Tuesday, May 5, 2009

INFLUENZA A (H1N1) - WORLDWIDE (11): COINCIDENT H3N2 VARIATION

Date: Tue 5 May 2009 12:08:07 -0700
From: Danuta Skowronski
<Danuta.Skowronski@bccdc.ca>


Recent mutations away from the 2008-09 influenza vaccine strain among
North American A/H3N2 virus coincident with emergence of novel A/H1N1

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The BC [British Columbia] Centre for Disease Control (BCCDC) Virology
Laboratory routinely sequences the hemagglutinin (HA) gene from a
sample of influenza viruses submitted each season by community
clinicians, hospitals and care facilities across the province of
British Columbia, Canada.

Until mid-February 2009, amino acid sequences of the HA gene of H3
viruses in BC were virtually identical to the vaccine strain [A/
Brisbane/10/07 (H3N2)], with the exception of a Lys189Gln change at
antigenic site B. In early March 2009, however, we detected
additional differences from the vaccine strain among BC viruses
collected from facility outbreak settings at antigenic site B to
include change from the vaccine strain at Asp160Lys (as well as
Lys189Gln) and at antigenic site D at Val229Ala. These changes were
seen only in viruses from care facility outbreaks and not from
community specimens submitted by our network of sentinel physicians.

After the novel North American influenza A/H1N1 virus was reported
from Mexico as well as California during the 4th week of April 2009,
specimens from returning travelers and others in BC with
influenza-like illness were tested including influenza subtype
determination and sequencing. Among approximately 900 respiratory
specimens submitted to the BCCDC laboratory between 24 Apr 2009 and 3
May 2009, the majority was negative for influenza; an equal number of
influenza A detections were of the H1 or H3 subtype.
We have sequenced the HA gene of one of the H3 viruses from an ill
traveler returning from Mexico and find it shares the same amino acid
changes noted above.


These amino acid substitutions do not fulfill the criteria proposed
by Cox as corresponding to meaningful antigenic drift (requiring at
least 2 amino acid substitutions at 2 or more defined antigenic sites
A-E)[1] They may, however, signal important evolution in the HA gene.
During late March and early April 2009 we reported an unexpected
number of late-season care facility outbreaks due to H3 influenza. We
should thus remain vigilant for further H3N2 evolution and reduced
vaccine relatedness since A/Brisbane/10/07(H3N2) has been retained as
the proposed vaccine component for both the 2009 southern and 2009-10
northern hemisphere influenza seasons.
Ongoing gene sequence analysis
of H3 viruses from other countries would be informative. In BC, these
H3 mutations arose sometime in early March 2009 and we observe at
least one returning traveler to have likely acquired illness due to
this virus in Mexico (specimen collected in BC 26 Apr 2009). We thus
also wonder to what extent the profile of influenza-like illness
initially reported from mid-March in Mexico may in part be attributed
to this H3N2 variant in addition to emergence of the novel A/H1N1 virus.

Reference:
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[1] Cox NJ, Bender CA. The molecular epidemiology of influenza
viruses. S/eminars in /VIROLOGY 1995; 6:359-370.

Authors:
Danuta M Skowronski MD, MHSc, FRCPC, Tracy Chan BSc, Naveed Z Janjua
MD, DrPH, Travis Hottes MSc, Annie Mak BSc, Martin Petric PhD, FCCM,
Mel Krajden MD, FRCPC, Patrick Tang MD, PhD, FRCPC, David Patrick MD,
MHSc, FRCPC, Robert Brunham MD, FRCPC.

At: The BC Centre for Disease Control Provincial Laboratories and
Epidemiology Services

--
Communicated by:
Phil Temples
<phil@temples.com>

[The novel observations reported above reveal the occurrence of
progressive variation in the HA gene of H3N2-type seasonal influenza
virus which if maintained may have consequences for the outcome of
the next seasonal influenza vaccination programme. More intriguing is
the observation that the same novel mutational changes were detected
among viruses isolated from patients in care facilities in Canada as
in a virus isolated from a traveler from Mexico. The authors suggest
that the profile of influenza-like illness initially reported from
mid-March 2009 in Mexico may in part be attributed to this H3N2
variant in addition to the emergence of the novel A/H1N1 virus. This
is a matter that merits urgent investigation as it might help to
explain some of the unusual features of the current epidemic. - Mod.CP]

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