Japanese encephalitis

• Causative agent: Japanese encephalitis virus (JEV), a single-stranded RNA Flavivirus.
• Transmission: Transmitted by the bite of infected Culex mosquitoes, particularly Culex tritaeniorhynchus. The main reservoirs are pigs and wading birds.
• Mechanism: Virus replicates locally, leading to viremia and potential invasion of the central nervous system (CNS). Neuroinvasive disease occurs when the virus crosses the blood-brain barrier. Humans are considered dead-end hosts as they don't develop sufficient viremia to transmit to mosquitoes.
• Risk: Most common in rural, agricultural areas of East Asia, Southeast Asia, and the Western Pacific, especially during rainy seasons.

Clinical Presentation

• Incubation period: 5-15 days.
• Asymptomatic: >99% of infections are asymptomatic or cause only mild, nonspecific febrile illness.
• Symptomatic Disease (<1%):
  • Prodrome: Abrupt onset of fever, headache, vomiting, and malaise.
  • Encephalitis: Altered mental status (disorientation, confusion, coma), seizures (especially common in children), and focal neurologic deficits.
  • Movement disorders: A classic feature is a Parkinsonian syndrome with mask-like facies, tremor, rigidity, and choreoathetoid movements.
  • Other: Acute flaccid paralysis (poliomyelitis-like), neck rigidity.

Diagnosis

• Gold Standard: Detection of JEV-specific IgM antibodies in CSF is the most reliable method for diagnosis.
• Serology: JEV-specific IgM in serum can also be used. A four-fold rise in IgG titers between acute and convalescent sera is also diagnostic. Cross-reactivity with other flaviviruses (e.g., Dengue, West Nile) can complicate interpretation.
• CSF Analysis: Shows lymphocytic pleocytosis with elevated protein and normal glucose, typical for viral encephalitis.
• Imaging: MRI may show characteristic bilateral thalamic lesions, though this finding is not always present.
• PCR: Limited utility on CSF or blood due to the short duration of viremia.

DDx (Differential Diagnosis)

• Other viral encephalitides: West Nile Virus, Herpes Simplex Virus (HSV) encephalitis (often shows temporal lobe involvement), enteroviruses.
• Bacterial meningitis: Differentiated by CSF analysis (neutrophilic pleocytosis, low glucose).
• Cerebral malaria: In travelers from endemic regions, presents with fever and altered mental status.
• Acute Disseminated Encephalomyelitis (ADEM): Post-infectious/post-vaccination demyelination.

Management/Treatment

• No specific antiviral therapy exists for Japanese encephalitis.
• Supportive Care: Treatment is focused on managing symptoms. This includes:
  • Hospitalization for close monitoring.
  • Managing elevated intracranial pressure (e.g., mannitol).
  • Controlling seizures with anticonvulsants.
  • Airway protection and respiratory support if needed.
  • Antipyretics (acetaminophen preferred over NSAIDs due to bleeding risk) and fluid management.
• Prevention: Vaccination is the most effective preventive measure for travelers to endemic areas and for residents in high-risk regions. The IXIARO vaccine is available in the US. Personal protective measures against mosquito bites are also crucial.

Key Associations/Complications

• High mortality: Case-fatality rate for those who develop encephalitis is approximately 20-30%.
• Severe neurologic sequelae: 30-50% of survivors have long-term neurologic, cognitive, or psychiatric problems.
• Common sequelae: Parkinsonism, seizure disorders, cognitive impairment, weakness/paralysis, and behavioral changes.