Announcement

**HenryN** · January 6, 2009, 12:36 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Looks like clade 2C (Hong Kong) has been eliminated.

**sharon sanders** · January 6, 2009, 12:49 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Striking results. Anyone have any ideas as to how these high levels (90%+) of resistance have apparently spread to all areas of the globe so quickly?

**HenryN** · January 6, 2009, 12:56 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by Florida1 View Post

Striking results. Anyone have any ideas as to how these high levels (90%+) of resistance have apparently spread to all areas of the globe so quickly?

Hitch hiking.

**Giuseppe** · January 6, 2009, 12:57 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by Florida1 View Post

Striking results. Anyone have any ideas as to how these high levels (90%+) of resistance have apparently spread to all areas of the globe so quickly?

It seems that H1N1 with H274Y owns some sort of evolutionary advantage against non-H274Y H1N1, perhaps affecting antigenic properties...

Another question: is possible to use the spread pattern of H1N1 as a prototypical scenario of a novel pandemic strain?

**sharon sanders** · January 6, 2009, 01:01 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by ironorehopper View Post

It seems that H1N1 with H274Y owns some sort of evolutionary advantage against non-H274Y H1N1, perhaps affecting antigenic properties...

Another question: is possible to use the spread pattern of H1N1 as a prototypical scenario of a novel pandemic strain?

This is what I am thinking. The speed at which this has occurred gives thought to the possibilities........

**HenryN** · January 6, 2009, 01:29 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Commentary

H1N1 Tamflu Resistance Near 100% In Japan

http://www.recombinomics.com/News/01060902/H274Y_Japan_100.html

Recombinomics Commentary

**HenryN** · January 6, 2009, 01:45 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by ironorehopper View Post

It seems that H1N1 with H274Y owns some sort of evolutionary advantage against non-H274Y H1N1, perhaps affecting antigenic properties...

Another question: is possible to use the spread pattern of H1N1 as a prototypical scenario of a novel pandemic strain?

No. H274Y has hopped on board the fastest car. Its all about hitch hiking.

**HenryN** · January 6, 2009, 01:46 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by Florida1 View Post

This is what I am thinking. The speed at which this has occurred gives thought to the possibilities........

It is hitch hiking that has nothing to do with Tamiflu or H274Y selection.

**gsgs** · January 6, 2009, 01:46 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

we have bottlenecks each year, presumably in SE-Asia. (at least with
H3N2)

Here usually the strains emerge in Summer,Autumn which will be dominant
in US,EU in winter.

Maybe China, maybe Korea, maybe Japan, maybe swine

so, it depends which strain is successful there

**HenryN** · January 6, 2009, 01:49 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by gsgs View Post

we have bottlenecks each year, presumably in SE-Asia. (at least with
H3N2)

Here usually the strains emerge in Summer,Autumn which will be dominant
in US,EU in winter.

Maybe China, maybe Korea, maybe Japan, maybe swine

so, it depends which strain is successful there

Wrong. The dominant strain did not come out of Asia.

**AlaskaDenise** · January 6, 2009, 06:04 PM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Originally posted by niman View Post

Commentary

http://www.recombinomics.com/News/01...Japan_100.html

<table style="text-align: left; width: 775px; font-family: helvetica,arial,sans-serif; color: rgb(190, 5, 1);" border="0" cellpadding="0" cellspacing="0"><tbody><tr><td style="width: 515px; vertical-align: top;" colspan="5"><big><big>Commentary</big></big>
H1N1 Tamflu Resistance Near 100% In Japan
Recombinomics Commentary 18:19
January 6, 2009

WHO has received several reports from National Influenza Centres (NIC) in the northern hemisphere regarding influenza A(H1N1) virus resistance to oseltamivir for the beginning of 2008/2009 influenza season (week 41-44).

Among A(H1N1) viruses tested, 13 of 14 in the United Kingdom,1 of 1 in Israel, 1 of 1 in Ghana and 1 of 1 in Canada had the specific neuraminidase mutation (H275Y; numbered according to N1 sequence) associated with oseltamivir resistance.

Japan also reported that 13 of 14 A(H1N1) viruses tested were resistant.

The above comments are from the December 30, 2008 WHO report on oseltamivir resistance (H274Y in the northern hemisphere). The number of samples tested is low, because the report covers a very small time period at the beginning of the flu season. Data from the UK has been updated at the UK website to 29/30. The only sensitive isolate was from the very beginning of the season. The same was true in the United States. The one sensitive sample was reported with one resistant sample in the first report. After that, the next 69 isolates had H274Y.

The same sequence of events will probably hold for Japan. As additional samples are collected, the frequency will approach 100%. The figures for Japan are somewhat surprising since last season there was a significant level of clade 2C (Hong Kong), which was oseltamivir sensitive. The same was true for Hawaii in the United States, but this season all reported H1N1 tests have had H274Y in Hawaii, suggesting clade 2B had gain dominance over clade 2C.

The data above for Japan indicates the same dominance had happened there, suggesting the frequency of almost 100% in Europe and North America extends to other northern countries in Asia, like Japan, China, and Russia.

Therefore, it seems likely that clade 2C may have been displaced throughout the northern hemisphere by clade 2B, which is now represented by a dominant sub-clade that has acquired and fixed H274Y.

.

**Giuseppe** · January 7, 2009, 03:21 AM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Tamiflu Is Unlikely to Thwart Flu Strain in Europe, Report Says - Bloomberg.com: Japan

Tamiflu Is Unlikely to Thwart Flu Strain in Europe, Report Says

By Jason Gale
Jan. 7 (Bloomberg) --

Tamiflu is unlikely to stop one of the three most-common seasonal flu strains circulating in North America and Europe this winter, with studies showing more than 90 percent resistance to Roche Holding AG's drug.

Since the emergence of a Tamiflu-evading variant of the H1N1 flu virus was reported to the World Health Organization by Norway a year ago, the bug has been found in more than 50 countries. Preliminary data from the U.K., Japan and other northern hemisphere countries last quarter show almost all H1N1 viruses are resistant to the best-selling anti-flu pill, the WHO said in a statement posted on its Web site yesterday.

The discovery is prompting health officials to recommend other medicines, such as GlaxoSmithKline Plc's Relenza, to fight a disease the WHO estimates causes 250,000 to 500,000 deaths annually. All three common flu strains -- H1N1, H3N2 and type B -- are susceptible to Relenza, an inhaled powder. H1N1 is the most-common flu virus circulating in the U.S. this winter, while H3N2 has so far dominated in Europe.

``Since most clinicians are unaware of the flu strain they are trying to treat, it makes sense for them to prescribe, where appropriate, a medication that's effective against the broadest range of viruses,'' said Jennifer McKimm-Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne and a member of an international committee undertaking global surveillance on potential drug resistance.

McKimm-Breschkin was among a group of scientists in Australia that developed Relenza.

Prescribing Advice
In the U.S., doctors prescribing anti-flu treatments should give their patients Relenza or a combination of Tamiflu and an older drug called rimantadine, the Centers for Disease Control and Prevention said in a Dec. 19 statement. Basel, Geneva-based Roche had worldwide Tamiflu sales of $1.74 billion in 2007 and $2.1 billion in 2006.

Of the 73 H1N1 viruses tested in the U.S. since Oct. 1, 99 percent were resistant to Tamiflu, and all were susceptible to Relenza, rimantadine and amantadine, a similar drug, the CDC said in its latest weekly flu report.

Among H1N1 viruses tested last quarter from Ghana, Canada, Israel, Norway, U.K. and Japan, Tamiflu-resistance levels varied from 93 percent to 100 percent. In Argentina, testing of one H1N1 sample found no resistance, according to WHO.

Both Tamiflu and Relenza work by blocking a protein on the surface of influenza particles called neuraminidase which allows the virus to spread from infected cells to other cells in the body. Scientists say some H1N1 viruses have evolved to evade Tamiflu through a single mutation in the neuraminidase that prevents the medicine from clinging to the viral protein, thereby enabling the pathogen to spread. Relenza is unaffected by the change.

To contact the reporters on this story: Jason Gale in Singapore at j.gale@bloomberg.net
Last Updated: January 6, 2009 22:44 EST
-

<cite cite="http://www.bloomberg.com/apps/news?pid=20601101&sid=alahF2Rlhw2o&refer=japan">Bloomberg.com: Japan</cite>

**HenryN** · January 7, 2009, 06:36 AM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Japan tree (and sequences)

http://blog.goo.ne.jp/publichealth

http://66.102.1.101/translate_c?hl=e...OgxtsxLr7VW5FA

**HenryN** · January 7, 2009, 07:58 AM

Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Sequences from H1N1 at elementay school in Sendai, Japan, in October (outbreak closed school) have three RBD changes, G189V, A193T, H196R, which match sequences from Pennsylvania, Texas, and Hawaii this season.