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]


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 (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.


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.



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]

Contributor Information and Disclosures

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.


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.


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

  1. Lobigs M, Diamond M. Feasibility of cross-protective vaccination against flaviviruses of the Japanese encephalitis serocomplex. Expert Rev Vaccines. 2012 Feb. 11(2):177-87. [Medline]. [Full Text].

  2. Solomon T, Ni H, Beasley DW, Ekkelenkamp M, Cardosa MJ, Barrett AD. Origin and Evolution of Japanese Encephalitis Virus in Southeast Asia. J Virol. 2003 Mar. 77(5):3091-8. [Medline]. [Full Text].

  3. Takhampunya R, Kim HC, Tippayachai B, Kengluecha A, Klein TA, Lee WJ, et al. Emergence of Japanese encephalitis virus genotype V in the Republic of Korea. Virol J. 2011 Sep 23. 8:449:[Medline]. [Full Text].

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

  5. 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. 2010 Jan. 12(1):37-45. [Medline].

  6. Shukla V, Shakya AK, Shukla M, Kumari N, Krishnani N, Dhole TN, et al. Circulating levels of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases during Japanese encephalitis virus infection. Virusdisease. 2016 Mar. 27(1):63-76. [Medline].

  7. Hills SL, Stoltey J, Martinez D, Kim P, Sheriff H, Zangeneh A, et al. Journal of Travel Medicine. 2014 Sep-Oct. 21(5):310-313. [Full Text].

  8. Hills SL, Griggs AC, Fischer M. Japanese encephalitis in travelers from non-endemic countries, 1973-2008. Am J Trop Med Hyg. 2010 May. 82(5):930-6. [Medline]. [Full Text].

  9. Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, et al. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ. 2011 Oct 1. 89(10):766-74E. [Medline]. [Full Text].

  10. 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. 1996 Sep 2. 165(5):256-60. [Medline].

  11. Baylis M, Barker CM, Caminade C, Joshi BR, Pant GR, Rayamajhi A, et al. Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?. Trans R Soc Trop Med Hyg. 2016 Apr. 110(4):209-11. [Medline]. [Full Text].

  12. 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. 2006 Jul 15. 43(2):123-31. [Medline].

  13. Li X, Cui S, Gao X, Wang H, Song M, Li M, et al. The Spatio-temporal Distribution of Japanese Encephalitis Cases in Different Age Groups in Mainland China, 2004 - 2014. PLoS Negl Trop Dis. 2016 Apr 6. 10(4):[Medline]. [Full Text].

  14. WHO. Japanese Encephalitis Vaccines: WHO position paper, February 2015 - Recommendations. Vaccine. 2016 Jan 12. 34(3):302-3. [Medline].

  15. Sarkari NB, Thacker AK, Barthwal SP, Mishra VK, Prapann S, Srivastava D, et al. Japanese encephalitis (JE) part II: 14 years' follow-up of survivors. J Neurol. 2012 Jan. 259 (1):58-69. [Medline].

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

  17. Bandyopadhyay D, Ganesan V, Choudhury C, Kar SS, Karmakar P, Choudhary V, et al. Two Uncommon Causes of Guillain-Barré Syndrome: Hepatitis E and Japanese Encephalitis. Case Rep Neurol Med. 2015. 2015:[Medline]. [Full Text].

  18. Handique SK, Das RR, Saharia B, Das P, Buragohain R, Saikia P. Coinfection of Japanese encephalitis with neurocysticercosis: an imaging study. AJNR Am J Neuroradiol. 2008 Jan. 29(1):170-5. [Medline]. [Full Text].

  19. CDC. Japanese Encephalitis in Two Children — United States, 2010. MMWR Morb Mortal Wkly Rep. 2011 Mar 11. 60(9):276-8. [Medline]. [Full Text].

  20. Suman V, Roy U, Panwar A, Raizada A. Japanese Encephalitis Complicated with Obstructive Hydrocephalus. J Clin Diagn Res. 2016 Feb. 10(20):OD18-20. [Medline]. [Full Text].

  21. Chen WL, Liao MF, Chiang HL, Lin SK. A possible case of acute disseminated encephalomyelitis after Japanese encephalitis. Acta Neurol Taiwan. 2013 Dec. 22(4):169-73. [Medline]. [Full Text].

  22. Verma R, Praharaj HN, Patil TB, Giri P. Acute transverse myelitis following Japanese encephalitis viral infection: an uncommon complication of a common disease. BMJ Case Rep. 2012 Sep 24. 2012:[Medline].

  23. 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. 1998 Jul. 36(7):2030-4. [Medline]. [Full Text].

  24. 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. 1992 Apr. 165(4):631-7. [Medline].

  25. 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. 1985 Jun. 16(2):332-6. [Medline].

  26. 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. 2003 Mar 8. 361(9360):821-6. [Medline].

  27. Rayamajhi A, Nightingale S, Bhatta NK, Singh R, Kneen R, Ledger E, et al. A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal. PLoS One. 2015 Apr 17. 10(4):[Medline]. [Full Text].

  28. 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. 2006 Jan. 69(1):31-8. [Medline].

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

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

  31. Dutta K, Basu A. Use of minocycline in viral infections. Indian J Med Res. 2011 May. 133:467-70. [Medline]. [Full Text].

  32. Mishra MK, Basu A. Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis. J Neurochem. 2008 Jun. 105(5):1582-95. [Medline]. [Full Text].

  33. Kumar R, Basu A, Sinha S, Das M, Tripathi P, Jain A, et al. Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial. BMC Infect Dis. 2016 Feb 4. 16(1):67. [Medline]. [Full Text].

  34. Topno R, Khan SA, Chowdhury P, Mahanta J. Pharmacodynamics of aminoglycosides and tetracycline derivatives against Japanese encephalitis virus. Asian Pac J Trop Med. 2016 Mar. 9(3):241-6. [Medline]. [Full Text].

  35. Lowry F. Traveling Children Should Get Japanese Encephalitis Vaccine. Medscape Medical News. Jun 19 2013. Available at http://www.medscape.com/viewarticle/806601. Accessed: Jun 26 2013.

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

  37. 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. 2007 Jun. 8(2):197-9. [Medline]. [Full Text].

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

  39. 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. 2006 Mar 24. 24(14):2669-73. [Medline].

  40. Connor BA, Bunn WB. The Changing Risk of Japanese Encephalitis for Business Travelers. Workplace Health Saf. 2015 Dec. 63 (12):568. [Medline].

  41. 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. 1994 Jul. 90(1):67-72. [Medline].

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

  43. Chokephaibulkit K, Houillon G, Feroldi E, Bouckenooghe A. Safety and immunogenicity of live attenuated Japanese encephalitis chimeric virus vaccine (Imojev®) in children. Expert Rev Vaccines. 2015 Nov 20. [Medline].

  44. 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. 2008 Mar. 86(3):178-86. [Medline]. [Full Text].

  45. Fischer M, Lindsey N, Staples JE, Hills S; Centers for Disease Control and Prevention (CDC). Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 May 12. 59:1-27. [Medline]. [Full Text].

  46. Dwibedi B, Mohapatra N, Rathore SK, Panda M, Pati SS, Sabat J, et al. An outbreak of Japanese encephalitis after two decades in Odisha, India. Indian J Med Res. 2015 Dec. 142 Suppl:S30-2. [Medline]. [Full Text].

  47. Centers for Disease Control and Prevention. CDC Health Information For International Travel 2016. New York: Oxford University Press; 2016.

  48. Burke DS, Nisalak A, Ussery MA, Laorakpongse T, Chantavibul S. Kinetics of IgM and IgG responses to Japanese encephalitis virus in human serum and cerebrospinal fluid. J Infect Dis. 1985 Jun. 151(6):1093-9. [Medline].

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