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Japanese Encephalitis Workup

  • Author: Antonette B Climaco, MD; Chief Editor: Burke A Cunha, MD  more...
 
Updated: May 07, 2016
 

Approach Considerations

Japanese encephalitis virus (JEV) infection should be suspected in a patient with symptoms and signs of neurologic infection who has recently traveled in an endemic country.

CBC count

A complete blood cell (CBC) count often shows nonspecific modest leukocytosis in the first week of illness. This may be followed by a relative leukopenia. A mild anemia may also be present. In one study, 15% of children with Japanese encephalitis had thrombocytopenia.

Serum sodium levels

Serum sodium levels may be depressed owing to inappropriate antidiuretic hormone secretion.

Liver function tests

A study of Indian children during the Uttar Pradesh Japanese encephalitis outbreak in 2005 noted elevated liver function test results in a large number of patients (all had elevated aspartate aminotransferase [AST] levels; 47.2% had elevated alanine aminotransferase levels).[12]

Serology

IgM antibody can be detected in CSF by 4 days after the onset of symptoms and in the serum by 7 days after symptom onset. See Immunoassays for more details.

Viral isolation

Isolation of Japanese encephalitis virus from clinical specimens or even the identification of positive genetic viral sequences in tissue, blood, or CSF is diagnostic. However, virus isolation is reported to be difficult in humans because of transient and low-level viremia.

For laboratory worker safety, a biosafety level 3 is required for working with Japanese encephalitis virus.

MRI and CT scanning

Magnetic resonance imaging (MRI) and computed tomography (CT) scans often show bilateral thalamic lesions with hemorrhage, with MRI being more sensitive. The basal ganglia, putamen, pons, spinal cord, and cerebellum may also show abnormalities. Hyperintense lesions may be observed in the areas of the thalamus, cerebrum, and cerebellum on T2-weighted MRIs.

Electroencephalography

Electroencephalography (EEG) often reveals diffuse continuous delta slowing, a diffuse delta pattern with spikes, theta waves, and burst suppression.

EEG changes do not correlate with the severity of Japanese encephalitis or its outcome.

Histologic findings

Changes are found in the thalamus, substantia nigra, brain stem, hippocampus, cerebellum, and spinal cord and include focal neuronal degeneration with diffuse and focal microglial proliferation and lymphocytic perivascular cuffing.

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Lumbar Puncture

Lumbar puncture is performed to obtain CSF samples for diagnosis and for ruling out other causes of encephalitis.

The opening pressure is usually normal but may be raised.

CSF protein levels are mildly elevated, often less than 900 mg/dL. CSF glucose levels are often normal.

CSF cell count will show between 10 and several hundred white blood cells with lymphocytic predominance.

Japanese encephalitis virus may be isolated from the blood during the first week of illness. The CSF rarely yields virus, except in severe or fatal cases.

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Immunoassays

The diagnosis of Japanese encephalitis is supported by a capture immunoassay methodology demonstrating IgM antibody in the CSF or the serum. Alternatively, 4-fold increase between the acute-phase and convalescent-phase serum may be used to establish a diagnosis of recent infection.

Japanese encephalitis virus–specific IgM capture-enzyme-linked immunoassay (ELISA) on serum or CSF is the standard diagnostic test for Japanese encephalitis. Sensitivity is nearly 100% when both serum and CSF are tested. False-negative results may occur if the samples are tested too early (eg, within the first week of illness). IgM antibody can be detected in CSF by 4 days after the onset of symptoms and in the serum by 7 days after symptom onset. Of note, IgM may be found in the serum but not in the CSF in vaccinated persons or in those with asymptomatic infections.

Some cross-reactivity may arise from other flaviviruses (eg, dengue and West Nile virus) and from Japanese encephalitis and yellow fever vaccinations. This phenomenon may contribute to misdiagnosis; parallel testing for Japanese encephalitis virus and other flaviviruses (eg, dengue) may be necessary.

IgM dot enzyme immunoassays for CSF and serum are simple, portable tests that compare favorably with capture ELISA for field diagnosis (sensitivity of 98.3% and specificity of 99.2% when compared with capture ELISA as the standard).[23]

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Contributor Information and Disclosures
Author

Antonette B Climaco, MD Attending Physician, Division of Infectious Diseases, Department of Medicine, Albert Einstein Medical Center

Antonette B Climaco, MD is a member of the following medical societies: Infectious Diseases Society of America, Philippine Medical Association, HIV Medicine Association, American Academy of HIV Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Katherine Talcott Melhado, DO Resident Physician, Department of Internal Medicine, Einstein Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Asim A Jani, MD, MPH, FACP Clinician-Educator and Epidemiologist, Consultant and Senior Physician, Florida Department of Health; Diplomate, Infectious Diseases, Internal Medicine and Preventive Medicine

Asim A Jani, MD, MPH, FACP is a member of the following medical societies: American Association of Public Health Physicians, American College of Physicians, American College of Preventive Medicine, American Medical Association, American Public Health Association, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

Joseph F John Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Alexander J Kallen, MD Instructor of Medicine, Department of Internal Medicine, Division of Outcomes Research, Dartmouth Medical School, Veterans Affairs Medical Center of White River Junction, VT

Alexander J Kallen, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, California Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Sepracor None None

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Japanese Encephalitis Virus Geographic Distribution. Photo Courtesy of CDC.
Japanese encephalitis, 2006. Courtesy of the WHO.
 
 
 
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