Japanese encephalitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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.

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]

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 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]

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]

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]

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]

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]

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]

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]

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.

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]

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

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.

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

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

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]

There are no secondary preventive measures available for Japanese encephalitis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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.

Japanese encephalitis was first discovered in 1871 following a large number of recurring outbreaks in the summer months. There have been several outbreaks of Japanese encephalitis, which occurred in 1927, 1934, and 1935.^[1] The association between Culex tritaeniorhynchus as a vector and the involvement of birds and pigs as reservoir hosts for Japanese encephalitis was made in 1938.^[2] In 1930, the first vaccine was developed to prevent Japanese encephalitis; today, there are approximately 15 vaccines available.^[3]

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

Japanese encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Japanese encephalitis may also be classified according to neuroinvasiveness of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive. Japanese encephalitis is also known as an arbovirus, or an arthropod-borne virus.

Japanese encephalitis may be classified according to location of the disease into 2 subtypes: systemic or encephalitic. Japanese encephalitis may also be classified according to neuroinvasiveness of the disease into 2 subtypes: neuroinvasive and non-neuroinvasive. 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.

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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. 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.

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. The following table is a summary of the Japanese encephalitis virus:^[1][2]

Japanese encephalitis is contracted by the bite of an infected mosquito, primarily Culex tritaeniorhynchus. Japanese encephalitis virus circulates between a mosquito vector and either pigs or water birds (such as herons) in Southeast Asia.^[3] 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.^[4] 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.^[5]

Japanese encephalitis virus is transmitted in the following pattern:^[1]

1. Attachment of the viral envelope protein E to host receptors mediates internalization into the host cell by clathrin-mediated endocytosis, or by apoptotic mimicry.
2. Fusion of virus membrane with host endosomal membrane. RNA genome is released into the cytoplasm.
3. The positive-sense ssRNA virus is translated into a polyprotein, which is cleaved into all structural and non-structural proteins necessary for RNA synthesis (replication and transcription).
4. Replication takes place at the surface of endoplasmic reticulum in cytoplasmic viral factories. A dsRNA genome is synthesized from the genomic ssRNA(+).
5. The dsRNA genome is transcribed/replicated, thereby providing viral mRNAs/new ssRNA(+) genomes.
6. Virus assembly occurs at the endoplasmic reticulum. The virion buds via the host endosomal sorting complexes required for transport (ESCRT), and is sent to the Golgi apparatus.
7. The prM protein is cleaved in the Golgi, thereby maturing the virion which is fusion competent.
8. New virions are released by exocytosis.

On microscopic histopathological analysis, the enveloped, spherical, and icosahedral-like virion shape are characteristic findings of Japanese encephalitis.

• 
  Culex mosquito laying eggs. (Photograph by Richard G. Weber)
• 
  Diagram illustrates the methods by which the arbovirus, Japanese encephalitis virus (JEV) reproduces and amplifies itself in the avian populations, and is subsequently transmitted to human beings as the dead end host. From Public Health Image Library (PHIL). ^[6]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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]

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]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

Japanese encephalitis must be differentiated from other diseases that cause nondescript symptoms, which include fever, headache, and vomiting, such as meningitis, brain abscess, and other demyelinating diseases.

Japanese encephalitis must be differentiated from other diseases that cause fever, headache, and vomiting, such as:^{[1][2][3][4][5]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

The incidence of Japanese encephalitis in patients younger than 19 years old is approximately 10-100 per 100,000 individuals worldwide. 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.

There are 24 countries in Southeast Asia and Western Pacific regions that have Japanese encephalitis virus transmission risk, a population of over 3 billion people.^[1]

The incidence of Japanese encephalitis in patients younger than 19 years old is approximately 10-100 per 100,000 individuals worldwide.^[2]

The case-fatality rate of Japanese encephalitis is approximately 20-30% worldwide.^[3]

Japanese encephalitis more commonly affects individuals younger than 18 years of age. In rural areas where Japanese encephalitis is endemic, seroprevalance approaches 100%; approximately 1 in 300 infected children develop Japanese encephalitis.^[4]

Japanese encephalitis usually affects individuals of the Asian race.

Japanese encephalitis is most commonly observed in the summer months within temperate climate zones. Year-round transmission is observed in tropical climate zones.^[5]

The majority of Japanese encephalitis cases are reported in South and Southeast Asia. There have been suspected cases on the Indian subcontinent.

Japanese encephalitis is a rare disease that tends to sporadically cause outbreaks which affect U.S. territories in the Western Pacific.

Japanese encephalitis is a common disease that tends to affect approximately 30,000 to 70,000 individuals in Asia annually.^[1]

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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.

Common risk factors in the development of Japanese encephalitis are:^[1][2][3]

• Residents or military in Southeast Asia and Western Pacific regions
• Summer season
• Outdoor recreational activities
• Accommodations in endemic ares that lack air conditioning, bed nets, or window screens
• Age extremes
• Contact with:
  • Mosquitos
  • Birds
  • Pigs

Template:WS Template:WH

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]

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.

If left untreated, 50% of patients with Japanese encephalitis may progress to develop severe neurological deficits, such as deafness, hemiparesis, and aphasia.^[1][2]

Common complications of Japanese encephalitis include:^[3][4]

• Seizures
• Coma
• Disorientation
• 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.^[1][3]

Template:WS Template:WH