Japanese encephalitis (JE) is caused by the Japanese encephalitis virus, an arthropod-borne virus (arbovirus) that belongs to the genus Flavivirus in the Flaviviridae family. JE virus is closely related to other members of Flavivirus, such as yellow fever, West Nile, dengue viruses, and St. Louis encephalitis. JE is endemic across Asia and the western Pacific region, especially in rural and suburban areas. It has expanded its geographic range reaching into the northern part of Australia and Papua New Guinea.

The JE virus undergoes an enzootic cycle primarily between wading birds and pigs by the vector Culex spp. mosquitoes. The virus is transmitted to humans through the bite of an infected Culex mosquito (predominantly Culex tritaeniorhynchus). Humans are incidental dead-end hosts because viremia in humans is not adequate to infect feeding mosquitoes, although there is a report of transmission via blood transfusion. The transmission season is typically from April to November in temperate regions, whereas it occurs year-round in tropical and subtropical regions of the Pacific Ocean and Southeast Asia, often intensifying during the monsoon season.

Most JE infections (> 99%) are subclinical or nonspecific febrile illnesses. JE is a childhood disease with a slight male predominance. More than 80% of young adults have immunity in endemic areas, resulting from subclinical infection during childhood. In patients (< 1%) who develop symptomatic neuroinvasive disease, it usually presents with aseptic meningitis after 1-2 weeks of incubation. If disease progresses to the acute encephalitis form of JE virus infection, it usually causes altered mental status and seizures in 85% of children and 10% of adults. Other clinical presentations of JE virus encephalitis include movement disorders such as parkinsonism, jaw dystonia, orofacial dyskinesia, choreoathetosis, opisthotonus, myoclonus, and opsoclonus-myoclonus. Cranial nerve palsies or acute flaccid paralysis can also occur. There was a strong association between some cases of JE virus and subsequent Guillain-Barré syndrome.

Diagnosis depends on cerebrospinal fluid (CSF) studies and brain imaging. CSF findings classically show elevated opening pressure, lymphocytic pleocytosis, normal glucose, and increased protein. Typical brain MRI images include high T2-weighted intensity signal in the thalami, basal ganglia, and brain stem. Diagnosis is confirmed by JE virus-specific immunoglobulin (IgM) capture ELISA in serum or CSF, which requires a confirmatory test called plaque-reduction neutralization testing (PRNT) offered by the US Centers for Disease Control and Prevention (CDC). Detection of JE virus by polymerase chain reaction (PCR) assay in serum or CSF is not useful in the diagnosis of JE because of the transient nature of viremia by the time clinical symptoms have appeared.

In patients with encephalitis from the JE virus, the mortality rate is high, up to 30%. Fifty percent of survivors have severe long-term neurologic sequelae. Poor prognostic factors include altered consciousness, seizures, high CSF opening pressure, positive CSF JE virus PCR, and low titer of CSF JE virus-specific antibody response.