Denmark - Dane with novel H1N1 found resistant to Tamiflu

[theforeigner]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

The danish Tamiflu resistent patient was a woman:


Black highlight, my translation:

We have sent messages out to all laboratories in the world, because they should be aware that it can change. And we have also sent the news to all news media in Denmark because we dont want to be blamed that we hide anything. We want to provide transparacy, said MD Steffen Glisman from Statens Serum Institut to politiken.dk

The woman has recovered long time ago, ensure Steffen Glismann.

http://politiken.dk/indland/article742866.ece

Kamp mod svineinfluenza 29. jun 2009 kl. 16:41

Dansker skriver svineinfluenza-historie

Medicinen Tamiflu har vist sig ikke at have nogen virkning p? en dansk kvinde. Hele verden er advaret.

N?rmest alle lande i hele verden har opk?bt lagre af medicinen Tamiflu for at sikre sig mod en epidemi af fugle- eller svineinfluenza.

Nu har en dansk kvinde, vist sig ikke at v?re modtagelig over for Tamiflu.

?Vi har sendt meddelelsen ud til samtlige laboratorier i hele verden, fordi de skal v?re opm?rksomme p?, at det kan ?ndre sig. Og s? har vi sendt nyheden ud til de danske medier, for vi ikke skulle blive beskyldt for at skjule noget. Vi ?nsker at skabe gennemsigtighed?, siger overl?ge Steffen Glismann fra Statens Serum Institut til politiken.dk.
Kvinden er blevet rask
Kvinden er for l?ngst blevet rask, beroliger Steffen Glismann.

?Det er undtagelsen, der bekr?fter reglen. M?ske er det en tilf?ldighed, at det f?rste tilf?lde lige er i Danmark, eller ogs? er det fordi, vi har en meget aktiv opsporing?, p?peger Steffen Glismann.

Der er ingen ?ndringer i Statens Serum Instituts anbefalinger.

Verdenssundhedsorganisationen WHO opfordrer p? baggrund af det danske tilf?lde til en ?get opm?rksomhed p? muligheden for udvikling af resistens hos det pandemiske influenzavirus A H1N1v - det som vi i folkemunde kalder svineinfluenza.

[Gert van der Hoek]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

thank you foreigner!

full google translation of the report, handle with care as always:


Dane writes swine flu story

Medicine Tamiflu has been shown to have no effect on a Danish woman. The whole world is warned.

Almost all countries around the world have bought stocks of Tamiflu medicine to guard against an epidemic of avian or swine influenza.

Now, a Danish woman turned out not to be susceptible to Tamiflu.

"We have sent the message to all laboratories in the world, because they must be aware that it can change. And then we sent the news out to the Danish media, so that we would not be accused of hiding something. We want to create transparency, "says senior consultant Steffen Glismann from Statens Serum Institut for politiken.dk.

She has been healthy

She has since long been cured, reassures Steffen Glismann.

"It is the exception to the rule. Perhaps it is a coincidence that the first case just in Denmark, or it is because we have a very active tracing, notes Steffen Glismann.

There are no changes in the Statens Serum Institute recommendations.

World Health Organization (WHO) calls out of the Danish case for increased attention to the possibility of development of resistance in the pandemic influenza A H1N1v - that which we call the people lead pig influenza.

http://politiken.dk/indland/article742866.ece

[HenryN]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

UNE 29, 2009, 11:31 A.M. ET

The Danish patient, who has since recovered, was taking the drug as a prevention to avoid the contraction of swine flu, Reddy said. He was probably already infected with the virus, and resistance to the drug emerged because he was given the lower prevention dose.


http://online.wsj.com/article/BT-CO-...29-709515.html

Spinning so hard that he even got the gender of the patient wrong.

Hopes and dreams (as in PURE fanatsy).

[the doctor]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

I thought the first instance of Tamiflu resistance found in the novel H1N1 strain was reported from Shanghai on 10Jun2009. This specimen was recovered from someone who had been traveling in the US before becoming ill upon their return to China.

Is this correct?

GW

[Mamabird]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

I thought the first instance of Tamiflu resistance found in the novel H1N1 strain was reported from Shanghai on 10Jun2009. This specimen was recovered from someone who had been traveling in the US before becoming ill upon their return to China.

Is this correct?

GW

No, the Shanghai isolate was the E627K mutation of the PB2 gene segment. Tamiflu resistance relates strictly to the NA segment.

[St Michael]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Spinning so hard that he even got the gender of the patient wrong.

Hopes and dreams (as in PURE fanatsy).

Dutchy posted this on another thread:

Another Dane, affected by H1N1

Published 05.06.09

A stay in Argentina has probably resulted in influenza H1N1 on a Danish traveler. The person has ordinary flu symptoms and is in solitary confinement, according to Health.

Board assesses still not that people generally have reason for concern. Outside of Mexico, the disease has so far proven to be generally milder course compared with conventional winter flu. And it is not surprising that there will be found another instance, says Head prevention Else Smith.

- We have known about the new virus for many weeks and seen it spread to, and in many countries. So it is expected that there will be more cases in Denmark. It is very difficult to avoid infection brought from the outside world and to do so. The new cases therefore do not alter our preparedness, "says Else Smith.

The infection has come to Denmark with Air France AF 2350 from Paris, which landed in Kastrup, 2 June kl. 14.45. Passengers who have sat at number 13-17 on the aircraft, please contact the Health on tel 7022 0268. They will be offered preventive treatment by their own doctor or physician office.

The other passengers do not need to take special precautions. If they have flu symptoms with fever over 38 ?, they should contact their doctor informs Health.
http://translate.google.com/translat...ce&sl=da&tl=en

So what are the chances this resistance originated in the clusters of (more virulent) cases in Argentina?

Any monitoring for Tamiflu resistance going on in the Argentina cases?

[Mamabird]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Dutchy posted this on another thread:



So what are the chances this resistance originated in the clusters of (more virulent) cases in Argentina?

Any monitoring for Tamiflu resistance going on in the Argentina cases?

The monitoring for Tamiflu resistance is going on continuously for all countries that have provided genetic sequences. We have only one isolate from Denmark, and like all the rest of the NA segments available for Swine Flu in GISAID and GenBank, it is Tamiflu sensitive.

Notice to the Southern Hemisphere countries: Please post your sequences.

[HenryN]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

<a rel="nofollow" href="http://www.recombinomics.com/News/06290903/H274Y_Swine_Roche.html">Commentary</a>

[AlaskaDenise]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

<a rel="nofollow" href="http://www.recombinomics.com/News/06290902/Pandemic_H1N1_Resistance.html">Commentary</a>

Commentary

Tamiflu Resistant Pandemic H1N1 in Denmark Raises Concerns

Recombinomics Commentary 16:11
June 29, 2009


The first case in the world of resistance to influenza drug Tamiflu in people with influenza H1N1 has been found in Denmark. The person is now healthy, and there is no further evidence of infection with resistant virus, according to Statens Serum Institut.

We do not expect that the longer exist, says Nils Strandberg Pedersen, Managing Director, Statens Serum Institut, and refers to the mutated form of H1N1. The infected Dane had been in close contact with another infected person, and was therefore prevented treatment with Tamiflu.

Yet the person had flu symptoms and are instead treated with another type of flu drugs, Relenza.

The above translation describes the detection of oseltamivir (Tamiflu) resistance in a patient infected with pandemic H1N1. Although details of this breaking news are sketchy, it sounds like resistance (likely H274Y) develop during prophylactic treatment, much like the first reported case of resistance in H5N1 in Vietnam in 2005.

In Vietnam, the sister of an infected patient was given a prophylactic dose of oseltamivir and developed symptoms. Resistance (H274Y and N294S) was found in isolates from the contact. However, she recovered after the treatment dose was increased, and the resistant H5N1 did not spread.

However H274Y was subsequently found in seasonal H1N1, which was evolutionarily fit and did spread worldwide.

The latest results with pandemic H1N1 do not address fitness if the first patient did not have resistant H1N1, and the ability of a pandemic H1N1 with H274Y or N294S is unclear. However, the description appears to rule out acquisition of resistance via reassortment with seasonal flu with H1N1.

More detail on the above case, as well as the sequence of the resistant H1N1, as well as H1N1 from the contact, would be useful.

.

[AlaskaDenise]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

<a rel="nofollow" href="http://www.recombinomics.com/News/06290903/H274Y_Swine_Roche.html">Commentary</a>

Commentary

Roche Comments on Tamiflu Resistant H1N1 Raise Concerns

Recombinomics Commentary 16:11
June 29, 2009

While receiving the drug, the patient appeared to develop resistance to it," David Reddy, Roche's pandemic taskforce leader, told reporters on a conference call on the Danish case. "This is the first report we have of it in H1N1."

The Danish patient, who has since recovered, was taking the drug as a prevention to avoid the contraction of swine flu, Reddy said. He was probably already infected with the virus, and resistance to the drug emerged because he was given the lower prevention dose

The above comments in media reports following the Roche conference call raise serious doubts about the claim that the osletamivir (Tamiflu) resistance arose in the Danish female patient because of prophylactic treatment. The patient had been exposed to an H1N1 positive contact outside of Denmark and was given a prophylactic dose of Tamiflu as a precaution. She subsequently developed symptoms and recovered when treated with Relenza.

However, there has been no data presented to show that wild type H1N1 infected the Danish patient or the patient who infected the Danish patient. Moreover, the use of the qualifiers "appear" and "probably" suggests that no such data exists.

Patients have been known to develop resistance in response to treatment. In Vietnam, a contact (sister) of a patient developed resistance at two NA positions (H274Y and N294S), which are two changes known to confer resistance and which were not detected in H5N1 from her brother, supporting development of resistance in response to treatment of his sister.

However, in the Danish case, no such evidence was presented. If resistance was present in the contact that infected the Danish case, the result would have been as described, the prophylactic treatment would have had little effect, and the resistant H1N1 would still have been sensitive to Relenza.

Therefore, the report of Tamiflu resistance (which was probably H274Y) raises concerns that resistance will spread via recombination, as happened for H274Y in seasonal flu. Initially, the polymorphism was rare. It was first in clade 2C in China, followed by clade 1 in the US and UK, followed by clade 2B. In each sub-clade the polymorphism appeared on multiple genetic backgrounds in the absence of Tamiflu treatment.

The hitch hiking led to an expansion of H274Y, and when it paired up with HA A193T, the subclade expanded and both acquistions became fixed.

The large reservoir of H274Y in seasonal flu provides donor sequences for H274Y acquisition in swine H1N1. The report of resistance in the Danish patient raises concerns that the resistance can rapidly spread under the section pressure of Tamiflu treatment.

Information on the contact location for the Danish patient, as well as sequence data on samples collected before and after treatment would be useful. However, since some media reports suggest she was on prophylactic Tamiflu for five days prior to symptoms, there probably is no isolate collected prior to treatment. However, H1N1 from her contact would be useful, although the existence of such material is doubtful, based on the qualifiers in the Roche statements, as well as the failure to provide any hard data supporting the contention that the resistance developed in response to treatment in Denmark.

Absent such evidence, the resistance is likely to have developed prior to treatment, and represents an evolutionarily fit H1N1.

Sequence data from the patient will help trace this sub-clade to provide additional evidence on the likelihood that the resistance emerged in Denmark, which, at this point, appears to be doubtful.

.

[Mamabird]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

And importantly, if the contact person that passed on the resistent strain came on the flight from Argentina where they may have been infected, then we have a source in the Southern Hemisphere that may still be flying under the radar.

[pjie2]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Let's hold on a minute before pressing panic buttons here. What we know is that patient A got swine flu and passed it to patient B. Patient B turned out to have a resistant strain. It's not known whether the resistance arose de novo in patient B (due to prophylactic Tamiflu treatment), or whether patient A also had drug-resistant flu.

This is not a reason to panic, nor is it a reason to throw around wild speculations such as this one:

"Absent such evidence, the resistance is likely to have developed prior to treatment"

Absence of evidence is simply absence of evidence, and can be spun either way. For example, one could say "There is no evidence that patient A had drug resistant flu, therefore it is likely to have developed de novo in patient B". It's flim-flam and unscientific to make a call either way. Moreover, we don't need sequence data to give us the answer. Drug resistance is a phenotype, not a genotype. What we need to know is whether patient A was treated with Tamiflu, and whether their infection was susceptible to it.

[Mamabird]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Let's hold on a minute before pressing panic buttons here. What we know is that patient A got swine flu and passed it to patient B. Patient B turned out to have a resistant strain. It's not known whether the resistance arose de novo in patient B (due to prophylactic Tamiflu treatment), or whether patient A also had drug-resistant flu.

This is not a reason to panic, nor is it a reason to throw around wild speculations such as this one:

"Absent such evidence, the resistance is likely to have developed prior to treatment"

Absence of evidence is simply absence of evidence, and can be spun either way. For example, one could say "There is no evidence that patient A had drug resistant flu, therefore it is likely to have developed de novo in patient B". It's flim-flam and unscientific to make a call either way. Moreover, we don't need sequence data to give us the answer. Drug resistance is a phenotype, not a genotype. What we need to know is whether patient A was treated with Tamiflu, and whether their infection was susceptible to it.

The evidence is that if Tamiflu is administered within 24 to 48 hours of symptom onset, and given this drug's effectiveness in treating influenza, including highly pathogenic H5N1 Bird Flu, and given the fact that in the immediate case this antiviral was administered five days before symptom onset, I feel that I have every right to panic.

Now, if the Danes and Argintines would provide some genetic sequences, then I may have no reason to panic at all. But this lack of information in the light of the above evidence, makes me really nervous.

[tropical]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

#72:
"Therefore, the report of Tamiflu resistance (which was probably H274Y) raises concerns that resistance will spread via recombination, as happened for H274Y in seasonal flu. Initially, the polymorphism was rare. It was first in clade 2C in China, followed by clade 1 in the US and UK, followed by clade 2B. In each sub-clade the polymorphism appeared on multiple genetic backgrounds in the absence of Tamiflu treatment.

The hitch hiking led to an expansion of H274Y, and when it paired up with HA A193T, the subclade expanded and both acquistions became fixed.

The large reservoir of H274Y in seasonal flu provides donor sequences for H274Y acquisition in swine H1N1. The report of resistance in the Danish patient raises concerns that the resistance can rapidly spread under the section pressure of Tamiflu treatment."


Pardon my non-gen.-sci. question, but why is that the resistance now can rapidly spread under the pressure of Tamiflu treatment,
when previously, the seasonal resistance could prevail in absence of Tamiflu treatment?

___

#71: "if the contact person that passed on the resistent strain came on the flight from Argentina where they may have been infected, then we have a source in the Southern Hemisphere that may still be flying under the radar."

If it does, and it will be the pandemic wave2, could we admit that the "anti-quarantine policies" spreads the next wave another time everywhere, instead of trying to contain it ...
(I know, it could insurge in every country autonomously ..., yes but this way it roaming faster)
___

#73: "But this lack of information in the light of the above evidence, makes me really nervous."

#61/62: ""We have sent the message to all laboratories in the world, because they must be aware that it can change. And then we sent the news out to the Danish media, so that we would not be accused of hiding something. We want to create transparency, "says senior consultant Steffen Glismann from Statens Serum Institut for politiken.dk."

So, conspiracy hiding, or not?

[HenryN]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Let's hold on a minute before pressing panic buttons here. What we know is that patient A got swine flu and passed it to patient B. Patient B turned out to have a resistant strain. It's not known whether the resistance arose de novo in patient B (due to prophylactic Tamiflu treatment), or whether patient A also had drug-resistant flu.

This is not a reason to panic, nor is it a reason to throw around wild speculations such as this one:

"Absent such evidence, the resistance is likely to have developed prior to treatment"

Absence of evidence is simply absence of evidence, and can be spun either way. For example, one could say "There is no evidence that patient A had drug resistant flu, therefore it is likely to have developed de novo in patient B". It's flim-flam and unscientific to make a call either way. Moreover, we don't need sequence data to give us the answer. Drug resistance is a phenotype, not a genotype. What we need to know is whether patient A was treated with Tamiflu, and whether their infection was susceptible to it.

Drug resistance in H1N1 is a GENOTYPE (H274Y).

I went through the evidence against the resistance Roche is describing (along with its hopes and dreams).

The evidence for H274Y acquistion is as follows.

Media reports indicate the patient was asymptomatic for 5 days after returning, which argues against a raging infection, which is what usually leads to resistance. It is harder for resistance to be selected when the viral load is low, so the low viral load counters the low dose (prophylactic) of Tamiflu.

Reports also indicate that the "mutation" is similar to what happened in seasonal flu, strongly suggesting that the resistance is H274Y.

H274Y is fixed in H1N1 seasonal flu, which is why it was predicted to jump to H1N1 swine flu via recombiantion. Some argued for reassortment, but there is no hint of reassortment in this case.

Acquistion via recombination was predicted because the level of H274Y in circulation is so high in seasonal flu.

The timing is right for movement of H274Y from seasonal to swine flu because the level of swine flu in human populations is now high, and seasonal flu season is begining in the southern hemisphere.

The start of season flu season in the southern hemisphere is associated with a spike in deaths in Argentina, Chile, and Australia, supporting the start of evolution of swine flu into a more human adapted version.

Recent sequence data out of South America is limited, so the spread of H274Y there would be largely under the radar.

Travelers to Denmark with H1N1 from Argentina have been noted (which has also happened to Rugby players who played in Argentina and returned to France and South Africa - thus Argentina is a significant swine H1N1 exporter, along with recent changes).

As more sequences arise, the H274Y in swine H1N1 will become glaringly obvious, as predicted months ago.