Influenza Activity and Virus Characterizations (Northern Hemisphere)

5thMeeting of NICs in the WPR and SEAR 7-10 June, 2011 Laos

Takato Odagiri

WHO Collaborating Center for References and Research on Influenza,

National Institute of Infectious Diseases, Tokyo, Japan

Influenza subtypes 2010- 2011: Northern Hemisphere (as of May 23,2011)

B

H1N1pdm09

H3N2

WHO, FluNet

B

A(H1N1)pdm09

Former seasonal A(H1N1) 6 viruses (China, Malaysia, Russia, Tunisia, USA)A(H3)

A (not subtyped)

A(H5N1), 14 viruses- Cambodia (1) ： CL 1 - Hong Kong (1) ： CL2.3.2- Egypt (10) ： CL 2.2.1 - Indonesia (2) ： CL 2.1.2

Percentage of influenza viruses by subtypes(From 29 August 2010 – 29 January 2011)

31%

27%21%

21%

WHO, FluNet

54% 32% 14%

98% 2%

0%

Antigenic and genetic characterizations

A(H1N1)pdm09 viruses

Antigenic analysis of A (H1N1)pdm09 viruses by HI testsMar –Aug, 2010

JPN, China, Taiwan,Korea, Mongol, Laos,

Myanmar, Singapore

N+C America,EU, Asia, Africa, AU, NZ

NIID CDC

=4-fold low >8-fold low2% 1%

Sept, 2010 –Feb, 2011

A/Cal-likeA/Cal-like

=4-fold low 1%

99%

A/Cal-like

94%

=4-fold low 6%

A/Cal-like

89%

=4-fold low

9%

>8-fold low2%

95%

A/Cal-like

83%

>8-fold low

2%

A/Cal-like99%

NIMR

EU, Africa

>8-fold low1%

A/Cal-like

100%

C-CDC

China

>8-fold low2%

A/Cal-like

98%

Antigenic cartography of A(H1N1)pdm09 isolates

(Cambridge University)

Antigenic cartography of A(H1N1)pdm09 isolates

(Cambridge University)

Vast majority of A(H1N1)pdm09 viruses remained antigenically homologous to the A/California/07/2009 vaccine virus.

A/California/07/2009

Amino acid substitutions in H1N1pdm-HA protein that result in antigenic change from

A/Cal/7/2009

Position 155G to E

Position 156N to D

Position 157S to L

Colin, Derek et al, Cambridge U.

外

2010/11 Early phase(2010. Sept to 2011. Jan）

2009/10 late phase(2010, April to July）

Majority clade

Vaccine strain

Vaccine strain

3

12

526712321

1

1

25

1111

612

21

1

275Y 1.9% (53/2761)275H/Y 0.3% (8/2761)

China -CDCNIID

Detection of Antiviral resistant H1N1pdm09 viruses with 275Y substitution

  May 2009-April 2010 May 2010-April 2011

Source Total Tested

Number H275Y Genotyped

Number Phenotyped

Number Resistant Percentage Total Tested

Number H275Y Genotyped

Number Phenotyped

Number Resistant Percentage

Community 1098 882 216 0 0.0 682 625 57 7 1.0Hospital 4489 3855 634 45 1.0 2818 2738 80 49 1.7Total 5587 4737 850 45 0.8 3500 3363 137 56 1.6

US-CDC

NIMR

Detection of Antiviral resistant H1N1pdm09 viruses with 275Y substitution

A(H3N2) viruses

Antigenic and genetic characterizations

Antigenic analysis of A (H3N2) viruses by HI tests

Sept, 2010 –Feb, 2011

NIID CDC

Mar –Aug, 2010

JPN, China, Taiwan,Korea, Mongol, Laos,

Myanmar, Singapore

N+C America,EU, Asia, Africa, AU, NZ

>8-fold low

A/Perth/16-likeA/Perth/16-like

A/Perth/16-like A/Perth/16-like

83%

17%=4-fold low

=4-fold low

53% 42%

5%

>8-fold low

=4-fold low

81% 72%

27%

1%

=4-fold low19%

NIMR

EU, Africa

C-CDC

China

A/Perth/16-like91%

>8-fold low

9%

Low HA viruses

>8-fold low

5%

A/Perth/16-like95%

A/Perth/16-like71%

>8-fold low

29%

2009/10 Late phase (2010, April to July）

2010/11 Early phase(2010. Sept to 2011.

Jan）

Majority clade

JPN virusesVaccine

strain

Vaccine strain

Summary of A(H3N2) cartography(Cambridge University)

A/Brisbane/10/07

A/Perth/16/09

2008/09 season 2009/10 season

A/Brisbane/10/07

A/Victoria/208/09

A/Perth/16/09

A/Brisbane/10/07

A/Perth/16/09

CDC data

NIID data

A/Brisbane/10/07

A/Vic/208/09　cluster

2010/11 season

A/Vic/208/09　cluster

B viruses

Antigenic and genetic characterizations

96%

4%

80%

20%

78%

22%

86%

14%

91%

9%

ChinaN+C America,EU, Asia, Africa, AU, NZ

EU, Africa, ME Asia, HK

AU, NZ, Pacific, SE Asia, E Asia

NIID China CDC CDC NIMR Melbourne

Proportion of B/Vic- and B/Yama-lineage viruses in the world

B/Yama

B/Vic

JapanMar -Aug 2010

B/Yama

B/Vic

2%

98%

B/VicB/Yama

B/Vic B/Vic B/Vic B/Vic

B/Yama B/Yama B/Yama B/Yama

B/Yama B/Yama

B/Vic B/Vic B/Vic65%

35%

84%

16%

83%

17%

100%

Sept, 2010 –Feb, 2011

Antigenic analysis of B/Vic-lineage viruses by HI tests

4-low

>8-low

1%

Bris/60-like99%

49%40%

11%

NIID CDC

Mar -Aug 2010

Bris/60-like

>8-low

Sept, 2010 –Feb, 2011

Bris/60-like Bris/60-like

4-low>8-low

86%

5% 9%

58%

40%

4-low

>8-low2%

Bris/60-like

98%

>8-low2%

39%Bris/60-like

61%

>8-low

NIMR

Bris/60-like99%

>8-low

1%

Bris/60-like85%

15%

>8-low

China CDC

Vaccine strain

2009/10 Late phase(2010, April to July）

2010/11 Early phase(2010. Sept to 2011.

Jan）

B/Vic-lineage viruses

Antigenic cartography of the antigenic variant against B/Brisbane60/2008 with K165N

substitution

HI data from NIID

197N

B/Brisbane/60 MDCKx/1 B/Brisbane/60 E4/E4B/Brisbane/60 MDCKx/1 B/Brisbane/60 E4/E4

Receptor-binding site

197S

N-linked glycan

Lack of potential glycosylation site was observed in egg-grown virus

Variants with 165N in B/Bris/60 clade

Antigenic cartography of B/Yamagata viruses (Cambridge University)

Vaccine viruses recommended by WHO

2011/12 (Northern Hem) season:

an A/California/7/2009 (H1N1)-like virus an A/Perth/16/2009 (H3N2)-like virusa B/Brisbane/60/2008-like virus

No change from last season

Increase of Low HA A(H1N1)pdm09 viruses in Japan

Low HA A(H1N1)pdm09 viruses increased from Jan 2011

HA titration of recent A/H1N1pdm09 viruses using various RBCs

Strains Subtype Sample datePassagehistory

HA titreTCID50/mL TCID50/HA

0.5%TRBC 1%GRBC

Reference

A/Wisconsin/10/1998 A/H1N1 1998 C3/C3E2 +2 64 32 ND ND

A/California/07/2009 A/H1pdm 2009/04/09 E2 +3 32+/- 32+/- ND ND

A/NARITA/1/2009 A/H1pdm 2009/05/08 E2 +1 32 4+/- ND ND

A/NARITA/1/2009 A/H1pdm 2009/05/08 MDCK 1 +2 16+/- 32+/- ND ND

A/Utah/20/2009 A/H1pdm 2009/07/25 C 2 +1 64 64+/- ND ND

A/YAMAGATA/752/2009 A/H1pdm 2009/12/03 MDCK 2 +1 64 8 ND ND

High HA A/FUKUSHIMA/112/2010 A/H1pdm 2010/08/10 MDCK 2 +1 64 64+/- 7.7 7.8×105

A/CHIBA/17/2010 A/H1pdm 2010/08/10 MDCK 1 +1 256 128+/- 7.7 2.0×105

Low HA

A/NIIGATA/62/2011 A/H1pdm 2011/01/18 MDCK 1 +2 2 2+/- 5.7 2.5×105

A/GIFU-C/14/2011 A/H1pdm 2011/01/24 MDCK 1 +2 4 2+/- 6.5 7.9×105

A/HOKKAIDO/12/2011 A/H1pdm 2011/01/17 MDCK 2 +2 4 2 6.3 5.0×105

A/SAPPORO/19/2011 A/H1pdm 2011/01/14 MDCK 1 +2 4 2 5.5 7.9×104

A/SAKAI/6/2011 A/H1pdm 2011/01/07 MDCK 1 +2 2 2+/- 4.7 2.5×104

A/SHIGA/30/2011 A/H1pdm 2011/01/21 MDCK 1 +2 4 2+/- 6.3 5.0×105

A/KITAKYUSYU/1/2011 A/H1pdm 2011/01/04 MDCK 1 +2 4 2+/- ND ND

A/HIROSHIMA/24/2011 A/H1pdm 2011/01/14 MDCK 3 +2 4 4+/- ND ND

A/NIIGATA/53/2011 A/H1pdm 2011/01/17 MDCK 1 +2 4 4+/- ND ND

A/SAKAI/2/2011 A/H1pdm 2011/01/04 MDCK 1 +2 4 2 ND ND

A/SHIGA/32/2011 A/H1pdm 2011/01/06 MDCK 1 +2 4 2 ND ND

A/SHIGA/43/2011 A/H1pdm 2011/01/08 MDCK 1 +2 4 2 ND ND

A/KAGAWA/1/2011 A/H1pdm 2011/01/31 MDCK 0 +1 4 2+/- ND ND

December 2010 in BlueJanuary 2011 in GreenFebruary 2011 in OrangeMarch 2011 in Pink#: Fatal case@: Oseltamivir resistanceLow: Low HA

OITA/77/2011 FEB Low @ OITA/72/2011 FEB G155E/G @ HOKKAIDO/32/2011 JAN Low

HIROSHIMA/45/2011-OR FEB @ KUMAMOTO-C/7/2011 JAN

EHIME/4/2011 JAN Korea/664/2010.CDC DEC

GIFU-C/31/2011 FEB Low FUKUOKA-C/37/2010 NOV HIROSHIMA/55/2011 FEB Low @ IWATE/1008/2011-OR JAN Low @ SAGAMIHARA/5/2011 JAN Low KAGAWA/1/2011 JAN Low @

SHIZUOKA/37/2011 FEB Low @ Gyeongnam/3110/2010 DEC G155G/E

SHIMANE/140/2011 FEB Low NewHampshire/03/2011.CDC FEB SHIGA/43/2011 JAN Low

FUKUOKA-C/39/2010 DEC California/23/2010.CDC OCT

Connecticut/04/2011.CDC FEB Incheon/2434/2010 NOV

WAKAYAMA-C/6/2011 JAN K153Q @ CHIBA/1027/2011 JAN Low @

TOTTORI/8/2011 JAN # K153E HIROSHIMA/50/2010 NOV

ISHIKAWA/22183/2011 JAN Low SHIMANE/24/2011-OR JAN

HIROSHIMA/49/2011 FEB Low @ AKITA/1/2011-OR JAN Low

KITAKYUSYU/1/2011 JAN Low @ SHIZUOKA-C/8/2011 JAN Low

KOBE/463/2011-OR JAN HIROSHIMA/22/2011 JAN Low KUMAMOTO/7/2011 JAN G155G/E

KAGAWA/2/2011 FEB @ FUKUSHIMA/138/2010 DEC G155G/E

AKITA/5/2011 FEB Low @ SHIGA/45/2011 JAN Low

YOKOHAMA/29/2011-OR JAN @ NewYork/11/2010.CDC DEC

YAMAGATA/752/09 DEC G155E YAMAGATA/752/09 DEC G155E Laos/O066/2010 NOV

Washington/08/2011.CDC FEB Montana/06/2011.CDC MAR

Nebraska/10/2011.CDC MAR Bangladesh/5513/2011.CDC FEB

OKINAWA/40/2011 JAN @ Arkansas/01/2011.CDC JAN

Georgia/3/2011.NIMR DEC HIROSHIMA/1/2011 JAN

Florida/12/2011.CDC MAR Maryland/07/2011.CDC FEB @

Indiana/05/2011.CDC FEB Colorado/04/2011.CDC MAR

HongKong/6931/2010.CDC DEC Wisconsin/11/2011.CDC FEB

Michigan/02/2011.CDC FEB Georgia/51/2011.NIMR JAN

England/404/2010.NIMR DEC Kentucky/09/2010.CDC NOV # G155E D222G

Montana/03/2011.CDC FEB England/151/2010.NIMR NOV DARWIN/178/2010.Aus DEC

DARWIN/2/2011.Aus JAN HIROSHIMA/66/2011 FEB @

Kansas/06/2011.CDC FEB Alaska/09/2011.CDC FEB

Gyeonggi/2623/2010 NOV G155G/E SHIZUOKA/20/2011-OR JAN Low @

NIIGATA/1563/2010 DEC Texas/08/2011.CDC MAR Maryland/04/2011.CDC FEB @

Maine/03/2011.CDC MAR Georgia/25/2010.CDC DEC

NARA/54/2011 FEB @ WAKAYAMA/49/2010 DEC WAKAYAMA-C/53/2010 DEC

Christchurch/16/10E.Aus JUL D222N Soria/16/2011.NIMR JAN

OSAKA-C/25/2010 DEC SAKAI/47/2010 DEC

Taiwan/151/2010 AUG YAMAGATA/203/2011 FEB HIROSHIMA-C/28/2011 JAN

YAMAGATA/54/2011 JAN Low Washington/09/2011.CDC MAR

Pennsylvania/01/2011.CDC JAN VICTORIA/1204/2010.Aus OCT

Mississippi/07/2011.CDC FEB Laos/I969/2010 OCT

Shanghai-Zhangning/SWL1700/2010.CNIC DEC Myanmar/JP-S-026/10 JUL

OSAKA/60/10 JUL England/195/09.CDC APR

Utah/20/09.CDC JUL Utah/20/09.CDC JUL NARITA/1/09E MAY NARITA/1/09E MAY

Mexico/InDRE4487/09 APR California/07/09E X179A.CDC California/07/09E X179A.CDC

California/07/09E.CDC APR California/07/09E.CDC APR

0.001

S143G

A197T

D97NS185T

S83T

A134TS183P

N31DK146N

S203T

S162N

N125D

Vaccine

Recent majority clade

Low HA virus clade

Acknowledgement

Influenza virus surveillance group in Japan

Pathogen genomic center, NIIDDrs. Motomura, Yokoyama and Sato

Infectious Disease Surveillance Center, NIIDDrs Yamashita, Yasui and Okabe

National Influenza Centers

WHO 　 Collaborating Center for Reference and Research on InfluenzaUS CDC, Atlanta (N. Cox, A. Klimov)

NIMR, London (J. McCauley, R. Daniels)VIDRL, Melbourne (A. Kelso, I. Barr)

China CDC, Beijing (Y. Shu, D. Wang)

Cambridge University (D. Smith, C. Russel)