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流感

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  • 3

    !!

    (Seasonal Influenza or Seasonal Flu) H1N1H3N2 A/ B!

    )Influenza Season or Flu Season* 7 1 6 30

    )Influenza Epidemic Period* 11 3 6 9

    (Complicated Influenza ) ()()

    (Pneumonia and Influenza, P&I) 1975 (ICD-9) 480-487

    (480)(481)(482)(485*(486)(487)

    (Cluster) !!!!

    3

  • 4

    !

    2008 2009 H1N1 2011 9 2012 2011 12H5N1 ICRapiacta

    2013

    4

  • 5

    (Description of Disease)

    (Influenza )

    (Influenza virus) 1 4(1,2)

    (1-3) 10

    3~7 2(2,3)common cold

    (Influenza)

    (Common Cold)

    200

    / 3-4 1-2 2-5

    () ()

    5

  • 6

    (Reye syndrome)(1-5)

    1933Wilson Smith(1-3) A(H1N1) ABC A B A B 1977A(H1N1 H3N2) B

    )Orthomyxoviridae)

    ABC Segmented RNA 80-120nmenvelope 2 - HemagglutininHA, H NeuraminidaseNA, N (1-5)M1M2A B 8 (-)RNA (-)RNA NucleoproteinNPTranscriptaseRNA PB1PB2PA C 7(1,3,4)

    (HA NA) A (H ) (N )

    6

  • 7

    H 17 H1-H17N 10 N1-N10(1-4,7) HA NA H1N1 A HA-1 NA-1 H3N2 A HA-3 NA-2 B C(1-4)

    A B A H1N1H2N2H3N2 H1N1H7N7 H3N8 B BC(1,3,4)

    A 1957 1968 ( A/H2N2 A/H3N2)

    A B C 8 8 7 11 11 9 (Antigenic

    drift) (Antigenic shift)

    (Antigenic drift)

    (Antigenic drift)

    A

    7

  • 8

    2009 H1N1

    1. A B 8 RNA C 7

    2. 3.

    4. 5. Zanamivir(Relenza ) Oseltamivir(Tamiflu )

    6. Reassortment

    ABC 1980(WHO) H N (1,6)A (HnNn) A/swine/Lowa/15/33 (H1N1) A1933 Lowa H1N1 15A/Beijing/262/95 (H1N1) A 1995 262Beijing H1HA N1NA(1-4) B /// HA NAB/Beijing/243/97 C(1-4)

    8

  • 9

    A -(1,3,4) RNA RNA"""# HA NA"Antigenic drift""" A B "Antigenic shift""" 20-30(1,3,4) A

    48 60 5 10 (1,3,6)

    (NA)SheddingViremia(1-4)

    9

  • 10

    Mode of transmission!

    Incubation period 1~4 2

    12 3

    Period of communicability 3~5 7-10 (1,2) 24-48 24-72 5 (4,6)(1,2,5) 21

    Susceptibility and resistance Antigenic drift(2,5) (2,5)

    AB

    A C

    10

  • 11

    Pandemics(Seasonal epidemics)(Sporadic cases*

    (WHO) 3 5 25 50(1)(Centers for Disease Control and Prevention, CDC) 10 3 10 4 2~4 5 100(100/100,000) 500/100,000(2,6,8)2012-2013 11 1A/H3N2 (9)11 3 42012-2013 12 2(EuroFlu) 2012-2013 94,000 63% A 2009 A/H1N1( 66%) (9)! Centre for Health Protection 12 7 82012-2013 A/H3N2 2009 A/H1N1(10) 2012-201311 2013 1 2 A/H3N2(9,11) (National Notifiable Diseases Surveillance System(NNDSS)) 5-6 8-9 2013 (1 1 8 4 )1,164 A/H3N2(12)

    11

  • 12

    7 1 6 30 11 12 3 11%(13) B A/H3N2 2009 H1N12009 7 H1N12010-2011 A/H3N2 12 2009 A/H1N1 2011-2012 BA/H3N2 2012-2013 2010-2011

    2009-2013

    2008-2009 282009-2010 1,3122010-2011 1,7852011-2012 1,7042012-2013 968 749140155 68 2009

    12

  • 13

    H1N12008-2009 651-62009-2010 H1N1 180-6 65(13)2010-2011 650-32012-2013 65 50-642009 A/H1N1 0-6 65

    (http://www.cdc.gov.tw)//

    7 10

    10-20 40-50

    13

  • 14

    B A BA Antigenic drift Antigenic shift

    1-2

    665 65 1996 2011 7.7% 10.9%

    14

  • 15

    (Surveillance System)

    1.

    2. 3. 4. 5. 6.

    IC

    1999 2000 2004 2007 2011 9

    15

  • 16

    3 39

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    * M38 N O

    16

  • 17

    ()

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    2.()

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    21382

    17

  • 18

    ( )

    ()()

    1.Possible case

    2.Probable case

    3.Confirmed case

    (1)

    (2) 14 ()

    (3)

    ( ) (http://nidss.cdc.gov.tw) /

    1.() 2. 3. 4.4

    18

  • 19

    1.()2.

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    19

  • 20

    () 1999 3

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    3. 2 2012 8

    20

  • 21

    4. (1)

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    (A) Transtube

    21

  • 22

    (2) a. 4 b. 24 c. (*

    (3) (real-time PCR*

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    a. 4 b. 24

    (3)(real-time RT- PCR*

    2.

    1. Virus isolation

    2. Real-time

    PCR

    Real-time PCR() Virus isolation ()

    Real-time PCR() Virus isolation ()

    Real-time PCR() Virus isolation ()

    Real-time PCR() Virus isolation ()

    Real-time PCR() Virus isolation ()

    Real-time PCR(+)rapid antigen testvirus isolation(+) 14 21 21 21 H1H3 INF untype,

    !Real-time PCR

    22

  • 23

    ( ) (http://cdc.gov.tw)////

    ( ) !

    IC Real-time Outbreak and Disease

    SurveillanceRODS1999 9 2004 RODS2006 11 ICD-9-CM1701080%ICD-9-CM

    RODS2008ICIC RODS

    23

  • 24

    RODS(http://nidss.cdc.gov.tw)//!

    2009H1N1 H1N1

    6

    ( )

    (1) 38

    24

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    (2) (3)

    () 1. https://ida4.cdc.gov.tw/phb/

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    25

  • 26

    !!https://203.65.72.161/ida2/

    2/,!3/A+H1H3

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    !

    26

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    2002665 ( ) 1. 38C 2.

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    27

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    5.

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    28

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    24

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    29

  • 30

    Long term care facilityThe elderly apartmentInstitution for disabilityProtectoryVeterans homePrisonNursing homeDay-care center for mental recovery

    ( ) 1.

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    2.

    !1. 38 37.5

    2. 3

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    (http://iss.cdc.gov.tw)

    30

  • 31

    2. 24

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    31

  • 32

    (http://www.cdc.gov.tw)//

    @

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    32

  • 33

    () 1.Nasal swab

    2.Nasopharyngeal swab 3.Nasal wash fluid

    4.Throat swab 5. Transtracheal aspirateBronchoalveolar lavage fluidSputumLung biopsy Post-mortem lung or Tracheal tissue 6. Acute serumConvalescent serum

    ()

    3(Nasopharyngeal aspirate)Throat swab

    Immunofluorescence staining

    assay, IFA 4 4 48-72-70

    33

  • 34

    () 1. 10g veal infusion broth 2g bovine albumin fraction V 400 ml

    2. 0.8 ml gentamicin sulfate solution (50mg/ml) 3.2 ml amphotericin B (250ug/ml)

    3. () 0.8NaCl

    ()Rapid antigen detection Enzyme immunoassay

    Nucleoprotien, NP A B 15-30

    ()Virus culture 7-14 MDCK(Madin-Darby Canine Kidney cell)Cytopathic Effect, CPEHemagglutination- inhibition, HI () RT-PCR Real-time RT-PCR

    7-14 Reverse transcriptase-Polymerase chain reaction (RT-PCR) Realtime RT-PCR

    34

  • 35

    RT-PCR Realtime RT-PCR(Primer)(RT-PCR)(Realtime RT-PCR)

    ()

    Paired sera104

    Neutralization test, NT Hemagglutination inhibition test, HINTHISubtypeStrainHI

    Immunofluorescence staining assay, IFA IFA

    A B A H1 H3 H5 Anti-mouse IgG FITC conjugate

    Virus Culture

    MDCK cell(HI)()

    35

  • 36

    RT-PCR Real-time RT-PCR RT-PCR

    RNAPCRReverse transcriptase, RTRNAcDNAPCRHANAMWHO

    RT-PCRRT-PCRRT-PCRInternal control

    36

  • 37

    27X10(2,3,4)A B A B B A (Viral pneumonia)(Bacterial pneumonia)(Encephalitis)(Encephalophy)(Myocarditis)(Pericarditis)(Tansverse myelitis).(Guillain-Barr syndrome)Reye syndrome(2-5) 65() 72

    37

  • 38

    48 48 65 M2 protein(Neuraminidase)M2 protein Aneuraminidase AB () M2 protein

    Amantadine Rimantadine M2 protein (ion channel) M2 protein Amantadine Rimantadine M2 protein M2 protein

    Amantadine Rimantadine Amantadine Amantadine CatecholamimeRimantadine

    Amantadine 10% 2% Rimantadine A (* () (Neuraminidase)

    38

  • 39

    Zanamivir (Relenza TM)Oseltamivir (Tamiflu) Peramivir (Rapiacta)A(Hemagglutinin)(Neuraminidase)N-acetylneuraminic acid ( Sialic acid) hemagglutininneuraminidaseSialic acid neuraminidase neuraminidase A BZanamivir 78% 15% 5-15% 2%Oseltamivir oseltamivir carboxylate 75%) 6-10 99%Rapiacta ZanamivirOseltamivir Peramivir 36-48 1-2 0.4% neuraminidase 4% )*!M2 protein A Amantadine Rimantadine

    () Neuraminidase Oseltamivir Zanamivir 1-1.5

    39

  • 40

    () M2 protein M2 proteinAmantadine Rimantadine H3N2 H1N1 100%

    () Neuraminidase 1.5% Oseltamivir

    M2 protein Neuraminidase M2 protein A B Neuraminidase Oseltamivir Zanamivir A B

    M2 protein Neuraminidase

    M2 protein Neuraminidase Amantadine Rimantadine Oseltamivir Zanamivir Peramivir Symmetrel, Symadine

    Flumadine Tamiflu Relenza Rapiacta

    A A A B A B A B 1 1 1-1.5 1-1.5 1 (10%) (2%) (2%) (1.5%) (90-100%) (90-100%) (1.5%)

    () Oseltamivir (Tamiflu)

    13() 40 1()

    40

  • 41

    1.(10) 2 5 2.(10) 1 10 () Zanamivir (Relenza)

    5()

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    41

  • 42

    -ACIP6185 50

    body-mass indext35)

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    A(A/H1N1A/H3N2)B

    3(2A1B)4(2A2B)1B2013-2014

    11T 2 6570-90%(3-5)3070% (Pneumonia and Influenza, P&I)3040%50~60%80%(2,5,6)76128(15)

    universal influenza vaccine

    43

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    12 3 9 11 65 661-6

    6 3 0.25 ml3 0.5 ml8 1 1

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    44

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    Guillain-Barr 1976 2009 H1N1Guillain-Barr

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    45

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    53

  • 54

    !!

    1. World Health Organization.The world health report 2007 : a safer future : global public health security in the 21st century. World Health Organization; 2007: 45-48.

    2. Mandell, GL., Bennett, JE., and Dolin, R. Principles and Practice of Infectious Diseases, 6th eds. Elsevier Inc. 2005: 2060-2078.

    3. U.S. Centers for Disease Control and Prevention, National Center for Prevention Services. Prevention and Control of Vaccine-Preventable Diseases: Influenza, 7th eds. U.S. Dept. of Health and Human Services. 2003; 2006: 235-56.

    4. Cox N.J. and Subbarao K. Influenza. Lancet; 1999;354: 1277-82. 5. Nicholson K.G., Wood J.M. and Zambon M. Influenza. Lancet; 2003; 362:1733-45. 6. U.S. Centers for Disease Control and Prevention. Prevention and control of

    Influenza.Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(RR 10):1-42.

    7. Centers for Disease Control and Prevention. Influenza Type A Viruses and Subtypes, 2013. Available at: http://www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm

    8. World Health Organization. Influenza. Available athttp://www.who.int/csr/disease/influenza/en/

    9. World Health Organization. Weekly Epidemiological Record. Review of the 2012-2013 Winter Influenza Season, Northern Hemisphere; 2013; 88:225-232

    10. Sentinel Surveillance. Centre for Health Protection in Hong Kong. Monthly summary tables of influenza virus isolation 2012, 2013. Available at: http://www.chp.gov.hk/en/sentinel/26/44/292.html

    11. National Institute of Infectious Disease. Isolation/detection of influenza virus in Japan, week 36/2012-week 11/2013 (as of March 18, 2013). Available at: http://www.nih.go.jp/niid/en/iasr-inf-e.html#graph

    12. Australian Government Department of Health and Ageing. Australian Influenza Surveillance Report; 2013 No.4

    13. 2002 2004; 20:478-487

    14. 2010 2012; 28:113-126

    15. Masahiko Katayose et al. The effectiveness of trivalent inactivated influenza vaccine in children over six consecutive influenza seasons. Vaccine 2011;29:1844-49.

    54

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