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.
ICD10CM: A83.0 – Japanese encephalitis
SNOMEDCT: 52947006 – Japanese encephalitis virus disease
Differential Diagnosis & Pitfalls
The differential diagnose of JE includes other encephalitides, especially arbovirus encephalitides seen in the United States:
West Nile virus (WNV) encephalitis (see WNV) – There is widespread distribution in the continental United States, and it is the most common arboviral infection in the United States. The majority of cases occur in late summer through fall. Neuroinvasive WNV can present as encephalitis, meningitis, flaccid paralysis, or a mixed pattern.
St. Louis encephalitis (SLE) – Elderly patients are more prone to have symptomatic infections. Prior to the onset of neurologic symptoms, patients experience fever, generalized malaise, and myalgias. Some patients have dysuria, hematuria, or sterile pyuria. Neurologic manifestations include meningitis and encephalitis. Patients may present with myoclonus, tremors, opsoclonus, ataxia, or nystagmus. CSF studies show lymphocytic pleocytosis, and MRI findings are nonspecific although MRI may show T2 signal intensity in the substantia nigra.
Eastern equine encephalitis (EEE) – Most human cases in the United States occur along the Atlantic and Gulf coasts during summer. It has the highest mortality rate (as high as 75%) among arboviral encephalitides in the United States.
Western equine encephalitis (WEE) – Occurs mainly in the western and Midwestern United States and in western Canada. Human cases of WEE are now exceedingly rare, with only 5 confirmed cases in the last 20 years. Focal temporal activity on electroencephalography (EEG) mimicking herpes simplex encephalitis has been reported in patients with WEE.