mouse-brain derived vaccine is likely to be replaced by a cell culture derived vaccine that is both safer and cheaper to produce. China licensed a live attenuated vaccine in 1988 and more than 200 million doses have been given; this vaccine is available in Nepal, Sri Lanka, South Korea and India. There is also a new chimeric vaccine based on the yellow fever 17D vaccine that is currently under development[2].
Initative for Vaccine Research (IVR) monitors and advises on research related to the design of optimal strategies for immunization, including the selection of age groups for catch-up and the definition of at-risk populations, and the impact of vaccination. The duration of protection and booster needs, and well as immunization of special target groups, also require further analysis. Regulatory guidelines for production, quality control and evaluation of novel live, chimeric vaccines are in preparation.
References
- ↑ Tauber E, Dewasthaly S (2008). "Japanese encephalitis vaccines--needs, flaws and achievements". Biol Chem. 389 (5): 547–50. PMID 18953721.
- ↑ Tom Solomon (2006). "Control of Japanese Encephalitis—within our grasp?". 355 (9): 869–871.