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Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

AlaskaDenise said:
That answers a long standing question - that WSN is lab created and only W-S is natural. Thanks.

Very scarey genes there.

.
Click to expand...
No. WSN/33 was SELECTED. Viral isolates are MIXTURES and components can be selected through appropriate selection measures.

Prior to Qinghai Lake, all H5N1 with PB2 E627K were from isolates that passaged through mammals (like mouse brain - same as WSN/33 or humans in Hong Kong and Vietnam).
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
More NA matches

gb|GQ369275.1| Influenza A virus (A/Stockholm/37/2009(H1N1)) ... 2224 0.0
gb|GQ365448.1| Influenza A virus (A/Sapporo/1/2009(H1N1)) seg... 2224 0.0
gb|GQ355297.1| Influenza A virus (A/Catalonia/387/2009(H1N1))... 2224 0.0
gb|GQ160533.1| Influenza A virus (A/New Jersey/01/2009(H1N1))... 2224 0.0
Click to expand...
It is worth noting that in addition to the patient in Hong Kong, the sequences in Sweden and Japan were from patients who had traveled from the US in June, yet the only matching sequence from the United States was from a Bergen county woman infected in April in New Jersey.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Likely description of Sapporo/1

Thursday, June 11, 2009
Comprehensive Measures Division Department of Health and Welfare Health Center of Infectious Diseases, Sapporo, Japan
Contact:觜three fine Sea Phone :622 -5199
Avian flu in Sapporo (influenza A/H1N1)
The incidence of patients (II)
2009 Thursday, June 11 for the simulated patient on the afternoon of avian flu
And, provided it has been confirmed as avian flu patients.
And item description
Teens age 20 years (men)
Runny nose symptoms, cough, chills, fever (37.3 degrees)
Travel Awards
Thursday, June 4 from Monday, June 8 United States (Hawaii)
Stay in Tuesday, June 9 return.
Designated medical institutions for infectious diseases
Hospitalized
Thursday, June 11 Officials at the time, the infection ward of Sapporo Municipal Hospital
Hospitalization.
The patient's condition is stable.
Route of infection is estimated to be U.S. (Hawaii) estimated that in the infected site.
Availability of tests
Thursday, June 11 morning, the health center physician, rapid diagnostic kits
The tests confirmed that influenza A-positive, doubtful
Similar patient and determined.
Samples (nasal swab) and sent to the Institute of Public Health, Sapporo, PCR
We conducted the tests, Thursday, June 11 after six o'clock in the afternoon, the new
Was found positive for influenza.
How to detect
Thursday, June 11 around 9:15 minutes, from the person to health centers, "with
From a friend I went to Hawaii, from the accompany of avian flu
Contact with the patient occurred. "There was a consultation.
Summary details of the action is as attached.
Notes
As dense contacts, and patients who live with the name of an oral prevention drug

http://www.city.sapporo.jp/city/influ/pdf/210611hassei.pdf
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Summary of action

<NOBR>日　時</NOBR>​
<NOBR>Date</NOBR>

<NOBR>行動概要・症状等</NOBR>​
<NOBR>Overview of symptoms and behavioral</NOBR>

<NOBR>６月４日</NOBR>​
<NOBR>June 4</NOBR>

<NOBR>ハワイへ出国</NOBR>​
<NOBR>Left for Hawaii</NOBR>

<NOBR>６月８日</NOBR>​
<NOBR>June 8</NOBR>

<NOBR>倦怠感</NOBR>​
<NOBR>Fatigue</NOBR>

<NOBR>６月９日</NOBR>​
<NOBR>June 9</NOBR>

<NOBR>１５時３０分</NOBR>​
15:30

<NOBR>１９時３０分</NOBR>​
19:30

<NOBR>２１時０５分</NOBR>​
21:05

<NOBR>ハワイから帰国　成田国際空港到着　ＪＯ　０７３便</NOBR>​
<NOBR>Narita International Airport and arrived back from Hawaii flights</NOBR> JO 073

<NOBR>空港内飲食店で食事</NOBR>​
<NOBR>Meal at a restaurant in the airport</NOBR>

<NOBR>バスを利用し、羽田空港に到着</NOBR>​
<NOBR>The bus arrived at Haneda Airport</NOBR>

<NOBR>新千歳空港到着　ＪＡＬ５４５便</NOBR>​
<NOBR>New Chitose Airport Flight Arrival JAL545</NOBR>

<NOBR>ＪＲを利用し、札幌駅到着</NOBR>​
<NOBR>JR uses the arrival of Sapporo Station</NOBR>

<NOBR>札幌駅から徒歩で自宅まで帰宅</NOBR>​
<NOBR>Walk from home to</NOBR> home <NOBR>in Sapporo</NOBR>

<NOBR>６月１０日</NOBR>​
<NOBR>June 10</NOBR>

<NOBR>外出なし</NOBR>​
<NOBR>No go</NOBR>

<NOBR>咳症状出現</NOBR>​
<NOBR>Symptomatic cough</NOBR>

<NOBR>６月１１日</NOBR>​
<NOBR>June 11</NOBR>

<NOBR>９時１５分頃</NOBR>​
<NOBR>Around</NOBR> 9:15 <NOBR>minutes</NOBR>

<NOBR>１０時２０分頃</NOBR>​
<NOBR>Around</NOBR> 10:20 <NOBR>minutes</NOBR>

<NOBR>１２時３０分</NOBR>​
12:30

<NOBR>本人から保健所に相談あり</NOBR>​
<NOBR>In his talk to a health center from</NOBR>

<NOBR>発熱（３７．３度）</NOBR>​
<NOBR>Fever (37.3 degrees)</NOBR>

<NOBR>迅速診断キットによる検査を実施（Ａ型陽性）</NOBR>​
<NOBR>Rapid diagnostic test kits</NOBR> conducted <NOBR>by (A-positive)</NOBR>

<NOBR>市立札幌病院に入院</NOBR>​
<NOBR>Sapporo Municipal Hospital</NOBR>

<NOBR>別紙</NOBR>​
<NOBR>Attachment</NOBR>
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

<a rel="nofollow" href="http://www.recombinomics.com/News/07110901/H274Y_Fit_Failure.html">Commentary</a>
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

I'm not sure I follow the Jersey Girl argument and the lack of monitoring. While agree that we are likely find more examples of Tamiflu resistant Swine Flu, the following sequences seem to be closely related to Jersey Girl:

New York/1682
New York/3183
New York/3099
New York/3100
Delaware/04
Delaware/05
Delaware/06
Delaware/07
Delaware/08
Maryland/05
District of Columbia/02
New Hampshire/02

If that is the case, then monitoring seems to be going reasonably well. Clearly a couple of hundred more labs would be nice, but the ones we have are serving us as best they can.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Mamabird said:
I'm not sure I follow the Jersey Girl argument and the lack of monitoring. While agree that we are likely find more examples of Tamiflu resistant Swine Flu, the following sequences seem to be closely related to Jersey Girl:

New York/1682
New York/3183
New York/3099
New York/3100
Delaware/04
Delaware/05
Delaware/06
Delaware/07
Delaware/08
Maryland/05
District of Columbia/02
New Hampshire/02

If that is the case, then monitoring seems to be going reasonably well. Clearly a couple of hundred more labs would be nice, but the ones we have are serving us as best they can.
Click to expand...
Close, but no cigar. The point is exact matches (at the nucleotide level) are being found in Hong Kong, Japan, Spain, and Sweden, and the detection is in patients flying out of the US, yet the only US match is from April.

Thus, this sequence serves as a marker of efforts to find this precursor, with or without H274Y, yet the only sites detecting it are outside the US, but are detecting it in travelers FROM the US. Thus, the identical sequences are widespread in the US and have been since April, but the number of matches by labs in the US since April remains at ZERO.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
Close, but no cigar. The point is exact matches (at the nucleotide level) are being found in Hong Kong, Japan, Spain, and Sweden, and the detection is in patients flying out of the US, yet the only US match is from April.

Thus, this sequence serves as a marker of efforts to find this precursor, with or without H274Y, yet the only sites detecting it are outside the US, but are detecting it in travelers FROM the US. Thus, the identical sequences are widespread in the US and have been since April, but the number of matches by labs in the US since April remains at ZERO.
Click to expand...

Well, my sense is that we will soon find additional patients will Tamiflu resistant viruses, but that they will not necessarily exactly match those that you have sited. Wisely, the CDC and California have stepped up surveillance in the area of the last detection, so their concern (and yours) is being actively investigated.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Mamabird said:
Well, my sense is that we will soon find additional patients will Tamiflu resistant viruses, but that they will not necessarily exactly match those that you have sited. Wisely, the CDC and California have stepped up surveillance in the area of the last detection, so their concern (and yours) is being actively investigated.
Click to expand...
I agree that more will be found. I expect it to evolve as happened with H274Y in seasonal H1N1. The evolution and spread could be monitored via phylogenetic analysis, and sub-clades were defined by various branches on the tree. Not all branches were formed by non-synonymous changes, and the synonymous changes made it easy to follow the evolution.

The branch with the Hong Kong isolate has the New Jersey sequence from April, as well as the recent isolates from Japan, Sweden, and Spain, but no other isolates from the US, signaling a need to pick up surveillance because even if the isolates are Tamiflu sensitive, there should be matches in San Francisco, Hawaii, and where ever the toddler in Sweden originated. If all of these other countries can find precursors (in travelers from the US), but the US can't, then there is a significant US surveillance shortfall (and if the precursor, which is widespread, is being missed, then Tamiflu resistant versions will also be missed).
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
<a rel="nofollow" href="http://www.recombinomics.com/News/07110901/H274Y_Fit_Failure.html">Commentary</a>
Click to expand...
Commentary

Tamiflu Resistant Pandemic H1N1 Surveillance Failures in US

Recombinomics Commentary 14:41
July 11, 2009

The recent <a rel="nofollow" href="http://www.recombinomics.com/News/07030901/H274Y_HK_SF.html">report</a> of osletamivir resistant pandemic H1N1 in Hong Kong in a traveler (16F) from San Francisco, A/Hong Kong 2369/2009 raised concerns because the traveler had not take osletamivir and her case was mild. She recovered without any antiviral treatment, but the presence of H274Y raised concerns that resistant virus was silently circulating because most mild cases in the United States were no longer tested or reported.

The publication of the sequence increased concerns, because the NA sequence, except for H274Y, exactly matched the sequence from the first case in New Jersey, A/New Jersey/1/2009, a Bergen county women (22F) infected in April. Since the Hong Kong case was in June, the identity between the two sequences indicated that the virus had spread across the United States undetected between April and June, and was only detected when it was exported to Hong Kong, through routine osletamivir resistant testing of pandemic isolates.

The sequence in Hong Kong <a rel="nofollow" href="http://www.recombinomics.com/News/07100901/H274Y_Fit.html">matched</a> a sequence from Japan, A/Sapporo/1/2009, which was published in Genbank a few days later. Like New Jersey, the Japan sequence did not have H274Y, but it also was detected in a traveler (20M) from the United States (Hawaii), increasing concerns that this sequence was transmitting in the United States undetected.

The next day, two more sequences were released. One was a partial NA sequence from Catalonia, Spain (A/Catalonia/387/2009), which also exactly matched the sequence from New Jersey and Japan, while the other was from Vastra Gotalands , Sweden (A/Stockholm/37/2009), which also matched the above sequences, but had one additional change. The isolate from Sweden was also from a traveler (2M) from the United States. Both isolates were also from patients infected in June, so the Tamiflu flu resistant sequence, or precursor, was detected in Hong Kong, China, Sapporo, Japan, Catalonia, Spain, and Vastra Gotalands, Sweden in the month of June, and at least three of the four isolates were from patients traveling from the United States. However, the only match in isolates from the United States was in a New Jersey patient infected in April.

The export of infections from a country not reporting corresponding infections signals a poor surveillance system. Although the number of sequences from the United States is the highest in the world, the failure to identify the oseltamivir resistant precursor sequences matching those found worldwide in travelers from United States is cause for concern.

After the resistant isolate was announced, assurances were given, citing on the lack of detection of resistance in the United States. This failure however may be due an emphasis on severe cases and lack of testing of mild cases. Moreover, even if precursor sequences are detected, a low abundance version would not be identified in a consensus sequence.

In any event, the failure to identify the precursor since April, when the sequence is detected worldwide in June travelers from the United States, raises serious concerns about surveillance programs which focus efforts on severe cases and largely ignore milder cases.

.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Are the viruses from the more severe or fatal cases in the US (and elsewhere) being sequenced? From what I've seen in the news, it appears that few are being sequenced. Have any of the viruses responsible for the fatalities in Argentina been sequenced?
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Zac said:
Are the viruses from the more severe or fatal cases in the US (and elsewhere) being sequenced? From what I've seen in the news, it appears that few are being sequenced. Have any of the viruses responsible for the fatalities in Argentina been sequenced?
Click to expand...
There are no recent public sequences from Argentina.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Note from HK SAR:

A resistant strain?

(...)
[On the Filipino patient in critical conditions]

Secretary for Food and Health:
I do not have the detailed information regarding this particular patient, but I think she is still in a critical condition in the intensive care unit of the United Christian Hospital. Whether Hong Kong has a fatal case or not will not affect our emergency measures at the moment. Of course, we will investigate the nature of the virus. We are doing genetic sequencing to see whether there is any significant change of the virus.
(...)

From: http://www.info.gov.hk/gia/general/200907/13/P200907130139.htm
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

ironorehopper said:
Note from HK SAR:

A resistant strain?

(...)
[On the Filipino patient in critical conditions]

Secretary for Food and Health:
I do not have the detailed information regarding this particular patient, but I think she is still in a critical condition in the intensive care unit of the United Christian Hospital. Whether Hong Kong has a fatal case or not will not affect our emergency measures at the moment. Of course, we will investigate the nature of the virus. We are doing genetic sequencing to see whether there is any significant change of the virus.
(...)

From: http://www.info.gov.hk/gia/general/200907/13/P200907130139.htm
Click to expand...
Yes, they switched from Tamiflu to Relenza and by now that should have a sequence (at least in the region encompassing H274Y).
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
More NA matches

gb|GQ369275.1| Influenza A virus (A/Stockholm/37/2009(H1N1)) ... 2224 0.0
gb|GQ365448.1| Influenza A virus (A/Sapporo/1/2009(H1N1)) seg... 2224 0.0
gb|GQ355297.1| Influenza A virus (A/Catalonia/387/2009(H1N1))... 2224 0.0
gb|GQ160533.1| Influenza A virus (A/New Jersey/01/2009(H1N1))... 2224 0.0
Click to expand...
gb|GQ379856.1| Influenza A virus (A/Catalonia/517/2009(H1N1))... 32.2 11
gb|GQ379852.1| Influenza A virus (A/Catalonia/502/2009(H1N1))... 32.2 11
gb|GQ379840.1| Influenza A virus (A/Catalonia/476/2009(H1N1))... 32.2 11
gb|GQ379833.1| Influenza A virus (A/Catalonia/442/2009(H1N1))... 32.2 11
gb|GQ369275.1| Influenza A virus (A/Stockholm/37/2009(H1N1)) ... 32.2 11
gb|GQ365448.1| Influenza A virus (A/Sapporo/1/2009(H1N1)) seg... 32.2 11
gb|GQ355297.1| Influenza A virus (A/Catalonia/387/2009(H1N1))... 32.2 11
gb|GQ351316.1| Influenza A virus (A/Hong Kong/2369/2009(H1N1)... 32.2 11
gb|GQ338380.1| Influenza A virus (A/Oklahoma/03/2009(H1N1)) s... 32.2 11
gb|GQ160533.1| Influenza A virus (A/New Jersey/01/2009(H1N1))... 32.2 11
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

The Tamiflu resistant precursor is spreading in Spain. The most recent additions were collected this month (July 3), yet the number of recent sequences (since April) in the US remains at ZERO.
HA sequence hasn't been released, but it likely has D225E.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

niman said:
The Tamiflu resistant precursor is spreading in Spain. The most recent additions were collected this month (July 3), yet the number of recent sequences (since April) in the US remains at ZERO.
HA sequence hasn't been released, but it likely has D225E.
Click to expand...

Agreed, and S206T as well.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Another possible case of oseltamivir-resistant pandemic H1N1 2009 virus infection in Belgium: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19270

(...)
No complications have been detected so far.

One confirmed case, already under treatment with oseltamivir, was hospitalised because influenza symptoms persisted and the patient had asthma as underlying condition.

Respiratory samples from this patient are currently being cultured and tested for resistance against oseltamivir.

One pregnant woman was confirmed to be infected with influenza A(H1N1)v.

Information on underlying factors for the other 41 patients was not available.
(...)
-
------
 
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