Japanese Encephalitis (JE) Virus: Life Cycle, Pathogenesis, Diagnosis

Fig: Geographic Distribution of Japanese Encephalitis Virus
Fig: Geographic distribution of Japanese encephalitis virus

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

mosquito

The virus is maintained in an enzootic cycle between mosquitoes and amplifying vertebrate hosts (mainly pigs). 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 (JEV)

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 the 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 the human disease usually peaks in summer and fall.
  • Seasonal transmission varies with monsoon rains and irrigation practices
  • Travelers are 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 20-30% may die (CFR of 20-30%).
  • Symptoms start to appear after 5-15 days of the mosquito bite. Common symptoms of JE are;
  • sudden onset of headache
  • high fever
  • vomiting
  • seizures (common in children)
  • disorientation
  • paralysis
  • tremors and
  • convulsions and
  • coma

The classical description of JE includes Parkinsonian syndrome with masklike facies, tremor, cogwheel rigidity, and choreoathetoid movements. 30%–50% of people with encephalitis develop permanent neurologic or psychiatric sequelae.

Laboratory Diagnosis of Japanese Encephalitis

Japanese encephalitis (JE) should be considered in a patient with evidence of a neurologic infection (e.g., meningitis, encephalitis, or acute flaccid paralysis) who has recently traveled to or resided in an endemic country in Asia or the western Pacific. Diagnosis of JE is based on a combination of clinical signs and symptoms and specialized laboratory tests of blood or CSF.

Magnetic resonance imaging (MRI) of the brain can be done to see JE-virus-associated abnormalities in the thalamus (appearance of thalamic lesions), basal ganglia, midbrain, pons, and medulla.

Laboratory diagnosis of JE is generally accomplished by testing serum or cerebrospinal fluid (CSF) to detect virus-specific IgM antibodies.

Sample

CSF and serum

  • CSF is drawn by spinal tap (lumbar puncture at the level of L4-L5).
  • Should be performed in all suspected patients unless absolutely contraindicated
  • Typical CSF picture
    • Nonspecific pleocytosis (leukocytosis) with a predominance of lymphocytes
    • Slightly elevated protein level (normal-15-50 mg/dl)
    • Normal glucose (40-100 mg/dl) level (meningitis: Low)

Serology

  • Detection of IgM antibody against JE virus by IgM capture ELISA in CSF
  • 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.
  • Points to consider in serological tests Interpretation:
    • Vaccination history
    • Date of onset of symptoms
    • information regarding other flaviviruses known to circulate in the geographic area

Polymerase chain reaction (PCR)

Amplification of JE virus nucleic acid from CSF or brain tissue can be done using PCR methods. Viremia in humans is transient and low level. So virus isolation and nucleic acid amplification tests from blood are insensitive and should not be used for ruling out a diagnosis of JE.

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)

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

References

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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