What are the clinical features, diagnosis, and treatment of Japanese encephalitis in a patient who has recently traveled to or resides in rural areas of Asia?

Japanese Encephalitis: Causative Agent, Clinical Features, Diagnosis, and Treatment

Causative Agent

Japanese encephalitis is caused by Japanese encephalitis virus (JEV), a single-stranded positive-sense RNA virus belonging to the family Flaviviridae, genus Flavivirus 1. The virus is transmitted through a zoonotic cycle between mosquitoes (primarily Culex species), pigs, and water birds, with humans serving as accidental dead-end hosts due to low-level and transient viremia 1.

Clinical Features

Spectrum of Disease

• Most JEV infections are asymptomatic, with 25-1000 subclinical cases occurring for every symptomatic patient 1
• Symptomatic infection manifests as nonspecific febrile illness, aseptic meningitis, or encephalitis 1

Neurological Manifestations

• Encephalitis presents with altered sensorium, seizures, and focal neurological deficits 1
• Acute flaccid paralysis occurs in some patients due to anterior horn cell involvement, with clinical features similar to poliomyelitis 2, 1
• Movement disorders are common, occurring in 20-60% of patients, particularly transient Parkinsonian features and dystonia (affecting limbs, axial muscles, and orofacial regions) 1
• High fever, headache, and impaired consciousness are typical presenting symptoms 3

Anatomical Distribution

• JE primarily affects the thalamus, corpus striatum (basal ganglia), brainstem, and spinal cord 1, 3
• Hippocampus and white matter may also be involved 3

Diagnosis

Serological Testing

The IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) is the preferred diagnostic test for Japanese encephalitis 4. This test has high sensitivity and specificity 1.

• JE virus IgM antibodies can be detected in cerebrospinal fluid (CSF) within 4 days of symptom onset 4
• The presence of JE virus IgM antibodies in CSF provides strong evidence of JE virus as the cause of neurologic illness 4
• Plaque reduction neutralization tests (PRNTs) can confirm recent infection by demonstrating a fourfold or higher rise in virus-specific neutralizing antibodies between acute and convalescent serum specimens 5, 4

Important Diagnostic Considerations

• Cross-reactivity with other flaviviruses can occur in both ELISA and neutralization assays, particularly in patients previously infected with or vaccinated against other flaviviruses (e.g., yellow fever) 5
• Vaccination history, symptom onset date, and knowledge of other circulating arboviruses in the geographic area must be considered when interpreting results 5
• Diagnostic testing is available at select state public health laboratories and at the CDC 5

Neuroimaging

• MRI demonstrates JE lesions as hyperintense on T2-weighted images and hypointense on T1-weighted images 3
• Look for changes in the thalamus, basal ganglia, mesencephalon, pons, medulla, and abnormalities of spinal cord gray matter 2
• Hemorrhagic transformations may occur with corresponding T1 and T2 signal changes 3

Clinical Suspicion Criteria

JE should be suspected in any patient with evidence of neurologic infection (encephalitis, meningitis, or acute flaccid paralysis) who has recently returned from or resides in Asia or the western Pacific where JE is endemic 5, 2.

Treatment

No Specific Antiviral Therapy Available

Japanese encephalitis treatment is limited to supportive care and management of complications, as no specific antiviral agent or medication is available to mitigate the effects of JE virus infection 5, 4.

Failed Therapeutic Interventions

Multiple controlled clinical trials have demonstrated that the following interventions do NOT improve clinical outcomes 5, 4:

• Corticosteroids 5, 4, 2
• Interferon alpha-2a 5, 4, 2
• Ribavirin 5, 4, 2
• Minocycline 5, 4
• Intravenous immunoglobulin 5, 4

Supportive Care Measures

The cornerstone of JE management involves aggressive supportive care with the following specific interventions 4:

• Maintain adequate hydration with intravenous fluids 4
• Provide respiratory support in severe cases with declining consciousness 4
• Monitor and manage increased intracranial pressure 4
• Administer anticonvulsants for seizure control as needed 4
• Carefully monitor respiratory and bulbar function, as generalized weakness frequently affects these systems 2

Prognosis and Sequelae

Mortality

Japanese encephalitis has a case-fatality ratio of 20-30% 5, 4, 2. Deaths may occur after either a short fulminant course or prolonged coma 5.

Long-Term Neurological Sequelae

Among survivors, 30-50% experience neurologic or psychiatric sequelae that persist even years after infection 5, 4. These include:

• Seizures 5, 4
• Upper and lower motor neuron weakness 5, 4
• Cerebellar and extrapyramidal signs 5, 4
• Flexion deformities of the arms and hyperextension of the legs 5
• Cognitive deficits 5
• Language impairment 5
• Psychiatric issues 5
• Learning difficulties and behavioral problems 5

Clinical Implications

Because of the lack of specific antiviral therapy, high case-fatality rate, and substantial morbidity, prevention of JE through vaccination and mosquito precautions is critically important 5, 4.

Prevention

Vaccination is the most effective prevention strategy for Japanese encephalitis 4. Additional protective measures include:

• Use insect repellents containing DEET, picaridin, or IR3535 4
• Wear long-sleeved shirts and long pants 4
• Stay in accommodations with air conditioning or window/door screens 4