Influenza viruses resistant to oseltamivir, news and updates

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

H1N1 is dominant serotype in US, but typing is lagging and H274Y data is lagging even more than serotyping:

<TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD class=content vAlign=top>154.</TD><TD class=content vAlign=top width=161>United States of America</TD><TD class=content vAlign=top>A (H1)</TD><TD class=content vAlign=top align=middle>41</TD><TD class=content vAlign=top align=middle>2008</TD><TD class=content vAlign=top align=middle>4</TD><TD class=content vAlign=top align=middle>view</TD></TR><TR><TD class=content vAlign=top>155.</TD><TD class=content vAlign=top width=161>United States of America</TD><TD class=content vAlign=top>A (H1)</TD><TD class=content vAlign=top align=middle>42</TD><TD class=content vAlign=top align=middle>2008</TD><TD class=content vAlign=top align=middle>12</TD><TD class=content vAlign=top align=middle>view</TD></TR><TR><TD class=content vAlign=top>156.</TD><TD class=content vAlign=top width=161>United States of America</TD><TD class=content vAlign=top>A (H1)</TD><TD class=content vAlign=top align=middle>43</TD><TD class=content vAlign=top align=middle>2008</TD><TD class=content vAlign=top align=middle>14</TD><TD class=content vAlign=top align=middle>view</TD></TR><TR><TD class=content vAlign=top>157.</TD><TD class=content vAlign=top width=161>United States of America</TD><TD class=content vAlign=top>A (H1)</TD><TD class=content vAlign=top align=middle>44</TD><TD class=content vAlign=top align=middle>2008</TD><TD class=content vAlign=top align=middle>2</TD><TD class=content vAlign=top align=middle>view</TD></TR></TBODY></TABLE>

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Commentary

http://www.recombinomics.com/News/11180801/H274Y_Japan.html

[AlaskaDenise]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Commentary

http://www.recombinomics.com/News/11...74Y_Japan.html

Commentary

Evolution of H1N1 Tamiflu Resistance in Japan
Recombinomics Commentary 18:37
November 18, 2008

in Tottori Prefecture during the 22 stocks in the 68-resistant strain, the frequency has been outstanding and 32.4 percent.

The above comments are from an updated Japan NIH report on Tamiflu resistance in Japan in the 2007/2008 season. As noted above, the most concentrated Prefecture for H274Y was Tottori, where the rate was above 32&#37; in H1N1 isolates. The new report has an updated phylogenetic tree that demonstrates that H1N1 in Tottori included the dominant Brisbane sub-clade that accounted for the majority of H274Y cases in Europe and the United States, but also included isolates on branches that had isolate that did and did not have H274Y, indicating the H274Y positive isolates had independently acquired H274Y (see list below), supporting acquisition via homologous recombination.

As seen in the updated tree, the majority of cases reported in Japan were in isolates that were not on the dominant branch (shaded in pink), but were on multiple separate branches.

Similar data was seen in recent sequences released from England, where several of the H274Y isolates (England/654/2007 and England/684/2007) did not map on the branch with the dominant sub-clade, providing evidence for more independent acquisitions which are most easily explained by homologous recombination. These multiple branches ion England and Japan offer additional clades which could become dominant this season.

Recent data from the southern hemisphere over the summer, and early isolates in the northern hemisphere this season, raise concerns that the resistance levels will approach 100% of H1N1 isolates in many countries. Sequence data on isolates, including the US where H1N1 is the dominant serotype this season, would be useful.

Dominant Brisbane sub-clade

Okayama/11/08
Tottori/41/08
Tottori/42/08
Tottori/43/08
Tottori/44/08
Tottori/46/08
Tottori/50/08
Tottori/52/08
Tottori/53/08
Tottori/55/08
Tottori/56/08
Tottori/57/08
Tottori/59/08
Tottori/60/08
Tottori/67/08
Yokohama/77/08
Yokohama/78/08
Yokohama/79/08

Other branches

Branch 1
Yamagata/68/08

Branch 2
Shimane/59/08

Branch 3
Tochigi/34/08
Tochigi/39/08

Branch 4
Tottori/28/08
Tottori/29/08
Tottori/34/08
Tottori/35/08
Tottori/37/08
Tottori/63/08

Branch 5
Gifu-C/17/08
Gifu-C/38/08
Tottori/21/08
Tottori/23/08

Branch 6
Aichi/76/08
Kobe/27/08
Kobe/31/08
Kobe/32/08

Branch 7
Yokohama/22/08
Yokohama/30/08
Yokohama/31/08
Yokohama/34/08
Yokohama/35/08

Branch 8
Tochigi/8/08

Branch 9
Nagano/1100/08
Nagano/1107/08


.

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

The "early" movers of H274Y into Bisbane/59

gb|FJ445025.1| Influenza A virus (A/England/654/2007(H1N1)) s... 48.1 4e-04
gb|FJ445066.1| Influenza A virus (A/England/594/2006(H1N1)) s... 48.1 4e-04
gb|FJ445080.1| Influenza A virus (A/England/494/2006(H1N1)) s... 48.1 4e-04
gb|FJ403587.1| Influenza A virus (A/Scotland/5/2007(H1N1)) se... 48.1 4e-04
gb|FJ403586.1| Influenza A virus (A/England/684/2007(H1N1)) s... 48.1 4e-04
gb|FJ179361.1| Influenza A virus (A/Pennsylvania/13/2007(H1N1... 48.1 4e-04
gb|EU551821.1| Influenza A virus (A/Paris/963/2008(H1N1)) neu... 48.1 4e-04
gb|EU716580.1| Influenza A virus (A/Florida/02/2008(H1N1)) se... 48.1 4e-04
gb|EU516199.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 48.1 4e-04
gb|EU516198.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 48.1 4e-04
gb|EU516197.1| Influenza A virus (A/Georgia/20/2006(H1N1)) se... 48.1 4e-04
gb|EU516141.1| Influenza A virus (A/Minnesota/23/2007(H1N1)) ... 48.1 4e-04
gb|EU516125.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 48.1 4e-04
gb|EU516123.1| Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 48.1 4e-04
gb|EU516112.1| Influenza A virus (A/Hawaii/21/2007(H1N1)) seg... 48.1 4e-04
gb|EU516028.1| Influenza A virus (A/Massachusetts/05/2007(H1N... 48.1 4e-04
gb|EU516027.1| Influenza A virus (A/Texas/31/2007(H1N1)) segm... 48.1 4e-04
gb|CY027037.1| Influenza A virus (A/Kansas/UR06-0104/2007(H1N... 48.1 4e-04

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

21 November 2008

Oseltamivir resistant influenza A(H1N1) virus in the UK, 2008/09


The below article was published in the Health Protection Agency publication Health Protection Report 21 November 2008 , Volume 2, No 47.
Following the recently reported, first UK oseltamivir resistant influenza A case (H1N1) in the 2008/09 season [1], several further cases have been detected. From week 36/08 up to 19 November 2008, twelve of the 13 influenza A(H1N1) isolates detected in England have been found to be resistant to oseltamivir. All these cases are from the south west of England. Two oseltamivir resistant influenza A(H1N1) cases have also been detected in Scotland. All the H1N1 cases from England remain sensitive to zanamivir and amantadine and are antigenically similar to the H1N1 reference strain A/Brisbane/59/2007, which is included in this season's influenza vaccine.
Since the start of the current 2008/09 flu season, between weeks 40/08 and 46/08, sporadic laboratory-confirmed influenza infections have been detected across the UK including 58 influenza A(H3), 13 influenza A(H1), 57 influenza A (not subtyped) and three influenza B viruses [2]. Although clinical indicators of influenza activity remain below base-line levels throughout the UK, a recent trend of increasing levels in these indicators is apparent.
The oseltamivir resistant cases are focused in one geographical area of England. Most cases, where age is known, have occurred in the 20-29 year age group. Investigation of the cases by the Avon, Gloucestershire and Wiltshire Health Protection Unit, in collaboration with HPA South West and HPA Centre for Infections, is continuing. There is no evidence of any increased morbidity in these cases to date.
It remains too early to predict which strain(s) of influenza virus will predominate this season. The Agency will continue to monitor closely the characteristics of circulating isolates including drug susceptibility. It remains important that respiratory samples are taken from suspected influenza cases, and that outbreaks of acute respiratory illness are investigated. Respiratory samples confirmed as influenza virus positive should be forwarded to the HPA Centre for Infections Respiratory Virus Unit for culture and anti-viral testing.
Efforts should continue to encourage people in the CMO-defined influenza risk groups to take up the recommendation of seasonal influenza vaccination [3].
Influenza virus detections across Europe remain low so far in this season. Oseltamivir-resistant influenza A(H1N1) isolates have also been reported in a small number of other countries. Oseltamivir-resistant influenza A(H1N1) viruses emerged last season in association with the H274Y mutation, which confers resistance to oseltamivir, but not to zanamivir. By the end of the 2007/08 season, 26 of 34 reporting European countries had reported H1N1 oseltamivir resistance and, in the UK, 38 out of 347 (11%) were found to be oseltamivir resistant [4, 5]. The epidemiological evidence from the 2007/08 season suggested no reported increase in morbidity associated with these confirmed oseltamivir-resistant cases.
References
1. HPA. Identification in the UK of the first oseltamivir resistant-influenza virus (H1N1). Health Protection Report [serial online] 2008, 2(43): news, 24 October 2008. Available at:
http://www.hpa.org.uk/hpr/archives/2008/news4308.htm#ah1n1.
2. Weekly HPA influenza report, week 46. http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1226478484902.
3. DH. PL CMO (2008)3, PL CNO (2008)2, PL CPHO (2008)1: The influenza immunisation programme 2008/09. http://www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Professionalletters/
Chiefmedicalofficerletters/DH_083812.
4. European Centre for Disease Prevention and Control. Antivirals and antiviral-resistant influenza ? resistance to oseltamivir (Tamiflu) in some influenza A(H1N1) virus samples. ECDC website [online] September 2008 [cited 24 October 2008]. http://ecdc.europa.eu/Health_topics/influenza/antivirals.html.
5. WHO. Influenza A(H1N1) virus resistance to oseltamivir. 13 October 2008. http://www.who.int/csr/disease/influenza/h1n1_table/en/index.html.

http://www.hps.scot.nhs.uk/news/spdetail.aspx?id=175

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

It looks like the two H1N1 isolates with H274Y represent 100&#37;. In report for weeks 43 & 44 only 1 influenza A was isolated

http://www.documents.hps.scot.nhs.uk/respiratory/seasonal-influenza/flu-update/2008-11-03.pdf

same for weeks 45 & 46

http://www.documents.hps.scot.nhs.uk/respiratory/seasonal-influenza/flu-update/2008-11-17.pdf

earlier reports indicate no influenza A detected

http://www.hps.scot.nhs.uk/resp/influenzareports.aspx

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Commentary

http://www.recombinomics.com/News/11210801/H274Y_Scotland_100.html

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

The first influenza A in Canada was H1N1 and Tamiflu resistance and reported a mont ago

http://www.recombinomics.com/News/10230801/H274Y_Canada.html

They are now in a don't ask / don't tell mode. The latest report on Tamiflu resistance (which includes the positive of a month ago):

http://www.phac-aspc.gc.ca/fluwatch/08-09/w46_08/index-eng.php

The NML has also tested 5 influenza isolates (1 A/H1N1, 1 A/H3N2 & 3 B) for oseltamivir (Tamiflu) resistance and found that the H1N1 isolate tested was resistant to oseltamivir due to the H274Y mutation whereas the H3N2 and B isolates were susceptible; resulting in 20&#37; (1/5) resistance among all influenza isolates tested.

[HenryN]

Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_

Neuraminidase inhibitor susceptibility testing on 30 A (H3) isolates since week 36/08 showed that all are sensitive to
oseltamivir and zanamivir but resistant to amantadine. All of the four influenza B isolates received since week 36/08
are sensitive to oseltamivir and zanamivir

. Fourteen of fifteen A (H1) specimens tested in the same time frame are
resistant to oseltamivir but sensitive to zanamivir and amantadine. The majority of these resistant viruses come from
the south west of England with the remaining from Wales and northern England. Two influenza A (H1) isolates have

been found to be resistant to oseltamivir in Scotland this season.

http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1227688116018

[Giuseppe]

Re: Influenza viruses resistant to oseltamivir, news and updates

ECDC Health Content: Possible scientific basis for neuraminidase inhibitor activity of resistant influenza viruses

SCIENTIFIC ADVANCES ? Antiviral Resistance

Possible scientific basis for neuraminidase inhibitor activity of resistant influenza viruses

Lakenby A, Thompson C, Democratis J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Inf Dis 2008; 216: 626-638. For Abstract click here

Description:
In this review the authors describe our as yet limited understanding of the scientific basis for lack of susceptibility in influenza viruses to neuraminidase inhibitors. The authors focus on two influenza sub-types particularly A(H1N1) but also A(H5N1).

ECDC Comment:
When influenza A(H1N1) viruses resistant to oseltamivir (type H274Y) emerged early this year a degree of surprise was expressed as though some such viruses had seen seen before, even with the H(274)Y mutation, notably in Japan, they were not at all fit, that is those viruses were unable to transmit readily. However the new A(H1N1) viruses proved top be fit for example resulting in outbreaks without pressure of antiviral treatment. This article suggests a number of reasons why this might be the case.

<cite cite="http://ecdc.europa.eu/en/health_content/sciadv/081218_sciadv.aspx">ECDC Health Content</cite>

[Giuseppe]

Re: Influenza viruses resistant to oseltamivir, news and updates

Change in U.S. guidance on use of antivirals by clinicians for seasonal influenza ? less likely to be applicable in Europe because of epidemiological differences - ECDC Health Content

Change in U.S. guidance on use of antivirals by clinicians for seasonal influenza ? less likely to be applicable in Europe because of epidemiological differences


Description:

In a recent report of a Public Health Development (issued December 18th) ECDC highlighted apparent differences between the United States and Europe during the early stages of their 2008-2009 season influenza epidemics.

At week 49/50 there are still few data but what are available confirms that the United States is presently observing a predominance of influenza A(H1N1) and a minority of A(H3N2) while in Europe the relative amounts are the other way around.

In both situations the majority of typed A(H1N1) viruses have been shown to be resistant to oseltamivir but susceptible to zanamivir and most of the A(H3N2) viruses tested to date were resistant to amantadine and rimantidine (see Table below with links to US and European surveillance reports).

Antivirals are used to a greater extent in the United States than in Europe for treating people testing positive for influenza or with presumed influenza and the US Centers for Disease Control promulgate recommendations on their use from an advisory group through the 2008 ACIP Guidance on Prevention and Control of (seasonal) Influenza.

In the light of these recent findings and specifically the fact that at this stage the majority of sub-typed influenza A viruses in the USA are A(H1N1) and are resistant to oseltamivir CDC has now revised its guidance to clinicians and public health authorities.


ECDC Comment (December 23rd 2008):

ECDC does not issue recommendations on the clinical management of patients as that is outside its mandate.

However it is worthwhile noting that given the different epidemiological circumstances at this early stage of the winter epidemics, namely that in Europe A(H1N1) viruses are far less common than A(H3N2) such changes in recommendations on drug use in the USA will be less applicable in Europe.

The US findings are based on results from only a few centres and it may be that in time greater heterogeneity in the level of oseltamivir resistance of A(H1N1) viruses may be observed, as experienced in the 2007-8 season in Europe.

Since then while over all the picture remains heterogeneous the global summary issued and updated by WHO indicates there have been reports of more uniformly high proportions of A(H1N1) viruses being oseltamivir resistant in the later 2008 Southern Hemisphere epidemics (e.g. in South Africa, Argentina and Australia).

Some country level reports have to be viewed cautiously as they are based on low numbers and little is known about how the samples are taken.

Finally it should be remembered that what is true at one point in an influenza season can change over time.

At the start of the European 2007-8 epidemics influenza A(H1N1) viruses were in the majority but by the end it was influenza B viruses that predominated.


United States (CDC) / Weeks 40 to 49 (cumulative) / Europe (EISS-ECDC) / Weeks 40 to 50 (cumulative)

* Influenza A(H1) / 157 (Of 46 tested, 45 were resistant to oseltamivir, while all were susceptible to zanamivir. None of 25 were resistant to amantadine or rimantadine) / 34(Of 20 tested for resistance to neuraminidase inhibitors, 19 were resistant to oseltamivir but none to zanamivir. Only 1 of 11 tested was resistant to amantadine and rimantadine)

* Influenza A(H3) / 18 (All viruses tested were sensitive to oseltamivir and zanamivir. All five viruses tested were resistant to amantadine and rimantadine) / 516 (No resistance to neuraminidase inhibitors was detected among 27 tested. All 26 tested were resistant to amantadine and rimantadine)

* All influenza A (including not subtyped) / 408 (233 unsubtyped) / 1022 (472 unsubtyped)

* Influenza B / 99 / 65

Comment to: influenza@ecdc.europa.eu
-

<cite cite="http://ecdc.europa.eu/en/health_content/phdev/081223_ph.aspx">ECDC Health Content</cite>

[HenryN]

Re: Influenza viruses resistant to oseltamivir, news and updates

With resistant viruses, doctors face dilemma treating flu this season

Provided by: Canadian Press
Written by: Helen Branswell, Medical Reporter, THE CANADIAN PRESS
Dec. 19, 2008


TORONTO - Early signs from this flu season suggest doctors face a vexing dilemma in treating the illness.
Testing to date in Canada, the United States and Europe shows that nearly all H1N1 viruses are resistant to oseltamivir (sold as Tamiflu) and susceptible to the adamantane drugs, amantadine and rimantadine. The inverse is true for H3N2 viruses, which are universally resistant to the adamantanes and susceptible to oseltamivir.
Given that in reality little point-of-care testing is done to determine whether a patient actually has influenza, let alone which variety of the bug is behind the illness, the resistance situation could see doctors making choices that lead to treatment failure this season.

"This is a very challenging situation," Dr. Tim Uyeki, deputy chief of influenza surveillance and prevention for the U.S. Centers for Disease Control admitted about the bizarre resistance picture coming into focus in the early days of the flu season.

"It definitely adds to the complexity of trying to manage influenza," Dr. Maria Zambon, head of the respiratory viruses unit of Britain's Health Protection Agency, agreed in an interview.
In the face of these early results, the CDC issued a health alert Friday to bring the U.S. medical community up to speed and recommend changes in the usage of flu drugs for the time being.
The upshot? When in doubt - and when the patient's age and health permits - use the only other option, the drug zanamivir, which is sold under the brand name Relenza. So far, all influenza A viruses (H1N1 and H3N2 are subtypes of influenza A) as well as influenza B viruses seem to be susceptible to zanamivir.
Oseltamivir could be used in combination with one of the adamantane drugs, but should only be used alone when local surveillance shows the viruses circulating are likely to be H3N2 or influenza B, the CDC guidance says.
As U.S. surveillance suggests most disease there so far this season is being caused by the H1N1 viruses, zanamivir appears to be a better bet than oseltamivir - or at least it is for patients who can use it. Zanamivir isn't licensed for use in children under seven years of age, and can't be used by people with chronic underlying airways disease or who can't manage the drug's inhalation device.
While they struggle to craft guidance for doctors, both the CDC and the Public Health Agency of Canada have a straightforward piece of advice for the public: Get a flu shot. This year's vaccine is well matched to the H1N1 viruses and the majority of H3N2 viruses currently making the rounds.
On the issue of antivirals, Canadian authorities aren't yet offering new treatment advice to the medical community in this country, though they are closely monitoring the situation, said Dr. Arlene King, director general for the Public Health Agency of Canada's centre for immunization and respiratory infectious diseases.
The National Microbiology Laboratory in Winnipeg has only tested 16 influenza viruses so far this season, finding all the H1N1s (three) resistant to oseltamivir and all the H3N2s (five) resistant to the adamantane drugs. The British Columbia Centre for Disease Control has tested another 19 H1N1 viruses, with 14 showing resistance and the results from the other five deemed inconclusive.
King said for now the recommendation is that doctors treating patients in long-term care facility outbreaks, for instance, should use oseltamivir. But they should be aware of the situation and be ready to shift gears.
"If physicians feel that treatment is merited, then they need to be obviously aware of this issue and should there be issues related to treatment failures, then they would have to consider other alternate drugs - zanamivir being, of course, a good choice," she said.
In Europe, the resistance pattern looks identical to what's being seen in North America, said Zambon. But H3N2 viruses currently appear to be responsible for about 90 per cent of confirmed flu cases, leading European authorities to conclude oseltamivir will probably be effective in most situations.
In the first few years after oseltamivir's introduction to the market, it was thought drug resistance wasn't likely to pose too much of a problem for the drug. Laboratory testing suggested resistant viruses, if they developed, would be too weak to spread.
That theory proved far off the mark when earlier this year reports emerged from Europe of a new resistant strain of H1N1 viruses. The strain has disseminated widely and rapidly; 100 per cent of H1N1 viruses tested in South Africa during that country's recent winter carried the mutation that makes the viruses resistant.
In the face of this development, doctors who have already expressed skepticism over the merits of the available flu drugs may be even more reluctant to prescribe them in an out-patient setting or use them in hospitalized patients.
Experts, who feel the drugs are already underutilized, hope that isn't the case.
"I think that these recommendations are really meant to provide physicians with guidance on how they should use or could use antivirals," said Dr. Joe Bresee, the CDC's chief of influenza surveillance and prevention.
"So I really do hope these new recommendations won't scare anybody away from the use of antivirals but will in fact remind them about the value of use of antivirals and encourage them to use them appropriately."

http://chealth.canoe.ca/channel_health_news_details.asp?channel_id=8&relation_id=1299&news_channel_id=8&news_id=27016

[HenryN]

Re: Influenza viruses resistant to oseltamivir, news and updates

BRITISH COLUMBIA (BC)

INFLUENZA SURVEILLANCE

2008-2009

UPDATE

- 1 -
Travis Hottes, Naveed Janjua, & Danuta Skowronski Number 4: Weeks 49 and 50
BCCDC Influenza & Emerging Respiratory Pathogens Team Nov 30 – Dec 13, 2008

Influenza Activity Continues to be Sporadic in BC

Highlights

Influenza activity in BC remains limited with a
small increase in laboratory detections. During
weeks 49 and 50 (Nov 30 – Dec 13, 2008), BC
laboratories reported 12 positive respiratory
specimens for influenza A and no positive
specimens for influenza B. To date this
season (Dec 18), 83&#37; (19 / 23) of the
influenza isolates in BC have been sub-typed
as A/H1. Nineteen A/H1 viruses have been
assessed genotypically for oseltamivir
resistance; 14 showed this resistance
mutation, and the other 5 were indeterminate.
One school ILI outbreak (pathogen unknown)
was reported in week 50, and no facility
influenza outbreaks were reported. The rate of
ILI visits to physicians remains lower than
average for this time of year.

Please remember to notify BCCDC if an
outbreak of ILI occurs in your region, by
emailing

ilioutbreak@bccdc.ca and
attaching the outbreak report form (a copy
is found at the end of this report).
Sentinel Physicians

Based on the historic range for this time of
year, the rate of ILI visits to sentinel physicians
was lower than expected in both weeks. In
week 49, the percentage of all patient visits
due to ILI was 0.28%, and in week 50, the
percentage was 0.12%. (See graph and table
on page 4.)

ILI Outbreaks

One ILI outbreak (pathogen unknown) in a
school was reported in BC during week 50.
Since the start of the season (Sept 28),
specimens have been submitted to BCCDC
Laboratory Services in relation to 19 ILI
outbreak investigations. Rhino/enterovirus was
identified in 9 (47%) of the investigations, RSV
was identified in 1 (5%) investigation, and no
pathogen was identified in the other 9
investigations. (See graph on page 5.)

Laboratory Reports

During weeks 49 and 50 (Nov 30 – Dec 13,
2008), BCCDC Laboratory Services tested 96
respiratory specimens. Influenza A was
identified in 12 specimens. Of these, 11 were
sub-typed as H1, and 1 was sub-typed as H3.
Nine specimens tested positive for RSV, 8 for
rhino/enterovirus, 4 for parainfluenza, and 3
for adenovirus.
During week 49 (Nov 30 – Dec 6, 2008),
Children’s and Women’s Health Centre
Laboratory tested 55 respiratory specimens.
Twenty specimens tested positive for RSV and
1 tested positive for parainfluenza. (See
graphs on page 6.)

Contents:

Overview

Page 1

Sentinel Physicians

Page 1

ILI Outbreaks

Page 1

Laboratory Reports

Page 1

Oseltamivir Resistance

Page 1

Canadian Data

Page 2

International Data

Page 2

Avian Influenza

Page 2

Vaccine Composition

Page 3

Activity Level Definitions

Page 3

List of Acronyms

Page 3

Web Sites

Page 3

Weekly ILI Graph

Page 4

ILI by Health Authority

Page 4

ILI Outbreaks Graph

Page 5

Lab Summary Graphs

Page 6

ILI Outbreak Form

Page 7

BRITISH COLUMBIA (BC)

INFLUENZA SURVEILLANCE

2008-2009

UPDATE

- 2 -

Oseltamivir Resistance

During the 2007-08 season, oseltamivir
resistance was identified among circulating
A/H1N1 viruses worldwide. Testing in Canada
indicated that 26% of last season’s A/H1N1
isolates were resistant to oseltamivir. Influenza
activity remains low, and only a small sample
of viruses is yet available for assessment. To
date (Dec 18), BCCDC has assessed 19
A/H1N1 isolates for oseltamivir resistance; 14
show genotypic evidence of oseltamivir
resistance, and the other 5 are indeterminate.
These specimens were from communitybased
cases of ILI; none was associated with
an outbreak.

Health care providers considering use of
antivirals are advised to regularly consult
public health and surveillance updates and
to stay informed about influenza activity
and resistance patterns throughout the
season. This may be relevant to the
appropriate choice among antiviral
options.
CANADA
Flu Watch

During week 49, sporadic activity was reported
in BC, Ontario, and Quebec, and localized
activity was reported in Alberta. ILI outbreaks
in schools have been reported in Alberta and
BC during weeks 49 and 50. Since August 24,
2008 provincial/territorial laboratories have
detected 89 cases of influenza, 54 influenza A
and 35 influenza B. The national rate of ILI
visits to sentinel physicians (12 cases per
1,000 visits during week 49) is below the
expected range for this time of the season.

http://www.phac-aspc.gc.ca/fluwatch/

National Microbiology Laboratory

Since Sept 1, 16 influenza isolates from
provincial and hospital labs have been
characterized at the National Microbiology
Laboratory (NML):
1 A/Brisbane/59/07(H1N1)-like* from Nova
Scotia,
2 A/Brisbane/10/07(H3N2)-like* from BC
(week 43: Oct 19 – 25) and Ontario,
3 B/Florida/04/06(Yamagata)-like* from
Alberta and Ontario,
and 10 B/Malaysia/2506/04(Victoria)-like from
Alberta and Ontario.

* indicates a strain match to the vaccine component.

Antiviral Resistance

Drug susceptibility testing at the NML showed
that the H1N1 isolate from Nova Scotia was
sensitive to amantadine and zanamivir but
resistant to oseltamivir and that both H3N2
isolates were resistant to amantadine but
sensitive to oseltamivir and zanamivir. Eleven
influenza B viruses have been tested for
oseltamivir resistance, and all were found to
be sensitive. Nine influenza B viruses have
been tested for zanamivir resistance, and all
were found to be sensitive.

INTERNATIONAL

A low level of Influenza activity was reported
during week 49 (Nov 30 – Dec 6) in the United
States. Localized activity was reported in
Hawaii, Texas, and Massachusetts, and
sporadic activity was reported elsewhere. The
rate of ILI visits to sentinel physicians
remained below national baseline levels. To
date this season, US laboratories have typed
507 influenza-positive specimens: 408 (81%)
influenza A and 99 (20%) influenza B. Of the
influenza A isolates, 175 have been subtyped,
of which 90% were A/H1. Forty-five of
46 A/H1 viruses tested were found to be
resistant to oseltamivir. For information about
influenza surveillance indicators in the United
States, please visit:

http://www.cdc.gov/flu/weekly/

.
Most countries in Europe continued to report
lower than average activity during week 49. Of
the 668 influenza virus detections in Europe
since the start of the season (week 40), 621
(93%) were influenza A, and of those
subtyped, 92% were A/H3. For more
information, please visit: http://www.eiss.org.

BRITISH COLUMBIA (BC)

INFLUENZA SURVEILLANCE

2008-2009

UPDATE

- 3 -

Avian Influenza

Four additional cases of human H5N1 AI have
been reported by the WHO since Sept 10,
2008 (2 in Indonesia, 1 in Cambodia, and 1 in
Egypt). Since 2003, the WHO has confirmed
391 human AI cases and 247 deaths. For
more information on human avian influenza
cases please visit:

http://www.who.int/csr/disease/avian_influenza

For further information on confirmed avian
influenza outbreaks in poultry, please visit:

http://www.oie.int/downld/AVIAN%20INFLUEN
ZA/A_AI-Asia.htm

.

Vaccine Composition

This year’s (2008-09) influenza vaccine contains
the following virus antigens:



A/Brisbane/59/2007(H1N1)-like



A/Brisbane/10/2007(H3N2)-like
Note: A/Uruguay/716/2007(H3N2) is
antigenically equivalent to
A/Brisbane/10/2007(H3N2) and may be
included by vaccine producers.



B/Florida/04/2006(Yamagata lineage)-like

Activity Level Definitions

Sporadic influenza activity:

sporadically occurring
ILI and laboratory-confirmed influenza during
previous 4 weeks, with no outbreaks.

Localized influenza activity:

as for sporadic activity,
but with ILI outbreaks in schools and worksites, or
laboratory-confirmed influenza outbreaks in
residential institutions occurring in less than 50% of
the influenza surveillance regions during the week
of reporting.

Widespread influenza activity:

as for localized
activity, but with outbreaks occurring in greater
than or equal to 50% of the influenza surveillance
regions during the week of reporting.

Contact Us:

List of Acronyms
AI:

Avian Influenza

FHA:

Fraser Health Authority

HPAI:

Highly Pathogenic Avian Influenza

HSDA:

Health Service Delivery Area

IHA:

Interior Health Authority

ILI:

Influenza-Like Illness

LTCF:

Long Term Care Facility

NHA:

Northern Health Authority

NML:

National Microbiological Laboratory

OIE:

World Organization for Animal Health

RSV:

Respiratory syncytial virus

VCHA:

Vancouver Coastal Health Authority

VIHA:

Vancouver Island Health Authority

WHO:

World Health Organization

Web Sites
1. Influenza Web Sites

Canada – Flu Watch:

http://www.phac-aspc.gc.ca/fluwatch/

NACI Statement on Influenza Vaccination for the
2008-09 Season:

http://www.phacaspc.
gc.ca/publicat/ccdr-rmtc/08vol34/acs-3/indexeng.
php

Washington State Flu Updates:

http://www.doh.wa.gov/ehsphl/epidemiology/CD/H
TML/FluUpdate.htm

USA Weekly Surveillance reports:

http://www.cdc.gov/flu/weekly/

European Influenza Surveillance Scheme:

http://www.eiss.org/index.cgi

WHO – Global Influenza Programme:

http://www.who.int/csr/disease/influenza/mission/

WHO – Weekly Epidemiological Record:

http://www.who.int/wer/en/

Influenza Centre (Australia):

http://www.influenzacentre.org/

2. Avian Influenza Web Sites

World Health Organization – Avian Influenza:

http://www.who.int/csr/disease/avian_influenza/en/

World Organization for Animal Health:

http://www.oie.int/eng/en_index.htm

3. This Report On-line

http://www.bccdc.org/content.php?item=35

Epidemiology Services

BC Centre for Disease Control (BCCDC)
655 W. 12

th Ave, Vancouver BC V5Z 4R4
Tel: (604) 660-6061 / Fax: (604) 660-0197

InfluenzaFieldEpi@bccdc.ca

- 4 -

W

EEKLY ILI

Percentage of Patient Visits due to Influenza Like Illness (ILI) per Week
Compared to Average Percentage of ILI Visits for the Past 19 Seasons
Sentinel Physicians, British Columbia, 2008-2009

0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38

Week Number of the Year

% of patient visits due to ILI

0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
2008/2009 season 1989/90 to 2007/08 seasons (Average +/- (2 standard units))

I

NFLUENZA-LIKE ILLNESS BY HEALTH AUTHORITY

Week 49

Nov 30 – Dec 6

Week 50
HEALTH

Dec 7 – 13

AUTHORITY

ILI
Visits
Total
Visits
% ILI ILI
Visits
Total
Visits
% ILI

Fraser 5 2,448 0.20% 8 9,475 0.08%
Interior 1 570 0.18% 2 721 0.28%
Northern 1 370 0.27% 1 332 0.30%
Vancouver Coastal 7 1,680 0.42% 0 1,263 0.00%
Vancouver Island 5 1,809 0.28% 5 1,809 0.28%

BC Total 19 6,877 0.12% 16 13,600 0.12%

- 5 -

ILI O

UTBREAKS

Number of Influenza-Like Illness (ILI) Outbreaks Investigated or Reported,
Compared to Current ILI Rate and Average ILI Rate for past 19 years, per Week
British Columbia, 2008-2009

0
10
20
30
40
40
42
44
46
48
50
52
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38

Week #
# ILI Outbreaks
Investigated/Reported

-0.1
0.1
0.3
0.5
0.7
0.9
1.1
1.3
1.5

% of sentinel patient visits due to ILI

# Influ LTCF*
# Other LTCF*
# ILI (No Pathogen) LTCF*
# ILI Acute Hospitals
# ILI Schools
Avg ILI Rate
Current ILI Rate
* Influ LTCF = Long-term care facility, influenza identified
* Other LTCF = Long-term care facility, other pathogen identified (including RSV, parainfluenza, adenovirus, and rhino/enterovirus)
* ILI (No Pathogen) LTCF = Long-term care facility, no pathogen identified

- 6 -

http://www.bccdc.org/downloads/pdf/epid/reports/InfluUpdate_Number04_Weeks49-50_0809.pdf

[HenryN]

Re: Influenza viruses resistant to oseltamivir, news and updates

To date this
season (Dec 18), 83% (19 / 23) of the
influenza isolates in BC have been sub-typed
as A/H1. Nineteen A/H1 viruses have been
assessed genotypically for oseltamivir
resistance; 14 showed this resistance
mutation, and the other 5 were indeterminate.

[HenryN]

Re: Influenza viruses resistant to oseltamivir, news and updates

Comemntary

http://www.recombinomics.com/News/12290802/H274Y_Canada_Alert.html