Denmark - Dane with novel H1N1 found resistant to Tamiflu

[HenryN]

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

Dr. Niman: Given this comparison between H274K acquisition in H5N1 and seasonal H1N1, are you saying it may not follow the same 2-year spreading timeline as seasonal H1N1, i.e., started in 2006? and was present globally in 2008/2009 seasonal H1N1?

.

It will be MUCH easier to spread in swine flu.

In H5N1 it first appeared in patients being treated, but no hard evidence of spread.

Showed up in wild birds in Russia in summer of 2005, which may have led to first examples in H1N1 seasonal flu (clade 2C in China).

However it was still at low levels with a low reservoir and in 2006/2007 jumped to clade 1 in US and UK. Still at low level and still no real driver.

In 2007/2008 jumped again. This time to clade 2B and although some versions didn't expand (like Hawaii and Florida), it did take off in Europe and was discovered in Norway. Was at high levels in some countries (mostly northern Europe) and then paired up with A193T which became dominant in southern hemisphere in 2008.

This led to 100% levels in 2008/2009. All of this was done without Tamiflu pressure.

Swine flu however has a LARGE reservoir in seasonal H1N1 and now that swine has moved into human, this can lead to dual infections and a jump from human to swine. This will be VERY rapid because of the large reservoir in H1N1 and use of tamiflu, which will favor the jump from human to swine.

As a result, the resistance is starting to appear (Roche denials notwithstanding) and it is because H274Y in swine H1N1 is fit and can transmit WITHOUT tamiflu (but will move even faster with tamiflu, which will attack competing wildtype swine H1N1).

Thus, if the current patient was infected by H1N1 that already had H274Y, then it will spread very quickly, driven by the large seasonal flu pool of H274Y coupled with widespread use fo Tamiflu favoring jumps to swine flu and rapid transmission.

The virus knows EXACTLY what it is doing, even if drug makers / sequencers don't (and so far it is NO contest).

 

[Zac]

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

The first lots of swine flu vaccine are based on the virus without H274Y. Would that vaccine provide protection against the virus with H274Y?

 

[St Michael]

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

As a result, the resistance is starting to appear (Roche denials notwithstanding) and it is because H274Y in swine H1N1 is fit and can transmit WITHOUT tamiflu (but will move even faster with tamiflu, which will attack competing wildtype swine H1N1).

Thus, if the current patient was infected by H1N1 that already had H274Y, then it will spread very quickly, driven by the large seasonal flu pool of H274Y coupled with widespread use fo Tamiflu favoring jumps to swine flu and rapid transmission.

Your thoughts on the highlighted areas below (details I have not yet seen discussed)?

Drug-resistant swine flu seen in Danish patient
AP

By MIKE STOBBE, AP Medical Writer Mike Stobbe, Ap Medical Writer ? Mon Jun 29, 4:05 pm ET

ATLANTA ? For the first time, a case of swine flu has proven resistant to Tamiflu ? the leading pharmaceutical weapon against the new virus, international health officials said Monday.

The resistance was seen in a patient in Denmark, who has recovered.

"The goods news is they just found one," said Dr. Carolyn Bridges of the U.S. Centers for Disease control and Prevention.

It appears the strain developed in a patient who was taking the drug to prevent illness, and it has not spread to others. That's a much better scenario than if the patient had not been taking Tamiflu and picked up a drug-resistant strain already spreading through the public, said Bridges, associate director for science in the CDC's influenza division.

Also, it is not a mutation that includes pieces of both seasonal flu and the new pandemic form of the virus, according to Roche, the Switzerland-based pharmaceutical company that makes Tamiflu. Scientists have been worried about the new swine flu swapping genes with seasonal or other types of flu and perhaps mutating into a more dangerous or more infectious form.

Until an effective vaccine is developed, the drugs Tamiflu and Relenza have been considered the best available defense against the swine flu virus, which has caused nearly 28,000 reported illness in the United States, including more than 3,000 hospitalizations and 127 deaths.

Tamiflu resistance has not been seen in nearly 200 swine flu samples tested in the United States, Bridges said. But the resistance has been seen in other types of flu. Late last year, CDC officials reported that the most common flu bug circulating at the time was overwhelmingly resistant to Tamiflu. Health officials have believed it was probably a matter of time before a swine flu sample tested resistant, too.

The Danish case was isolated, however, and guidelines from the CDC and the World Health Organization continue to recommend Tamiflu as a treatment. No details were released on the patient's age or gender, or on when the patient was sick.

"It is possible to see occasional reports of resistance while a drug remains largely effective," said Terry Hurley, a Roche spokesman.

 

[HenryN]

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

They have provided ZERO data supporting a de novo mutation - it's just Roche wishful thinking swallowed hook line and sinker by the quoted scientist.
The second is no reassortment (but Tamiflu resistance will be via recombination, so the "no reassortment" means nothing).
No detail is SOP.

 

[the doctor]

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

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

Thanks Mamabird.

GW

 

[pjie2]

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

WRONG. Drug resistance in H1N1 is a GENOTYPE (H274Y).

Please. Drug resistance is a phenotype. This is high school definition time.

Phenotype = the observable characteristics and traits of an organism. In this case, we observe drug resistance.

Genotype = the genetic makeup of an organism. H274Y is one of several genotypes that can confer the phenotype of drug resistance.

Until and unless the sequences from the Danish patient are published, we do not know the genotype of the flu strain she had, but we do know that the phenotype was a drug resistant one. There are no grounds for the assertion that the resistance is due to H274Y. However, if the patient she caught it from had a non-resistant strain, then that would constitute very good evidence that the resistance is due to a de novo mutation in this individual patient, and not indicative of wider circulation of a resistant strain.

 

[theforeigner]

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

Danes infected with H1N1 Abroad
Danes Infected with H1N1 IN Denmark.

NOTE! that the dates is when the cases was REPORTED to the public,
meaning we don?t always know what date thise people were infected.:


Nr = danes infected in Denmark
DIA= danes infected abroad


April 29, 2009, danish Health ministers Jakob Axel Nielsen bought 40.000 courses of Relenza



DIA 1. reported may 1
Infected in US
returned from NY april 29 7:35 Flight: Co122N




DIA 2. reported June 3
. Infected in US
Returned May 29, from US Via Amsterdam Flight: KL:1345

DIA 3. reported June 3
. Infected in US
Returned May 29, from US Via Amsterdam Flight: KL:1345

Nr 1. reported June 3
Infected by relative who returned from US via/Amsterdam May 29,2009 13:55 PM on airplane KL1345
Same day 2 H1N1 reported, infected abroad




DIA 4. reported June 5
Infected in Argentina
Returned from Argentina via Paris June 2, 14:45 PM
Flight:AirFrance AF2350




DIA 5. reported June 6
infected in US
returned from NY via Geneve may 29 afternoon Flight: LX4672

Nr 2. reported June 6
(no detaild provided)




Nr.3 reported June 8
(no detaild provided)




DIA 6. reported June 9
infected abroad (no details)




DIA 7. reported June 11
infected abroad (no details)




DIA 8. reported June 12
infected abroad (no details)

Nr.4 reported June 12
male in jutlandno detaild provided)




Nr.5 reported June 15
(no detaild provided)




DIA 9. reported June 16
infected abroad (no details)

DIA 10. reported June 16
infected abroad (no details)




DIA 11. reported June 18
infected abroad (no details)

DIA 12. reported June 18
infected abroad (no details)

DIA 13. reported June 18
infected abroad (no details)

DIA 14. reported June 18
infected abroad (no details)

DIA 15. reported June 18
infected abroad (no details)

DIA 16. reported June 18
infected abroad (no details)



DIA 17. reported June 19
infected abroad (no details)



DIA 18. reported June 21
infected abroad (no details)

DIA 19. reported June 21
infected abroad (no details)

DIA 20. reported June 21
infected abroad (no details)

DIA 21. reported June 21
infected abroad (no details)

Nr.6 reported June 21
(no detaild provided)

Nr.7 reported June 21
(no detaild provided)

Nr.8 reported June 21
(no detaild provided)





DIA 22. reported June 22
infected abroad (no details)

Nr 9 reported Jun 22
(no detaild provided)

Nr 10 reported Jun 22
(no detaild provided)




Nr 11 reported Jun 23
(no detaild provided)

Nr 12 reported Jun 23
(no detaild provided)

Nr 13 reported Jun 23
(no detaild provided)

Nr 14 reported Jun 23
(no detaild provided)




DIA 23. reported June 24
infected abroad (no details)

Nr 15 reported Jun 24
(no detaild provided)




Nr 16 reported Jun 25
(no detaild provided)

Nr 17 reported Jun 25
(no detaild provided)



Nr 18 reported Jun 29
(no detaild provided)

Nr 19 reported Jun 29
(no detaild provided)

DIA 24. reported June 29
infected abroad (no details)

DIA 25. reported June 29
infected abroad (no details)

DIA 26. reported June 29
infected abroad (no details)

DIA 27. reported June 29
infected abroad (no details)

DIA 28. reported June 29
infected abroad (no details)

DIA 29. reported June 29
infected abroad (no details)

DIA 30. reported June 29
infected abroad (no details)

DIA 31. reported June 29
infected abroad (no details)

 

[sharon sanders]

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

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.

I agree.

 

[HenryN]

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

Please. Drug resistance is a phenotype. This is high school definition time.

Phenotype = the observable characteristics and traits of an organism. In this case, we observe drug resistance.

Genotype = the genetic makeup of an organism. H274Y is one of several genotypes that can confer the phenotype of drug resistance.

Until and unless the sequences from the Danish patient are published, we do not know the genotype of the flu strain she had, but we do know that the phenotype was a drug resistant one. There are no grounds for the assertion that the resistance is due to H274Y. However, if the patient she caught it from had a non-resistant strain, then that would constitute very good evidence that the resistance is due to a de novo mutation in this individual patient, and not indicative of wider circulation of a resistant strain.

The resistance will be due to H274Y (and there will zero evidence of who infected the patient, who didn't develop symtoms until 5 DAYS after returning - she could have been infected by a known contact in the originating country, at the airport there, on the plane, at the airport in Denmark, at the Drs office, or multiple locations in Denmark - incubation time is usually 2-4 days) so your IF is just hopes and dreams of Roche - and there will be NO virus isolate prior to treatment, because there is no evidence the patient was even infected prior to treatment.

 

[dr kockosh]

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

results of biota/Dankyos phase 3 study of LANI due out 31 july - they have already started the registration process in japan so i'm guessing the results look pretty good - and they also have 6 back up compounds - lets hope this line of second gen neuradimase inhibitors can be produced quickly - looks like we are going to need them

 

[HenryN]

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

My translation of the black highlighted part of the newsreport:

The person was originally not ill at all. The person was in precaution treatment with Tamiflu, because the person had been in close contact with a person who was infected with Swine Flu abroad (OR the person had been abroad and been in close contact with a H1N1 infected person, can?t be sure which it is). After 5 days treatment with Tamiflu, the person suddenly got sick with H1N1, but it didn?t seem like the treatment had any effect. It turned out via tests her in Denmark and in UK, that the person had developed resistance twards Tamiflu, explains Nils Strandberg ( President & CEO of -Statens Serum Institut )
Insted the person was treated with Relenza. - We can be glad that the person today is well and have not infected others said Nils Strandberg.

The Journalist ask Nils Strandberg:
But isen?t it a worrying perspectives that Tamiflu now no longer can be concidered a safe tratment against Swine Flu?

-Yes it is worrying if Tamiflu does not work on the most vulnerable groups. But there are still things that work if a vulnerable patient get infected with H1n1. There is another treatment Relenza.




http://ekstrabladet.dk/kup/sundhed/article1188161.ece

Dansker er resistent overfor Tamiflu



En dansker er som den f?rste i verden blevet resistent overfor medicin mod svineinfluenza H1N1. Dystre perspektiver for risiko-patienter

16:40 - 29. jun. 2009 | Frederik Bjerre Andersen, Gitte Hejberg


Statens Serum Institut har fundet den f?rste person i verden, der er resistent overfor medicinen oseltamivir, der s?lges under navnet Tamiflu og blandt andet har vist sig virksom mod svineinfluenzaen H1N1.

Det er det f?rste tilf?lde af resistens overfor medicinen p? verdensplan. Det er forventeligt, at influenzavirus kan mutere spontant. Resistensen har ikke ?ndret H1N1-virus? evne til at smitte eller fremkalde sygdom, meddeler instuttet.

- B?de bakterier og vira kan mutere og blive resistente. Og det er alts? det, der er sket her, bekr?fter administrerende direkt?r p? Statens Serums Institut Nils Strandberg.

- Vedkommende var til at begynde med slet ikke syg. Den p?g?ldende var i forebyggende behandling med Tamiflu, fordi vedkommende havde v?ret i t?t kontakt med en svineinfluenza-ramt i udlandet. Da der var g?et fem dage med Tamiflu, blev personen s? pludselig syg med H1N1, men det s? ikke ud til, at medicinen virkede. Det viste sig s? via pr?ver her og i England, at personen var blevet resistens, fort?ller Nils Strandberg.

Uheldigt for alvorligt syge
I stedet blev patienten behandlet med medicinen Relenza.

- Vi kan gl?de os over, at personen i dag er helt rask og ikke har smittet andre, siger Nils Standberg.

- Men der er vel dystre perspektiver i, at Tamiflu nu ikke l?ngere kan betragtes som et sikkert middel mod svineinfluenza?

- Ja, det er bekymrende, hvis Tamiflu ikke virker p? de mest udsatte grupper. Men der er stadig noget at g?re, hvis en svagelig patient bliver smittet med H1N1. Der er jo et andet stof, som man kan bruge.
Skruer ned for forebyggende brug
If?lge Nils Strandberg vil fundet af den resistente dansker betyde, at l?gerne fremover vil blive mere tilbageholdende med at bruge Tamiflu forebyggende - med mindre der alts? ligefrem er tale om meget syge og skr?belige patienter.

- Hvorfor er det netop en dansker, der bliver den f?rste resistente influenza-patient?

- Det beror nok mest p? et tilf?lde. Vi har et godt system, hvor vi er gode til at overv?ge situationen.

Episoden sl?r fast, at influenza-virus kan mutere, og at Tamiflu p? ingen m?de kan betragtes som mirakelmedicin. Tamiflu kan i forvejen ikke kurere influenza, men medicinen kan neds?tte symptomerne og forkorte forl?bet.

Epidemi til efter?ret
Selv om sommeren, udend?rslivet og de lukkede skoler er ensbetydende med mindre influenzasmitte i Danmark, vil danskernes rejseaktivitet sommeren over betyde, at der bliver sl?bt mere smitte til landet.

- Vi skal formodentlig frem til det sene efter?r eller vinter, f?r vi kan risikere en H1N1-epidemi herhjemme. Men det beh?ver ikke at give problemer, da det stadig er en ret mild influenzatype, siger Nils Standberg.

Google translation

Swine Influenza: Danish is resistant to Tamiflu
..
Statens Serum Institut have found the first person in the world who are resistant to the medication oseltamivir, sold under the name Tamiflu, and among others have proven company against swine flu H1N1.

It is the first case of resistance to the drug worldwide. It is expected that influenza virus can mutate spontaneously. Resistance has not changed the H1N1 virus' ability to infect or cause disease, shall instuttet.

- Both bacteria and viruses can mutate and become resistant. And that is what has happened here, confirms CEO at Statens Serum Institut Nils Strandberg.

- He had to start with no ill. That was in the preventive treatment with Tamiflu, because he had been in close contact with a swine influenza hit abroad. Since there had been five days of Tamiflu, the person suddenly ill with H1N1, but it not appear that the medicine worked. It appeared as through the samples here and in England that the person had been resistance, "says Nils Strandberg.

Disadvantageous for the seriously ill
Instead, the patient was treated with medication Relenza.

- We can rejoice that the person is today is quite healthy and has not infected others, says Nils Stand Berg.

- But there is surely bleak prospects that Tamiflu will no longer be regarded as a safe weapon against swine flu?

- Yes, it is worrying if Tamiflu does not work on the most vulnerable groups. But there is still something to do if a sickly patient become infected with H1N1. There is another substance that can be used.

Turn down the preventive use
According to Nils Strandberg would find the resistant Dane mean that doctors will be more reluctant to use preventive Tamiflu - unless there actually are very sick and frail patients.

- Why is it just a Dane who is the first resistant influenza patient?

- It probably depends most on a case. We have a good system where we are good to monitor the situation.

The incident confirms that influenza virus can mutate and that Tamiflu can not be regarded as miracle drugs. Tamiflu is already not cure flu, but the medication can reduce symptoms and shorten the process.

Epidemic in the autumn
Even in summer, outdoor life and the closed schools will mean less flu infection in Denmark, the Danes will travel over the summer mean that there will be dragged more infections in the country.

- We should probably until the late autumn or winter before we can risk a H1N1 epidemic at home. But it need not cause problems, since it is still a relatively mild influenza, "says Nils Stand Berg.

 

[HenryN]

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

Google translation

- He had to start with no ill. That was in the preventive treatment with Tamiflu, because he had been in close contact with a swine influenza hit abroad. Since there had been five days of Tamiflu, the person suddenly ill with H1N1, but it not appear that the medicine worked. It appeared as through the samples here and in England that the person had been resistance, "says Nils Strandberg.

The above translation confirms that the patient had been in contact with an infected person abroad, but had been asymptomatic in Denmark for five before becoming ill. A sample was collected and sequenced in Denmark and England (Weybridge or Mill Hill) and both labs identified a resistance marker (almost certainly H274Y).

The long incubation time of 5 days leaves open the source of the infection. Since the patient was asymptomatic upon arrival, it is unlikley that there are samples collected prior to the start of prophylactic treatment and even if a sample existed, it is unlikely that virus could be isolated.

In fact the 5 day delay in disease onset leave open the strong possibility that the patient was NOT infected by the known foreign contact, and was in fact infected while traveling to Denmark or after arriving in Denmark.

The resistance was identified because the patient developed symptoms (five DAYS after arriving, suggesting the infecting dose was low if it originated outside of Denmark) while being treated, but there is NO evidence even remotely suggesting that the patient was infected by wild type H1N1, unless virus was isolated from the foreign contact, or that the two isolates matched (other than the acquired resistance markers). The article makes no mention of an isolate or sequence from the known contact, and without such a match, there is nothing to suggest that the resistance developed while under prophylactic treatment.

 

[theforeigner]

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

The above translation confirms that the patient had been in contact with an infected person abroad, but had been asymptomatic in Denmark for five before becoming ill. A sample was collected and sequenced in Denmark and England (Weybridge or Mill Hill) and both labs identified a resistance marker (almost certainly H274Y).

The long incubation time of 5 days leaves open the source of the infection. Since the patient was asymptomatic upon arrival, it is unlikley that there are samples collected prior to the start of prophylactic treatment and even if a sample existed, it is unlikely that virus could be isolated.

In fact the 5 day delay in disease onset leave open the strong possibility that the patient was NOT infected by the known foreign contact, and was in fact infected while traveling to Denmark or after arriving in Denmark.

The resistance was identified because the patient developed symptoms (five DAYS after arriving, suggesting the infecting dose was low if it originated outside of Denmark) while being treated, but there is NO evidence even remotely suggesting that the patient was infected by wild type H1N1, unless virus was isolated from the foreign contact, or that the two isolates matched (other than the acquired resistance markers). The article makes no mention of an isolate or sequence from the known contact, and without such a match, there is nothing to suggest that the resistance developed while under prophylactic treatment.

Hi Niman

I´m danish, and I have now read several of the Tamiflu resistant patient reports in danish, and I belive fully that this is the correct info due to what has been reported on Statens Serum Institut website and elsewere.
http://www.ssi.dk/sw174.asp?PAGE=1&ArtNo=3651423

It was only the report from "Ekstrabladet" which was written in a way that could be misunderstod in regards to were "A" had been infected, but it turn out that it was aimed to the location were "B" was infected; abroad.

So, here is the correct info:

The tamiflu resistent person "A" (a woman, according to newsreport) had NOT been abroad.
"A" had been in contact with a person, we name him/her "B"
"B" had recently been abroad and had gotten infected with H1N1
Therefore "A " was given Tamiflu as a precausionn treatment
After "A" had been taking Tamiflu for 5 days she devloped flu symptoms
A test showed that "A" was infected with H1N1
Additional tests at Statens Serum Institut showed that the virus in question, H1N1, had mutated. It (the H1N1) is resistent to tamiflu but is still sensetive to Relenza.

If I find additional info I´ll post it in this thread.


By the way the machin translation is VERY bad, belive me

 

[HenryN]

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

Hi Niman

I´m danish, and I have now read several of the Tamiflu resistant patient reports in danish, and I belive fully that this is the correct info due to what has been reported on Statens Serum Institut website and elsewere.
http://www.ssi.dk/sw174.asp?PAGE=1&ArtNo=3651423

It was only the report from "Ekstrabladet" which was written in a way that could be misunderstod in regards to were "A" had been infected, but it turn out that it was aimed to the location were "B" was infected; abroad.

So, here is the correct info:

The tamiflu resistent person "A" (a woman, according to newsreport) had NOT been abroad.
"A" had been in contact with a person, we name him/her "B"
"B" had recently been abroad and had gotten infected with H1N1
Therefore "A " was given Tamiflu as a precausionn treatment
After "A" had been taking Tamiflu for 5 days she devloped flu symptoms
A test showed that "A" was infected with H1N1
Additional tests at Statens Serum Institut showed that the virus in question, H1N1, had mutated. It (the H1N1) is resistent to tamiflu but is still sensetive to Relenza.

If I find additional info I´ll post it in this thread.


By the way the machin translation is VERY bad, belive me

Thanks for the clarification. That would narrow down the source of the woman's infection, and the 5 day delay included the time to get infected by the traveler contact, who was in Denmark (the classic 5 day gap in disease onset). However, even though the source was in Denmark, it still sounds like there was no data for the H1N1 from the source to show that the source was wild type. This is infered because the source recovered and was probably treated with Tamiflu, but many recover without Tamiflu treatment, so the recovery of the source does not signal wild type. However, the failure of the contact to recover in spite of treatment does signal resistance, so that sample was sequenced and was resistant (almost certainly H274Y). Thus, without the sequence from the traveler, there is still no evidence that the traveler didn't also have resistant H1N1 (or that the travel was the actual source of H1N1, since the only sequence described was from the patient who failed to respond to tamiflu).

 

[HenryN]

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

Hi Niman

I´m danish, and I have now read several of the Tamiflu resistant patient reports in danish, and I belive fully that this is the correct info due to what has been reported on Statens Serum Institut website and elsewere.
http://www.ssi.dk/sw174.asp?PAGE=1&ArtNo=3651423

It was only the report from "Ekstrabladet" which was written in a way that could be misunderstod in regards to were "A" had been infected, but it turn out that it was aimed to the location were "B" was infected; abroad.

So, here is the correct info:

The tamiflu resistent person "A" (a woman, according to newsreport) had NOT been abroad.
"A" had been in contact with a person, we name him/her "B"
"B" had recently been abroad and had gotten infected with H1N1
Therefore "A " was given Tamiflu as a precausionn treatment
After "A" had been taking Tamiflu for 5 days she devloped flu symptoms
A test showed that "A" was infected with H1N1
Additional tests at Statens Serum Institut showed that the virus in question, H1N1, had mutated. It (the H1N1) is resistent to tamiflu but is still sensetive to Relenza.

If I find additional info I´ll post it in this thread.


By the way the machin translation is VERY bad, belive me

Do the reports indicate that she "suddenly" developed symptoms (at day 5)? The sudden development would also suggest that she was infected with H1N1 that was already resistant. The prophylatic tamiflu did nothing. She was exposed for 5 days and the sudden onset suggests that she had a significant exposure, leading to sudden disease onset, instead of a milder infection that became more severe as the Tamiflu sensitive H1N1 declined due to tamiflu treatment and was replaced by resistant H1N1.

 

[HenryN]

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

<TABLE class=lan18 border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD class=hei22 height=25 vAlign=bottom>First Tamiflu-resistant case in Denmark
</TD></TR><TR><TD bgColor=#ffffff height=4></TD></TR></TBODY></TABLE><TABLE border=0 cellSpacing=0 cellPadding=0 width="50%" align=center><TBODY><TR><TD height=8></TD></TR></TBODY></TABLE><TABLE border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD width="48%">www.chinaview.cn

2009-06-30 16:36:37 </TD><TD class=hui12 width="26%" align=middle> </TD><TD class=hui12 width="12%" align=middle>

Print</TD></TR></TBODY></TABLE><TABLE border=0 cellSpacing=0 cellPadding=0 width="80%"><TBODY><TR><TD height=20></TD></TR></TBODY></TABLE><TABLE class=lt14 border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD class=lt14>


BEIJING, June 30 (Xinhuanet) -- The first case of swine flu resistant to Tamiflu--the anti-viral drug to combat the pandemic, has been found in Denmark, the National Board of Health confirmed Monday.

The Danish patient was given the drug after exposure to the swine flu. Despite the medication, she became ill with the disease and has now recovered.
"It appears the strain developed in a patient who was taking the drug to prevent illness, and it has not spread to others. That's a much better scenario than if the patient had not been taking Tamiflu and picked up a drug-resistant strain already spreading through the public," said Bridges, associate director for science in the U.S. Centers for Disease control and Prevention'sinfluenza division. Tamiflu, if taken early, eases the symptoms of swine flu, making it less likely to spread. Scientists have been worried about the new swine flu swapping genes with seasonal or other types of flu and mutating into a more dangerous or more infectious form. So far this does not appear to be the case. Until an effective vaccine is developed, the drugs Tamiflu and Relenza have been considered the best available defense against the swine flu virus.

</TD></TR></TBODY></TABLE>
http://news.xinhuanet.com/english/2009-06/30/content_11627434.htm

 

[theforeigner]

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

Thanks for the clarification. That would narrow down the source of the woman's infection, and the 5 day delay included the time to get infected by the traveler contact, who was in Denmark (the classic 5 day gap in disease onset). However, even though the source was in Denmark, it still sounds like there was no data for the H1N1 from the source to show that the source was wild type. This is infered because the source recovered and was probably treated with Tamiflu, but many recover without Tamiflu treatment, so the recovery of the source does not signal wild type. However, the failure of the contact to recover in spite of treatment does signal resistance, so that sample was sequenced and was resistant (almost certainly H274Y). Thus, without the sequence from the traveler, there is still no evidence that the traveler didn't also have resistant H1N1 (or that the travel was the actual source of H1N1, since the only sequence described was from the patient who failed to respond to tamiflu).

Your welcom .
And yes you are right there is no info on the "traveler" whom I name "B".
Why the danish HA doesen?t release any info on "B" and also more detalied info on "A" is a mystery to me, we can only hope that WHO release detailes on both "B" and the tamiflu resisten patient whom I name "A"

Could you please explain "wild type" ?

 

[theforeigner]

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

Do the reports indicate that she "suddenly" developed symptoms (at day 5)? The sudden development would also suggest that she was infected with H1N1 that was already resistant. The prophylatic tamiflu did nothing. She was exposed for 5 days and the sudden onset suggests that she had a significant exposure, leading to sudden disease onset, instead of a milder infection that became more severe as the Tamiflu sensitive H1N1 declined due to tamiflu treatment and was replaced by resistant H1N1.

Yes that first scenario is correct; she "suddenly" developed symptoms at day 5 (after 5 days on prophylatic Tamiflu) and she had been in close contact with "B" who had been infected abroad.

 

[HenryN]

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

Your welcom .
And yes you are right there is no info on the "traveler" whom I name "B".
Why the danish HA doesen´t release any info on "B" and also more detalied info on "A" is a mystery to me, we can only hope that WHO release detailes on both "B" and the tamiflu resisten patient whom I name "A"

Could you please explain "wild type" ?

Wild type is the scientific term for the "normal" gene. In this case, it would be an NA gene that is not Tamiflu resistant.
As far as information is concerned, most countries have been very withholding of specifics, citing privacy laws. However, countries in Europe, including Denmark, have done a very minimal level of testing. They have focused on imported cases and contacts, as described in this case/cluster, but little real data has been released.

Although sequences have been released promptly, the number from Denmark remains at one. It was collected in late April and released promptly in early May, but of course it is almost July, so there is no public data on sequences from Denmark for almost the past 2 months.

Thus, the recent spread of Tamiflu resistance in Denmark would not be seen in public sequences, and many other European countries also have limited positives and even fewer sequences.

In all liklihood, there is no sequence from the contact, which is why statements include "probably" and "appears". There is no data showing that the H1N1 in the contact who traveled overseas was infected with tamiflu sensitive (wild type) H1N1, and the only reason the H1N1 was collected from the female patient was becasue she developed flu-like symptoms while taking tamiflu.

 

[theforeigner]

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

<TABLE class=lan18 border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD class=hei22 height=25 vAlign=bottom>First Tamiflu-resistant case in Denmark
</TD></TR><TR><TD bgColor=#ffffff height=4></TD></TR></TBODY></TABLE><TABLE border=0 cellSpacing=0 cellPadding=0 width="50%" align=center><TBODY><TR><TD height=8></TD></TR></TBODY></TABLE><TABLE border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD width="48%">www.chinaview.cn

2009-06-30 16:36:37 </TD><TD class=hui12 width="26%" align=middle> </TD><TD class=hui12 width="12%" align=middle>

Print</TD></TR></TBODY></TABLE><TABLE border=0 cellSpacing=0 cellPadding=0 width="80%"><TBODY><TR><TD height=20></TD></TR></TBODY></TABLE><TABLE class=lt14 border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD class=lt14>


BEIJING, June 30 (Xinhuanet) -- The first case of swine flu resistant to Tamiflu--the anti-viral drug to combat the pandemic, has been found in Denmark, the National Board of Health confirmed Monday.

The Danish patient was given the drug after exposure to the swine flu. Despite the medication, she became ill with the disease and has now recovered.
"It appears the strain developed in a patient who was taking the drug to prevent illness, and it has not spread to others. That's a much better scenario than if the patient had not been taking Tamiflu and picked up a drug-resistant strain already spreading through the public," said Bridges, associate director for science in the U.S. Centers for Disease control and Prevention'sinfluenza division. Tamiflu, if taken early, eases the symptoms of swine flu, making it less likely to spread. Scientists have been worried about the new swine flu swapping genes with seasonal or other types of flu and mutating into a more dangerous or more infectious form. So far this does not appear to be the case. Until an effective vaccine is developed, the drugs Tamiflu and Relenza have been considered the best available defense against the swine flu virus.

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http://news.xinhuanet.com/english/2009-06/30/content_11627434.htm

I?m not sure if this has any significance, but on the danish Statens Serum Institut report about the Tamiflu resistent patient "A", they also added this statement:



En tilsvarende udvikling af resistens over for oseltamivir (Tamiflu?) er ogs? set hos det vinter-influenzavirus A H1N1, der har cirkuleret de seneste to vinters?soner

My translation:
A corresponding development of resisitant twards oseltamivir (Tamiflu?) has been observed in the winter-influenzavirus A H1N1, which has circulated the last to vinter seasons


http://www.ssi.dk/sw174.asp?PAGE=1&ArtNo=3651423


29. juni 2009 - Resistens hos pandemisk influenza A H1N1v p?vist i Danmark

Det f?rste tilf?lde af resistens over for oseltamivir (Tamiflu?) hos det pandemiske influenzavirus A H1N1v er fundet i Danmark. Dette er det f?rste p?viste tilf?lde p? verdensplan.

Det er velkendt og forventeligt, at influenzavirus kan mutere spontant. Resistensen har ikke ?ndret virus? evne til at smitte eller fremkalde sygdom, og vurderingen er, at der fortsat er tale om en relativ mild influenza.

Personen er nu rask, og der er ikke p?vist yderligere smitte med det resistente virus. Den smittede var i forebyggende behandling med oseltamivir (Tamiflu?) p? grund af t?t kontakt med et tilf?lde, der var smittet i udlandet. Alligevel fik vedkommende influenzasymptomer. En pr?ve viste, at personen var inficeret med influenzavirus A H1N1v. Yderligere unders?gelser p? Statens Serum Institut har nu vist, at det p?g?ldende virus er muteret. Det er modstandsdygtigt over for det antivirale middel oseltamivir (Tamiflu?), mens zanamivir (Relenza?) fortsat kan anvendes til behandling.

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.

En tilsvarende udvikling af resistens over for oseltamivir (Tamiflu?) er ogs? set hos det vinter-influenzavirus A H1N1, der har cirkuleret de seneste to vinters?soner.

Det enkelte fund i Danmark er som n?vnt ikke uventet. Det udg?r ikke en risiko for folkesundheden og giver heller ikke anledning til at ?ndre anbefalingerne for brugen af oseltamivir (Tamiflu?).

I Danmark f?lges situationen fortsat t?t med overv?gning af sygdomsforekomst og unders?gelse af alle isolerede influenzavirus A H1N1v.

(SSI)