Announcement

Collapse
No announcement yet.

Denmark - Dane with novel H1N1 found resistant to Tamiflu

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • #76
    Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

    Pardon my non-gen. 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?
    If a fit virus with Tamiflu resistance has developed and has "gotten out" then it will continue to be fit in the absence of Tamiflu treatment, and with Tamiflu treatment it will continue to out-compete non-resistant strains.

    Now that seasonal flu has Tamiflu resistance it has not evolutionary pressure to remove that trait, my guess is that it didn't lose any advantages by picking that one up.
    Wotan (pronounced Voton with the ton rhyming with on) - The German Odin, ruler of the Aesir.

    I am not a doctor, virologist, biologist, etc. I am a layman with a background in the physical sciences.

    Attempting to blog an nascent pandemic: Diary of a Flu Year

    Comment


    • #77
      Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

      Originally posted by tropical View Post
      #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. 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?

      #73: ...

      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)
      If it can move without selection, it can move faster with selection. In seasonal flu H274Y did it the HARD way (hitchhiking). Widespread Tamiflu usage is a real driver = SLAM DUNK (quickly).

      Comment


      • #78
        Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

        Originally posted by Mamabird View Post
        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.
        As you should be.

        Comment


        • #79
          Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

          Originally posted by niman View Post
          If it can move WITHOUT selection, it can move FASTER with selection. In seasonal flu H274Y did it the HARD way (hitchhiking). Widespread Tamiflu usage is a real driver = SLAM DUNK (quickly).
          Thank you Dr. niman.

          Now we can start to blame the decisional folks WHO - who leave us several years (after initial bird flu blankets) of widespread Tamiflu usage, instead of enforcing additionaly other meds at the same time

          Stil, I remember that widespread Tamiflu usage in Japan, wasn't blamed as an resistance precursor, at the time (?)

          Comment


          • #80
            Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

            Originally posted by niman View Post
            If it can move WITHOUT selection, it can move FASTER with selection. In seasonal flu H274Y did it the HARD way (hitchhiking). Widespread Tamiflu usage is a real driver = SLAM DUNK (quickly).
            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?

            .
            "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

            Comment


            • #81
              Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

              Originally posted by AlaskaDenise View Post
              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).

              Comment


              • #82
                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?

                Comment


                • #83
                  Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

                  Originally posted by niman View Post
                  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.

                  Comment


                  • #84
                    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.

                    Comment


                    • #85
                      Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

                      Originally posted by Mamabird View Post
                      No, the Shanghai isolate was the E627K mutation of the PB2 gene segment. Tamiflu resistance relates strictly to the NA segment.
                      Thanks Mamabird.

                      GW
                      The Doctor

                      Comment


                      • #86
                        Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

                        Originally posted by niman View Post
                        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.

                        Comment


                        • #87
                          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)

                          Comment


                          • #88
                            Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

                            Originally posted by Mamabird View Post
                            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.

                            Comment


                            • #89
                              Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

                              Originally posted by pjie2 View Post
                              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.
                              Last edited by sharon sanders; June 30, 2009, 06:11 AM. Reason: typos

                              Comment


                              • #90
                                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

                                Comment

                                Working...
                                X