Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

[Giuseppe]

Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season

DOI: 10.3201/eid1504.081280
Suggested citation for this article: Meijer A, Lackenby A, Hungnes O, Lina B, van der Werf S, Schweiger B, et al. Oseltamivir-resistant influenza A (H1N1) virus, Europe, 2007?08 season. Emerg Infect Dis. 2009 April; [Epub ahead of print]

[Original PDF paper at this LINK. EDITED.]

Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season

Adam Meijer, Angie Lackenby, Olav Hungnes, Bruno Lina, Sylvie van der Werf, Brunhilde Schweiger, Matthias Opp, John Paget, Jan van de Kassteele, Alan Hay, and Maria Zambon, on behalf of the European Influenza Surveillance Scheme1

Author affiliations: Netherlands Institute for Health Services Research, Utrecht, the Netherlands (A. Meijer, J. Paget); National Institute for Public Health and the Environment, Bilthoven, the Netherlands (A. Meijer, J. van de Kassteele); European Surveillance Network for Vigilance against Viral Resistance (A. Lackenby, B. Lina, S. van der Werf, A. Hay, M. Zambon); Health Protection Agency, London, UK (A. Lackenby, M. Zambon); Norwegian Institute of Public Health, Oslo, Norway (O. Hungnes); Centre National de R?f?rence des Virus Influenza (R?gion Sud), Lyon, France (B. Lina); Centre National de R?f?rence des Virus Influenza (R?gion Nord), Paris, France (S. van der Werf); Robert Koch Institute, Berlin, Germany (B. Schweiger); Laboratoire National de Sant?, Luxembourg, Luxembourg (M. Opp); and World Health Organization Collaborating Centre Medical Research Council/National Institute of Medical Research, London, UK (A. Hay)

1European Influenza Surveillance Scheme members, 2007?08 season: P. Lachner, T. Popow-Kraupp, R. Strauss (Austria); B. Brochier, M. Sabbe, I. Thomas, V. Casteren, F. Yane (Belgium); T. Georgieva, M. Kojouharova, R. Kotseva, A. Kurchatova (Bulgaria); B. Aleraj, V. Drazenovic (Croatia); D. Bagatzouni-Pieridou, A. Elia (Cyprus); M. Havlickova, J. Kyncl (Czech Republic); S. Glismann, A. Mazick, L. Nielsen (Denmark); D.M. Fleming, A. Lackenby, J. Watson, M. Zambon (England); O. Sadikova, I. Sarv (Estonia); T. Ziegler (Finland); J.-M. Cohen, V. Enouf, B. Lina, A. Mosnier, M. Valette, S. van der Werf (France); U. Buchholz, W. Haas, B. Schweiger (Germany); A.G. Kossivakis, V. Kyriazopoulou-Dalaina, A. Mentis, G. Spala (Greece); G. Berencsi, A. Csoh?n, I. Jankovics (Hungary); S. Coughlan, L. Domegan, M. Duffy, M. Joyce, J. O?Donnell, D. O'Flanagan (Ireland); F. Ansaldi, P. Crovari, I. Donatelli, F. Pregliasco (Italy); R. Nikiforova, I. Van Velicko, N. Zamjatina (Latvia); A. Griskevicius, N. Kupreviciene, G. Rimseliene (Lithuania); M. Opp (Luxembourg); C. Barbara, T. Melillo (Malta); A. Arkema, T. Meerhoff, W.J. Paget, K. van der Velden, (EISS-CC, the Netherlands), F. Dijkstra, G. Donker, J.C. de Jong, A. Meijer, G. Rimmelzwaan, M. van der Sande, B. Wilbrink (the Netherlands); P. Coyle, H. Kennedy, H. O?Neill (Northern Ireland); O. Hungnes, B. Iversen (Norway); L. Brydak, M. Romanowska (Poland); I.M. Falc?o, J.M. Falc?o, H. Rebelo de Andrade (Portugal); V. Alexandrescu, E. Lupulescu (Romania); W. Carman, R. Gunson, J. Kean, J. McMenamin (Scotland); N. Milic, J. Nedeljkovic (Serbia); H. Blaskovicova, Z. Kristufkova, M. Sl?cikov? (Slovakia); K. Prosenc, M. Socan (Slovenia); I. Casas, A. Larrrauri, S. de Mateo, R. Ortiz de Lejarazu, P. P?rez-Bre?a, T. Pumarola Su??, T. Vega Alonso (Spain); M. Brytting, A. Linde, P. Penttinen, S. Rubinova (Sweden); Y. Thomas, M. Witschi (Switzerland); N. Yilmaz (Turkey); M. Aranova, A. Mironenko (Ukraine); A. Hay (United Kingdom); and R. Jones, D. Thomas (Wales).


In Europe, the 2007?08 winter season was dominated by influenza virus A (H1N1) circulation through week 7, followed by influenza B virus from week 8 onward.
Oseltamivir-resistant viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use.
By country, the proportion of ORVs ranged from 0% to 68%, with the highest proportion in Norway. The average weighted prevalence of ORVs across Europe increased gradually over time, from near 0 in week 40 of 2007 to 56% in week 19 of 2008 (mean 20%).
Neuraminidase genes of ORVs possessing the H275Y substitution formed a homogeneous subgroup closely related to, but distinguishable from, those of oseltamivir-sensitive influenza viruses A (H1N1).
Minor variants of ORVs emerged independently, indicating multiclonal ORVs.
Overall, the clinical effect of ORVs in Europe, measured by influenza-like illness or acute respiratory infection, was unremarkable and consistent with normal seasonal activity.
-
----

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

isn't it funny (and sad), how they talk around the central question
of multiple or single introduction into Europe ?
How they force you to read the whole article - only to realize
that they are not addressing the question at all ?



The earliest detection of ORVs was in France and the United Kingdom
in week 46 and in Norway in week 47.
Continuous detection of ORV began in Norway in week 47,France in week 49,
the UK in week 51,NL in week 52

so this was known since week~50, but they only told us on 28.Jan.2008
http://www.flutrackers.com/forum/showthread.php?t=51648&highlight=oseltamivir+resistant+norway


resistance was 0% in week 40 and 56% in week 19
but 60% in week 47 in Norway


H275Y sporadically in A/NewC/20/99 in 2006/7 in UK and USA

 

[Giuseppe]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

From above paper. Excerpts.

(...)

Discussion

Unexpectedly, influenza viruses A (H1N1) with a single amino acid substitution H275Y in the NA, which caused a several hundred-fold selective reduction in susceptibility to oseltamivir, emerged and were sustained in circulation in Europe during 2007?08, despite low antivirual drug use (Figure 1).

Before the 2007?08 season, <1% of viruses tested since the start of European antiviral surveillance in 2004 had IC50 values >100 nmol/L for NAI drugs (A. Lackenby et al., unpub. data), in concordance with results from worldwide surveillance (8,9).

In 2007?08, influenza viruses A (H3N2) and B circulating in Europe remained sensitive to NAI drugs.

This emergence of oseltamivir-resistant influenza virus A (H1N1) in Europe coincided with the dominant circulation of this virus subtype during the 2007?08 winter in Europe and the emergence of a new drift variant, A/Brisbane/59/2007 (30).

Of the last 12 influenza seasons, influenza viruses A (H1N1) were dominant only in 2000?01, which included a new drift variant, A/New Caledonia/20/99 (20).

In the other 10 seasons, influenza viruses A (H1N1) played a minor role, with influenza viruses A (H3N2) dominant in 9 seasons.

Compared with 2000?01, peak incidence rates for ILI or ARI in 7 of 13 countries were similar or lower in 2007?08 (Table).

In 6 countries, the peak incidence rates were significantly higher in 2007?08 than in 2000?01, but with a <2-fold difference in 5 countries and, in Spain only, a 4.8-fold difference.

Both the 2000?01 and 2007?08 seasons were unremarkable in the overall clinical impact of influenza, with normal seasonal activity as measured by comparison of peak incidence rates for all seasons since 2000?01.

Sporadically occurring A/New Caledonia/20/99-like ORVs with H275Y were detected during the 2006?07 season in the United Kingdom and United States but did not become epidemiologically important.

Indeed, the genetic background plays a role in retaining the replication efficiency and pathogenicity of recombinant influenza viruses A (H5N1) and A (H1N1) after introduction of tyrosine at position 275 (33).

Furthermore, other previously analyzed influenza viruses A (H1N1) with the H275Y mutation showed impaired replicative ability in cell culture and reduced infectivity and substantially compromised pathogenicity in animal models, compared with the corresponding wild-type virus (34,35).

The coincidental emergence of H275Y with the circulation of the A/Brisbane/59/2007 drift variant may have favored the emergence of fit transmissible ORVs.

This point is also illustrated by the emergence of A/Brisbane/59/2007-like ORVs in other parts of the Northern Hemisphere and their continued circulation during the 2008 Southern Hemisphere influenza epidemic season (36?38).

Since the last quarter of 2007, ORVs have been detected in continents other than Europe, with proportions of ORVs varying from 100% in South Africa and Australia to <5% in Japan.

Trend data are limited: a slight monthly increase was noted in China/Hong Kong and Japan; in Canada, the increase was similar to that in Europe, from 0% ORVs in November 2007 to 86% ORVs in April 2008 (36).

Using modeling, we showed that the prevalence of ORVs increased in the European region from ≈0% at the start to 56% at the end of the season.

The finding of a high prevalence of ORVs in the community and the overall temporal increase in resistance demonstrates that the previously documented reduced fitness of viruses bearing the H275Y mutation, ostensibly caused by structural and functional constraints (10), has been overcome in currently circulating influenza viruses A (H1N1).

The results of Rameix-Welti et al. (32) suggest that a combination of specific amino acid substitutions have increased the affinity of the NA of recent influenza viruses A (H1N1) (ORVs and OSVs) for substrate.

A better balance of NA and HA activities in ORVs compared with OSVs may have contributed to the overall fitness and transmissibility of ORVs.

However, growth curves conducted in tissue culture of pairs of ORVs and OSVs demonstrated no differences in growth kinetics or final virus yields.

Therefore, changes in other genes also may be involved in the overall impact on the fitness of ORVs, for which whole genome sequencing is necessary.

For Europe, no focal point of initiation of spread could be identified. The spread of ORV from west to east paralleled that of influenza virus A in Europe, and there was an average delay of 5.7 weeks for the appearance of ORVs after the start of influenza virus A circulation.

However, the low R2 values for both patterns make definitive conclusions difficult to draw about the spatial spread of either influenza viruses A or ORVs.

Several independent introductions into European countries of a sensitive and a resistant strain might explain the low R2 values.

Estimating whether a global focal point exists from which ORVs emerged to spread to the rest of the world is not possible, but the fact that Japan, the country with the highest per capita use of oseltamivir (5), had relatively low levels of circulating ORVs during the 2007?08 influenza season is relevant and reflects the limited circulation of the clade 2B A/Brisbane/59/2007-like viruses belonging to the European cluster in this region (31,36).

The close relationships between the NA sequences of most of the 2007?08 European ORVs and their segregation from those of OSVs suggest that resistance results in large part from the spread of a single variant.

Phylogenetic analyses show that this is a property of clade 2B A/Brisbane/59/2007-like viruses and is not associated with emergence of another antigenic variant.

However, identification of other resistant variants in the United Kingdom, some of which are more closely related to OSVs than to most ORVs (e.g., A/England/654/2007) indicates the independent parallel emergence of multiple resistant variants.

This is emphasized by small distinct clusters of closely related ORVs in Japan that are related to European OSVs, whereas only a few of the Japanese ORVs belonged to the large European ORVs cluster (31).

Resolution of the origin and frequency of emergence of ORVs and association with drug use clearly require substantially more intimate knowledge of the genetic relationships among OSVs and ORVs worldwide.

Our observations suggest that the new genetic background of influenza viruses A (H1N1) that appeared in 2007 enabled the virus to develop oseltamivir resistance independently at several locations in the world.

The combined effect of the relatively high level of circulation of influenza viruses A (H1N1) in Europe; the introduction of a new antigenic drift variant in a susceptible population, partly related to the lack of substantial influenza virus A (H1N1) circulation since the 2000?01 season; and the uncompromised transmissibility of the ORVs contributed to the epidemiologic success of the ORVs during the 2007?08 season.

This phenomenon shows clearly that continuation of antiviral susceptibility monitoring and increasing capacity for timely response are essential (21,39).

In addition, the appearance of viable transmitting ORVs is a reminder that the level of resistance to oseltamivir of seasonal or pandemic virus cannot be predicted, and therefore antiviral strategies should not rely on single drugs (40).

Although oseltamivir remains a valuable influenza antiviral agent, the emergence of natural resistance shifts attention from oseltamivir to other antiviral agents and to improved vaccination (e.g., greater vaccination coverage, more immunogenic and broadly reacting vaccines) in the fight against seasonal and pandemic influenza.
(...)
-
-----

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

isn't it funny (and sad), how they talk around the central question
of multiple or single introduction into Europe ?
How they force you to read the whole article - only to realize
that they are not addressing the question at all ?



The earliest detection of ORVs was in France and the United Kingdom
in week 46 and in Norway in week 47.
Continuous detection of ORV began in Norway in week 47,France in week 49,
the UK in week 51,NL in week 52

so this was known since week~50, but they only told us on 28.Jan.2008
http://www.flutrackers.com/forum/showthread.php?t=51648&highlight=oseltamivir+resistant+norway


resistance was 0% in week 40 and 56% in week 19
but 60% in week 47 in Norway


H275Y sporadically in A/NewC/20/99 in 2006/7 in UK and USA

The multiple OBVIOUS introductions were cited a year ago and require recombination, so they are NOT going to talk about mechanisms.

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

thanks ironorehopper.
I somehow missed that ... will read again

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

> for which whole genome sequencing is necessary.

only one H1N1 genome available from 2007/8 but hundredths from 2006/7

they used thousands of sequences, but apparantly keep them secret at the password
protected ECDC database.

> Several independent introductions into European countries of a sensitive and a resistant
> strain might explain the low R2 values.

you see it in the sequences. They examined them.
You won't examine R2 (whatever that is) to detect for independent introductions.

> suggest that resistance results in large part from the spread of a single variant
> However, identification of other resistant variants in the United Kingdom, some of which are
> more closely related to OSVs than to most ORVs (e.g., A/England/654/2007) indicates the
> independent parallel emergence of multiple resistant variants

I hadn't found that (overlooked it at first reading)

did they emerge in the UK or were the OSV and ORV introduced simultaneously ?

> This is emphasized by small distinct clusters of closely related ORVs in Japan that
> are related to European OSVs, whereas only a few of the Japanese ORVs belonged
> to the large European ORVs cluster (31).

timing would be critical. Which emerged first ?


...


---------edit------------
> Our observations suggest that the new genetic background of influenza viruses A (H1N1) that
> appeared in 2007 enabled the virus to develop oseltamivir resistance independently at several
> locations in the world.

page 10, bottom

--------edit---------
R2 is R^2 in the .pdf

-------edit----------
> estimating whether a global focal point exists from which ORVs(=275Y-viruses)
> emerged to spread to the rest of the world is not possible,

apparantly not possible to those authors, but others are doing it.
Keeping sequences secret can probably only delay this process

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

> for which whole genome sequencing is necessary.


> However, identification of other resistant variants in the United Kingdom, some of which are
> more closely related to OSVs than to most ORVs (e.g., A/England/654/2007) indicates the
> independent parallel emergence of multiple resistant variants

I hadn't found that (overlooked it at first reading)

You also overlooked it a year ago. The multiple introductions are in the OBVIOUS category and could been seen in multiple phylogenetic trees that were public, yet you continue cite this obvious fact as something to be determined.

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

apparantly not just me - see the paper.

> estimating whether a global focal point exists from which ORVs(=275Y-viruses)
> emerged to spread to the rest of the world is not possible,


those (rare) earlier sequences with H275Y were other strains.

>90% of current 275Y H1N1 are closely related, with MRCAD in 2007

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

> However, identification of other resistant variants in the
> United Kingdom, some of which are more closely related to
> OSVs than to most ORVs (e.g., A/England/654/2007)
> indicates the independent parallel emergence of multiple
> resistant variants.

no resistant viruses similar to A/England/654/2007
found at genbank.
I count 12 viruses from that group, none resistant,
some are missing NA


----------edit---------
viruses from that group with HA and NA available:

A/Latvia/1-938/2008-01-23
A/New Mexico/01/2008-01-03
A/Alaska/02/2008-01-16
A/Alaska/11/2007-12-03
A/England/545/2007-07-28

[I have doubts that this last date is correct]

-------edit------------

differences in HA+NA
1) A/England/654/2007-12-31
2) A/England/545/2007-07-28
3) A/Brisbane/59/2007-07-01
4) A/Beijing/262/1995

    1   2   3   4
------------------
1: 000 003 021 148
2: 003 000 020 145
3: 021 020 000 139
4: 148 145 139 000

MRCAD of England and Brisbane in mid 2006

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

>

> suggest that resistance results in large part from the spread of a single variant
> However, identification of other resistant variants in the United Kingdom, some of which are
> more closely related to OSVs than to most ORVs (e.g., A/England/654/2007) indicates the
> independent parallel emergence of multiple resistant variants

I hadn't found that (overlooked it at first reading)

-------edit----------
> estimating whether a global focal point exists from which ORVs(=275Y-viruses)
> emerged to spread to the rest of the world is not possible,

apparantly not possible to those authors, but others are doing it.
Keeping sequences secret can probably only delay this process

I think another quick review is in order because of the nonsense that continues to be posted.

Over a year ago, it was clear that H274Y in H1N1 was NOT due to selection of the change from patients being treated with Tamiflu. Norway was reporting levels of 68%, where use of Tamiflu is low, while Japan was reporting rates of 3%, where usage is high. Moreover, Tamiflu usage was investigated in specific cases and virtually none had taken Tamiflu. Moreover, Tamiflu resistance can lead to changes in multiple serotypes (H1N1, H3N2, influenza B) and at multiple positions in each serotype. yet the Tamiflu resistance level in H3N2 or influenza B was at 0%, while the Tamiflu resistance level was above of near 50% in H1N1 in multiple countries (all all resistance was due to one specific change, H274Y.

Thus, a YEAR ago it was clear that the high levels were not linked to recent Tamiflu usage, yet some wanted to discuss the increase and ignore all of the above.

Similarly, a YEAR AGO, it was clear that the H274Y levels involved multiple introductions. Although much of the resistance was linked to the expansion of a single introduction, numerous examples of new introductions could be seen in straight forward phylogenetic analysis, which is used worldwide by those who are conducting serious investigations. Phylogenetic analysis shows which isolates come from which isolates, much like a family tree. These relationships are based on shared polymorphisms and can been done with software that is widely available at no cost.

Since influenza is constantly evolving, new branches are frequently formed. If the isolates on a new branch have H274Y because of an earlier common introduction, all isolates on the new branch will have the change (other than RARE reversions). If however, a new branch is formed by isolates that do not have the change, and then some members of the branch do acquire the change, them the change is due to a new INDEPENDENT introduction. Such new independent introductions have been demonstrated MANY times in isolates collected a YEAR AGO, yet that data is also ignored so a fantasy discussion can be started, which is more annoying now than it was a year ago, because all of the above has been repeated MANY times (and again ignored).

The MULTIPLE INDEPENDENT introductions can be seen in HA or NA figures at

http://precedings.nature.com/documents/2832/version/1

All of the sequences are public and the number of diverse PUBLIC H1N1 sequences from last season (as well as this season) is without precedent (but whining continues about hidden sequences).

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

----------edit---------
viruses from that group with HA and NA available:

A/Latvia/1-938/2008-01-23
A/New Mexico/01/2008-01-03
A/Alaska/02/2008-01-16
A/Alaska/11/2007-12-03
A/England/545/2007-07-28

[I have doubts that this last date is correct]

On what are you doubts based??????

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

apparantly not just me - see the paper.

> estimating whether a global focal point exists from which ORVs(=275Y-viruses)
> emerged to spread to the rest of the world is not possible,


those (rare) earlier sequences with H275Y were other strains.

>90% of current 275Y H1N1 are closely related, with MRCAD in 2007

Please, stop. There are MANY examples of clade 2B (Brisbane/59) with H274Y that have acquired H274Y independently and these sequences have been public for months or in some cases for WELL over a year.

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

> However, identification of other resistant variants in the
> United Kingdom, some of which are more closely related to
> OSVs than to most ORVs (e.g., A/England/654/2007)
> indicates the independent parallel emergence of multiple
> resistant variants.

no resistant viruses similar to A/England/654/2007
found at genbank.
I count 12 viruses from that group, none resistant,
some are missing NA

654 IS resistant. It HAS H274Y (its NA sequences is PUBLIC). Yet it is NOT closely related to the resistant Brisbane/59 isolates. It is related to the SENSITIVE isolates. Therefore it is an INDEPENDENT INTRODUCTION!

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

how many is MANY ? did they spread ?

the current group (>95%) of resistant H1N1 goes back to a
common ancestor in mid 2007

there had been some resistance in prior years, but small.
See e.g. the first chapter under "discussion" with reference to [8],[9]

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

so, resistance increased from 0% to 56% in Europe during the
season.
Why ?
the resistant strains didn't grow better in the laboratory.

This could be due to drug use in the superspreaders,
like doctors,airplane,train personal, traveling salesmen

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

so, resistance increased from 0% to 56% in Europe during the
season.
Why ?
the resistant strains didn't grow better in the laboratory.

This could be due to drug use in the superspreaders,
like doctors,airplane,train personal, traveling salesmen

Nonsense.

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

so, resistance increased from 0% to 56% in Europe during the
season.
Why ?
the resistant strains didn't grow better in the laboratory.

This could be due to drug use in the superspreaders,
like doctors,airplane,train personal, traveling salesmen

H274Y did spread in the lab. They hitch hiked on a sub-clade that became dominant.

In 2007/2008 most (probably more than 90% were from the expansion of the same sub-clade). The other 10% represented MULTIPLE INDEPENDENT introductions.

Traveling did NOT explode in the 2007/2008, while H274Y did. How about martians?

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

so, resistance increased from 0% to 56% in Europe during the
season.
Why ?
the resistant strains didn't grow better in the laboratory.

This could be due to drug use in the superspreaders,
like doctors,airplane,train personal, traveling salesmen

This season H274Y is at 100% in H1N1 (and all have A193T).

You are posting utter nonsense which is NOT reality based.

I think you should start a fantasy thread to discuss the above possibilities.

 

[gsgs]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

I missed the NA of A/England/645 .
Apparantly it was not available on my last download on 11.Feb.2009


8 H1N1-genomes available now from this season

pairwise differences in in the 8 segments:
(~36 differences emerge per year in average in human H3N2)

                                               1   2   3   4   5   6   7   8   9  10  11  12   PB2 PB1  PA  HA  NP  NA   M  NS
----------------------------------------------------------------------------------------------------------------------------------------
  1 >A/England/654/2007(H1N1)12/31             0  18  20  59  68  66  75  70 277 273 270 416   100  91  98 164  82 125  46  82   102#  134   13141   5667      1:>A/England/654/2007(H1N1)12/31          
  2 >A/Washington/AF06/2007(H1N1)2008/01/10   18   0  16  56  66  64  72  67 279 269 272 418    97  80 102 160  76 131  46  93   100#  133   13210   5664      2:>A/Washington/AF06/2007(H1N1)01/10      
  3 >A/England/545/2007(H1N1)07/28            20  16   0  51  62  60  67  60 268 268 265 411    97  79  95 159  71 126  46  92    98#  129   13141   5665      3:>A/England/545/2007(H1N1)07/28          
  4 >A/Japan/AF07/2008(H1N1)01/25             59  56  51   0  59  57  65  62 278 267 268 413   103  91  92 153  78 138  71  80   103#  136   13209   5676      4:>A/Japan/AF07/2008(H1N1)01/25           
  5 >A/England/26/2008(H1N1)01/09             68  66  62  59   0  16  48  51 271 273 270 418   102  95  99 153  73 128  46  84   101#  133   13141   5661      5:>A/England/26/2008(H1N1)01/09           
  6 >A/England/557/2007(H1N1)11/15            66  64  60  57  16   0  46  49 269 271 268 416   112  96  88 148  73 128  46  74   100#  131   13141   5661      6:>A/England/557/2007(H1N1)11/15          
  7 >A/Kentucky/UR07-0061/2008(H1N1)02/20     75  72  67  65  48  46   0  51 276 276 275 425   107  81 105 164  84 131  63  92   105#  139   13212   5671      7:>A/Kentucky/UR07-0061/2008(H1N1)02/20   
  8 >A/Florida/UR07-0022/2008(H1N1)02/14      70  67  60  62  51  49  51   0 272 268 269 416   102  84  93 156  86 133  63  94   103#  136   13225   5677      8:>A/Florida/UR07-0022/2008(H1N1)02/14    
  9 >A/Kentucky/UR06-0061/2007(H1N1)01/22    277 279 268 278 271 269 276 272   0 223 225 374   216 130 202 330 111 242  89 122   189#  251   13241   5693      9:>A/Kentucky/UR06-0061/2007(H1N1)01/22   
 10 >A/New Caledonia/20/1999(H1N1)// In      273 269 268 267 273 271 276 268 223   0   3 193   165 154 138 251 136 181 122 140   163#  215   13141   5649     10:>A/New Caledonia/20/1999(H1N1)// In     
 11 >A/New Caledonia/20/1999(H1N1)// In      270 272 265 268 270 268 275 269 225   3   0 193   161 154 142 252 135 181 104 140   162#  214   13228   5653     11:>A/New Caledonia/20/1999(H1N1)// In     
 12 >A/Beijing/262/1995(H1N1)// In           416 418 411 413 418 416 425 416 374 193 193   0   230 218 221 410 241 340 134 258   257#  341   13222   5628     12:>A/Beijing/262/1995(H1N1)// In          
---------------------------------------------------------------------------------------------------------------------------------------------------
                                               1   2   3   4   5   6   7   8   9  10  11  12   132 112 122 208 103 165  73 112

------edit--------
A/England/545 seems to be earlier than the other 2007/8 genomes although Sept. would match
better than July, but well that's withing the tolerance.
Flu in England in July or travelor from the tropes or Southern hemisphere ?
It's clearly a different introduction, but only one sample of 6 is resistant(654),
so probably developed and not introduced. No indication yet that this mutation
did spread or did occur independently more often.
------edit-----------
> other resistant variants in the UK
not clear what they mean here. Other resistant viruses similar to A/England/654/2007 ?

 

[HenryN]

Re: Emerg Infect Dis. Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007?08 Season.

I missed the NA of A/England/645 .
Apparantly it was not available on my last download on 11.Feb.2009


8 H1N1-genomes available now from this season

pairwise differences in in the 8 segments:
(~36 differences emerge per year in average in human H3N2)

                                               1   2   3   4   5   6   7   8   9  10  11  12   PB2 PB1  PA  HA  NP  NA   M  NS
----------------------------------------------------------------------------------------------------------------------------------------
  1 >A/England/654/2007(H1N1)12/31             0  18  20  59  68  66  75  70 277 273 270 416   100  91  98 164  82 125  46  82   102#  134   13141   5667      1:>A/England/654/2007(H1N1)12/31          
  2 >A/Washington/AF06/2007(H1N1)2008/01/10   18   0  16  56  66  64  72  67 279 269 272 418    97  80 102 160  76 131  46  93   100#  133   13210   5664      2:>A/Washington/AF06/2007(H1N1)01/10      
  3 >A/England/545/2007(H1N1)07/28            20  16   0  51  62  60  67  60 268 268 265 411    97  79  95 159  71 126  46  92    98#  129   13141   5665      3:>A/England/545/2007(H1N1)07/28          
  4 >A/Japan/AF07/2008(H1N1)01/25             59  56  51   0  59  57  65  62 278 267 268 413   103  91  92 153  78 138  71  80   103#  136   13209   5676      4:>A/Japan/AF07/2008(H1N1)01/25           
  5 >A/England/26/2008(H1N1)01/09             68  66  62  59   0  16  48  51 271 273 270 418   102  95  99 153  73 128  46  84   101#  133   13141   5661      5:>A/England/26/2008(H1N1)01/09           
  6 >A/England/557/2007(H1N1)11/15            66  64  60  57  16   0  46  49 269 271 268 416   112  96  88 148  73 128  46  74   100#  131   13141   5661      6:>A/England/557/2007(H1N1)11/15          
  7 >A/Kentucky/UR07-0061/2008(H1N1)02/20     75  72  67  65  48  46   0  51 276 276 275 425   107  81 105 164  84 131  63  92   105#  139   13212   5671      7:>A/Kentucky/UR07-0061/2008(H1N1)02/20   
  8 >A/Florida/UR07-0022/2008(H1N1)02/14      70  67  60  62  51  49  51   0 272 268 269 416   102  84  93 156  86 133  63  94   103#  136   13225   5677      8:>A/Florida/UR07-0022/2008(H1N1)02/14    
  9 >A/Kentucky/UR06-0061/2007(H1N1)01/22    277 279 268 278 271 269 276 272   0 223 225 374   216 130 202 330 111 242  89 122   189#  251   13241   5693      9:>A/Kentucky/UR06-0061/2007(H1N1)01/22   
 10 >A/New Caledonia/20/1999(H1N1)// In      273 269 268 267 273 271 276 268 223   0   3 193   165 154 138 251 136 181 122 140   163#  215   13141   5649     10:>A/New Caledonia/20/1999(H1N1)// In     
 11 >A/New Caledonia/20/1999(H1N1)// In      270 272 265 268 270 268 275 269 225   3   0 193   161 154 142 252 135 181 104 140   162#  214   13228   5653     11:>A/New Caledonia/20/1999(H1N1)// In     
 12 >A/Beijing/262/1995(H1N1)// In           416 418 411 413 418 416 425 416 374 193 193   0   230 218 221 410 241 340 134 258   257#  341   13222   5628     12:>A/Beijing/262/1995(H1N1)// In          
---------------------------------------------------------------------------------------------------------------------------------------------------
                                               1   2   3   4   5   6   7   8   9  10  11  12   132 112 122 208 103 165  73 112

------edit--------
A/England/545 seems to be earlier than the other 2007/8 genomes although Sept. would match
better than July, but well that's withing the tolerance.
Flu in England in July or travelor from the tropes or Southern hemisphere ?
It's clearly a different introduction, but only one sample of 6 is resistant(654),
so probably developed and not introduced. No indication yet that this mutation
did spread or did occur independently more often.

Please. There are MANY examples of independent introductions. The report on this thread just used one example that is OBVIOUS.

Your speculation on troops, salesmen, or other hocus pocus has no basis. The resistance was specific to H1N1 and to H274Y in H1N1, which is in no way connected to your wild speculation (which is WELL beyond hand waving). Similarly, your speculation is not linked to levels rising from less than 1% in 2006/2007, to 50% in some countries in 2007/2008, to 100% in most countries in 2008/2009.