??? ?????????????? 2006?1?6? Taipei, Taiwan

1
??????????????????????????????
???
?????????????? 2006?1?6?
Taipei, Taiwan
2
??

• ??
• ??????????????
• ???????
• 1.??
• 2.??
• ?.???SARS?????????
• ?.???????

3
????????????

• ??(??) ????
• 1890???????????????
• 1918?????????H1N1??????,4000??????H1N1???????????
  ??
• 1957???????,H2N2?????10????
• 1968???????,H3N2????70????H2N2???H3N2????????????
  ???????,?????????
• 1997.5.21??????????H5N1???????18???????????????,6
  ??
• 1999?????????????????????????
• 2001?????????????????,???????????????????????
• 8. 2003.2????2???H5N1??????(1???) ?????????
• 9. 2003.2.28H7N7?????????????800???,?1100?????,83
  ???,1????

4
??(Influenza)

• A. ??A?B?C??,?A?B??????????
• B. (-)single-stranded RNA??,????
  (HA,NA,NP,M,NS,PA,PB1,PB2)
• C. ????
• Hemagglutinin(H, ?????)
• ??????????
• ??H1-H16,?H1,H3, ?H3N8,H5
• ??(1997???) H1-H3, 1997,2003-5H5, 2003H7,
  1999H9
• Neuraminidase(N, ??????)
• ???????????,????????
• ??N1-N9,??N1-N2, H1N2, ? H1N2, H3N1
• D. ??????
• ???( Antigenic drift )???????,??????????????
• ???(Antigenic shift, genetic reassortment
  )????????(pandemic)
• ??????(Interspecies transmission)
• ????(gene insertion) 2004 Canada

5
????????Ecology of Influenza Viruses
Migrating birds
Seal
Nature host
Mixing vessel
(Vaccine, 2002, 20 s16-20)
6
20??????????????Flu Pandemics in the 20th
Century
Ho, IBMS
7
1918-1919???????????????? Age Distribution of
influenza in 1918

• Death rate in 2nd and 3rd waves 1.5 of all
  clinical cases
• 10 fold higher than other influenza pandemics

1918 pandemic
Microbes and infection 2001381-7
8
1957-1958?,?????????19571958 Asian Flu (H2N2)

• China Singapore HK worldwide
  Europe
• Japan Taiwan
  North Am.
• Feb Apr Mar Nov
  Jan
• Affected 40-50 people
• Mortality gt 1 million
• Attack rate gt50 (children aged 5-19)
• Deaths due to secondary bacteria pneumonia

peak
1958
1957
First wave
Second wave
(Annu. Rev. Med., 2000, 5140721)
(Sem. Resp. Infect., 1992, 726-37)
9
1957????H2N2?????
Ho, IBMS
10
???????????????Theories for the Emergence of
Pandemic Viruses

• A.????(Genetic Reassortment)
• H2N2 and H3N2
• Pig with both avian and mammalian receptors as an
  intermediate host ( SA?2,3Gal vs. SA?2,6Gal )
• B. ????(Direct Transfer)
• H1N1 in 1918
• C.???(Re-emergence)
• H1N1 in 1977

H1N1
H2N2
H3N2
5
6
2
3
11
????????????

• 1. ?20????????????????,?1918??1957??1968?,????????
  ??????
• 2.??????????????(????)???????????????????(????)?,?
  ?????????????????,????????????????????????,???????
  ??????????????????????????????????????????????????
  ????
• 3.???2004??H5N1????????????????,????????????,?????
  ???,??????????????????????????????,?????????????
  ?
• 4.??????????????????,????????????H5N1?????????,??H
  5N1?????????????????
• ????? ????? ??????

12
?????

• 1.????A???????????????,??????????????,????????????
  ??????????A??????HA?16???,???H5?H7????????????
• 2.???/??????????,????????????????????,????????????
  ?????HA???????????????(basic amino
  acids),????????????,??????100?
• 3.???????/??(??),?????????????????(reservoir),????
  ????????????
• 4.????????????????????(live bird
  markets)????????????????????????????

13
?????

• A. ????????????????,?????????
• B.????????????
• (1)????(highly pathogenic Avian
  influenza),?H5N1 in
• Asia during 2003-2005?
• (2)????(low-pathogenic Avian influenza),?H5N2
  in
• Taiwan during 2003-2004?
• C.????????
• 1.??????,?56??3???60??30???100?
  ?1?????????????????????, ?????
• 2.???????,???????????????? ??????
• D ??????
• ????????????????????????????????????
• E. ????????
• ????????????????,?????????????????????????
• F. ????????
• ????????????????????,???????????

14
1997???H5N1?????H5N1 Hong Kong Flu (1997)
More than 1 million chickens, ducks, and geese
were gassed in Hong Kong , Dec. 1997.
15
1997?H5N1?????????????
?? ?? ????/?? ??
Mounts et al. JID, 1999 ????? ????(gt80) ??????? 15/18 H5N1 ??(41?)?? ??????? ??????? (OR4.5)
Katz et al. JID, 1999 ???? ????(gt80)/?????,??????? 17 H5N1 1.??(51) 2.??(50) 3.???(26) H5????? 1.???? 12 2.?? 0 3.??? 3.8
Bridges et al. JID, 2000 ??????? ????(gt80) ??????? ????? ?? (217?) ????(309?) 1. H5????? ???8/217(3.7) vs. ????2/309(0.7) (p0.01) 2. ?? (p0.01) ??? (p0.05)
16
2003?????/?????H5N1??????2003 Hong Kong/China
Avian Flu (H5N1)

• Epidemiology investigation

17
2003?????H7N7????????? 2003 Netherlands Avian
Flu (H7N7)

• Feb.28 ?????????
• Mar.1 ?????????????????
• Mar.7 ??????????????,????H7N7
• gtMar.7 ????????, ????????????
• End Mar. ????????????H7N7
• Early Apr. ???????H7N7??
• Apr.17 ?????????(56????)
• Apr.25 ??83?????,
• 3?????????
• 83 confirmed cases of H7N7,
• 3 probable human to human
• transmission cases

18
??????????????????
???
??
? ? ?
??
19
???????????-1
2005?5?
??????????,???H5N1???
6?
?????????????????H5N1
?????????????H5N1
8?
10?19?
???????H5N1???
???????????
10?20?
10?22?
???????????
20
???????????-2

• ????????????????????????????????10?14???????,?10?1
  9????H5N1?????,???6000???????,2600???,???91100??

21
???????????-3

• 10?19?????????????,???????????????????????(?10?25?
  ???H5N1)????2100????????,550???,?????

22
???????????-3

• 10?20???????????????????????(?10?25????H5N1),???68
  7????????,545???,?????
• ??????,???????,?????????!!

23
???????????-1
2005?10?
4?
??????
7?
Ceamurlia-de-Jos?Maliuc?Vulturu????
??Ceamurlia-de-Jos????H5???
13?
19?
??Ceamurlia-de-Jos????H5N1???
20?
??Maliuc?Vulturu?????H5N1???
21?
1???????H5
24
??? (???14?????H5N1??)
?? 2006?1?9?
???, Kastamonu, Corum, Samsun

• ???????1?8???5??????
• ?????3?5??2?????65?????Agri?Dogubeyazit?????9??3
  ?????
• ???????1?9???5??????????????????,Kastamonu,
  Corum, Samsun, Van 4????

Agri?, Van
???
???????????????,???????????????????H5N1 ???????,??
????????????,????????????????? ????????????,??????
????81????10????????H5N1,???????????
??????????
http//www.who.int/csr/don/2006_01_09/en/index.htm
l
25
??? (???3?4?????H5N1??)
?? 2006?1?7?
Van?

• ??????????????????,2???5??8????
• ???30????????????,?????,???Van??Dogubayazit???????
  12?????,???????????,???????H5N1,??????????????

???
??????,??????????????????????4?????,??????????????
???35??
??????????
http//www.who.int/csr/don/2006_01_07/en/index.htm
l
26
??? (???1?2?????H5N1??)
http//www.who.int/csr/don/2006_01_05/en/index.htm
l
??????????
?? 2006?1?5?
Agri?

• ?????????????????????,????????,??????Agri??Dogubay
  azit?,??????,??????????
• ????????????????????????????,?????????????????
• Dogubayazit???????????????????,?12?27????Igdir????
  ???????

• 10??????????????????????,12???Igdir???????????????
  ?,???????????,???????????????????

27
???? (???5?????H5N1??)
?? 2005?12?9?

• ???31???,????-???-,10?30???,11?29????
• 10??,???????????? H5N1?????????

???
??????????
http//www.who.int/csr/don/2005_12_09/en/index.htm
l
28
????(???6?????H5N1??)
?? 2005?12?16?

• ???35???,??????-???-?12?4?????,?????
• ????????????H5?????

???
??????????
http//www.who.int/csr/don/2005_12_16/en/index.htm
l
29
???? (???7?????H5N1??)
?? 2005?12?30?

• ???????41????12?6?????,12?8???,12?21????
• 12?13??????H5N1??,12?23????CDC????????????

???
??????????
http//www.who.int/csr/don/2005_12_30/en/index.htm
l
30
???/??????? ???????????? 2005/12/30 0856
??????/????

• ???????29?????,??????????????????,????????????????
  ?,????????????????? ??41??????????????,?12?6???,
  12?21???,????????,?????????????????,??????H5N1????
  ????????????????????????????H5N1??????
  ??????11?16?????,????7??????????,3???,??????????
  ????????????????????,??,????????,???????,???????H5
  N1??????  ????? ????????????? ??? 2006-01-02
  1910 (?????????????)?????????????H5N1???????,????
  ?????????,?????????????????????????????,??????????
  ??????,?????????????,???????????????????????????
  ??????????????????,?????????????????,????????????,
  ??????????????,???????????????,??????????????,????
  ????????,????????

31
???? (???8?????H5N1??)
?? 2006?1?10?

• 6????,???????,?????2?????H5N1???
• ????????????????????????????????H5N1???

???
????8?????5???? ??6?????????H5N1 ????????? ?????
????
??????????
http//www.who.int/csr/don/2006_01_10/en/index.htm
l
32
???????????????????? (?????)

• ?????1?18?????(www.moh.gov.cn)???,????????????????
  ??????
• ??????????,????????????????????????,?????35???????
  ??1?11????

33
????????????????

• ?????1?24????????????????,???????????????????????
  ?,??????????????????????,1?12???,
  1?22?????,???????????????????????????????????,???
  ??????????????????????,????????????,???????

34
??????????????????????
???? ??? ??? ?? ?? ?? ?? ?? ?? ??? ??? ?? ?? ?? ??
???? ??? ???? ??? ???? ??? ???? ??? ???? ??? ???? ??? ???? ? ? ? ????
2003 0 0 0 0 0 0 0 0 0 0 3 3 3 3
2004 0 0 0 0 0 0 17 12 0 0 29 20 46 32
2005 4 4 8 5 16 11 5 2 0 0 61 19 94 41
2006 0 0 2 2 3 3 0 0 4 2 0 0 9 7
?? 4 4 10 7 19 14 22 14 4 2 93 42 152 83

• ??????????,??????WHO?????????????

35
???????????????
4 2
10 7
93 42
22 14
4 4
19 14

• ??? ????

36
???????

• ????.?????????.????.????????? .????10-20
  .????40-50
• ???1-3?
• ????.??-?????3-5?.??-??7?
• ??.???????????????????.??????????????????.???
  ??2-7????,??????????

37
????????SARA??????
???? (H5N1?H7N2 ?H9N2) ??(H1?H2?H3?N1?N2) SARS (SARS????)
?? ?????????????????????????????????? ??????????????????????? ???(?38/37.5?)? ?????????????????????????
??? 5-9?,????????? 1-3?,????????? 3-10?,?????????????
???? ????????(??????????????)? ???? ????????? ???????,???????????????????
???? ??????,?? ????????????????????? ???????????????
?? ????????????-??? ???????-??? ??????????
?? ???????????-?????-???-????? ??? ???
???? 75?????? 75?????? 75??????
???? ???????? -- ????????
38
????????
?? ?? ?? ?? ???? ???
?? 1997 2004 2004 2005 2005
?? (N18) (N17) (N10) (N10) (N4)
??(?)
??? 9.5 14 13.7 19.4 22
?? 1-16 2-58 5-24 6-35 8-28
??-??() 8 (44) 9 (53) 6 (60) 3 (30) 1 (25)
????????????(?)
??? NS 4 3 NS NS
?? 2-8 2-4
?????? 1 2 1 1
????????-??/??() 11/16 (70) ??????? 14/17 (82) 8/9 (89) 6/6 (100) ??????? 3/4 (75)
???????????(?)
??? 3 NS 6 6 8
?? 1-7 3-8 4-7 5-8
????-??/??()
??(??gt38?) 17/18 (94) 17/17 (100) 10/10 (100) 10/10 (100) 4/4 (100)
?? 4/18 (22) NS NS 1/10 (10) 4/4 (100)
??? 2/18 (11) 9/17 (53) 0 2/10 (20) NS
?? 3/18 (17) 7/17 (41) 7/10 (70) NS 2/4 (50)
?? 3/18 (17) 4/17 (24) NS NS 2/4 (50)
?? 6/18 (33) 4/17 (24) NS 1/10 (10) 0
?? 12/18 (67) 16/17 (94) 10/10 (100) 10/10 (100) 4/4 (100)
?? NS 13/17 (76) 5/10 (50) 3/10 (30) NS
??? 4/18 (33) 12/17 (71) 0 0 1/4 (25)
??? 7/18 (58) 9/17 (53) 0 0 NS
???? 1/18 (6) 13/17 (76) 10/10 (100) 10/10 (100) NS
??? 11/18 (61) 17/17 (100) 10/10 (100) 10/10 (100) 4/4 (100)
????? 11/18 (61) 7/12 (58) NS 8/10 (80) 1/2 (50)
????? NS 4/12 (33) NS 8/10 (80) 1/2 (50)
???????? 11/18 (61) 8/12 (67) 5/6 (83) 7/10 (70) NS
39
??H5N1????????????????

• ??????????
• (a)????????????
  
• (b)???????????????? ??????????????
• 2. ??????????????????? (a)???????????????????
  ???????,???????,???????????????
  
• (b)?????(inactivated vaccine)????????????(qu
  ality control)??
• 3. ?????????????????????????

40
??

• ?????????????????????
• ?? ?????????????????????,??????????
• ?? ???????????????????(???)???(?)???
• ?? ?????????(??)???
• ?? ???????????????
• ?? ???????????????????
• ?? ????????????
• ?? ??????????
• ?? ??????????(?????????)?
• ?? ??????????????????

41
??

• ???????????????????,?????????
• ??High risk populations????????????
• ???????????????, 56???3???60???30???100???1??????
  ,???????????
• ????????????????????????????
• ?????????????,?????,???,?????????

42
??????????

• 1.???????????????,?????????????
• 2.??????????????,????????????????
• 3.????????????,?????????,???,????????????
• 4.????????,????????,??????????????????????????
• 5.????????????????????,????????????????????,??????
  ????????????,?????
• 6.????????,?????????????,?????????????????????????
  ??,???????????????
• ?????????????????????????????????????

43
??????

• 1.????????,???????????????
• 2.???????????????????,?????????
• 3.????????(???)???????,?????,????????????
• 4.??????,????????????????
• 5.?????,??????????????????,????SARS????????????,??
  ?????????????????????????,??????????????????

44
???????????? ????????????
?? ????
0? ????H5?N7?????????????????????????????????? 1.?????????????????? 2.??????????????????
A1? ????????????????????
A2? ???????????????????????????????????
B? ????????????????????
C? ??????????????????????????
45
?????????-1
46
?????????-2

• 92?12?????????????H5N1??
• 94?10?14?????????????????,????????????????????,??
  1500???????,??19???,???1037?????????,?276????????,
  ??????????????????????????????,?????,??700???????,
  ?38???,?10?19??????????????,????????????H5N1?????
• ?????????15???????????????????

47
??-???9/26??????????

• ??????9?29???,??????????27??????9?17??????????19??
  ?????????(Taimiflu)??,26????
• ?????????????,??????H5N1??????
• ?????????????????,????????????????

?????,??????(Tamiflu),??????????????,??????????,??
???
48
????????

• ??1??????????????
• 1.????????????????????
• ?????(???3???)
• ?????????????
• ????X???????
• ???????
• ???????
• ???10???????????
• ????????(?????)????????????????
• ????3?????????????????3????????
  ????????????????
• ?????????????????????????????????

49
?????????????????????

• (1)???????????
• (2)???????????????????????,?????????????????????
• (3)???????,????????????????(susceptibles)??????
• (4)??????????????????????????????????

50
A.???????
?????????????

1. ???????????,??????????????(?????????)
2. ?????????????????(?????????)
3. ????????(??????????????????????)
4. ????

51
?????????????B.????

1. ??????,???????(??????)
2. ?????????????
3. ??????????????
4. ????????????????????????
5. ??(???????)
6. ??????(a)??????(b)????????(c)???(d)????/????(
   e)????,????????

52
??????????????????????(pandemic)

• A. In the new survey of some of the nation's
  largest businesses,
• Two-thirds said their companies were inadequately
  prepared
• to protect themselves during a pandemic.
• 2) Demonstrating a surprising fatalism, 39
  percent believed
• there wasn't much they could do.
• 3) When asked if they would waive sick-leave
  restrictions to encourage workers with flu
  symptoms to stay home, 63 percent of the
  companies were undecided and 10 percent said they
  would not.
• - That contradicts the federal government's
  stance that having the potentially contagious
  stay home from work or school could prove key to
  stemming a pandemic.

53
??????????????????????(pandemic)

• B. ''That people have contingency plans that
  could accommodate between 10 and 20 percent of
  their work force being out at any given time for
  as much as two to four weeks,'' HHS Secretary
  Mike Leavitt told The Associated Press.
• 1. In two weeks, Microsoft Corp. will roll out
  the first phase of its pandemic plan an
  educational campaign for its 63,000 workers
  worldwide, along with bottles of hand sanitizers
  as a reminder that good hygiene helps prevent
  influenza. Companywide telecommuting -- like the
  software company already does when snow shuts
  down its Seattle-area headquarters -- and plans
  to distribute protective masks also are part of
  the effort.
• 2. ''Can you tell somebody, 'I'm sorry, you've
  got to come in here, we don't care that your
  family's sick?' Can we really do that? No,'' said
  Mike Maxwell, vice president of emergency
  preparedness for Pepco Holdings Inc., the utility
  that supplies electricity to almost 2 million
  people in the nation's capital and nearby states

54
??????????????????????(pandemic)

• 3. The utility has some masks and other
  protective gear, and a pandemic drill planned for
  January will help define further preparation ,
  who also is working to ensure the government
  provides stockpiled vaccines and other pandemic
  supplies to utility workers who need them.
• 4. A pandemic ''would be a cascading crisis for
  us as an organization,'' Maxwell said. ''The more
  we do upfront, the better off we are.'
• 5. HHS' Leavitt will stress next week that
  companies can learn from the months of disruption
  caused by the last century's three flu pandemics,
  including the 1918 flu that killed about 50
  million people worldwide, 500,000 in the U.S.
  alone.