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Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

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  • Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum
    1: Clin Infect Dis. 2006 Dec 15;43(12):1555-1561. Epub 2006 Nov 8.<SCRIPT language=JavaScript1.2><!--var PopUpMenu2_LocalConfig_jsmenu3Config = [ ["ShowCloseIcon","yes"], ["Help","window.open('/entrez/query/static/popup.html','Links_Help','resizable=no,scrollbars= yes,toolbar=no,location=no,directories=no,status=n o,menubar=no,copyhistory=no,alwaysRaised=no,depend =no,width=400,height=500');"], ["TitleText"," Links "]]var jsmenu3Config = [ ["UseLocalConfig","jsmenu3Config","",""]]//--></SCRIPT><SCRIPT language=JavaScript1.2><!--var Menu17109288 = [ ["UseLocalConfig","jsmenu3Config","",""], ["Books","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_AbstractPlus&cmd=Retrieve& db=pubmed&list_uids=17109288&dopt=Books'","",""], ["LinkOut","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_AbstractPlus&cmd=Retrieve& db=pubmed&list_uids=17109288&dopt=ExternalLink'"," ",""]]//--></SCRIPT> Links

    <DD class=abstract id=abstract17109288>Characterization of Multidrug-Resistant Influenza A/H3N2 Viruses Shed during 1 Year by an Immunocompromised Child.Research Center in Infectious Diseases of the Centre Hospitalier Universitaire de Quebec and Laval University, Quebec, G1V 4G2, Canada. Guy.Boivin@crchul.ulaval.ca.
    Background. Development of influenza drug resistance is an important problem in immunocompromised children that could result in treatment failure and viral transmission to others.Methods. A total of 17 influenza A/H3N2 isolates were recovered over a period of 1 year from an immunocompromised child who was initially treated with oseltamivir and then with amantadine and zanamivir for viral pneumonitis. Drug susceptibility phenotypes to oseltamivir, zanamivir, and peramivir were evaluated by neuraminidase (NA) inhibition assays, and sequence analysis of key viral genes (i.e., M2, NA, and hemagglutinin [HA]) was performed. The impact of NA mutations identified in oseltamivir-resistant isolates was analyzed using recombinant NA proteins.Results. An influenza A variant with NA mutations E59G, E119V, and I222V was first detected after 38 days of oseltamivir treatment. In an NA inhibition assay, this variant was 274 times more resistant to oseltamivir than the original isolate but was susceptible to zanamivir. The I222V substitution enhanced the level of oseltamivir resistance that was primarily conferred by the E119V mutation in recombinant NA proteins. Remarkably, the E119V mutation persisted for 8 months after cessation of oseltamivir. Amantadine therapy led to rapid emergence of the M2 mutation S31N, which is known to confer amantadine resistance. The patient shed the virus intermittently while receiving nebulized zanamivir therapy despite the absence of a resistance phenotype, which could be the result of nonoptimal drug delivery and impaired host immunity.Conclusions. This study highlights the potential for emergence and persistence of multidrug-resistant influenza isolates in immunocompromised subjects even after cessation of treatment, reinforcing the need for development of new anti-influenza compounds.
    PMID: 17109288 [PubMed - as supplied by publisher]

    </DD>
    Last edited by Mingus; November 22, 2006, 11:41 AM.

  • #2
    Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

    Ouch!

    If this as an indication of what we may expect from an H5N1 overlap with HIV+ patients then we have a serious problem if and when it occurs in countries with the resources to treat someone with both disease.

    There has been much speculation on the clinical course of H5N1 infection within the HIV+ population. If the virulence of H5N1 is primarily due to immune overreaction then, like this poor soul, HIV patients may suffer flu for a long time and be a source of drug resistance, on the other hand if it is 'just' a nasty flu regretfully they may not survive long enough for this to become a problem.

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    • #3
      Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child

      Also...
      1. Klimov AI, Rocha E, Hayden FG, Shult PA, Roumillat LF, Cox NJ. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients: detection by polymerase chain reaction-restriction analysis. J Infect Dis. 1995;172:1352?5.

      Comment


      • #4
        Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

        This appears to confirm R. Webster's observations, but is the shedding time longer in this case?

        .
        "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

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        • #5
          Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child

          I don't have access to the full article.



          Published by the University of Chicago Press
          <hr align="left" noshade="noshade" width="90%"> <table border="0" cellpadding="6" cellspacing="2" width="90%"> <tbody><tr> <td align="right" bgcolor="peachpuff" valign="top" width="5%"> Title </td> <td align="left" valign="top">Recovery of Drug-Resistant Influenza Virus from Immunocompromised Patients: A Case Series</td> </tr> <tr> <td align="right" bgcolor="peachpuff" valign="top"> Author(s) </td> <td align="left" valign="top">Michael G. Ison, Larisa V. Gubareva, Robert L. Atmar, John Treanor, and Frederick G. Hayden</td> </tr> <tr> <td align="right" bgcolor="peachpuff" valign="top"> Identifiers </td> <td align="left" nowrap="nowrap" valign="top"> The Journal of Infectious Diseases, volume 193 (2006), pages 760?764
          <code>DOI: 10.1086/500465</code>
          <code>PubMed ID: 16479508</code>
          </td></tr> <tr> <td align="right" bgcolor="peachpuff" valign="top"> Availability </td> <td align="left" valign="top"> This site: PS | HTML | PDF (88.5k) </td> </tr> <tr> <td align="right" bgcolor="peachpuff" valign="top"> Copyright </td> <td align="left" valign="top">? 2006, the Infectious Diseases Society of America.</td> </tr> <tr> <td align="right" bgcolor="peachpuff" valign="top"> Abstract </td> <td align="left" valign="top">Influenza virus with resistance to antiviral drugs emerges with increased frequency in immunocompromised patients and can limit the benefit of M2 and neuraminidase (NA) inhibitors. We document 3 cases of influenza in severely immunocompromised patients from whom virus variants with molecular markers of resistance to anti-influenza drugs were recovered. Virus variants recovered from 2 patients had mutations in the M2, NA (with a previously recognized Glu119Val NA substitution), and hemagglutinin genes. We describe a novel Asp198Asn NA mutation in an influenza B virus and its decreased susceptibility to both oseltamivir and zanamivir.</td> </tr> </tbody></table> <hr align="left" noshade="noshade" width="90%"> <table border="0" cellpadding="0" cellspacing="0" width="90%"> <tbody><tr> <td align="left"> help@www.journals.uchicago.edu

          http://www.journals.uchicago.edu/cgi-bin/resolve?id=doi:10.1086/500465&erFrom=3158757823973642535Guest

          </td> </tr> </tbody></table> <!-- /cgi-bin/res-page.epl v1.0.3, Tue Dec 12 21:33:08 2006, Location.pm v1.9.2, Metadata.pm v1.3, Translate.pm v1.2, <ADDRESS>Apache/1.3.33 Server at www.journals.uchicago.edu Port 80</ADDRESS> -->
          "In the beginning of change, the patriot is a scarce man (or woman https://flutrackers.com/forum/core/i...ilies/wink.png), and brave, and hated and scorned. When his cause succeeds, the timid join him, for it then costs nothing to be a patriot."- Mark TwainReason obeys itself; and ignorance submits to whatever is dictated to it. -Thomas Paine

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          • #6
            Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

            why did they keep that secret over the period of one year ?
            A period during which many nations increased their prepandemic
            stockpile of Tamiflu considerably.
            A period during which funding of research for other flu-drugs
            was withhold due to trust in Tamiflu.

            What else is in the pipeline worldwide, that we don't yet know about ?

            Something must be wrong with the whole publishing process.
            I'm interested in expert panflu damage estimates
            my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

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            • #7
              Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

              so, they found resistance to Oseltamivir and Amantadine,
              but not to Zanamivir or Peramivir (is it already available ?)

              But Zanamivir was not so effective presumably because of
              the inhaling procedure.

              The Tamiflu-resistant strain was viable in the Child, although
              we don't know, how capable it was in infecting other people.
              It must also be capable of leaving the body, surviving in the environment,
              entering another host, resisting it's immune response and replicating
              in the corresponding respiratory cells, not just persisting
              in the body as in that example.

              They should test the mutated-virus' capability to do this
              in ferrets.
              Well, maybe they have already but won't tell us before next year...
              I'm interested in expert panflu damage estimates
              my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

              Comment


              • #8
                Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

                "Reisitance is futile"------ or not! Webster et al have suggested what we have also expected. The war of mutations favors those that reassort/recombine with the most rapine velocity. When it comes to virus' evolution, H5N1 wins the Darwins favorite pet award.
                Too bad we are the meal
                21st Century Omega Man

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                • #9
                  Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

                  why did they keep that secret over the period of one year ?
                  A period during which many nations increased their prepandemic
                  It is not really a secret. Long persistence, severe disease and an unusual pathogenesis is comm in immunocompromised patients, frequently outgoing from hitherto quiescent chronic infections (typically with relatively "benign" microorganisms like herpes or cytomegaly) that are reactivated.

                  Volume 348:867-868 February 27, 2003 Number 9 <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>
                  Prolonged Shedding of Multidrug-Resistant Influenza A Virus in an Immunocompromised Patient<o:p></o:p>
                  http://content.nejm.org/cgi/content/extract/348/9/867<o:p></o:p>
                  Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings. <o:p></o:p>
                  <o:p></o:p>
                  To the Editor: Immunocompromised patients can persistently shed influenza, increasing the potential for resistance to antiviral drugs and for nosocomial transmission.1,2 We report the case of a 23-year-old man with acute lymphocytic leukemia who underwent transplantation of T-cell?depleted hematopoietic stem cells from his HLA-mismatched brother in August 1999 after receiving total body irradiation, thiotepa, fludarabine, and antithymocyte globulin. After transplantation, graft-versus-host disease developed (requiring treatment with prednisone and azathioprine), along with transplant-related nephropathy, avascular necrosis in both ankles, and restrictive lung disease. <o:p></o:p>
                  <o:p></o:p>
                  Last edited by Ganseerpel; January 19, 2007, 05:36 AM.

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                  • #10
                    Re: Multidrug-Resistant Influenza A Viruses Shed 1 Year by an Immunocompromised Child.

                    Numerous and contradictious are the estimates about the long term effectiveness of oseltamivir . Here is another report of moderate resistance to Tamiflu in non-immunecompromised persons

                    Avian influenza - situation in Egypt - update
                    18 January 2007
                    Viruses with a genetic mutation, linked in laboratory testing to moderately reduced susceptibility to oseltamivir, have been discovered in two persons previously reported with H5N1 infections in Egypt. Both patients had been on treatment with oseltamivir for two days before the clinical samples that yielded the viruses were taken.

                    Full text: http://www.who.int/csr/don/2007_01_18/en/index.html

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