What are the symptoms and treatment options for Japanese Encephalitis?

Japanese Encephalitis: Symptoms and Treatment

Japanese encephalitis (JE) treatment is limited to supportive care as there is no specific antiviral therapy available, focusing on managing symptoms and complications to reduce mortality and improve outcomes. 1

Clinical Presentation

Initial Symptoms

• Most JE virus infections (>99%) are asymptomatic, with less than 1% developing clinical encephalitis 2
• Incubation period ranges from 5-15 days after mosquito bite 2
• Initial symptoms are typically nonspecific and include:
  • Fever above 38°C with rigors 2, 3
  • Headache (often resembling meningitis) 2, 3
  • Vomiting and diarrhea 2
  • Myalgia (muscle pain) 3

Disease Progression

• Neurological symptoms typically develop over the next few days and may include:
  • Mental status changes and altered consciousness 2
  • Generalized weakness 2
  • Focal neurologic deficits (hemiplegia, tetraplegia, cranial nerve palsies) 2
  • Movement disorders 2
  • Seizures (especially common in children) 2
• A distinctive parkinsonian syndrome may develop, characterized by:
  • Mask-like facies 2
  • Tremor 2
  • Cogwheel rigidity 2
  • Choreoathetoid movements 2
• Acute flaccid paralysis similar to poliomyelitis may occur 2

Complications

• Status epilepticus 2
• Brain hypoxia 2
• Increased intracranial pressure 2
• Brainstem herniation 2
• Aspiration pneumonia 2

Diagnostic Approach

Laboratory Testing

• JE virus-specific IgM antibody detection is the preferred diagnostic method 1
  • IgM antibody-capture enzyme-linked immunosorbent assay (MAC ELISA) of CSF and serum 2
  • JE virus IgM antibodies can be detected in CSF within 4 days of symptom onset 2, 1
  • Serum antibodies typically appear by 7-8 days after onset 2
• Plaque reduction neutralization tests (PRNTs) can confirm recent infection 2, 1
• Virus isolation and nucleic acid amplification tests have low sensitivity and are not recommended for ruling out JE 2

Clinical Laboratory Findings

• Nonspecific findings may include:
  • Moderately elevated white blood cell count 2
  • Mild anemia 2
  • Hyponatremia 2
  • Thrombocytopenia and elevated hepatic enzymes in some cases 2
• CSF typically shows:
  • Lymphocytic pleocytosis 2
  • Moderately elevated protein levels 2

Neuroimaging

• MRI is superior to CT for detecting JE-associated brain abnormalities 2
• Characteristic findings include changes in:
  • Thalamus (most common) 2
  • Basal ganglia 2
  • Midbrain 2
  • Pons 2
  • Medulla 2

Treatment Approach

Supportive Care

• No specific antiviral agent or medication exists for JE virus infection; treatment is entirely supportive 2, 1
• Key supportive measures include:
  • Maintaining adequate hydration with intravenous fluids 1
  • Respiratory support in severe cases with declining consciousness 1
  • Monitoring and management of increased intracranial pressure 1
  • Anticonvulsants for seizure control 1

Ineffective Treatments

• Clinical trials have demonstrated that the following treatments do not improve outcomes:
  • Corticosteroids 2, 1
  • Interferon alpha-2a 2, 1
  • Ribavirin 2, 1
  • Minocycline 2, 1
  • Intravenous immunoglobulin 2, 1

Prognosis and Sequelae

Mortality and Long-term Outcomes

• JE has a case-fatality ratio of 20-30% 2, 1
• Among survivors, 30-50% experience neurologic or psychiatric sequelae even years after infection 2, 1
• Common long-term sequelae include:
  • Seizures 2, 1
  • Upper and lower motor neuron weakness 2, 1
  • Cerebellar and extrapyramidal signs 2, 1
  • Flexion deformities of the arms 2
  • Hyperextension of the legs 2
  • Cognitive deficits 2
  • Language impairment 2
  • Psychiatric issues 2
  • Learning difficulties 2
  • Behavioral problems 2

Prevention

Vaccination

• Vaccination is the most effective prevention strategy for JE 1
• Recommended for:
  • Residents in endemic areas, particularly children 1
  • Travelers staying for prolonged periods in rural areas with active JE virus transmission 1

Personal Protection Measures

• Use insect repellents containing DEET, picaridin, or IR3535 1
• Wear long-sleeved shirts and long pants 1
• Stay in accommodations with air conditioning or window/door screens 1

Clinical Pitfalls and Considerations

• JE should be suspected in any patient with neurologic infection who has recently returned from Asia or the Western Pacific 2
• Cross-reaction with other flaviviruses can occur in serological testing, requiring careful interpretation of results 2
• Consider vaccination history and information about other arboviruses in the geographic area when interpreting diagnostic results 2
• The risk for travelers to Asia is very low (less than one case per million travelers) but increases with prolonged stays in rural areas during transmission seasons 2