Influenza Virus A/h1n1 Resistant To Oseltamivir: W.h.o. Preliminary Summary

[ironorehopper]

Influenza A(H1N1) virus resistance to oseltamivir - Last quarter 2007 to first quarter 2008 - Preliminary summary and future plans

13 June 2008

The detection of an increased number of A(H1N1) viruses with resistance to oseltamivir was initially reported to WHO by Norway on 25 January 2008 (http://www.who.int/csr/disease/influ.../en/index.html).

The viruses carried a specific neuraminidase (NA) mutation (H274Y) that confers high-level resistance to oseltamivir in N1-containing influenza viruses(1) .

Prior to the recent report from Norway, such resistance was rarely observed in community isolates of influenza A or B.

During the previous northern hemisphere winter season (2006/2007), surveillance through the Global Influenza Surveillance Network (GISN)(http://www.who.int/csr/disease/influ.../en/index.html) laboratories found no oseltamivir-resistant H1N1 viruses among isolates from Japan or Europe, and less than 1% prevalence among H1N1 isolates from the United States of America.

WHO has been collecting global data about this phenomenon from multiple laboratories participating in GISN.

Oseltamivir resistance data has been obtained by phenotypic and/or genotypic analysis.

Data from European countries participating in the European Influenza Surveillance Scheme (EISS)(http://www.eiss.org/index.cgi) has been provided by EISS and the European Surveillance Network for Vigilance against Viral Resistance (VirGil)(http://www.virgil-net.org/).

In most northern hemisphere countries, influenza activity has now peaked for the 2007–2008 season, with activity decreasing to levels usually seen outside of the winter period.

Data collection is still ongoing, however WHO has now compiled the preliminary findings from available data on the prevalence of oseltamivir resistance in H1N1 viruses.

Overall summary
The 2007–2008 northern hemisphere season saw low levels of influenza activity in general compared with the same period in recent years.

In Asia and North America influenza activity began in November and increased in December–January, while in Europe activity began in December and increased in January.

In most countries, influenza activity peaked between weeks 4 and 8, 2008.

Influenza A(H1N1) viruses predominated in most parts of the northern hemisphere.

Influenza A(H3N2) virus activity was sporadic in many countries except for the United States of America where the proportion of A(H3N2) viruses increased rapidly during January and became the predominant virus for the season overall.

At the beginning of the season, influenza B viruses circulated at low levels in most countries, however, later in the season (around week 9, 2008) the proportion of influenza B viruses increased and in some countries, especially in Europe, predominated over influenza A viruses.

§ The Weekly Epidemiological Record (WER), 15 February 2008, vol. 83, 7 (pp 61–68)(http://www.who.int/wer/2008/wer8307.pdf)
§ The Weekly Epidemiological Record (WER), 29 February 2008, vol. 83, 9 (pp 77–88) (http://www.who.int/wer/2008/wer8309.pdf)
§ The Weekly Epidemiological Record (WER), 28 March 2008, vol. 83, 13 (pp 109–116) (http://www.who.int/wer/2008/wer8313.pdf)

From the last quarter of 2007 until 13 June 2008, a total of 6978 influenza A(H1N1) viruses have been tested for oseltamivir resistance worldwide and 1077 (15%) were found to be resistant (see Table below).

Fifty-two countries and territories reported on the test results, the majority of countries being from the European Region (see Map).

The number of viruses tested varied considerably by country/territory, ranging from 1–1544, leading to difficulties in the interpretation of comparative data for some countries/territories or Regions.

§ Table: Influenza A(H1N1) virus resistance to oseltamivir - Last quarter 2007 to 2 June 2008 (Update 13 June 2008) [pdf 19kb] (http://www.who.int/entity/csr/diseas...e200806013.pdf)

§ Map: Prevalence of oseltamivir-resistant H1N1 viruses, Last quarter 2007 - First quarter 2008 [pdf 189kb] (http://www.who.int/entity/csr/diseas...esistance2.pdf)

Data from the European Region of WHO indicated that 25% of the A(H1N1) isolates tested showed resistance.

Finland, France, Luxemburg, the Netherlands, Norway, the Russian Federation and Ukraine all reported a prevalence of 25% or greater of oseltamivir-resistant A(H1N1) viruses with Norway reporting the highest prevalence (67%).

Some countries recorded variations in prevalence across regions.

In Norway, the highest prevalence was recorded in the southern-most counties and in France, the north-west of the country.

Oseltamivir use in influenza-infected patients is generally uncommon in these European countries, and no link between oseltamivir exposure and resistance at the individual patient level was noted.

The preliminary analysis suggests that the resistant mutants do not share a single origin and further genotypic analysis is ongoing.

None of the H1N1 viruses from the Eastern Mediterranean Region (11 tested) or the African Region (77 tested) of WHO had the specific NA mutation (H274Y).

Thailand was the only country that submitted data from the South-East Asia Region of WHO and 1 resistant virus out of 13 A(H1N1) viruses was found.

In the Western Pacific Region of WHO, China, Hong Kong Special Administrative Region reported a prevalence of 11% oseltamivir resistance in A(H1N1) viruses, while Japan reported a relatively low prevalence (3%) despite having the world's largest per capita use of oseltamivir in clinical practice.

Australia reported three resistant viruses, two of which were isolated from presumed imported cases.

China, Guam, Malaysia, Mongolia, New Zealand, the Philippines, Singapore and the Republic of Korea did not find any resistant viruses.

In the WHO Region of the Americas, Canada and the United States of America reported prevalence rates of 26% and 11%, respectively.

Of the 20 viruses tested from countries in Central America, three were found to be resistant, all of which were from Monserrat.

§ Preliminary summary reports from countries, areas or territories (http://www.who.int/entity/csr/diseas.../en/index.html)

Preliminary summary reports on oseltamivir resistance by country have been submitted by several National Influenza Centres. Additional summary reports will be made available in due course.

Preliminary summary reports from countries, areas or territories

Summary table update and future activities
The summary table will be updated on a monthly basis, unless the situation changes. WHO will continue to monitor the situation in order to address important public health questions1 with regard to the phenomenon.

Global data of relevance to this issue will continue to be collated and analysed in collaboration with GISN members and other partners, such as the European Centre for Disease Prevention and Control (ECDC)(http://ecdc.europa.eu/Health_topics/...ntivirals.html) which is coordinating activities in collaboration with WHO European Region Office, across the European Union and in countries within the European Economic Area where the viruses have been observed.
-
1) The mutation in N1 neuraminidase of human influenza virus which confers high-level resistant to oseltamivir is a single amino acid substitution of the relevant histidine (H) to tyrosine (Y) at position 275.
Most of the early work on structure and inhibitor design is based on two other subtypes (N2 and N9) and the corresponding amino acid in these subtypes is at position 274. Consequently, some scientists use 'N2 numbering' (H274Y) and some use the actual 'N1 numbering' (H275Y).
2) http://www.who.int/csr/disease/influ.../en/index.html
-
http://www.who.int/csr/disease/influ.../en/index.html
-----

[ironorehopper]

This post contains two further attached pdf files: Norway and The Netherlands.

[gsgs]

what's the MRCAD or the maximum number of differences
for any two of these resistant H1N1-viruses this year ?

Just one number.They could answer this without revealing too
much info about the sequences, which (still) must remain secret
for some reason.



----edit1--------

> The preliminary analysis suggests that the resistant mutants do not share a single origin

what do they mean ? Any two influenza viruses do share a common origin.
Or better : for each segment, if we account or reassortment.
(ignoring recombination which is rare in humans)
For H1 it's later than 1977

the so far published resistant N1s rom 2008 suggest a common origin in 2007

[HenryN]

Originally Posted by gsgs

what's the MRCAD or the maximum number of differences
for any two of these resistant H1N1-viruses this year ?

Just one number.They could answer this without revealing too
much info about the sequences, which (still) must remain secret
for some reason.



----edit1--------

> The preliminary analysis suggests that the resistant mutants do not share a single origin

what do they mean ? Any two influenza viruses do share a common origin.
Or better : for each segment, if we account or reassortment.
(ignoring recombination which is rare in humans)
For H1 it's later than 1977

the so far published resistant N1s rom 2008 suggest a common origin in 2007

Please. The were at least 2 independent introduction in Brisbane strain in the US (and the results are PUBLISHED).
Please stop posting misleading information, includingn nonsense about recombiantion being rare. All that is rare is the maintanace of long streches of acquired sequences.

H274Y is a single nucleotide change (no long sequence exchanges required).

[HenryN]

Originally Posted by gsgs

what's the MRCAD or the maximum number of differences
for any two of these resistant H1N1-viruses this year ?

Just one number.They could answer this without revealing too
much info about the sequences, which (still) must remain secret
for some reason.



----edit1--------

> The preliminary analysis suggests that the resistant mutants do not share a single origin

what do they mean ? Any two influenza viruses do share a common origin.
Or better : for each segment, if we account or reassortment.
(ignoring recombination which is rare in humans)
For H1 it's later than 1977

the so far published resistant N1s rom 2008 suggest a common origin in 2007

The data from Japan clear shows MULTIPLE independent introductions, including those in the "Hawai" group. Hawai is in the United States and the positives are PUBLISHED. The Hawaian group is similar to other isolates in California (also in the United States and also PUBLISHED).

You continue to most misleading information which is well into the nonsense category.

Please stop with the nonsense.

Those without a "common origin" map to a seperate branch on the tree. H274Y is on NA. It has NOTHING to do with reassortment, and reassortment has NOTHING to do with sequence changes.

Your postings in fluenza evolution remain beyond absurd.

[HenryN]

For those interested in the science underlying this thread, phylogenetic analysis is used to identify the relationships between evolving genes. It presents a tree with branches representing viruses with a common origin. For the H274Y explosion, the main focus of the analysis is to see if there was one isolate which acquired H274Y, and then spread throughout the infected countries (common origin), or if the H274Y was acquired by isolates on separate branches (multiple origins, especially if it is only in a subset of isolates on a given branch).

Prior published data from the US identified multiple introductions. The first positives were from the 2006/2007 season and were on a New Caledonia background. For the 2007/2008 season, H274Y was on two DISTINCT Brisbane/59 backgrounds

http://www.recombinomics.com/News/03...dependent.html

One of the DISTINCT backgrounds (isolates from Hawaii), match a subset of the isolates from Japan.

The sudden acquisition of the same polymorphism on multiple genetic backgrounds supports acquisition by recombination.

[gsgs]

yes, thanks, the Japan-file has some info, I had missed that.

resistant viruses:
2C:1
2B,Europe:3
2B,Hawaii:18

2B,EU has 354G - just one mutation distinguishes EU from Hawaii

---edit-------

Hawaii seems to be similar to A/Hawaii/21/2007(H1N1) , presumably from summer/fall 2007
(not much seasonality in Hawaii)

http://www.setbb.com/fluwiki2/viewtopic.php?p=929

~7 differences in NA of the US and European resistant viruses from that Hawaii
virus for a MRCAD ~early 2007, which is the supposed date, when this
new Tamiflu-resistance had emerged. Earlier Tamiflu resistance was on a different genetical
background and only sporadic (~1%)

[HenryN]

Originally Posted by gsgs

yes, thanks, the Japan-file has some info, I had missed that.

resistant viruses:
2C:1
2B,Europe:3
2B,Hawaii:18

2B,EU has 354G - just one mutation distinguishes EU from Hawaii

Please. The phylogentic tree from Japan clear shows more than one change when Hawaii is compaired to the northern group. Each branch requires at least one change.

What is 354G supposed to mean?

[HenryN]

Originally Posted by gsgs

yes, thanks, the Japan-file has some info, I had missed that.

resistant viruses:
2C:1
2B,Europe:3
2B,Hawaii:18

2B,EU has 354G - just one mutation distinguishes EU from Hawaii

The Japan data has the phyogenetic tree that includes the positives from Japan along with positives in the US and Europe.

It is THE new data which CLEARLY demonstrates MULTIPLE independent introductions of H274Y onto Brisbane/59, which indicates recombination involving the same polymorphisms appended onto mltiple genetic backgrounds (just like NA G743A in various H5N1 isolates).

http://precedings.nature.com/documents/459/version/4

[HenryN]

Originally Posted by gsgs

yes, thanks, the Japan-file has some info, I had missed that.

resistant viruses:
2C:1
2B,Europe:3
2B,Hawaii:18

2B,EU has 354G - just one mutation distinguishes EU from Hawaii

Sequence differences do NOT require protein changes, The phylogentic trees are base on the NUCLEOTIDE differences between the various NA sequences.

The NUCLEOTIDE differences show MULTIPLE introductions of H274Y.

Citing protein differences has NOTHING to do with the independent origins of the isolates in the NA tree from Japan.

http://www.flutrackers.com/forum/att...0&d=1215765752

Please stop.

[gsgs]

354G was mentioned in the Japan .pdf
I just only saw it, before I studied the tree.

That .pdf has protein-mutations, see the link below for nucleotide-mutations

Hawaii seems to be similar to A/Hawaii/21/2007(H1N1) , presumably from summer/fall 2007
(not much seasonality in Hawaii)

http://www.setbb.com/fluwiki2/viewtopic.php?p=929



~7 differences in NA of the US and European resistant viruses from that Hawaii
virus for a MRCAD ~early 2007, which is the supposed date, when this
new Tamiflu-resistance had emerged. Earlier Tamiflu resistance was on a different genetical
background and only sporadic (~1%)

[HenryN]

Originally Posted by gsgs

354G was mentioned in the Japan .pdf
I just only saw it, before I studied the tree.

That .pdf has protein-mutations, see the link below for nucleotide-mutations

Hawaii seems to be similar to A/Hawaii/21/2007(H1N1) , presumably from summer/fall 2007
(not much seasonality in Hawaii)

http://www.setbb.com/fluwiki2/viewtopic.php?p=929



~7 differences in NA of the US and European resistant viruses from that Hawaii
virus for a MRCAD ~early 2007, which is the supposed date, when this
new Tamiflu-resistance had emerged. Earlier Tamiflu resistance was on a different genetical
background and only sporadic (~1%)

There are MULTIPLE branches in the tree from Japan which have both H274Y positive and negative isolates, indicating there were MULTIPLE introductions of H274Y onto various genetic backgrounds, putting "random mutations" into the garbage can, where it belongs.

[HenryN]

Originally Posted by gsgs

354G was mentioned in the Japan .pdf
I just only saw it, before I studied the tree.

That .pdf has protein-mutations, see the link below for nucleotide-mutations

Hawaii seems to be similar to A/Hawaii/21/2007(H1N1) , presumably from summer/fall 2007
(not much seasonality in Hawaii)

http://www.setbb.com/fluwiki2/viewtopic.php?p=929



~7 differences in NA of the US and European resistant viruses from that Hawaii
virus for a MRCAD ~early 2007, which is the supposed date, when this
new Tamiflu-resistance had emerged. Earlier Tamiflu resistance was on a different genetical
background and only sporadic (~1%)

ALL of the earlier "sporadic" isolates were in the 2006/2007 season (which is the season before 2007/2008). There were ZERO isolates prior to 2006/2007 season. Please stop with the nonsense.

[gsgs]

submitted H1N1 sequences increased a lot in 2007.

Occasional resistance was reported earlier, but maybe the sequences
weren't submitted. I'm not sure whether/(how much) we had H274Y earlier

2006/2007 was a different genetical background.

Something created this resistant strain in ~ early 2007

Or maybe created a strain in which genetical background H274Y
can survive and spread better than before - and then the mutation
happened several times independently.
Let's see .

Do you have examples of Japanese/other different "clades" with and
without H274Y ?

I may go through that phylo-tree in the japan.pdf later too


---edit1----
of course, drug usage having created the resistance is also a possibility,
we haven't ruled this out yet. But not much evidence for this, except
timing with increased Tamiflu-usage.

[HenryN]

Originally Posted by gsgs

submitted H1N1 sequences increased a lot in 2007.

Occasional resistance was reported earlier, but maybe the sequences
weren't submitted. I'm not sure whether/(how much) we had H274Y earlier

2006/2007 was a different genetical background.

Something created this resistant strain in ~ early 2007

Or maybe created a strain in which genetical background H274Y
can survive and spread better than before - and then the mutation
happened several times independently.
Let's see .

Do you have examples of Japanese/other different "clades" with and
without H274Y ?

I may go through that phylo-tree in the japan.pdf later too


---edit1----
of course, drug usage having created the resistance is also a possibility,
we haven't ruled this out yet. But not much evidence for this, except
timing with increased Tamiflu-usage.

Yes, the key is the fact that only some isoaltes on a given branch have H274Y, indicating the acquistion came AFTER the branch was formed and represents an independent introduction.

I have showed this in great deal for H5N1 G743A

http://precedings.nature.com/documents/459/version/4

which was also confirmed through plaque purification (showing that the SAME chnage was on multiple backgrounds found in unique isolates (no lab contamination required).

In the "Hawian" group from the US, there are multiple US isolates (in Hawaii/18/2007, Hawaii/31/2007, Hawaii/35/2007 and California/28/2007) that do NOT have H274Y and there are SEVERAL more examples in the tree released for Japan.

I will be detailing the specific examples in a commentary shortly.

The MULTIPLE examples in Brisbane/59 branches, supports the independent introdution into New Caledonia in the US in 2006/2007 which preceded the increase in Brisbanyne/59 in the US and many other countries.

[HenryN]

Originally Posted by gsgs

submitted H1N1 sequences increased a lot in 2007.

Occasional resistance was reported earlier, but maybe the sequences
weren't submitted. I'm not sure whether/(how much) we had H274Y earlier

2006/2007 was a different genetical background.

Something created this resistant strain in ~ early 2007

Or maybe created a strain in which genetical background H274Y
can survive and spread better than before - and then the mutation
happened several times independently.
Let's see .

Do you have examples of Japanese/other different "clades" with and
without H274Y ?

I may go through that phylo-tree in the japan.pdf later too


---edit1----
of course, drug usage having created the resistance is also a possibility,
we haven't ruled this out yet. But not much evidence for this, except
timing with increased Tamiflu-usage.

There actually are three Brisbayne/59 branches in the US representing 3 independent intoductions onto the Brisbayne/59 backbone. In addition to the large branch and the Hawaiian branch, there is a Florida branch

http://www.recombinomics.com/News/05...Y_Florida.html

[HenryN]

Commentary

http://www.recombinomics.com/News/07...ent_Japan.html

[HenryN]

Originally Posted by gsgs

submitted H1N1 sequences increased a lot in 2007.


---edit1----
of course, drug usage having created the resistance is also a possibility,
we haven't ruled this out yet. But not much evidence for this, except
timing with increased Tamiflu-usage.

The reason the influenza "experts" were "startled" was the lack of an association with Tamiflu usage. You have ZERO evidence to support the above "possibility" and have many comments from experts indicating that your "possibilty" is at odds with the facts.

Please avoid speculation that is in clear conflict with the data. This story has been quite clear since Norway first reported the explosion of H274Y cases several months ago, and now the data from Japan clearly shows that your "possibility" has no merit, and although you may not have ruled out selection by Tamiflu, the influenza "experts" have.

[HenryN]

As noted in the commentary, the data from Japan has many examples of independent introductions of H274Y into multiple genetic backgrounds this season. This pattern, and associated lack of Tamifly usage, causes major problems for random mutations, and is easily explained by the homologous recombination described in the two recent papers in J Virology (no lab error required - or remotely suggested).

[HenryN]

Originally Posted by gsgs

submitted H1N1 sequences increased a lot in 2007.

---edit1----
of course, drug usage having created the resistance is also a possibility,
we haven't ruled this out yet. But not much evidence for this, except
timing with increased Tamiflu-usage.

From Norway report

Oseltamivir use:

Generally, oseltamivir use before specimen collection in persons with resistant virus or in their prior contacts has been very uncommon. None of the 208 patients for which we have data both on resistance profile and antiviral use had received antivirals before sampling; 7 patients received

antiviral treatment subsequent to sampling.

http://www.who.int/csr/disease/influ...2008_06_25.pdf

[Oracle]

Apparently we have humor-challenged members. Message removed.


I do seem to remember reading reports that Norwegian nursing homes had been hit hard by seasonal influenza and that Tamiflu was being doled out like candy in an attempt to stop institutional epidemics.

Maybe in the elderly, it's very easy to select for drug resistance when tamiflu is used and drug resistant recombination quasi-strains are in circulation within the susceptible (in this case, geriatric) cases. They have been identified as high risk patient group for spreading influenza in the community (as have infants/toddlers).

However, tamiflu use in the latter age cohort was constrained by questions of correct dosing and toxicity (EU approved changes in dosing for young children, late 07).

[HenryN]

Originally Posted by gsgs

submitted H1N1 sequences increased a lot in 2007.


---edit1----
of course, drug usage having created the resistance is also a possibility,
we haven't ruled this out yet. But not much evidence for this, except
timing with increased Tamiflu-usage.

From the Netherlands

Oseltamivir use:
For the sentinel patients data on oseltamivir use was available for all 41 patients sampled. None of the sentinel patients (41) or their household contacts (40) reported the use of oseltamivir in the two weeks prior to the date of specimen collection.
For the non-sentinel patients, data on oseltamivir use was available for 15 patients (further data are currently being collected). None of the non-sentinel patients reported the use of oseltamivir in the two weeks prior to the date of specimen collection. Household contacts of one patient with an oseltamivir sensitive A(H1N1) virus had used oseltamivir in the two weeks prior to the date of specimen collection.

http://www.who.int/csr/disease/influ...2008_06_25.pdf

[sharon sanders]

Asking questions is one thing. Badgering is another.

I am asking that members do not antagonize each other either in tone, repeated questions, or actual words.


Thanks.

[HenryN]

Commentary at

http://www.recombinomics.com/News/07...t_Tottori.html

[HenryN]

More trees with Tamiflu resistance (slides 8 and 9)

http://www.fda.gov/ohrms/dockets/AC/...8-4348S2-3.pdf

[HenryN]

More trees with Tamiflu resistance (slides 5 and 6)

http://www.spc.int/phs/PPHSN/Surveil...RW_2008_11.pdf

[gsgs]

here the tables in text-format for computer-analysis
and better reading:




sequences from the japan.pdf NA-phylo-tree

resistant
  non-resistant
---------------------
Norway/1745/07
Norway/1747/07
Norway/1701/07
Norway/1731/07
Norway/1743/07
Norway/1736/07
Norway/1687/07
Arizona/03/07
New Jersey/16/07
England/557/07
New Jersey/15/07
Yokohama/77/08
Paris/0577/07
Yokohama/79/08
Yokohama/78/08
Paris/0644/07
Illinois/10/07
  Ishikawa/419/08
  South Dakota/06/07E
  Hawaii/19/07E
Toshigi/39/08
Toshigi/34/08
Yamagata/68/08
  Yamagata/35/08
Shimane/59/08
  Shizuoka-C/9/08
  Akita/8/08
  Fukui/21/08
  Kanagawa/17/08
  Nepal/4715/07E
  Washington/28/07
Tottori/29/08
Tottori/28/08
  Yamagata/31/08
  Hiroshima/22/08
  Kawasaki/27/08
  Johannesburg/67/07
  Hawaii/20/07
  Chiba/92/07
  Brisbane/59/07E
Kobe/27/08
Aichi/76/08
  Miyagi/23/08
  Hawaii/31/07E
Hawaii/28/07
Hawaii/21/07
Gifu-C/17/08
Tottori/23/08
Tottori/21/08
  Shimane/7/08
  Yamaguchi/14/08
Gifu-C/38/08
  Kyoto-C/1/08
  Yamagata/144/08
Yokohama/30/08
Yokohama/34/08
Yokohama/31/08
Yokohama/35/08
Yokohama/22/08
  Nagano/1041/08
Tochigi/8/08
  Shimane/32/08
  Niigata/66/08
  Nagano/1074/08
  Aomori/3/08
  Kobe/6/08
  Nagano/1089/08
  Okinawa/6/08
  Shizuoka/12/08
  Hyogo/31/07
  Texas/05/07
  St.Petersburg/96/07E

looks as if the H274Y mutation happened and was spread and isolated multiple times



Table2 Oseltamivir-resistant viruses, Japan season 2007/8
-------------------------------------------------------

A/Yokohama/91,2007/11/30, Y,O5,05,M,Kindergarten,u
A/Tochigi/8  ,2008/01/15,HY,O5,04,M,Nursery,v
A/Gifu-C/17  ,2008/01/25, Y,00,04,F,Outpatient,-
A/Tottori/29 ,2008/01/25, Y,uu,05,F,Outpatient,u
A/Tottori/28 ,2008/01/26, Y,uu,05,M,Outpatient,u
A/Yokohama/22,2008/01/28, Y,Z?,10,M,school,-
A/Yokohama/30,2008/01/28, Y,00,12,M,Outpatient,u
A/Yokohama/31,2008/01/28, Y,00,13,M,Outpatient,u
A/Yokohama/34,2008/01/28, Y,Z?,08,F,school,v
A/Yokohama/35,2008/01/28, Y,Z?,09,M,school,v
A/Tottori/23 ,2008/01/29, Y,??,04,M,Outpatient,u
A/Tottori,21 ,2008/01/30, Y,??,06,M,Outpatient,u
A/Tochigi/34 ,2008/02/18, Y,00,01,F,Outpatient,u
A/Tochigi/39 ,2008/02/18, Y,00,04,F,Outpatient,u
A/Aichi/76   ,2008/02/19, Y,Z5,08,F,Outpatient,u
A/Shimane/59 ,2008/02/26, Y,00,14,F,Outpatient,v
A/Yokohama/77,2008/02/26, Y,00,23,M,Outpatient,u
A/Yokohama/78,2008/02/28, Y,00,50,F,Outpatient,u
A/Yokohama/79,2008/02/28, Y,00,52,M,Outpatient,u
A/Gifu-C/38  ,2008/03/07, Y,00,04,F,Outpatient,v
A/Kobe/27    ,2008/03/11, Y,00,03,F,Outpatient,u
A/Yamagata/68,2008/03/11, Y,00,08,M,Outpatient,u

[HenryN]

Originally Posted by gsgs

here the tables in text-format for computer-analysis
and better reading:




sequences from the japan.pdf NA-phylo-tree

 
resistant
  non-resistant
---------------------
Norway/1745Y/07/NIMR
Norway/1747Y/07
Norway/1701Y/07
Norway/1731Y/07
Norway/1743Y/07
Norway/1736Y/07
Norway/1687Y/07
Arizona/03Y/07
New Jersey/16/07
England/557/07
New Jersey/15/07
Yokohama/77/08
Paris/0577/07
Yokohama/79/08
Yokohama/78/08
Paris/0644/07
Illinois/10/07
  Ishikawa/419/08
  South Dakota/06/07E
  Hawaii/19/07E
Toshigi/39/08
Toshigi/34/08
Yamagata/68/08
  Yamagata/35/08
Shimane/59/08
  Shizuoka-C/9/08
  Akita/8/08
  Fukui/21/08
  Kanagawa/17/08
  Nepal/4715/07E
  Washington/28/07
Tottori/29/08
Tottori/28/08
  Yamagata/31/08
  Hiroshima/22/08
  Kawasaki/27/08
  Johannesburg/67/07
  Hawaii/20/07
  Chiba/92/07
  Brisbane/59/07E
Kobe/27/08
Aichi/76/08
  Miyagi/23/08
  Hawaii/31/07E
Hawaii/28/07
Hawaii/21/07
Gifu-C/17/08
Tottori/23/08
Tottori/21/08
  Shimane/7/08
  Yamaguchi/14/08
Gifu-C/38/08
  Kyoto-C/1/08
  Yamagata/144/08
Yokohama/30/08
Yokohama/34/08
Yokohama/31/08
Yokohama/35/08
Yokohama/22/08
  Nagano/1041/08
Tochigi/8/08
  Shimane/32/08
  Niigata/66/08
  Nagano/1074/08
  Aomori/3/08
  Kobe/6/08
  Nagano/1089/08
  Okinawa/6/08
  Shizuoka/12/08
  Hyogo/31/07
  Texas/05/07
  St.Petersburg/96/07E

Table2 Oseltamivir-resistant viruses, Japan season 2007/8
-------------------------------------------------------

A/Yokohama/91,2007/11/30, Y,O5,05,M,Kindergarten,u
A/Tochigi/8  ,2008/01/15,HY,O5,04,M,Nursery,v
A/Gifu-C/17  ,2008/01/25, Y,00,04,F,Outpatient,-
A/Tottori/29 ,2008/01/25, Y,uu,05,F,Outpatient,u
A/Tottori/28 ,2008/01/26, Y,uu,05,M,Outpatient,u
A/Yokohama/22,2008/01/28, Y,Z?,10,M,school,-
A/Yokohama/30,2008/01/28, Y,00,12,M,Outpatient,u
A/Yokohama/31,2008/01/28, Y,00,13,M,Outpatient,u
A/Yokohama/34,2008/01/28, Y,Z?,08,F,school,v
A/Yokohama/35,2008/01/28, Y,Z?,09,M,school,v
A/Tottori/23 ,2008/01/29, Y,??,04,M,Outpatient,u
A/Tottori,21 ,2008/01/30, Y,??,06,M,Outpatient,u
A/Tochigi/34 ,2008/02/18, Y,00,01,F,Outpatient,u
A/Tochigi/39 ,2008/02/18, Y,00,04,F,Outpatient,u
A/Aichi/76   ,2008/02/19, Y,Z5,08,F,Outpatient,u
A/Shimane/59 ,2008/02/26, Y,00,14,F,Outpatient,v
A/Yokohama/77,2008/02/26, Y,00,23,M,Outpatient,u
A/Yokohama/78,2008/02/28, Y,00,50,F,Outpatient,u
A/Yokohama/79,2008/02/28, Y,00,52,M,Outpatient,u
A/Gifu-C/38  ,2008/03/07, Y,00,04,F,Outpatient,v
A/Kobe/27    ,2008/03/11, Y,00,03,F,Outpatient,u
A/Yamagata/68,2008/03/11, Y,00,08,M,Outpatient,u

Why is the a Y in the sample number for the patients from Norway?

[HenryN]

Public full sequences or phylograms showing North-EU subclade of 2B

Arizona/3/07
Arizona/13/07
Arizona/14/07
Arizona/15/07
England/557/07
Illinois/10/07
Lyon/1337/07
Maryland/04/07
New Jersey/5/07
New Jersey/10/07
New Jersey/15/07
New Jersey/16/07
New Jersey/20/07
Norway/1630/07
Norway/1651/07
Norway/1687/07
Norway/1701/07
Norway/1731/07
Norway/1736/07
Norway/1743/07
Norway/1745/07
Norway/1747/07
Paris/0577/07
Paris/0644/07
Sydney/142/07
Sydney/143/07
Sydney/144/07
Hawaii/1/08
Hawaii/2/08
Indiana/1/08
Memphis/3/08
Minnesota/1/08
New Jersey/06/08
North Carolina/2/08
Pennsylvania/2/08
Washington/1/08
Wisconsin/01/08
Yokohama/77/08
Yokohama/78/08
Yokohama/79/08

[gsgs]

Y removed. That was my first idea to mark H274Y, but indentation
seems better. It shows how resistant and non-resistant isolates alternate.

In my mutation tables this would look like vertically sprenkled
dots or multiple short lines or dots in the same column,
which is rare