Japanese Encephalitis Workup

  • Author: Asim A Jani, MD, MPH, FACP; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jan 6, 2012
 

Approach Considerations

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

CBC count

A complete blood count (CBC) 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 secondary 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).[6]

Viral isolation

Isolation of Japanese encephalitis virus (JEV) from clinical specimens or even the identification of positive genetic viral sequences in tissue, blood, or CSF is diagnostic. JEV has been isolated up to almost 4 months after the start of clinical symptoms.

Immunoglobulin M antibody

IgM antibody levels may be found even within 7 days of symptoms.

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 (often to rule out other causes of encephalitis).

The opening pressure is usually normal but may be raised.

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

Between 10 and several hundred mononuclear white blood cells may be observed on cell count.

The Japanese encephalitis virus (JEV) can 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

Overall, the diagnosis of Japanese encephalitis may be supported by a capture immunoassay methodology demonstrating IgM antibody in the CSF. Alternatively, the serum antibody level may be increased 4-fold.

IgM capture enzyme-linked immunoassay (ELISA) of 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).

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 JEV 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).[8]

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Contributor Information and Disclosures
Author

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, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

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

References

  1. Vazquez A, Jimenez-Clavero M, Franco L, et al. Usutu virus: potential risk of human disease in Europe. Euro Surveill. Aug 4 2011;16(31):[Medline].

  2. Ravi V, Taly AB, Shankar SK, Shenoy PK, Desai A, Nagaraja D, et al. Association of Japanese encephalitis virus infection with Guillain-Barré syndrome in endemic areas of south India. Acta Neurol Scand. Jul 1994;90(1):67-72. [Medline].

  3. Kuwayama M, Ito M, Takao S, Shimazu Y, Fukuda S, Miyazaki K, et al. Japanese encephalitis virus in meningitis patients, Japan. Emerg Infect Dis. Mar 2005;11(3):471-3. [Medline].

  4. Unni SK, Ružek D, Chhatbar C, Mishra R, Johri MK, Singh SK. Japanese encephalitis virus: from genome to infectome. Microbes Infect. Apr 2011;13(4):312-21. [Medline].

  5. Hanna JN, Ritchie SA, Phillips DA, Shield J, Bailey MC, Mackenzie JS, et al. An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995. Med J Aust. Sep 2 1996;165(5):256-60. [Medline].

  6. Kumar R, Tripathi P, Singh S, Bannerji G. Clinical features in children hospitalized during the 2005 epidemic of Japanese encephalitis in Uttar Pradesh, India. Clin Infect Dis. Jul 15 2006;43(2):123-31. [Medline].

  7. Richman DD, Whitley RJ, Hayden FG. Clinical Virology. New York, NY: Churchill Livingstone; 1997.

  8. Solomon T, Thao LT, Dung NM, Kneen R, Hung NT, Nisalak A, et al. Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme immunoassay. J Clin Microbiol. Jul 1998;36(7):2030-4. [Medline]. [Full Text].

  9. Hoke CH Jr, Vaughn DW, Nisalak A, Intralawan P, Poolsuppasit S, Jongsawas V, et al. Effect of high-dose dexamethasone on the outcome of acute encephalitis due to Japanese encephalitis virus. J Infect Dis. Apr 1992;165(4):631-7. [Medline].

  10. Harinasuta C, Nimmanitya S, Titsyakorn U. The effect of interferon-alpha A on two cases of Japanese encephalitis in Thailand. Southeast Asian J Trop Med Public Health. Jun 1985;16(2):332-6. [Medline].

  11. Solomon T, Dung NM, Wills B, Kneen R, Gainsborough M, Diet TV, et al. Interferon alfa-2a in Japanese encephalitis: a randomised double-blind placebo-controlled trial. Lancet. Mar 8 2003;361(9360):821-6. [Medline].

  12. Lee E, Pavy M, Young N, Freeman C, Lobigs M. Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses. Antiviral Res. Jan 2006;69(1):31-8. [Medline].

  13. Saxena SK, Mathur A, Srivastava RC. Inhibition of Japanese encephalitis virus infection by diethyldithiocarbamate is independent of its antioxidant potential. Antivir Chem Chemother. Mar 2003;14(2):91-8. [Medline].

  14. Swarup V, Ghosh J, Mishra MK, Basu A. Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan. J Antimicrob Chemother. Mar 2008;61(3):679-88. [Medline].

  15. Yang SE, Pan MJ, Tseng HF, Liau MY. The efficacy of mouse-brain inactivated Nakayama strain Japanese encephalitis vaccine--results from 30 years experience in Taiwan. Vaccine. Mar 24 2006;24(14):2669-73. [Medline].

  16. Harakuni T, Kohama H, Tadano M, et al. Mucosal vaccination approach against mosquito-borne Japanese encephalitis virus. Jpn J Infect Dis. Jan 2009;62(1):37-45. [Medline].

  17. Yang DK, Kweon CH, Kim BH, Hwang IJ, Kang MI, So BJ, et al. The seroprevalence of Japanese encephalitis virus in goats raised in Korea. J Vet Sci. Jun 2007;8(2):197-9. [Medline]. [Full Text].

  18. Solomon T, Thao TT, Lewthwaite P, Ooi MH, Kneen R, Dung NM, et al. A cohort study to assess the new WHO Japanese encephalitis surveillance standards. Bull World Health Organ. Mar 2008;86(3):178-86. [Medline]. [Full Text].

  19. Schiøler KL, Samuel M, Wai KL. Vaccines for preventing Japanese encephalitis. Cochrane Database Syst Rev. Jul 18 2007;CD004263. [Medline].

  20. Thongtan T, Cheepsunthorn P, Chaiworakul V, Rattanarungsan C, Wikan N, Smith DR. Highly permissive infection of microglial cells by Japanese encephalitis virus: a possible role as a viral reservoir. Microbes Infect. Jan 2010;12(1):37-45. [Medline].

 
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Geographic distribution of Japanese encephalitis. Courtesy of the CDC.
Japanese encephalitis, 2006. Courtesy of the WHO.
 
 
 
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