Japanese encephalitis

Japanese encephalitis is a mosquito-borne viral disease endemic in Asia and the Western Pacific. Disease transmission occurs through the bite of infected Culex tritaeniorhynchus mosquitoes. Clinically, Japanese encephalitis virus (JEV) infection can range from asymptomatic disease to acute encephalitis, which occurs in < 1% of patients. Despite its rarity, acute encephalitis with altered mental status and neurological deficits remains the most important clinical manifestation; it typically develops following a short period of non-specific febrile illness. Seizures are common, especially in children. Other known clinical manifestations include acute psychosis and spastic or flaccid paralysis. Elevations in white blood cell count and CSF pleocytosis are often present, along with characteristic thalamic lesions on brain MRI. Definitive diagnosis is made through serology. Vaccinations are available for travelers and as part of childhood immunization programs in some endemic areas.

• Distribution: endemic throughout most of Asia and parts of the Western Pacific region
• Incidence
  • A significant cause of viral encephalitis in Asia
  • ∼ 68,000 cases occur every year
  • Typically affects individuals < 15 years old
  • The incidence in travelers from non-endemic regions is estimated to be < 1 case per million.

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus
• Transmission
  • Two main patterns of transmission
    • During the warmer months in temperate areas of Asia (e.g., China, Japan, South Korea)
    • Year-round transmission in tropical areas (e.g., Cambodia, Thailand) with peaks during the rainy season
  • The primary mosquito vector is Culex tritaeniorhynchus .
  • Pigs and wading birds (e.g., herons and egrets) are major hosts in the JEV cycle.
    • Pigs are particularly important, as they develop high levels of viremia and are often kept in close proximity to human dwellings.
    • Humans are dead-end hosts.

References:^[1]

• Incubation period: 5–15 days
• > 99% of cases are subclinical.
• Acute encephalitis (most common clinical presentation)
  • Non-specific prodromal symptoms such as fever, vomiting, headaches, and generalized weakness
  • High fever and altered level of consciousness
  • Symptoms progress over a few days into focal neurological deficits, movement disorders, psychosis, or seizures.
  • In severe cases: coma, spastic or flaccid paralysis, death

References:^[1][2]

Laboratory findings

• ↑ White blood cell count
• Hyponatremia secondary to SIADH
• CSF analysis
  • Elevated opening pressure
  • Mild to moderate pleocytosis with a predominant lymphocytosis
  • Elevated protein
  • Normal glucose

Imaging

• Brain MRI: hyperintense lesions in the thalamus, basal ganglia, midbrain, pons, and medulla.

Diagnostic testing

• Serum or CSF immunoglobulin M (IgM) antibodies are diagnostic.
  • Usually detectable 3–8 days after illness
  • False-positive elevations in serum IgM antibodies can be positive post-vaccination.
  • Convalescent samples of immunoglobulin G (IgG) antibodies can be tested if acute (IgM) samples are negative.

References:^[1]

• Viral encephalitides (e.g., HSV encephalitis)
• Other arboviruses
  • St. Louis encephalitis virus
  • West Nile virus
  • Murray Valley encephalitis virus
• Aseptic meningitis
• Bacterial meningitis

The differential diagnoses listed here are not exhaustive.

• No specific treatment available
• Supportive care is the mainstay of treatment, with a particular focus on:
  • Control of intracranial pressure
  • Maintaining adequate cerebral perfusion
  • Seizure control
• Corticosteroids and ribavirin have shown no clear benefit.

• ∼ 30% of patients who develop acute encephalitis die.
• In survivors, neurologic, cognitive, and psychiatric sequelae are common.

Japanese encephalitis vaccine

• Indications
  • Travelers spending > 1 month in endemic areas
  • Travelers spending < 1 month in endemic areas during periods of JEV transmission
  • Children < 15 years who live in areas with high JEV transmission
• See “Vaccines before travel” for details.
• Contraindications: See general contraindications for vaccination.

Mosquito-bite prevention

• Wear light-colored clothing
• Use insect repellants
• Avoid activities between dusk and dawn (when Culex tritaeniorhynchus is most active)
• Place screens at doors and windows
• Remove open water containers to minimize mosquito breeding

References:^[3][4]