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H1 - H16 N1 - N9 Aquatic birds Poultry Humans Pigs Horses Aquatic mammals Cats Dogs Influenza Branch

( )

1997 H5N1 18 6

H5N1 HPAI 2004 36,169 7 5 210,431-27 Feb. 2004, Chickens 6, 1 12 Jan.2004 Chickens 17 Feb,2004 Bantams, duck -3 Mar. 2004, Chickens -7 Mar.2004, Crows -10 Mar. 2004

H5N1

2005 1

Lombok, Indonesia, 2008

2006 3

Clade 1 Clade 2.1 Clade 2.2 Clade 2.3 Clade 0 10

(2003 2008 12 Clade 2.2 Clade 2.3 Clade 1 Clade 2.1

Country 5) 2003 2004 2005 2006 2007 2008 2009 Total Azerbaijan 0 0 0 8 (5) 0 0 0 8 (5) Bangladesh 0 0 0 0 0 1 (0) 0 1(0) Cambodia 0 0 4 (4) 2 (2) 1 (1) 1 (0) 0 8 (7) China 1 (1) 0 8 (5) 13 (8) 5 (3) 4 (4) 7 (5) 38 (25) Djibouti 0 0 0 1 (0) 0 0 0 1 (1) Egypt 0 0 0 18 (10) 25 (9) 8 (4) 2 (0) 53 (24) Indonesia 0 0 19 (12) 56 (46) 42 (37) 24 (20) 2 (2) 143 (117) Iraq 0 0 0 3 (2) 0 0 0 3 (2) Laos 0 0 0 0 2 (2) 0 0 2 (2) Myanmar 0 0 0 0 1 (0) 0 0 1 (0) Nigeria 0 0 0 0 1 (1) 0 0 1 (1) Pakistan 0 0 0 0 3 (1) 0 0 3 (1) Thailand 0 17 (12) 5 (2) 3 (3) 0 0 0 25 (17) Turkey 0 0 0 12 (4) 0 0 0 12 (4) Vietnam 3 (3) 29 (20) 61 (19) 0 8 (5) 6 (5) 0 107 53) Total 4 (4) 46 (32) 97 (42) 116 (80) 88 (59) 44 (33) 11 (7) 407 (256)

.

H5N1 2003-2009

2005

2-8 ( ) 7-15

Emerg. Infect. Dis. J. 2005

De Jong et al. Nature Med 2006

- NP ( /

α

( ;

( ) ( ) (

(Russian Flu Pandemic)

1918

- 8

(1) (3) (2)

α α

HA Clade Receptor binding Receptor site specificity 192 226 227 228 Gln Leu Ser Ser α(2-3) Arg Glu Ser/Gly Gly α(2-6) A/goose/Guandong/1/96(H5N1) 3 Gln Leu Ser Ser α(2-3) A/Hong Kong/156/97(H5N1) 3 Gln Leu Ser Ser α(2-3) A/chicken/Vietnam/1/2004(H5N1) 1 Gln Leu Ser Ser α(2-3) A/Vietnam/1193/2004(H5N1) 1 Gln Leu Ser Ser α(2-3) A/Thailand/16/2004(H5N1) 1 Gln Leu Ser Ser α(2-3) A/duck/Cambodia/JP52A/2005(H5N1) 1 Gln Leu Ser Ser α(2-3) A/Vietnam/JPHN20408/2005(H5N1) 2-2 Gln Leu Ser Ser α(2-3) A/goose/Shantou/2086/2006(H5N1) 2-2 Arg Leu Gly Ser α(2-6) A/Turkey/15/2006(H5N1) 2-2 Arg Leu Gly Ser α(2-6) A/Egypt/2947/NAMRU2/2006(H5N1) 2-2 Arg Leu Gly Ser α(2-6) A/Indonesia/13/2006(H5N1) 2-1 Gln Leu Ser Ser α(2-3)

H5N1 HPAI

H3N8 H2N2 H2N2 H1N1 H5 H9 H6 H7 1980 H3N2 H1N1 1996 2002 885 1895 1905 1915 1925 1935 1945 1955 1965 1975 1985 1995 2005 1889 Russian Influenza H2N2 1900 Old HK Influenza H3N8 1918 Spanish Influenza H1N1 1957 1968 Asian Hong Kong Influenza Influenza H2N2 H3N2

) vs. PQ RERRRRKR GL - - - H5

HA1 HA2 Clade 0 A/ Hong Kong/ 258/ 97 A/ Hong Kong/ 156/ 97 PQ RERRRKKR PQ RERRRKKR GL - - - GL - - - Clade 1 A/ Viet Nam/ 1194/ 2004 PQ RERRRKKR GL - - - Clade 2.1 A/ Indonesia/05/2006 PQ RESRRKKR GL - - - A/ Indonesia/13/2006 PQ RESRRKKR GL - - - Clade 2.2 A/ Turkey/12/2006 PQ GERRRKKR GL - - - A/ Egypt/2616/NAMRU-3/2007 PQ GERRRRKR GL - - Clade 2.3 A/ Anhui/2/2005 PQ RE RRRKR GL - - A/ Myanmar/NIID-23/2008 PQ RERRRKKR GL - -

) NS1 ; TNFα F92E or D S42P : TNFα PB2 ; E627K (4 36 PB1-F2 N66S 2

PB2 RNA (. PB1-F2 HA. HA NS PDZ

H5N1 H9N2 H7N(2,3,7) H6N1 H2N2 +++ ++ + ++ + ++ + + +++ + + ~ ++ + + ++ ++ + +? +++ + ++ + + +++ ++ ++ ++ +

The big pandemic of 1918

1-3 5-6 4

1. 1. 2. 3. 4. 5. 6.

)

)

( 17 10 28 ( 17 10 28

2008 21 21

Deaths Rates / 100,000 Population (Annual Basis) 1918 Death Rates: Philadelphia v St. Louis 16000 14000 Philadelphia St. Louis 12000 10000 8000 6000 4000 2000 0 9/14/1918 9/21/1918 9/28/1918 10/5/1918 10/12/1918 10/19/1918 10/26/1918 11/2/1918 11/9/1918 11/16/1918 11/23/1918 11/30/1918 12/7/1918 12/14/1918 12/21/1918 12/28/1918 Date Weekly mortality data provided by Marc Lipsitch (personal communication)

St. Louis *Estimated attack rate before interventions: 2.2% 14000 12000 10000 8000 6000 4000 2000 0 1918/9/14 1918/9/21 1918/9/28 1918/10/5 1918/10/12 1918/10/19 1918/10/26 1918/11/2 1918/11/9 1918/11/16 1918/11/23 1918/11/30 1918/12/7 1918/12/14 1918/12/21 1918/12/28 Date *derived from mortality data using 2% CFR Death Rate / 100,000 Population (Annual Basis)

14000 Philadelphia *Estimated attack rate before interventions: 10.8% 12000 10000 8000 6000 4000 2000 0 9/14/18 9/21/18 9/28/18 10/5/18 10/12/18 10/19/18 10/26/18 11/2/18 11/9/18 11/16/18 11/23/18 11/30/18 12/7/18 12/14/18 12/21/18 12/28/18 Date *derived from mortality data using 2% CFR Death Rate / 100,000 Population (Annual Basis)

4

social distancing)

.

(Oseltamivir, Zanamivir) (Tamiflu) ( ) + (Relenza),

Clade 2.2 M2: L26I, S31N NA: H Y, S N Clade2

2 15 1 2 2 ICH E2B guideline

H5N1 VietNam/2004 Clade1 Clade2.1,Clade 2.2(, Clade2.3 1/2 8 Clade Pre-pandemic

Prepandemic

6 1 1

?

PPE

2 ( ) (

1930 3 5 5~6 4.8~5.5 1.5 1.8 4.4 (4.4 trillion) 349 180 20 4.1 30 6.1

1.4 0.7 14.2 2.0 71.0 4.8 180-250 5.5

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

9 10 11 1. 2. 3. 4. 5. 6. 7. 8.

1. 2. 3. 4. 5. 6. 7.

1. ( 2. 3. 4. 5.

1. 2. 3. 4. 5.

(BCP) Business Continuity Plan

P) M)

Business Continuation Plan,BCP)

~2

1. ( 2. 3.

1. ( 2. 3. 4. 5. 6. 7. 8.