Japanese Encephalitis (JE) Virus: Structure, life cycle, pathogenesis and diagnosis

Japanese Encephalitis (JE) virus was initially isolated in Japan in 1935. It is a leading cause of vaccine-preventable encephalitis (inflammation of the brain) in Asia and the western Pacific.


The virus is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts. The highest risk months for JE transmission are August, September and early October.

Properties of JE Virus:

  • member of the family flaviviruses
  • related to dengue, yellow fever and West Nile viruses, Saint Louis encephalitis viruses.
  • +ve stranded SS RNA Virus
  • linear non-segmented genomes
  • icosahedral shaped
  • Envelope is present
Structure of Japanese Encephalitis Virus
Structure of Japanese Encephalitis virus

Transmission Cycle of Japanese Encephalitis Virus 

  • Domestic pigs and wild birds are reservoirs of the virus
  • Virus exists in a transmission cycle between mosquitoes, pigs and/or water birds (enzootic cycle).
  • Spread by the bite of infected mosquitoes, primarily Culex spp (Culex tritaeniorhynchus).
  • Human are incidental dead end hosts. JE virus can not spread directly from person to person. Humans once infected do not develop enough concentration of JE virus in their bloodstream to infect feeding mosquitoes.
Fig: Japanese Encephalitis Virus Life Cycle
Fig: Japanese Encephalitis Virus Life Cycle

Population at risk

  • People with weakened immune systems (HIV, taking  immunosuppressant drugs)

In endemic countries: 

  • Primarily affects children.
  • Transmission principally occurs in rural agricultural areas or periurban settings often associated with rice farming.
  • Transmission is seasonal, and human disease usually peaks in summer and fall.
  • Seasonal transmission varies with monsoon rains and irrigation practices
  • Travelers at increased risk if extensive outdoor or nighttime exposure in rural areas during periods of active transmission.

Clinical Feature (Sign/symptoms)

  • Most human infections are asymptomatic or result in only mild symptoms. <1% of people infected with JE virus develop clinical disease, out of which 30% will die.
  • Symptoms (after 1-2 weeks):
    Fig: Geographic Distribution of Japanese Encephalitis Virus
    Fig: Geographic Distribution of Japanese Encephalitis Virus
    • sudden onset of headache
    • high fever
    • Seizures
    • disorientation
    • coma
    • paralysis
    • tremors and
    • convulsions
  • 30%–50% of people with encephalitis develops permanent neurologic or psychiatric sequelae . 

Diagnosis of Japanese Encephalitis

Diagnosis of Japanese encephalitis is based on a combination of clinical signs and symptoms and specialized laboratory tests of blood or CSF.

  • Sample: CSF
    • CSF is drawn by spinal tap (lumbar puncture at the level of L4-L5).
  • Should be performed in all patients unless absolutely contraindicated
  • 1/3-2/3 of encephalitis cases remains of unknown etiology.
  • Typical CSF Picture
    • Non specific
    • Nonspecific pleocytosis with a predominance of lymphocytes
    • Slightly elevated protein level (Normal-15-50 mg/dl)
    • Normal glucose (40-100 mg/dl) level (Meningitis: Low)
  • Diagnosis in the Microbiology lab is made by:
    • Detection of IgM antibody against JE virus by IgM capture ELISA in CSF
    • Amplification of JE virus nucleic acid from CSF or brain tissue by PCR.
    • CSF Culture: Limited value in case of viral encephalitis and is not recommended for routine clinical application.
      Isolation of JE virus in the CSF by co-culturing in phytohemagglutinin P-stimulated peripheral blood mononuclear leukocytes (rarely done)


  • Should be performed by using a JE virus–specific IgM-capture ELISA on CSF or serum.
  • JE virus–specific IgM can be measured in the CSF of most patients by 4 days after onset of symptoms and in serum by 7 days after onset.
  • A ≥4-fold rise in JE virus–specific neutralizing antibodies between acute- and convalescent-phase serum specimens.
  • Serological tests Interpretation..
  • Points to consider
    • Vaccination history
    • Date of onset of symptoms
    • information regarding other flaviviruses known to circulate in the geographic area

JE Vaccine

  • Approved for people 2 months of age and older
  • Given as a 2-dose series, with the doses spaced 28 days apart.
  • Booster dose- may be given to anyone who was vaccinated > one year ago and is still at risk of exposure
  • Recommended for:
    • Travelers to Asia  (visit rural areas or engage in outdoor activities, visit during peak season)
    • Laboratory workers at risk of exposure


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