Update on Influenza

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Update on Influenza Virus Surveillance Findings
in 2008/09 Season in Northern Hemisphere
Takato Odagiri, Ph.D.
Who Collaborating Center for Reference and
Research on Influenza at Center for Influenza
Virus Research, National Institute of Infectious
Diseases, Tokyo, Japan
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Weekly report of virus isolation/detection in
2008-09 season
By NIID
Pandemic A/H1N1 viruses
By CDC
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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 - Summary

• Oct 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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By NIMR
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By NIMR
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H3 low reactors in HI assays in WHOCCs

• 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

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 zanamivir
• Mar - 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
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 lineage
By NIMR
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B low reactors in HI assays in WHOCCs

• Victoria
  Yamagata
• CDC (Oct-) 71 60 48 40 low reactors
  (77) (23)
• NIID (Oct-) 18 40 2760 Low reactors
  (94) (67)
• NIMR 17 44 2256 Low reactors (76)
  (14)
• VIDRL (Oct-) 340 67 167 33 Low
  reactors (94) (62)
• Total 446 63 264 37Low reactors
  (91) (51)

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Evolutionary Relationships Among Influenza B
(Victoria Lineage) HA Genes
B/Brisbane/60/2008-like
B/Malaysia/2506/2004
K165N
Chinese clade
By Melbourne C.
10 nucleotides
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Evolutionary Relationships Among Influenza B
(Yamagata Lineage) HA Genes
By Melbourne C.
10 nucleotides
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March-July 2009
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HI reactions of influenza type B
virusesB/Victoria-lineage
By NIMR
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By CDC
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By Cambridge Univ.
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B/Victoria-lineage HA
Vaccine virus
Chinese viruses
By NIID
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B/Yamagata-lineage HA
Vaccine virus
By CDC
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Summary for influenza B viruses

• Oct 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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Acknowledgement
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