H1N1??????

1
H1N1??????

• ????????
• ?????
• ????

2
Influenza?????

• ???15????, influence of stars
• ????
• ?????
• 1878??fowl plague
• 1901????? ultrafilterable agents
• ?????1930
• ??????
• 1933A?,?1930??????
• 1940B?
• ???????

3
?????(Flu)

• ??(Flu)?????(cold)
• ??(Flu)H1N1, H2N2, H3N1,H5N1???????
• ??????????????,???????????????
• ??(cold or common cold)
• ???(Adenovirus)1-7,14,21?
• ???????(Respiratory syncytial virus)
• ???(Rhinovirus) gt101????
• ????(Corona virus)?13?
• ????????(Parainfluenza virus) PIV 1-4(?A,B??)

Influenza
4
??/??

• ??
• ????????
• ?? (??3?,??8?)
• ??
• ????????
• ??
• ??
• ???
• ??
• ??
• ????
• ????
• ????
• ????????????,????????
• B???????????
• ????????
• ??
• ??????
• ???????

• H5N1??(???)
• ????,??????
• ??,???41?
• ??
• ??
• ???
• ??
• ??
• ????
• ???
• ????????? (????????????? )
• ????????????
• ??????????
• ????????????
• ?????????????????????????

5
???????

• Virion ???????,??80-120 nm.
• Family Orthomyxoviridae(??????)
• Genus type A,B?type C
• ???????
• Nucleoprotein(NP)
• Matrix(M) protein
• Type
• Influenza A????????,???????????????(?????????????
  )??
• Influenza B,C ??????

A
B
C
Influenza
6
A????????

• ????(??)H-15(16), N-9.
• Hemagglutinin?????
• ??? sialic acid receptor??
• ????????????????????
• ?????????, ?????
• M2 protein (ion channel)(type A)
• For viral uncoating
• Neuraminidase?????
• ???????????????
• ????????
• ?????????
• ?? ??????,????
• Strain A?
• Type?/ host species??/site of origin????/isolate
  number????/ year of isolation????2?( subtype??).
• ?A/Beijing/262/95(H1N1)

H16
Influenza
7
A????????
PB2
PA
PB1
HA
NP
NA
M
NS

• 9 ????
• ????3 ?,?????(HA)?????(NA)?M2 ???(???????)?
• ???????M1 ???,????????????????
• ???????,?8 ???RNA,????(NP)?PA,PB1,PB2 ?3 ????
  (polymerase)?RNA ?????(RNP)????
• 8????
• 1-3.?????????? (PB1?PB2?PA)
• 4.????? ?HA??,
• 5.????NP ??,
• 6.??????NA??,
• 7. M1?? ?M2???M??,
• 8.??NS1?NS2???NS?? (nonstructural protein, NS)
  ?NS??

8
????

• Endemic?1-3?.?????????????????,
• Pandemic(??????)?10-15(20)?.?????????????????????
  ??????

Influenza
9
???????????? (USA)

• Period Years Annual average Mortality/105
• Pandemic 1918-1920 225,000 218.4
• Interpandemic 1920-1933 28,338 23.0
• Interpandemic 1933-1957 10,108 7.5
• Pandemic 1957-1960 38,567 22.0
• Interpandemic 1960-1968 14,363 7.5
• Pandemic 1968-1972 27,982 13.9
• Interpandemic 1972-1981 22,089 10.3
• Interpandemic 1981-1991 20,000 10.0
• Worldwide gt 21,000,000 fatal cases

10
??????????
Year and Country Virus Designation
1995, United Kingdom H7N7 A/Eng/268/95
1997, Hong Kong H5N1 A/HK/156/97 A/HK/148/97
1999, Hong Kong H9N2 A/HK/1073/99
2003, Hong Kong H5N1 A/HK/213/03
2003, the Netherlands H7N7 A/Neth/33/03 A/Neth/219/03
2003, Hong Kong H9N2 A/HK/2018/03
2004, Vietnam H5N1 A/VN/1203/04 A/VN/1194/04
2004, Thailand H5N1 A/Thai/16/04
2004, Canada H7N3 NA
2004, Egypt H10N7 NA
H5 and H9 viruses have generally been associated with respiratory disease, whereas H7 has generally been associated with conjunctivitis. NA denotes not available. H5 and H9 viruses have generally been associated with respiratory disease, whereas H7 has generally been associated with conjunctivitis. NA denotes not available. H5 and H9 viruses have generally been associated with respiratory disease, whereas H7 has generally been associated with conjunctivitis. NA denotes not available.
11
WHO???????????
10 September 2008
Country   2003 2003 2004 2004 2005 2005 2006 2006 2007 2007 2008 2008 Total Total
Country   cases deaths cases deaths cases deaths cases deaths cases deaths cases deaths cases deaths
Azerbaijan 0 0 0 0 0 0 8 5 0 0 0 0 8 5
Bangladesh 0 0 0 0 0 0 0 0 0 0 1 0 1 0
Cambodia 0 0 0 0 4 4 2 2 1 1 0 0 7 7
China 1 1 0 0 8 5 13 8 5 3 3 3 30 20
Djibouti 0 0 0 0 0 0 1 0 0 0 0 0 1 0
Egypt 0 0 0 0 0 0 18 10 25 9 7 3 50 22
Indonesia  0 0 0 0 20 13 55 45 42 37 20 17 137 112
Iraq 0 0 0 0 0 0 3 2 0 0 0 0 3 2
Lao People's Democratic Republic 0 0 0 0 0 0 0 0 2 2 0 0 2 2
Myanmar 0 0 0 0 0 0 0 0 1 0 0 0 1 0
Nigeria 0 0 0 0 0 0 0 0 1 1 0 0 1 1
Pakistan 0 0 0 0 0 0 0 0 3 1 0 0 3 1
Thailand 0 0 17 12 5 2 3 3 0 0 0 0 25 17
Turkey 0 0 0 0 0 0 12 4 0 0 0 0 12 4
Viet Nam 3 3 29 20 61 19 0 0 8 5 5 5 106 52
Total 4 4 46 32 98 43 115 79 88 59 36 28 387 245
12
H1N1 ???????????

• ?2009.08.19 ?

??-H1N1???? ??????? ??-H1N1???? ??????? ??-H1N1???? ??????? ??-H1N1???? ???????
Argentina ???404 Ecuador ???23 Malaysia ????62 Singapore ???11
Australia ????108 El Salvador ????12 Mexico ???162 South Africa ??3
Bolivia ????14 Guatemala ????10 New Zealand ???14 Spain ???11
Brazil ??192 Honduras ????7 Panama ???4 Thailand ??97
Canada ???66 India ??24 Paraguay ???39 United Kingdom ??49
Chile ??105 Indonesia ??3 Peru ??45 United States ??477
Hong Kong ??4 Israel ???8 Philippines ???8 Uruguay ???22
Colombia ????18 Jamaica ???4 Samoa ???2 Venezuela ????12
Costa Rica ?????28 Korea, Republic of ??2 Saudi Arabia ??????11 Vietnam ??2
Dominican Republic ????5
13
H1N1????

• H1N1 ????(???)??????????? ??,??A ?????,?????H1N1?
  H1N2?H3N1 ?H3N2?
•  ?????????,??????????? ??????,????????????
• ????????????????,??H1N1?????,????????????????????
  ??????????

14
    H1N1??

• ????H1N1??????????????,?????????????????????????,?
  ????????????,?????????????

15
   ????

• H1N1 ????????????????,???????????????
• ??????????1 ?????7 ?? ????,??????????,??
  ???????????????

16
   ???

• ??H1N1?????????????????,??????????(???????6.0-7.0
  )?
• ???0.4

17
????????
530???? 7?5???? 1?4????

• ????????????????, ???1?4?????
• ?????6-20?????, 10-48?????
• SARS??--2003?37??346?????,73???(?????SARS?37?)

18
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19
???????

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

• ????
• A?????H1-3,N1-2
• ???????????
• ?????H1-15,N1-9(H5N1,H7N7,H7N3,H9N2)
• ???????????????????
• ????3??,22??4?,0??30?
• ???
• ???????????
• ???????????
• ??????????????,
• ????????????

20
???????

• ???10-40??,??5-6?
• ???
• ??18-72??(1-3?),
• H5N1(???)2-9?
• ???
• ?????????????????
• ???
• ??3-5?(H5N1??7?)
• ??7?(H5N1??21?)

• ??
• ????
• ????(????)
• ?????
• ??
• ???????(??)
• ????1 -4 ??7 ??12 ?
• ????
• ??????
• ???????????????????
• ??????,????
• ????(??)
• ???????????(??????????)???????

21
??/??

• ??
• ????????
• ?? (??3?,??8?)
• ??
• ????????
• ??
• ??
• ???
• ??
• ??
• ????
• ????
• ????
• ????????????,????????
• B???????????
• ????????
• ??
• ??????
• ???????

• H5N1??(???)
• ????,??????
• ??,???41?
• ??
• ??
• ???
• ??
• ??
• ????
• ???
• ????????? (????????????? )
• ????????????
• ??????????
• ????????????
• ?????????????????????????

22
H1N1????

• ????642?H1N1?????????????????H1N1?????,??????????
  ???????,?????????????????????? ???????????????,???
  ??????????????????H1N1????,???????????????(???????
  ??????????????????????)???????,????10??50?????????
  ???,?????????9,8?? ICU, 2???,???????1 N Engl J
  Med. 2009 Jun 18360(25)2605-15

23
???????

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

• ???
• ??(?????)lt0.1(1/5000-10000)
• ????
• H1N1 0.4 ?
• ???(H5N1)
• H5N1 gt30(78)

?????
24
?????????

• ????????????85,????
• ????

30??
1?
7-10?
25
1
?????????,?????? ???????
2
??????
26
3
??????
4
????????????
27
5
???????????????? ???????10?
6
???????????
28
7
?????
8
??????????2?3???? ???????
29
9
??????????
10
????????15?????? ??
30
????
31
????(Laboratory criteria)

• ???????????????????,??H1N1????????,?????????????
  
• 1.real-time RT-PCR?
• 2.?????
• 3.H1N1??????????4????
• ?????????????????????

32
??

• ????????
• ??????aspirin?
• ??????????????,?????????1-2?,???????24-48????,????
  ????
• Adamantane(???)??M2 protein??,block
  uncoating,??A?????,????
• ???(amantadine)
• Rimantadine?????
• Neuraminidase inhibitorA,B??????
• ???(Oseltamivirtamiflu) ?????
• Zanamivir(Relenza)???
• ????????? ??????
• oseltamiviramantadine?

33
?????????

• ???(Tamiflu 75mg)
• ????
• ???? ??2?,??1?,??5??
• ???? ??1?,??1?,??7-10?
• ???(Relenza)
• ????
• ???? ??2?,???2?,??5??
• ???? ??1?,???2?,??7-10?
• ?????48??????????????????????(1-2?),?????????????
  ?????

34
????? - 2

• Neuraminidase inhibitor
• Zanamivir?????
• Oseltamivir (Tamiflu) ??
• ?????????
• ??
• ?? 75 mg bid X 5 ?
• ???
• ?? 75 mg bid X 7-10?
• ?? 150mg bid x7-10?
• 1???????lt 15 kg,30 mg twice a day
• gt15--23 kg,45 mg twice a day
• gt23--40 kg,60 mg twice a day
• gt40 kg,75 mg twice a day
• 13?????75 mg twice daily
• CCr 10--30 mL/min,?????? 75 mg once daily,
• ????????
• ??????? (?10), ???
• Tamiflu 1)?????? ??????????????
• 2) ?????? ??????

35
?????

• Amantadine?rimantadine
• ?????????
• ?????????5-8?,???? 75-90
• ??????50
• ??100mg bid x 5?
• ???1-10
• Amantadine,?????????????????????
• Rimantadine????????

36
????

1. ???,????????,???????????,?????????
2. ????,????,???????
3. ?????????????
4. ????????????????
5. ????????????????, ????????
6. ?????gt38?????,??????????177??,???????????????????
   ?
7. ?????
8. ?????,????????????????????
9. SARS?????????????????????????
10. SARS????????(??????)?N-95??
11. ?????????????,???????
12. ??????????????????N-95??
13. ???????????????????????

37
????

• 1.??????????????????????H1N1????????
• 2.???????????,??????????????????????????????,????
  ????????????????????
• ?????? ???? ? ?????????

38
????

• 3.????????????????,?????????????????????????????
  ?,???????????
• 4.?????????????,???????????,???????,?????????????
  ???,?????

39
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40
????

• 5.???????????????????????????,?????2???????,?????
  ????????????
• 6.?????????????,?????????????????
• 7.???????????????????????,????????????

41
???????-??

• ??
• ??????,?????5-7??
• ???(H5N1)????7??,??21??
• ??
• ????
• ?????
• ??(??,??)????
• ??????

42
????

• ?????
• ????
• ????????2A?B?
• ????
• ???? 40-90
• ????6????,
• ????????
• ???
• ?????? 1/4 1/2 (?)
• ?? 1-2
• ??(??)

• ????????
• ??????????
• ???????????
• ?????????HA?NA??,???????????? (cold adaptation)
  ????????????
• ???1977?????????
• ???????????????
• ?????????????????,???0-12

43
??????????????

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

44
?????????

• ????-??????
• ??-????????,?????
• ?????,?????, ?????????????,????????

45
????????????

• ??????????????????,????????????
• ???????90??5????,?????,???????????,?????????????
  ???????????????????????

46
????????????

• ?????????????????,??????,??????????????????,?????
  ?????????
• N95?????95???????,? ?????,????????????,?????????
  

47
??????

• N95 ???????5 ?,?????????3?,?????????3
  ?,???????????,?????????????????????????? ??????

48
???????

• ?????????????
• ???????????????? ???
• (?????)
• ?????? (24?????)
• H5N1??
• ??
• ??
• ??????????(SARS)
• ???
• ???

49
??????

• ???????????,??????????????? 1.?????(Pulmonary
  complications)???? 2.???????(Neurological
  complications) 3.???(myocarditis)?????(pericardit
  is) 4.???????(Invasive bacterial infection)
  5.??(Other)?????1-4?????,???????????,?????
• ???(8/18)?????,????25?H1N1??????,?4????????,??????
  ?

50
????

• ??????????????????????????????????????????????????
  ?????????,???(8/18)????????????
• ?????????????
• (?)??????????????????,?3???????2???(?2?)???????
  ????????,??????5?(????)????325???,????????

51
????
52
????H1N1 ??????
?? ????
H1N1 ???????? 85
H1N1 ???????? 0
?? (??????????) 73
??? 12
53
N Engl J Med 20053532667-72
54
?????

• Neuraminidase inhibitor
• Zanamivir?????
• Oseltamivir (Tamiflu) ??
• ?????????
• ??
• ?? 75 mg bid X 5 ?
• ???(H5N1)
• ?? 75 mg bid X 7-10?
• ?? 150mg bid x7-10?
• 1???????lt 15 kg,30 mg twice a day
• gt15--23 kg,45 mg twice a day
• gt23--40 kg,60 mg twice a day
• gt40 kg,75 mg twice a day
• 13?????75 mg twice daily
• CCr 10--30 mL/min,?????? 75 mg once daily,
• ????????
• ??????? (?10)

55
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