季節性流感防治工作手冊(103年12月修訂版)

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紺 紺 紺 紺 紺

紺 紺 Practical Guideline for Prevention and Control of Seasonal Influenza 紺

紺 2014 紺 紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺

12


紺紺紺 紺 1 2 3

紺紺紺紺紺 紺紺紺紺紺紺紺紺

紺 紺紺

紺紺

紺紺紺

紺 紺

4 5 5 6 紺紺紺

10 13 15 15

紺紺紺

15 32 33 37 37 38 42

紺紺紺 紺紺紺 紺紺

46 46 49

紺紺

51 54

紺紺紺紺紺 紺

1


紺 紺 紺紺紺紺紺紺紺紺紺

17 紺

19 (A)

(B)

21 26 29 32 紺 5

紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺

7

紺 紺

21 M2 protein

Neuraminidase

40

紺 紺 (

) (

55 )

57 58

60

67 71 紺

2


紺 紺

(Seasonal Influenza or Seasonal Flu) H1N1

H3N2

A

/

紺 噁Influenza Season or Flu Season) )

7

1

6

30

噁Influenza Epidemic Period) )

11 6

9

(Severe Complicated Influenza ) ( )

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

(ICD-9) (480) (485)

B

(486)

(481) (487)

(482)

(Cluster)

紺紺紺 紺

3

3


2008

2012

2013

2014

/

4

8

1


(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

(

)


(1-5)

(Reye syndrome)

1933

·

Wilson

(1-3)

Smith

A (H1N1) A

A B C

B

A B 1977

A

(H1N1

H3N2)

B

噁Orthomyxoviridae) A

B

C

Segmented

RNA

80-120nm -

Hemagglutinin

Neuraminidase

NA,

M2

B

A

N

HA,

2

H

(1-5)

M1 8

(-)RNA Transcriptase 7

envelope

(-)RNA

RNA

PB1

(1,3,4)

6

Nucleoprotein PB2

PA

C

NP


A

-

(H

H N1-N11(1-4,7-8)

11 A

18 HA

HA-1 HA-3

) H1-H18

)

N

NA

H1N1

NA-1

NA-2

(N

H3N2

B

A

C

lineage

B B/Victoria(1-

B/Yamagata

4,8)

A

B

A

H1N1

H2N2

H3N2 B

C (1,3,4)

A

B

8 11

C

8 11

7 9

(Antigenic (Antigenic drift)

drift) (Antigenic shift)

A

” ”

A

1957

1968

7

(Antigenic drift)


(

A/H2N2 2009

( )

A/H3N2)

H1N1

A

B

8

RNA

C

7 (

)

(

)

( ) (

)

Reassortment

A B C H

(WHO)

N (1,6)

1980

A

(HnNn) A/swine/Iowa/15/30 (H1N1)

A

1930 15 1995

N1

NA

Iowa

H1N1

A/Beijing/262/95 (H1N1) 262

A

Beijing

H1

(1-6)

B

/ HA

/

NA

/

B/Beijing/243/97

(1-6)

8

C

HA


A -

(1,3,4)

RNA

RNA "

HA

"

"

"

NA

" A

Antigenic drift

"

"

"

B

"

Antigenic shift

"

"

" (1,3,4)

20-30

48

A

60 5

10

(1,3,6)

(NA)

Shedding

Viremia (1-4)

9


ç´ş

Mode of transmission

Incubation period 1~4

2

1~2

12

3

Period of communicability 3~5

7-10

24-48 24-72

5

(4,6)

(1,2,5)

21

Susceptibility and resistance

(2,5)

Antigenic drift

(2,5)

A

B A

C

10

(1,2)


Pandemics epidemics)

(Seasonal

(Sporadic cases) (WHO) 25

3

5

(1)

50

(Centers for Disease Control and Prevention, CDC)

10 10

4 2~4

100

3

5

(100/100,000) 500/100,000(2,6,8) 2013-2014

2009 A/H1N1

18

64

(10)

6 11

3

4

2013-2014

1

3

2009 A/H3N2 (10) ç´ş

A/H1N1

Centre for Health Protection 12 7

8

2013-2014

A/H3N2

2009 A/H1N1 2014

(11)

B

2

2009 A/H1N1

A/H3N2

2013-

B (10)

B

2013-2014

2009 A/H1N1

B

(12)

5-6

8-9

2014

62,918 2009 A/H1N1

2013

(13)

11

(1

1

10

10

)


7 11

12

1

6

30

3

11%

(14)

B 2009 2010-2011 2009 A/H1N1

A/H3N2 7

2009

H1N1

A/H3N2

12

2011-2012

A/H3N2

B

2012-2013

2013-2014

2010-2011

A/H3N2

A/H1N1

H1N1

1

2009

B

2010-2014

2008-2009 2010-2011

28 7

50

140

12

2011-2012

2009-2010

1312

1785


2011-2012 1,703

968

2012-2013

2013-2014

1,873

154

171

69

65 2009-2010

H1N1

18

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

/

7

10

10-20 40-50

13

/


B

A

B drift

A Antigenic shift

1-2

65 1996

65 2011

7.7%

10.9%

14

Antigenic


(Surveillance System)

IC

1999 2000 2004 2007 2011

9

15


2014

3

(

8

39

)

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( )

* 1

38

2 3 (

) 1.

( ) 2.

(https://ida4.cdc.gov.tw/hospital/)

3. -

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

4.

16


10鼋 7

1.

1

:https://ida4.cdc.gov.tw/hospital

2. (

)

( )

1. (

)

:https://ida4.cdc.gov.tw/phb

2.

( )

17


(

)

(

1.

)

(

Possible case

2.

3.

1.

)

Probable case

Confirmed case

(

)

2. 3. 4.

(

4

)

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

18


臨床醫師發現疑似流感併發重症個案 一週內通報

衛生局接獲通報個案

【衛生局、醫院】 1. 收集檢體(咽喉擦拭液) 2. 進行檢體送驗事宜 檢體請依標準作業程序運送

【本部認可檢驗機構或本署呼吸道病毒實驗室】 1. 進行相關檢體檢驗事宜 2. 上網登錄檢驗結果

【衛生局】 1. 檢核醫師以網路或書面(須協助登錄通 報系統)通報之資料*,包括臨床表 現、流感疫苗接種史及流行病學接觸 史等 2. 每週定期追蹤及維護個案狀況至個案 出院或死亡

【傳染病個案通報系統】 依據附加資訊中之「臨床表現」、「流行病學 」資料及「綜合檢驗結果」進行個案自動研判

臨床表現資料 是否符合通報條 件

不接受通報

綜合檢驗結果

陰性或 超過21日 無檢驗結果

「附加資訊 -流行病學接觸史」 是否有流行病學 接觸史

可能病例

陽性

「附加資訊 -個案狀況維護」入住ICU 日是否有值

「附加資訊 -個案狀況維護」 死亡日有值

極可能病例

「附加資訊-個案狀況維護」 死亡日有值,由本署防疫醫師 進行死因相關性審查**

確定病例 死因具相關性 列為死亡個案

* **

:

紺 :

19


(

)

(

) 1999

3

1. 2. 3.

1.

(1)

38

(2)

2.

255

(

) 3.

2

2014

20

8


4. (1)

(

)

(

)

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Transtube

(B) (2) a.

4

b.

24

21


c. )

(

(3)

A

(

H1

H3)

5.

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

/

/

/

6. (

)

(

)

1. (1) (2) a.

4

b.

24

(3)

(real-time RTPCR)

2.

1. Virus isolation 2. Real-time PCR

※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 (–) rapid antigen test virus isolation(+) 21 21

22

21

14


H1

H3

INF untype,

紺 Real-time PCR

IC Real-time Outbreak and Disease Surveillance RODS

1999

9

2004 2006

RODS

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ICD-9-CM

170

10

80%

ICD-9-CM

RODS 2008 IC IC

RODS

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

/

2009

H1N1

H1N1

23


6

(

)

(1)

38

(2) (3) (

) 1.

https://ida4.cdc.gov.tw/phb/ 2.

(

)

24


1. 2.

3. bar-code

( )

(

)

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

/

/

25


26


2002 682

(

)

≥ 38°C

1. 2.

(

) 1.

2.

3. ( ) 4.

27


5.

6. (

)

(http://cdc.gov.tw)

28

/

/

/


24 24

24

.

.

1: 1.

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2.

吸 1.

38 0報

29

2.

3.

4.


Long term care facility apartment

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The elderly

Day-care center for mental recovery

)

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(1) (2)

2.

紺 1. 38 37.5 2.

(

Prison

3

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

30


2.

24

3.

/

10 4. (

)

(

)

(

)

/ /

31


/

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

32

/


(

) 1.

Nasal swab

2.

Nasopharyngeal swab

3.

Nasal wash fluid

4.

Throat swab

5. Transtracheal aspirate Bronchoalveolar lavage fluid biopsy

Sputum

Lung

Post-mortem lung or Tracheal tissue

6. Acute serum Convalescent serum

(

)

3 aspirate)

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Throat swab

Immunofluorescence staining 4

assay, IFA

4 48-72 -70

( )

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1.

10g veal infusion broth

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400 ml 2.

0.8 ml gentamicin sulfate solution (50mg/ml)

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Rapid antigen detection Enzyme immunoassay Nucleoprotien, NP

A

B

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(

)

Virus culture 7-14

MDCK

Canine Kidney cell)

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Hemagglutination- inhibition, HI

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)

RT-PCR

Real-time RT-PCR

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Real–time RT-PCR

(Primer)

34

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(RT-PCR

(

)

(Real–time RT-PCR

)

)

Paired sera 10 4

Neutralization test, NT Hemagglutination inhibition test, HI Subtype Strain

NT HI

HI

Immunofluorescence staining assay, IFA IFA A A

H1

H3

B H5

Anti-mouse IgG FITC conjugate

Virus Culture

MDCK cell (HI) (

) RT-PCR

Real-time RT-PCR

RT-PCR RNA

PCR

35


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RNA

cDNA

PCR HA NA

WHO RT-PCR RT-PCR

RT-PCR Internal control

36

M


2

7

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10 (2,3,4)

A B

A

B

B

A

(Viral pneumonia) (Bacterial pneumonia) (Myocarditis) -

(Encephalitis)

(Pericarditis)

(Encephalophy) (Tansverse myelitis)

(Guillain-BarrĂŠ syndrome)

Reye syndrome

65 ( 72

37

)

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48 48 65

M2 protein (Neuraminidase)

M2 protein

neuraminidase

A

A B

( ) M2 protein Amantadine

Rimantadine

M2 protein

(ion channel)

M2

protein Rimantadine

Amantadine M2 protein

M2

protein Amantadine Rimantadine

Amantadine

Amantadine

Catecholamime

Amantadine

Rimantadine 10%

2% Rimantadine

38


A

(

)

( )

(Neuraminidase) Zanamivir (Relenza TM

Peramivir (Rapiacta速)

) Oseltamivir (Tamiflu速

A

) (Hemagglutinin)

(Neuraminidase)

N-acetylneuraminic acid (

acid)

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hemagglutinin neuraminidase Sialic acid neuraminidase

neuraminidase

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Zanamivir

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oseltamivir carboxylate ( 6-10

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)

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39

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Amantadine

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Zanamivir 1-1.5

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H1N1

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M2 protein

Neuraminidase

protein

M2

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B

Neuraminidase Zanamivir

A

Oseltamivir B

M2 protein M2 protein Amantadine Rimantadine Symmetrel, Flumadine Symadine A A

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body-mass index≼35) ≼50

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6 65 6

50-64

Inactivated trivalent influenza vaccines, TIV

(Live-

attenuated influenza vaccine, LAIV)(2,6)

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NA (cell based) influenza virus-like particle, VLP WHO

83

110 2

42


A

3 4

(2

A

1

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A/H3N2)

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A

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)

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)

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7

6

12 (16)

8

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43

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12

3

9 11

65

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6

3

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(

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8.

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噁http://eir.cdc.gov.tw/ ) 7. (1) 7 (2) 噁http://eir.cdc.gov.tw/ )

53


1. Cox N.J. and Subbarao K. Influenza. Lancet; 1999;354: 1277-82. 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. Nicholson K.G., Wood J.M. and Zambon M. Influenza. Lancet; 2003; 362:1733-45. 5. 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. 6. World Health Organization. A revision of the system of nomenclature for influenza viruses: a WHO Memorandum. Bulletin of the World Health Organization. 1980: 58(4):585-591 7. Centers for Disease Control and Prevention. Influenza Type A Viruses and Subtypes, 2013. Available at: http://www.cdc.gov/flu/avianflu/influenza-a-virussubtypes.htm 8. Centers for Disease Control and Prevention. Types of Influenza Viruses Available at: http://www.cdc.gov/flu/about/viruses/types.htm 9. World Health Organization. Influenza. Available at: http://www.who.int/csr/disease/influenza/en/ 10. World Health Organization. Weekly Epidemiological Record. Review of the 20132014 Winter Influenza Season, Northern Hemisphere; 2014; 89:245-256 11. Sentinel Surveillance. Centre for Health Protection in Hong Kong. Monthly summary tables of influenza virus isolation 2013, 2014. Available at: http://www.chp.gov.hk/en/sentinel/26/44/292.html 12. National Institute of Infectious Disease. Isolation/detection of influenza virus in Japan, week 36/2013-week 35/2014 (as of October 3, 2014). Available at: http://www.nih.go.jp/niid/en/iasr-inf-e.html#graph 13. Australian Government Department of Health and Ageing. Australian Influenza Surveillance Report; 2014 No.8 14. 2002 2004; 20:478-487 2010 15. 2012; 28:113-126 16. Masahiko Katayose et al. The effectiveness of trivalent inactivated influenza vaccine in children over six consecutive influenza seasons. Vaccine 2011;29:184449. 17. Galvao T.F. et al. Influenza vaccination in pregnant women: a systematic review. ISRN Prev Med. 2013; 2013: article ID879493 18. Nordin J.D. et al. Maternal safety of trivalent inactivated influenza vaccine in pregnant women. Obstet Gynecol. 2013; 121(3):519-25 19. World Health Organization. Weekly Epidemiological Record. Vaccines against influenza WHO position paper-November 2012. 2012; 87: 461–476.

54


紺 紺

紺 55


56


編號:VL-001

紺 紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺紺

紺 紺

紺 紺

紺 紺 Fever

紺 C

Diarrhea

紺 紺 紺 紺

Headache

Myalgia

Pharyngeal vesicles or ulcers

Malaise

Rhinorrhea

Paralysis

Skin rash

Cough

Sore throat

Vomiting

Others紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 紺 1

38

2

Bar-code

Throat swab Nasopharyngeal secretion or swab Others____________ Throat swab Nasopharyngeal secretion or swab Others____________

/

/

/

/ ______

______ _______

57

紺紺

紺紺紺紺紺紺紺紺疱疱.0姙.饋6

100.01.01

※本項防疫檢驗,不得用以申請健保給付


紺 紺

02-23123456*66908 02-87923311*13568 03-2118800

04-23592525

5497

5701

04-7238595

5930

06-2353535

2653

07-7317123*2578

03-85618255

58

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, 。 紺

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38℃ 37.5℃ 紺紺

, 紺紺

紺 紺

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2.

/

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3.

/ 紺

1. 紺紺紺紺紺紺

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MK-2 cell H292 cell 200 µl 0.45m MDCK 15 Acetone Influenza A Influenza B indirect immunofluorescence staining assay IFA apple green 2.

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7-10 CPE 1 mL PBS monoclonal antibody

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Influenza A virus HA typing by RT-PCR method

67

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RNA Qiagen Viral RNA Mini Kit 140 µl 50 µl AVE buffer RT (a). (b).

RNA RT

RNA

follow Promega RT procedure 15 µl RNA 70 40 µl RNA 15 µl 5X buffer 5 µl 100mM dNTP mix 0.5 µl RT 1 µl Random primer 1 µl H2O 17.5 µl

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PCR follow Qiagen PCR core kit procedure a. PCR 5X Q solution 10 µl 10X buffer 5 µl 25mM MgCl2 4 µl 10mM dNTP 4 µl RT template 2 µl A/H1 (H3)-1 10 µM 1 µl A/H1 (H3)-2 10 µM 1 µl Taq polymerase 0.5 µl H2O 22.5 µl b. PCR program 40cycles 94 2 94 1 52 2 72 3 72 7

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(fiollow TaqMan one-step RT-PCR master mix reagents procedure) Real-time RT-PCR 2X Master mix buffer 12.5 µL RT reaction 48℃ 30 FluA-F primer 10 µM 1.0 µL Taq activation 95℃ 10 FluA-R primer 10 µM 1.0 µL PCR reaction FluB-F primer 10 µM 1.0 µL 95℃ 15 FluB-R primer 10 µM 1.0 µL 60℃ 1 45 cycles FluA probe 5 µM 0.5 µL FluB probe 5 µM 0.5 µL RNA enzyme mix 0.67 µL RNase-free water 1.83 µL template 5.0 µL Roche

(LightCycler 480 RNA master hydrolysis probes reagents procedure)

RNase-free water FluA-F primer 10 µM FluA-R primer 10 µM FluB-F primer 10 µM FluB-R primer 10 µM FluA probe 5 µM FluB probe 5 µM Enzyme master mix Enhancer Activator RNA sample

0.3 µL 1.0 µL 1.0 µL 1.0 µL 1.0 µL 0.5 µL 0.5 µL 7.4 µL 1.0 µL 1.3 µL 5.0 µL

Real-time RT-PCR RT reaction 63℃ 3 Taq activation 95℃ 30 PCR reaction 95℃ 10 58℃ 30 紺 72℃ 3 45 cycles

69


紺 Primer A/H1 H1-1: 5’-GAT GCA GAC ACA ATA TGT AGA GG-3’ Primer A/H1 H1-2: 5’-CNC TAC AGA GAC ATA AGC ATT T-3’ Primer A/H3 H3-1: 5’-TCA GAT TGA AGT GAC TAA TGC T-3’ Primer A/H3 H3-2: 5’-AAT TTT GAT GCC TGA AAC CGT-3’ FluA-F : 5’- AAG ACC AAT YYT GTC ACC TYT GA -3’ FluA-R : 5’- TAA AGC GTC TRC GYT GCA GTC C -3’ FluA probe: 5’FAM - TTT GTN TTC ACG CTC ACC GT -3’TAMRA (For ABI ) FluA probe: 5’FAM – TTT GTN TTC ACG CTC ACC GT -3’BBQ (For Roche ) FluB-F: 5’- GAG ACA CAA TTG CCT ACC TGC TT -3’ FluB-R: 5’- TTC TTT CCC ACC GAA CCA AC -3’ FluB probe: 5’VIC-AGA AGA TGG AGA AGG CAA AGC AGA ACT AGC -3’TAMRA (For ABI FluB probe: 5’HEX-AGA AGA TGG AGA AGG CAA AGC AGA ACT AGC -3’BBQ (For Roche Run gel and read data 1.5 agarose gel 100

40

Ethidium bromide

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