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![Page 1: Update on Influenza Virus Surveillance Findings in 2008/09 Season in Northern Hemisphere Who Collaborating Center for Reference and Research on Influenza.](https://reader036.fdocuments.in/reader036/viewer/2022062515/56649f555503460f94c7954f/html5/thumbnails/1.jpg)
Update on InfluenzaVirus Surveillance Findings in 2008/09
Season in Northern Hemisphere
Who Collaborating Center for Reference and Research on Influenza at Center for Influenza Virus Research, National Institute of Infectious Diseases,
Tokyo, Japan
Takato Odagiri, Ph.D.
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Weekly report of virus isolation/detection in 2008-09 season
By NIID
By CDC
Pandemic A/H1N1 viruses
3584(32%)
2071(19%)
2475(22%)
2949(27%)
H1N1
H1N1pdm
H3N2
BAs of 11 Aug
248(11%)
201 (9%)
625(28%)
1186(52%)
H1N1
H1N1pdm
H3N2
B
As of week 30
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A(H1N1) viruses September 2008-January 2009
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H1N1, Sept 2008 – Jan 2009
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H1N1 antigenic analysis
By NIID
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H1N1 antigenic analysis
By CDC
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Summary of antigenic analysis of A/H1N1 in four WHO CCs
A/Br/59/07-like low-reactors (≥ 8-f)
• CDC (Oct-) 179 [100%] 0 [0%]• NIID (Oct-) 72 [95%] 4 [5%]• NIMR (Oct-) 62 [87%] 9 [13%]• VIDRL (Oct-) 119 [97.5%] 3 [2.5%]• Total 432 [96%] 16 [4%]
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March-July 2009
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By CDC
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By NIMR
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Antigenic characterization of AH1N1 viruses isolated after March
By NIID
By CDC
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By CDC
Number of oseltamivir resistance viruses isolated in Japan
(Oct 2008-May 2009)
By NIID
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H1N1 viruses - SummaryOct 2008-Feb 2009• Influenza A(H1N1) viruses predominated in many Asian and North
American countries• The majority of viruses were antigenically closely related to
A/Brisbane/59/2007 by HI analysis• Phylogenetically the majority of H1N1 viruses grouped into the
A/Brisbane/59/2007 clade (2B) based on their HA gene. • Recent 2B viruses share H275Y indicative of resistance to
oseltamivir. They were antigenically similar to osel-sensitive viruses.• Recent viruses from China fall within the A/Hong Kong/2652/2006
clade (2C) and these viruses were similar antigenically to clade 2B viruses. Clade 2C viruses are sensitive to oseltamivir and resistant to amantadine/rimantadine
Mar - July 2009• The features of viruses were similar to those observed earlier in
2009.• Majority of recent A(H1N1) viruses were antigenically closely related
to A/Brisbane/59/2007 and formed clade 2B sharing H275Y.• In the few clade 2C viruses, dual resistance to oseltamivir and
amantadine/rimantadine were detected.
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A(H3N2) viruses September 2008-January 2009
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H3N2, Sept 2008 – Jan 2009
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By NIID
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Table 4B. Antigenic analyses of influenza A H3N2 viruses - Guinea Pig RBCs (05/02/2009)
Viruses Collection A/Wis A/Trieste A/Wis A/Bris A/Uru A/Fin A/JHB A/Eng A/BrisDate 67/05 25c/07 3/07 10/07 716/07 9/08 15/08 394/08 24/08
F18/08 F5/07 F15/07 F29/08 F26/08 F12/08 F22/08 F32/08 F3/09
REFERENCE VIRUSES
A/Wisconsin/67/2005 31/08/2005 SpfCk3E3 \3 1280 1280 640 1280 2560 640 640 80 1280A/Trieste/25c/2007 Jan-07 MDCKx \2 80 160 160 320 160 80 160 160 160A/Wisconsin/3/2007 21/01/2007 Ex \2 5120 5120 2560 5120 5120 2560 2560 640 5120A/Brisbane/10/2007 06/02/2007 E2 \3 1280 2560 640 1280 2560 1280 1280 320 2560A/Uruguay/716/2007 21/06/2007 spfck1, E3 \2 1280 2560 640 1280 2560 2560 1280 320 1280A/Finland/9/2008 07/01/2008 MDCK2 \1 160 160 320 320 320 320 320 320 320A/Johannesburg/15/2008 25/06/2008 MDCKx \2 160 320 320 320 320 320 320 320 640A/England/394/2008 22/09/2008 MDCK2 \7 160 320 320 320 640 160 320 640 320A/Brisbane/24/2008 23/06/2008 E5 \1 2560 2560 2560 5120 5120 2560 2560 320 5120
TEST VIRUSES
A/Singapore/N474/2008 21/05/2008 Cx \1 1280 2560 1280 2560 5120 1280 2560 640 2560A/Singapore/N486/2008 21/05/2008 Cx \1 640 1280 320 1280 1280 640 640 320 640A/Singapore/N510/2008 04/06/2008 Cx \2 1280 2560 1280 2560 5120 2560 2560 640 1280A/Singapore/N593/2008 15/09/2008 Cx \1 1280 2560 640 1280 2560 1280 1280 640 2560A/Sweden/3/08 15/10/2008 MDCK2 \1 1280 1280 640 1280 1280 1280 1280 320 640A/England/694/2008 05/12/2008 SIAT P1 \1 1280 1280 640 1280 2560 640 1280 640 640A/England/687/2008 30/12/2008 MDCK P1 \2 640 1280 320 1280 2560 1280 1280 320 640A/Switzerland/1370948/2008 12/12/2008 MDCK2 \2 640 640 320 640 1280 320 320 160 320A/Seoul/4436/2008 05/12/2008 MDCK-P2 \1 640 640 320 640 1280 640 640 320 640A/Slovenia/60/2009 06/01/2009 MDCKx \1 640 640 320 640 1280 640 640 160 640A/Slovenia/51/2009 05/01/2009 MDCKx \1 160 80 160 160 320 160 160 160 160A/Baden-Württemburg/199/2008 15/12/2008 C4 \2 320 320 160 320 640 160 320 160 320A/Parma/17/09 12/01/2009 I MDCK \1 80 80 160 160 160 80 80 160 160A/Singapore/N565/2008 12/08/2008 Cx \2 1280 1280 320 1280 1280 640 1280 320 640A/Switzerland/1409256/2008 29/12/2008 cs \2 1280 1280 320 1280 1280 640 640 160 640A/Switzerland/1409281/2008 31/12/2008 cs \2 640 1280 320 640 1280 320 640 160 640A/Leon/5/2009 13/01/2009 MDCK1 \1 1280 2560 640 1280 2560 1280 2560 640 640A/Belgium/G211/2009 30/12/2008 MDCK1 \1 1280 2560 640 1280 2560 1280 1280 640 640A/Belgium/G228/2009 30/12/2008 MDCK1 \1 1280 1280 320 1280 1280 640 1280 320 640A/Belgium/G278/2009 08/01/2009 MDCK1 \1 1280 2560 640 1280 2560 1280 1280 640 640A/Belgium/G298/2009 12/01/2009 MDCK1 \1 1280 2560 640 1280 2560 1280 2560 640 640
1. < = <40 Vaccine strains
Passage History
Haemagglutination inhibition titre1
Post infection ferret sera
By NIMR
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Table 5B. Antigenic analysis of influenza A H3N2 viruses (Neutralisation)
Viruses Collection A/Well A/Bris A/Uru A/Eng A/BrisDate 1/04 10/07 716/07 394/08 24/08
F13/04 F18/07 F3/07 F32/08 F3/09
REFERENCE VIRUSES
A/Wellington/1/2004 26/01/2004 E3 \1 1280 320 320 320 320A/Brisbane/10/2007 06/02/2007 E2 \3 320 2560 5120 320 2560A/Uruguay/716/2007 21/06/2007 spfck1, E3 \1 320 1280 2560 160 1280A/England/394/2008 22/09/2008 TC P2 \1 80 2560 2560 2560 1280A/Brisbane/24/08 23/06/2008 E5 160 1280 2560 320 2560
TEST VIRUSES
A/Paris/130/2008 20/10/2008 C2 \1 160 640 1280 320 1280A/Egypt/59/2008 16/11/2008 C1 \1 160 1280 1280 320 1280A/Toulouse/1317/2008 14/11/2008 P3MDCK \1 160 1280 2560 640 2560A/Norway/2308/2008 15/12/2008 MDCK1 \1 320 2560 2560 640 2560A/Denmark/191/2008 13/11/2008 MDCK3 \1 160 1280 2560 320 2560A/Sweden/6/2008 08/12/2008 MDCK2 \1 160 1280 1280 320 1280A/Paris/458/2008 1/12/2008 C1 \1 320 2560 5120 640 5120A/HongKong/3197/2008 26/11/2008 MDCK2 \1 160 1280 1280 320 1280A/England/669/2008 30/12/2008 MDCK P1 \1 80 1280 1280 320 1280A/Norway/1/2009 30/12/2008 MDCK1 \1 160 640 1280 320 1280
1 Based on 50% plaque reduction compared to serum negative controls2 RDE treatedAgglutinate guinea pig RBCs only
Vaccine strains
Passage History
Neutralisation titre1
Post-infection ferret sera2
By NIMR
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A/Brisbane/10/07-like low-reactors (≥ 8-f)
• CDC (Oct-) 45 [90%] 5 [10%]
• NIID (Oct-) 32 [56%] 25 [44%]
• NIMR (Oct-) 160 [90%] 18 [10%]*
• VIDRL (Oct-) 145 [93%] 11 [ 7%]
• Total 382 [87%] 59 [13%]
H3 low reactors in HI assays in WHOCCs
*0% by virus neutralization
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Vaccine virus
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March-July 2009
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By NIMR
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By NIID
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Vaccine virus
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By Cambridge Univ.
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H3N2 viruses - Summary Oct 2008-Feb 2009• H3N2 viruses co-circulated with H1N1 and B viruses in many countries• Majority were antigenically similar to A/Brisbane/10/07 and
A/Uruguay/716/07 by HI tests with turkey RBCs or guinea pig RBCs.• The ‘low reactors’ were antigenically indistinguishable from vaccine
viruses by Neutralization tests. • HA and NA sequences fairly homogeneous and fell within the
A/Brisbane/10/07 clade • M2 sequences possessed S31N mutation, indicative of amantadine
resistance• Sensitive to oseltamivir and zanamivirMar - July 2009• Majority were antigenically similar to vaccine viruses.• An increasing number of H3N2 isolates have been shown to be
antigenically distinct from vaccine viruses and related to A/Hawaii/7/09, A/HK/1985/09 and A/Perth/16/09.
• The majority of HA sequences of those viruses formed a separate clade characterized by aa subsitutions E62K, N144K, K158N and N18K.
• They retained resistance to amantadine/rimantadine and were sensitive to oseltamivir and zanamivir.
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B viruses September 2008-January 2009
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B, Sept 2008 – Jan 2009
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Numbers of 2 lineages of B viruses detected in GISN since week 40
2008
0
5
10
15
20
25
30
35
40
45
40 41 42 43 44 45 46 47 48 49 50 51 52 1 2 3 4
week #
B-Y B-V
B-Victoria lineage
B-Yamagata lineage
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HI reactions of influenza type B viruses
By NIID
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HI reactions of influenza type B virusesB/Victoria-lineage
By NIMR
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HI reactions of influenza type B viruses B/Yamagata lineageTable 7. Antigenic analyses of influenza B viruses (Yamagata lineage)
Viruses Collection B/Fl3 B/Eg B/Fl B/Bris B/Barc2 B/Eng2 B/Vall2 B/Ban B/Indi
date 4/06 144/05 4/06 3/07 143/08 145/08 18/08 3333/07 1/08Sh 478 F3/07 F19/07 F24/07 F11/08 F9/08 F10/08 F21/08 CDC174/08
REFERENCE VIRUSES
B/Egypt/144/2005 01/05/2005 E2 \2 2560 160 320 640 10 40 20 160 1280B/Florida/4/2006 15/12/2006 E2 \1 5120 160 640 640 10 80 20 160 1280B/Brisbane/3/2007 03/09/2007 E2 \2 5120 160 640 640 10 80 20 160 1280B/Barcelona/143/2008 06/01/2008 MDCK1 \2 5120 80 160 320 320 160 320 320 640B/England/145/2008 Ex \2 320 40 < 40 10 160 10 20 640B/Valladolid/18/2008 18/02/2008 MDCK1 \2 2560 80 160 80 160 160 320 160 1280B/Bangladesh/3333/2007 19/08/2007 E4 \1 2560 80 160 160 20 40 20 160 1280B/Indiana/1/2008 10/03/2008 E2 \1 1280 40 80 160 20 40 20 320 640
TEST VIRUSES
B/Mendoza/R530/2008 Aug-08 M2 /1 5120 160 160 320 160 160 160 320 NDB/Ghana/MH-31/2008 19/08/2008 MDCKx /1 2560 160 160 320 160 160 320 320 NDB/Dakar/06/2008 19/08/2008 MDCK2 /1 5120 160 640 640 320 640 320 640 NDB/Ghana/MH-36/2008 29/08/2008 MDCKx /1 2560 160 160 320 160 160 320 320 NDB/Ghana/NG-PK-01/2008 09/09/2008 MDCKx /1 5120 160 160 160 320 320 320 320 NDB/Hong Kong/1355/2008 09/09/2008 MDCK2 \2 2560 80 160 160 160 160 160 320 NDB/Ghana/MH-41/2008 12/09/2008 MDCKx /1 2560 80 40 40 80 160 160 160 NDB/Hong Kong/1372/2008 25/09/2008 MDCK2 \1 5120 160 160 160 160 320 160 160 640B/Ghana/FS301/2008 09/10/2008 MDCK2 \1 5120 80 160 320 320 160 320 320 640B/Hong Kong/1374/2008 17/10/2008 MDCK2 \1 2560 80 160 320 160 160 160 160 640B/Ghana/FS347/2008 31/10/2008 MDCK2 \1 2560 80 80 80 160 160 320 160 1280B/Ghana/FS351/2008 31/10/2008 MDCK2 \1 5120 80 160 80 320 160 320 320 640B/Paris/236/2008 03/11/2008 C2 \1 640 40 < < 10 80 40 40 NDB/Ghana/FS355/2008 04/11/2008 MDCK2 \2 640 < < < 80 80 160 80 NDB/Ghana/FS383/2008 17/11/2008 MDCK2 \1 5120 160 320 640 640 320 640 640 1280B/Ghana/FS385/2008 18/11/2008 MDCK2 \1 5120 160 160 160 320 320 320 320 1280B/Ghana/FS428/2008 09/12/2008 MDCK2 \1 5120 80 80 80 160 160 320 160 640B/Ghana/FS433/2008 11/12/2008 MDCK2 \3 2560 40 80 80 160 160 160 160 NDB/Ghana/FS435/2008 12/12/2008 MDCK2 \3 2560 40 80 80 160 80 160 160 NDB/Ghana/FS388/2008 18/11/2008 MDCK2 \2 2560 80 80 80 160 160 320 160 NDB/Switzerland/1334249/2008 04/12/2008 MDCK1 \1 2560 80 160 320 320 160 320 320 NDB/Egypt/133/2009 14/01/2009 Ex \1 160 < < < < 20 < 10 ND
1. < = <40; 2. < = <10; 3. hyperimmune sheep serum
ND = not done
Vaccine strains
Haemagglutination inhibition titre1
Passage
History
Post infection ferret sera
By NIMR
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Victoria Yamagata• CDC (Oct-) 71 [60%] 48 [40%]
low reactors (77%) (23%)• NIID (Oct-) 18 [40%] 27[60%]
Low reactors (94%) (67%)• NIMR 17 [44%] 22[56%]
Low reactors (76%) (14%)VIDRL (Oct-) 340 [67%] 167 [33%]
Low reactors (94%) (62%)
Total 446 [63%] 264 [37%]Low reactors (91%) (51%)
B low reactors in HI assays in WHOCCs
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10 nucleotides
B/Brisbane/60/2008-like
Evolutionary Relationships Among Influenza B (Victoria Lineage) HA Genes
B/Malaysia/2506/2004
K165N
Chinese clade
By Melbourne C.
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Evolutionary Relationships Among Influenza B (Yamagata Lineage) HA Genes
10 nucleotides By Melbourne C.
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March-July 2009
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By NIMR
HI reactions of influenza type B virusesB/Victoria-lineage
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By CDC
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By Cambridge Univ.
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B/Victoria-lineage HA
By NIID
Vaccine virus
Chinese viruses
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By CDC
B/Yamagata-lineage HA
Vaccine virus
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Summary for influenza B virusesOct 2008-Feb 2009
• Influenza B viruses circulated in many countries however regional outbreaks were limited.
• Viruses of both B/Victoria/2/87 and B/Yamagata/16/88 lineages continued to co-circulate in many countries
• B/Victoria-lineage viruses predominated in most countries and were mostly antigenically closely related to B/Brisbane/60/2008.
• Viruses mainly from China fell into a separate phylogenetic clade
• B/Yamagata-lineage viruses were antigenically closely related to B/Florida/4/2006 & B/Brisbane/3/2007 vaccine viruses.
• Three phylogenetic clades were apparent but were antigenically indistinguishable.
Mar - July 2009
• B/Victoria-lineage viruses predominated and were mostly antigenically closely related to vaccine strain B/Brisbane/60/2008.
• Many viruses isolated in China were closely related to B/Fujian Gulou/1272/08 and B/Hubei-Songzi/51/08.
• B/Yamagata-lineage viruses were antigenically closely related to B/Florida/4/2006 and mostly fell into their HA sequences of the B/Bagladesh/3333/07 clade.
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WHO Collaborating Centers
(US-CDC, NIMR, Melbourne)
Cambridge University
NICs
(China-CDC, Korea-CDC, NHL-Myanmar,
NCLE-Lao PDR, NIH-Mongolia and other NICs of WHO GISN)
Taiwan-CDC
Local PHLs in Japan
Acknowledgement