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2011 12 Japanese Encephalitis MM

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    Japanese Encephalitis

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    Backgroundo Japanese encephalitis virus (JEV) represents the most significant etiology of arboviral

    encephalitis worldwide and is a neurologic infection closely related to St. Louis encephalitisand West Nile encephalitis.

    o It is the most important form of epidemic and sporadic encephalitis in the tropical regions

    of Asia including Japan, China, Taiwan, Korea, Philippines, all of the Southeast Asia andIndia.

    o Countries with the proven epidemics of Japanese encephalitis (JE) are India, Pakistan,Nepal, Sri Lanka, Burma, Laos, Vietnam, Malaysia, Singapore, Philippines, Indonesia,China, maritime Siberia, Korea, and Japan (Vaughn and Hoke 1992).

    o In the past 50 years however; geographic area affected by JE virus (JEV) has expanded.Epidemic activity in Northern India, Central India and Nepal has increased since the early

    1970s.o Since 1990s the virus has continued to spread in Pakistan (Igarashi et al 1994), Nepal

    (Zimmerman et al1997), and Australia (Hanna et al1996, 1999).

    Japanese Encephalit is . Asim A Jani, Burke A Cunha, MD.Medsacpe Reference http://emedicine.medscape.com/article/233802-overview

    http://emedicine.medscape.com/article/233802-overview
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    Distributiono Based on endemicity, epidemics, isolation of virus from patients and vectors and general

    serological surveys, the virus has been shown to be widely prevalent in most parts ofSouthcentral, Northern and Northeast states of India.

    o Apparently, part of Maharashtra and states like Gujarat, Rajasthan and Madhya Pradesh

    are free from JE.

    Japanese Encephalit is . Asim A Jani, Burke A Cunha, MD.Medsacpe Reference http://emedicine.medscape.com/article/233802-overview

    http://emedicine.medscape.com/article/233802-overview
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    Clinical Spectrumo JEV infections are mostly asymptomatic in about 90% of the cases and an estimated ratio of

    symptomatic to asymptomatic infection has been 1 to 251000 (average of 1:300).

    o Meningo-encephalitis is the most important and serious form of JEV infection resulting indeath in 535% cases.

    o About 50-60% of the survivors suffer from serious long-term neurologic sequelae manifested

    as convulsions, tremors, paralysis, ataxia, memory loss, impaired cognition, behaviouraldisturbance and other such symptoms (Halstead and Jacobson 2003).

    Preventive strategies for frequent outbreaks of Japanese encephalitis in Northern India.Vandana Saxena and Tapan N Dhole.J. Biosci. 33(4), November 2008

    The clinical picture of this infection has four stage si. Prodormal Stage Lasts 2-3 days.ii. Acute Stage Lasts 3-4 daysiii. Subacute Stage Lasts 7-10 days.iv . Convalascent Stage Lasts 4-7 weeks.

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    Laboratory criteria for diagnosis:WHO surveillance guidelines for JELaboratory confirmation of a JE virus infection includes:1. Presence of JE virus-specific IgM antibody in a single sample of cerebrospinal fluid

    (CSF) or serum as detected by an IgM-capture ELISA specifically for JE virus;

    OR

    2. Detection of JE virus antigens in tissue by immunohistochemistry;OR

    3. Detection of JE virus genome in serum, plasma, blood, CSF, or tissue by reversetranscriptase PCR or an equally sensitive and specific nucleic acid amplification test;

    OR

    4. Isolation of JE virus in serum, plasma, blood, CSF, or tissue;

    OR

    5. A four-fold or greater rise in JE virus-specific antibody as measured byhemagglutination inhibition (HI) or plaque reduction neutralization assay (PRNT) inacute and convalescent-phase serum samples. The samples should be collected 14days apart.

    WHO Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. March 2007

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    Options for Diagnostic tests in HumansI. Isolation, amplification, or antigen detection?

    i. Viraemia in JE is low and short so the likelihood of a positive result is low.

    ii. High technology requirement and expensive.

    II. Antibody-based (serology) methods?

    i. High sensitivity (if properly timed samples).

    ii. Options include PRNT, ELISA, and HI.

    WHO Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. March 2007

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    Antibody-based (Serology) Methods1. Plaque reduction neutralization assay (PRNT)

    o Least cross-reactivity; most specific.

    o Upto 14 days to complete test.

    o High biosafety level requirements.

    o Early acute phase specimen less likely to test positive with PRNT than ELISA

    o Requires acute & convalescent-phase serum.2. Haem agglutination Inhibition (HI)

    o High levels of cross-reactivity with other flaviviruses, low specificity.

    o Anamnestic response with secondary flavivirus infection.

    3. JE-specific IgM capture ELISAo Advantages

    Simple.

    Sensitivity of IgM detection good as competition by IgG molecules eliminated.

    o Disadvantages

    Some cross-reactivity with other flaviruses.

    ELISA is m ost feasible testing methodo logyWHO Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. March 2007

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    Molecular Diagnosiso PCR assays are not recommended for routine diagnosis; however, PCR assays combined

    with sequencing can be useful for providing information about the molecularepidemiology and evolution of viruses.

    WHO Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. March 2007

    Genom e Detection PCR

    Serological Tests Haemagglutination

    Inhibition (HI) ELISA (IgM, IgG) Neutralisation

    Antigen D etection Antigen capture ELISA

    Immunofluorescencetest

    JEV Diagnosis

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    Tests Offered at SRL7987ImmunochromatographySerum/Plasma

    Japanese EncephalitisVirus IgM antibodies

    1

    7595Real Time PCRCSFJapanese EncephalitisVirus RNA Detection

    2

    Test Codeethodampleest Nam er.No.

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    Thank You!


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