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Emergence of seasonal influenza viruses type A/H1N1 with oseltamivir resistance in some European Countries at the start of the 2007-8 influenza

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  • #16
    Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

    Thank you ironorehopper, and Dr. Niman:

    "... Clade 1 viruses appear to be 15 to 30 times more sensitive to oseltamivir than clade 2 isolates from Indonesia and Turkey,56,57 although the possible clinical relevance of such differences in oseltamivir susceptibility remains to be determined.
    During oseltamivir therapy, the emergence of highly resistant variants with an H274Y neuraminidase mutation may be associated with a fatal outcome. ..."
    ___
    Influenza experts admitted today that they have been startled by the discovery this season of an unexpectedly high number of human flu viruses that appear to be naturally resistant to Tamiflu, the drug that countries around the world are stockpiling for use in the next flu pandemic.
    The viruses have been isolated from people infected with influenza A viruses of the H1N1 subtype in a number of European countries.
    And Canada's National Microbiology Laboratory in Winnipeg has reported finding one such virus, in a child who is believed to have been infected with influenza in Sudan before travelling to Canada.
    ___
    "... At the Los Alamos sequence database, there are 1030 N1 sequences from H1N1 human isolates. 340 are from 2007 and all of the sequences below are from 2007.

    Thus, although the percentage of samples was low, all were from 2007 and all were Solomon Island-like.

    These Solomon-Island lake sequences trace back to Asia, where Tamiflu blankets are frequently applied in the treatment of H5N1.

    The N1 in H5N1 has donor sequences for human N1 in the region adjacent to the acquisition which generates H274Y, which is the precise change found in the most common form of oseltamivir resistance in H5N1 patients, primarily in Vietnam. ..."
    ___

    From the above, the Tamiflu blankets aplied on humans beeing infected also/only with seasonal flu, induced an insurgence of an Tamiflu resistant strain of human seasonal flu AH1N1, which is now disseminated in USA/Canada/Europe/.../.

    On the other side EU wroted:
    "... Therefore it can be assumed that viruses carrying the H274Y mutation represent community influenza transmissions in Europe (rather than importations or a focused outbreak).""

    Comment


    • #17
      Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

      Originally posted by tropical View Post
      Thank you ironorehopper, and Dr. Niman:

      "... Clade 1 viruses appear to be 15 to 30 times more sensitive to oseltamivir than clade 2 isolates from Indonesia and Turkey,56,57 although the possible clinical relevance of such differences in oseltamivir susceptibility remains to be determined.
      During oseltamivir therapy, the emergence of highly resistant variants with an H274Y neuraminidase mutation may be associated with a fatal outcome. ..."
      ___
      Influenza experts admitted today that they have been startled by the discovery this season of an unexpectedly high number of human flu viruses that appear to be naturally resistant to Tamiflu, the drug that countries around the world are stockpiling for use in the next flu pandemic.
      The viruses have been isolated from people infected with influenza A viruses of the H1N1 subtype in a number of European countries.
      And Canada's National Microbiology Laboratory in Winnipeg has reported finding one such virus, in a child who is believed to have been infected with influenza in Sudan before travelling to Canada.
      ___
      "... At the Los Alamos sequence database, there are 1030 N1 sequences from H1N1 human isolates. 340 are from 2007 and all of the sequences below are from 2007.

      Thus, although the percentage of samples was low, all were from 2007 and all were Solomon Island-like.

      These Solomon-Island lake sequences trace back to Asia, where Tamiflu blankets are frequently applied in the treatment of H5N1.

      The N1 in H5N1 has donor sequences for human N1 in the region adjacent to the acquisition which generates H274Y, which is the precise change found in the most common form of oseltamivir resistance in H5N1 patients, primarily in Vietnam. ..."
      ___

      From the above, the Tamiflu blankets aplied on humans beeing infected also/only with seasonal flu, induced an insurgence of an Tamiflu resistant strain of human seasonal flu AH1N1, which is now disseminated in USA/Canada/Europe/.../.

      On the other side EU wroted:
      "... Therefore it can be assumed that viruses carrying the H274Y mutation represent community influenza transmissions in Europe (rather than importations or a focused outbreak).""
      The startled "experts" should also be startled by the fact that H274Y is coded by C763T and the transition is IDENTICAL in human H1N1 and human/avian H5N1 (and is flying around in mute swans with Qinghai H5N1 in Astrakhan in 2005).

      Just another of the "coincidences" of random mutations!

      Comment


      • #18
        Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

        Some ordinary flu strains resist Tamiflu in study


        Sarah Edmonds and Douwe Miedema , Reuters


        STOCKHOLM/ZURICH - Some seasonal influenza viruses are resistant to Roche Holding AG's Tamiflu, a study showed, but Roche said no doubts had been raised about the drug's power to combat any deadly bird flu pandemic.
        Of 148 samples of influenza A virus isolated from 10 European countries during November and December, 19 showed signs of resistance to Tamiflu, the European Centre for Disease Control said on Monday, citing a preliminary survey.
        Of 16 samples from Norway, 12 tested positive for resistance against Tamiflu, which is also known by the generic name oseltamivir, Stockholm-based ECDC said.
        View Larger Image A warehouse manager takes a carton of Tamiflu, which contains the antiviral drug oseltamivir, for packing at a pharmaceuticals storage facility in Singapore March 21, 2007. Sewage systems do not break down Tamiflu, which means the main weapon against bird flu could seep into natural waters and make certain viruses resistant to the drug during a pandemic, Swedish researchers said on Wednesday. REUTERS/Nicky Loh



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        "Given the initial indication of a high level of resistance to oseltamivir in the A H1N1 viruses circulating in Norway, late last week ... the Norwegian authorities notified their EU partners and the World Health Organization (WHO) of this situation," the ECDC said.
        Tamiflu sales have been lacklustre as Roche completed government orders for pandemic influenza stockpiles to fight a possible pandemic spread among humans of the deadly H5N1 virus, which so far has mainly killed birds.
        The resistant strains found by the study were normal seasonal flu viruses, and not avian or pandemic flu, Roche said. The study was also too small to draw firm conclusions.
        "These are preliminary results, which are in contrast to previous years, when little or no resistance to Tamiflu was observed," a spokeswoman said.
        "More extensive surveillance globally is required to establish the relative prevalence and geographical distribution of the resistant viruses," she said.
        Markets shrugged off the results of the study and Roche shares were down 0.7 percent by 1100 GMT, roughly in line with the Dow Jones Stoxx health index.
        "The nature of the viruses does not make resistance surprising in our view," Landsbanki Kepler said in a research note, adding that the Tamiflu's limited usefulness against ordinary flu strains had long been known.
        The H5N1 avian flu virus, wiping out bird flocks from Indonesia to Africa, rarely infects people but has killed 221 out of 353 people sick since the virus re-emerged in Hong Kong in 2003, according to the World Health Organization.
        The ECDC institute said the Norwegian Public Health Institute late last week published an advisory to doctors and the public on its website.
        "At this stage it is impossible to say what the level of resistance is in influenza across Europe," it said.
        "However from the limited data, the proportion of influenza viruses exhibiting resistance to oseltamivir must be significant, but not as high as in Norway."
        It said the oseltamivir-resistant strain of A(H1N1) did not seem to make patients any sicker than non-resistant varieties.
        (Editing by Rory Channing/Elizabeth Fullerton)

        http://www.canada.com/topics/bodyand...a-f20dc8ddd44e

        Comment


        • #19
          Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

          Commentary at

          http://www.recombinomics.com/News/01...iflu_H1N1.html

          Comment


          • #20
            Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

            INFLUENZA A (H1N1) VIRUS, OSELTAMIVIR RESISTANCE (02): EUROPE
            ************************************************** ***********
            A ProMED-mail post
            <http://www.promedmail.org>
            ProMED-mail is a program of the
            International Society for Infectious Diseases
            <http://www.isid.org>

            Date: Tue 29 Jan 2008
            Source: European Centre for Disease Prevention and Control (ECDC) [edited]
            <http://ecdc.europa.eu/Press/press_releases/080127_pr.html>


            Resistance to oseltamivir (Tamiflu) found in some European influenza virus
            samples
            ---------------------------------------------------------------------------
            Preliminary results from a survey of antiviral drug susceptibility among
            seasonal influenza viruses circulating in Europe has revealed that some of
            the A (H1N1) viruses in circulation this winter [2007-2008] are resistant
            to the antiviral drug, oseltamivir (brand name Tamiflu). So far, 148
            samples of influenza A(H1N1) viruses isolated during November and December
            [2007] from 10 European countries [see comment below - Mod.CP] have been
            tested by the EU funded VIRGIL [European surveillance network for vigilance
            against viral resistance.] Of the 148 samples, 19 showed evidence of
            resistance to oseltamivir.

            Of the samples that tested positive for resistance to oseltamivir 12 came
            from Norway. This was from a total of 16 virus samples sent for testing.
            Given the initial indication of a high level of resistance to oseltamivir
            in the A H1N1 viruses circulating in Norway, late last week [21-27 Jan
            2008] once the information came to their attention, the Norwegian
            authorities notified their EU partners and the World Health Organization
            (WHO) of this situation. The Norwegian Public Health Institute also
            published an advisory notice to doctors and the public on its website that
            evening.

            Experts from the European Centre for Disease Prevention and Control (ECDC),
            the European Commission, and WHO are currently assessing the significance
            of the data from the VIRGIL network. An interim joint assessment will be
            published in the coming days, based on the limited data currently available.

            At this stage it is impossible to say what the level of resistance is in
            influenza across Europe. However from the limited data, the proportion of
            influenza viruses exhibiting resistance to oseltamivir must be significant,
            but not as high as in Norway. People who become ill with the oseltamivir
            resistant strain of A(H1N1) do not appear to become any [sicker] than
            people infected with "normal" seasonal influenza. That said, it should be
            remembered that any influenza A can cause severe disease or death in
            vulnerable people (older people, those with debilitating illnesses, and the
            very young).

            For further information see ECDC's Interim Risk Assessment available at
            <http://ecdc.europa.eu/pdf/080127_os.pdf>.

            --
            communicated by:
            Professor Angus Nicoll CBE
            Senior Expert, Influenza Coordination
            European Centre for Disease Prevention and Control (ECDC)
            17183, Stockholm
            Sweden
            <Angus.Nicoll@ecdc.europa.eu>

            [The Summary Statement of the ECDC Risk Assessment -- 27 Jan 2008 --
            Emergence of seasonal influenza viruses type A/H1N1 with oseltamivir
            resistance in some European Countries at the start of the 2007-2008
            influenza season -- indicates that Denmark, France, and the United Kingdom
            are the other countries in addition to Norway that have detected
            oseltamivir-resistant A(H1N1) influenza virus.

            The full Summary Statement reads: "Ordinary seasonal influenza viruses with
            significant resistance to the antiviral oseltamivir (Tamiflu) have been
            detected within the earliest part of this winter's influenza epidemics in
            Europe. The viruses are known as influenza A/H1N1 (H274Y), and they were
            fully sensitive to other influenza antivirals. These viruses have been
            detected by a European research and surveillance project known as VIRGIL
            (<http://www.virgil-net.org/>), which has been undertaking routine
            surveillance for resistance in circulating influenza strains since
            2004-2005. H1N1 viruses are predominant in this winter's epidemics
            worldwide, and these resistant viruses are a new phenomenon this winter. A
            limited amount of specialist testing has been undertaken for 10 countries
            and a proportion of A/H1N1 viruses detected in 4 countries Denmark, France,
            Norway, and the UK, have been found resistant to oseltamivir. Overall in
            Europe the proportion with oseltamivir resistant is around 13 per cent but
            the proportions resistant are variable with Norway showing a markedly high
            proportion resistant (12 of 16). If the 16 Norwegian viruses are excluded
            the proportion with resistant would fall to around 5 per cent. Data from
            Norway indicate that these viruses were transmitted in the country. To date
            there are no reports that they are making people any more ill than do other
            influenza A viruses. Normally A/H1N1 viruses as a group cause milder
            disease than some other human influenza viruses. However it must be
            realised that all influenza A viruses are potentially lethal for vulnerable
            individuals (the old and the very young and those with chronic debilitating
            conditions). It also needs to be remembered that antiviral resistant is a
            relative not absolute term. Patients ill with viruses that are deemed
            resistant in the laboratory often still seem to benefit when they receive
            antivirals." - Mod.CP]

            [see also:
            Influenza A (H1N1) virus, oseltamivir resistance - Norway 20080128.0361
            2007
            ---
            Avian influenza, human (101): Indonesia, Tamiflu resistance 20070622.2021
            Influenza B virus, neuraminidase inhibitor resistance 20070404.1143
            Avian influenza, human (15): Egypt, drug resistance 20070119.0253
            Avian influenza, human (15): Egypt, drug resistance 20070118.0238
            2006
            ---
            Avian influenza, human (162): oseltamivir resistance 20061010.2907
            2005
            ---
            Avian influenza, human - East Asia (203): Tamiflu resistance 20051222.3659
            Influenza viruses, drug resistance (06) 20051016.3021
            Influenza viruses, drug resistance (05) 20051015.3014
            Influenza viruses, drug resistance (04) 20051015.2999
            Influenza viruses, drug resistance (03) 20051007.2924
            Influenza viruses, drug resistance (02): RFI 20051001.2878
            Influenza viruses, drug resistance 20050930.2863
            2004
            ---
            Avian influenza A (H5N1) virus, drug resistance (02) 20040127.0316
            Avian influenza A (H5N1) virus, drug resistance 20040125.0298
            2001
            ---
            Influenza virus, neuraminidase inhibitor resistance (02) 20010928.2372
            2000
            ---
            Influenza virus, neuraminidase inhibitor resistance 20010926.2350]

            ...............cp/mj/sh

            Comment


            • #21
              Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

              Originally posted by niman View Post
              Commentary

              H1N1 Tamiflu Resistance in the United States in 2007

              Recombinomics Commentary 03:11
              January 29, 2008

              The European Centres for Disease Control said that while Tamiflu could still provide benefits, 13 per cent of samples of the H1N1 seasonal flu virus affecting Europe tested last November and December ? most in Norway ? contained a mutation associated with high levels of resistance.

              The above comments describe the appearance of the oseltamivir resistance marker, H274Y, in recent H1N1 isolates in Europe.

              However, a search of public sequences identifies H274Y suddenly appearing in 2007 H1N1 isolates from the United States (see list below. The number of complete human influenza sequences has grown steadily, largely because of the NIAID influenza sequencing project. At the Los Alamos sequence database, there are 1030 N1 sequences from H1N1 human isolates. 340 are from 2007 and all of the sequences below are from 2007. Thus, although the percentage of samples was low, all were from 2007 and all were Solomon Island-like.

              These Solomon-Island lake sequences trace back to Asia, where Tamiflu blankets are frequently applied in the treatment of H5N1. The N1 in H5N1 has donor sequences for human N1 in the region adjacent to the acquisition which generates H274Y, which is the precise change found in the most common form of oseltamivir resistance in H5N1 patients, primarily in Vietnam.

              In 2005 a milder version of H5N1 emerged in northern Vietnam. However, initial data supporting widespread mild infections of H5N1 were denied, even after initial results were independently confirmed.

              Testing continued until negatives were achieved. The possibility of widespread H5N1 in people in Vietnam was largely discounted and use of Tamiflu in contacts of suspect patients was common.

              Now Tamiflu chickens may be coming home to roost.

              ISDN282211 A/Hawaii/21/2007 H1N1
              ISDN282224 A/Hawaii/28/2007 H1N1
              ISDN282222 A/Hawaii/28/2007 H1N1
              CY027037 A/Kansas/UR06-0104/2007 H1N1
              ISDN282240 A/Minnesota/23/2007 H1N1
              ISDN263890 A/Texas/31/2007 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


              • #22
                Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                Originally posted by niman View Post
                Commentary

                H5N1 Tamiflu Blankets and Resistance in European H1N1

                Recombinomics Commentary 16:58
                January 29, 2008

                Influenza experts admitted today that they have been startled by the discovery this season of an unexpectedly high number of human flu viruses that appear to be naturally resistant to Tamiflu, the drug that countries around the world are stockpiling for use in the next flu pandemic.

                The viruses have been isolated from people infected with influenza A viruses of the H1N1 subtype in a number of European countries.

                The World Health Organization is convening a virtual meeting of experts tomorrow to try to get a handle on how far afield the resistant virus has been found, how common it is and what the findings signify.

                "I think this is a very concerning change in influenza virus resistance patterns," Dr. Frederick Hayden, a leading antiviral expert and a member of the WHO's Global Influenza Program, said from Geneva.

                The above comments express surprise and concern regarding the sudden appearance of oseltamivir (Tamiflu) resistance in H1N1 seasonal flu, and fail to draw the connection between this dramatic change and the widespread use of Tamiflu blankets to treat H5N1. The change in the human N1 in H1N1 is identical to the avian/human N1 change in H5N1. Both N1’s have created H294Y via the identical nucleotide change, C763T. Although this change has been found in H5N1 patients in Vietnam and Indonesia treated with Tamiflu, it has also been found avian isolates, including mute swans in Astrakhan in 2005 (A/swan/Astrakhan/Russia/Nov-2/2005(H5N1) and A/swan/Astrakhan/1/2005(H5N1)) .

                Question of fitness have been raised previously, but the presence of H294Y in wild birds flying around Europe as early as 2005 indicates the change does not carry a significant fitness penalty. Moreover, H294Y was found as early as 2002 in a chicken in Hong Kong, A/chicken/Hong Kong/3123.1/2002(H5N1).

                H294Y can move from the N1 in H5N1 to the N1 in H1N1 via recombination. The opportunity for co-infections involving seasonal and pandemic influenza can be found in patients with mild H5N1 infections.

                Such infections were suspect in 2005 in northern Vietnam. In contrast to outbreaks in 2004, the case fatality rates of H5N1 in northern and southern Vietnam were dramatically different in early 2005. In the north the clusters were larger and the infections were milder, suggesting H5N1 in humans was becoming more common, and transmitting more efficiently. Almost 1000 samples were collected for analysis. H5N1 was detected locally, so samples were sent to the CDC in Atlanta for confirmation. Positives were also seen in Atlanta, so samples were repeatedly tested until they turned negative. However, the lab results had little effect of the H5N1 in circulation, which was commonly treated with Tamiflu.

                This treatment would select for human H1N1 or avian H5N1 with H294Y. This change began to appear in the United States in 2007. The isolates with H294Y were Solomon Island-like, which link back to Asia. Similarly, H5N1 outbreaks in the Middle East were also treated with Tamiflu. In Egypt, a scenario similarly to Vietnam developed in 2007. Early cases in the north were largely fatal, but outbreaks in southern Egypt were mild, again allowing for more efficient spread and co-infections with H1N1 seasonal flu. These co-infections would again create conditions for the movement of H294Y from H5N1 to H1N1 in areas where Tamiflu was used excessively.

                Thus, the appearance of H294Y began in 2007 and now is becoming increasingly common in human H1N1 in 2008.

                This increasing frequency of Tamiflu resistance in seasonal H1N1 is cause for concern, as is the potential for additional expansion in H5N1.


                .
                "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


                • #23
                  Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                  From Reveres EM:
                  http://scienceblogs.com/effectmeasur...n_seasonal.php

                  <FORM class=blogSearch action=http://scienceblogs.com/effectmeasure/fastsearch method=get></FORM>Tamiflu resistance in seasonal flu: the devil is in the details


                  "... The NA protein comes in 9 different forms. Humans are routinely infected with the N1 and N2 forms, and these aren't the same with respect to Tamiflu. The drugs were designed to work against the N2 form, which was the one where we had x-ray crystallography structures. Recently the N1 form was crystalized, permitting an investigation of the differences in how they react to these drugs. For Tamiflu to interfere with NA action it needs to nestle into a pocket. NA can change shape and for Tamiflu, but not Relenza, to work it needs to nestle into a pocket that forms during that shape change. It is thought the H274Y mutation causes Tamiflu resistance by preventing the formation of the pocket (the binding of Tamiflu is produced by rotating an amino acid near position 274 and its binding to another amino acid at position 224; it's complicated. See Moscona's Perspective in the New England Journal for more explanation). ..."

                  Comment


                  • #24
                    Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                    Originally posted by tropical View Post
                    From Reveres EM:
                    http://scienceblogs.com/effectmeasur...n_seasonal.php

                    <FORM class=blogSearch action=http://scienceblogs.com/effectmeasure/fastsearch method=get></FORM>Tamiflu resistance in seasonal flu: the devil is in the details


                    "... The NA protein comes in 9 different forms. Humans are routinely infected with the N1 and N2 forms, and these aren't the same with respect to Tamiflu. The drugs were designed to work against the N2 form, which was the one where we had x-ray crystallography structures. Recently the N1 form was crystalized, permitting an investigation of the differences in how they react to these drugs. For Tamiflu to interfere with NA action it needs to nestle into a pocket. NA can change shape and for Tamiflu, but not Relenza, to work it needs to nestle into a pocket that forms during that shape change. It is thought the H274Y mutation causes Tamiflu resistance by preventing the formation of the pocket (the binding of Tamiflu is produced by rotating an amino acid near position 274 and its binding to another amino acid at position 224; it's complicated. See Moscona's Perspective in the New England Journal for more explanation). ..."
                    This is old news and there is no devil in the detail. H274Y knocks down the efficiency of Tamiflu by 500-1000X, and Tamiflu effectiveness is borderline for N1, without the resistance.

                    Comment


                    • #25
                      Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                      Thank you Dr. Niman.

                      From bad to worst.

                      P.S.
                      The EM news pasus intention was to additionaly auto-respond to an myself previously posed question (in a case anybody watching this thread was thinking also that Tamiflu can contrasted all NA's):
                      " I always (wrongly?) think that the Tamiflu potential of usage is on ALL kind of flu virus strains.""
                      with the cited excerpts from one EM post:
                      "... Humans are routinely infected with the N1 and N2 forms.
                      ... Tamiflu. The drugs were designed to work against the N2 form, which was the one where we had x-ray crystallography structures.
                      ... For Tamiflu to interfere with NA action it needs to nestle into a pocket.
                      ... It is thought the H274Y mutation causes Tamiflu resistance by preventing the formation of the pocket, etc ..."

                      Comment


                      • #26
                        Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                        Tamiflu-resistant flu viruses found in Canada

                        Updated Wed. Jan. 30 2008 8:19 AM ET
                        The Canadian Press

                        <!-- dateline -->TORONTO <!-- /dateline -->-- Canada's National Microbiology Laboratory is reporting a high level of Tamiflu resistance among H1N1 viruses circulating so far this flu season in this country, one of a number of labs to see a phenomenon that is unsettling influenza experts. <!-- CPPara1End--><!-- CPPara2-->Nearly 10 per cent of H1N1 viruses tested so far this year by the Winnipeg lab are resistant to the drug, a cornerstone of pandemic planning for many countries around the globe. In the past, fewer than one per cent of circulating human flu viruses were thought to be resistant to Tamiflu. <!-- CPPara2End-->
                        <!-- CPPara3-->"That's quite a surprise," the lab's scientific director, Dr. Frank Plummer, said, noting the resistance mutation spotted in the Winnipeg testing is the same one that has been reported over the past few days from Norway, several other European countries and the United States. <!-- CPPara3End-->
                        Eight of 81 H1N1 viruses tested carry the H274Y mutation - one each from British Columbia and Newfoundland and Labrador, and six from Ontario. Plummer said that total includes one virus (from British Columbia) recovered from a child who is believed to have been infected in Sudan.
                        His surprise is shared by experts with the World Health Organization's Global Influenza Program, which convened a teleconference of about 50 scientists from leading influenza laboratories around the world Tuesday to try to get a handle on how far this virus has spread, how common it is in places where it is being found and what is driving the spread.
                        Dr. Frederick Hayden, a leading antiviral expert working at the WHO, said the resistance virus has been reported over a broad geographic range, both in terms of countries and within countries themselves.
                        "We do know that again within the countries that have the information, it's not just focal pockets. There are multiple sites, for example, within France or within Norway where this has been detected," he said from Geneva.
                        The United States has reported that 5.5 per cent of tested H1N1 viruses there are resistant to the drug. European countries known to have found resistant viruses include Norway, Denmark, France and the United Kingdom. Hayden suggested more countries have found these viruses, but said he wasn't at liberty to name names.
                        Perplexingly, Japan - the country that uses more Tamiflu by far than any other in the world - has not found any of these resistant viruses this flu season, Hayden said.
                        Reports worldwide still number in the "few dozens." But that is enough to send up red flags, especially given that in all of the cases where details are known, people who caught the virus hadn't taken Tamiflu.
                        It wouldn't be startling to see people who've used the drug shedding viruses that are resistant to it. Like antibiotic resistance, resistance to antiviral drugs can develop in people who use them, though rates of drug-triggered resistance are low with Tamiflu.
                        But it had been thought that viruses that acquired this H274Y resistance mutation would pay for that gain with a corresponding loss in their ability to transmit. The belief was that if they developed in someone using Tamiflu, they would be unlikely to infect contacts of that person and start to circulate more widely - in essence, that they would be too weak to compete with regular flu viruses in the race to infect human respiratory tracts.
                        These recent findings suggest the drug is more vulnerable to the development of drug resistance than had been previously thought, experts fear.
                        "This mutation is not going to affect the fitness of the viruses as much as we thought," said Jennifer McKimm-Breschkin, a virologist with Australia's Commonwealth Science and Industrial Research Organization in Melbourne.
                        McKimm-Breschkin was one of the scientists involved in the discovery of Tamiflu's competitor, Relenza. Though the two drugs are in the same class, Relenza is still effective against viruses with the H274Y mutation.
                        "We're now seeing the ability of this virus that we thought would not have the ability to compete (with unmutated viruses) spreading globally," she said, suggesting that doesn't bode well if H5N1 avian flu starts a pandemic. The same mutation creates Tamiflu resistance in H5N1 viruses.
                        Hayden said the appearance of resistant H1N1 viruses across such a broad expanse "does raise a lot of questions."
                        Dr. Joe Bresee, chief of flu epidemiology and prevention at the U.S. Centers for Disease Control, questioned Monday whether there was a true rise in the number of resistant viruses.
                        Bresee cautioned that increased influenza surveillance prompted by concerns over the H5N1 virus may be turning a spotlight on something that always existed but went unnoticed in the past.
                        Hayden disagreed, saying an international network of antiviral experts has been watching for this resistance pattern but it has only been found rarely.
                        "Basically it was present at very low frequencies, less than a half per cent. In most studies, (it was) not even detected. So I think this is a new phenomenon and one that we need to understand better."
                        He said work is already underway to try to catalogue cases and to sequence resistant viruses to see if their genomes hold clues to how the resistance arose.

                        http://www.ctv.ca/servlet/ArticleNew...130?hub=Canada

                        Comment


                        • #27
                          Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                          Commentary

                          http://www.recombinomics.com/News/01...274Y_H5N1.html

                          Comment


                          • #28
                            Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                            Just a short update and a question.

                            The use of Tamiflu in Norway is uncommon. Why do we see such high numbers of the mutation here?

                            70% (26 out of 37 ) viruses from different patients and from different parts of Norway have the mutation. (High level of resistance against Tamiflu)

                            This according to the latest update from The Norwegian Institute of Public Health(Folkehelsa)
                            (link)
                            http://fhi.no/eway/default.aspx?pid=...1:5569:1:::0:0

                            Comment


                            • #29
                              Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                              the virus probably came from outside Norway.
                              Much (most?) flu is reintroduced each winter from the tropes.

                              It is unclear, whether some flu also "oversummers".

                              So the mutation may have been created elsewhere
                              and the virus reached Norway by airplane or ship.

                              Just bad luck, that they have so many resistant viruses this year.
                              I'm interested in expert panflu damage estimates
                              my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                              Comment


                              • #30
                                Re: :::Emergence of seasonal influenza viruses type A/H1N1 with:::

                                most Tamiflu is used in Japan
                                number of reported H1-seasonal flu samples:

                                2007,40,Japan,5
                                2007,41,Japan,10
                                2007,42,Japan,22
                                2007,43,Japan,22
                                2007,44,Japan,23
                                2007,45,Japan,46
                                2007,46,Japan,71
                                2007,47,Japan,58
                                2007,48,Japan,128
                                2007,49,Japan,145
                                2007,50,Japan,230
                                2007,51,Japan,163
                                2007,52,Japan,62
                                2008,01,Japan,14
                                2008,02,Japan,55
                                2008,03,Japan,13

                                so, the peak was in week 50.
                                Could those cases be linked to Japan travellers ?
                                I'm interested in expert panflu damage estimates
                                my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                                Comment

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