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  • WHO. Recommended use of antivirals (August 21, 2009, edited)

    WHO. Recommended use of antivirals (August 21, 2009, edited)
    Recommended use of antivirals - Pandemic (H1N1) 2009 briefing note 8

    21 AUGUST 2009 | GENEVA


    WHO is today issuing guidelines for the use of antivirals in the management of patients infected with the H1N1 pandemic virus.

    The guidelines represent the consensus reached by an international panel of experts who reviewed all available studies on the safety and effectiveness of these drugs. Emphasis was placed on the use of oseltamivir and zanamivir to prevent severe illness and deaths, reduce the need for hospitalization, and reduce the duration of hospital stays.

    The pandemic virus is currently susceptible to both of these drugs (known as neuraminidase inhibitors), but resistant to a second class of antivirals (the M2 inhibitors).

    Worldwide, most patients infected with the pandemic virus continue to experience typical influenza symptoms and fully recover within a week, even without any form of medical treatment. Healthy patients with uncomplicated illness need not be treated with antivirals.

    On an individual patient basis, initial treatment decisions should be based on clinical assessment and knowledge about the presence of the virus in the community.

    In areas where the virus is circulating widely in the community, clinicians seeing patients with influenza-like illness should assume that the pandemic virus is the cause. Treatment decisions should not wait for laboratory confirmation of H1N1 infection.

    This recommendation is supported by reports, from all outbreak sites, that the H1N1 virus rapidly becomes the dominant strain.


    Treat serious cases immediately

    Evidence reviewed by the panel indicates that oseltamivir, when properly prescribed, can significantly reduce the risk of pneumonia (a leading cause of death for both pandemic and seasonal influenza) and the need for hospitalization.

    For patients who initially present with severe illness or whose condition begins to deteriorate, WHO recommends treatment with oseltamivir as soon as possible. Studies show that early treatment, preferably within 48 hours after symptom onset, is strongly associated with better clinical outcome. For patients with severe or deteriorating illness, treatment should be provided even if started later. Where oseltamivir is unavailable or cannot be used for any reason, zanamivir may be given.

    This recommendation applies to all patient groups, including pregnant women, and all age groups, including young children and infants.

    For patients with underlying medical conditions that increase the risk of more severe disease, WHO recommends treatment with either oseltamivir or zanamivir. These patients should also receive treatment as soon as possible after symptom onset, without waiting for the results of laboratory tests.

    As pregnant women are included among groups at increased risk, WHO recommends that pregnant women receive antiviral treatment as soon as possible after symptom onset.

    At the same time, the presence of underlying medical conditions will not reliably predict all or even most cases of severe illness. Worldwide, around 40% of severe cases are now occurring in previously healthy children and adults, usually under the age of 50 years.

    Some of these patients experience a sudden and very rapid deterioration in their clinical condition, usually on day 5 or 6 following the onset of symptoms.

    Clinical deterioration is characterized by primary viral pneumonia, which destroys the lung tissue and does not respond to antibiotics, and the failure of multiple organs, including the heart, kidneys, and liver. These patients require management in intensive care units using therapies in addition to antivirals.

    Clinicians, patients, and those providing home-based care need to be alert to warning signals that indicate progression to a more severe form of illness, and take urgent action, which should include treatment with oseltamivir.

    In cases of severe or deteriorating illness, clinicians may consider using higher doses of oseltamivir, and for a longer duration, than is normally prescribed.


    Antiviral use in children

    Following the recent publication of two clinical reviews, [1,2] some questions have been raised about the advisability of administering antivirals to children.

    The two clinical reviews used data that were considered by WHO and its expert panel when developing the current guidelines and are fully reflected in the recommendations.

    WHO recommends prompt antiviral treatment for children with severe or deteriorating illness, and those at risk of more severe or complicated illness. This recommendation includes all children under the age of five years, as this age group is at increased risk of more severe illness.

    Otherwise healthy children, older than 5 years, need not be given antiviral treatment unless their illness persists or worsens.


    Danger signs in all patients

    Clinicians, patients, and those providing home-based care need to be alert to danger signs that can signal progression to more severe disease. As progression can be very rapid, medical attention should be sought when any of the following danger signs appear in a person with confirmed or suspected H1N1 infection:
    • shortness of breath, either during physical activity or while resting
    • difficulty in breathing
    • turning blue
    • bloody or coloured sputum
    • chest pain
    • altered mental status
    • high fever that persists beyond 3 days
    • low blood pressure.


    In children, danger signs include fast or difficult breathing, lack of alertness, difficulty in waking up, and little or no desire to play.

    -
    [1] Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials. Shun-Shin M, Thompson M, Heneghan C et al. BMJ 2009;339:b3172; doi:10.1136/bmj.b3172
    [2] Prescription of anti-influenza drugs for healthy adults: a systemic review and meta-analysis. Burch J, Stock C et al. Lancet Infect Dis 2009; doi:10.1016/S1473-3099(09)70199-9
    -
    <cite cite="http://www.who.int/csr/disease/swineflu/notes/h1n1_use_antivirals_20090820/en/index.html">WHO | Recommended use of antivirals</cite>

  • #2
    Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

    This post is extremely important and from personal experience, it is enforced here: no prescription of Tamiflu for healthy children with no underlying conditions .

    Another news that I received this morning from a nurse at the same hospital: "we received a memo that we have a shortage in Tamiflu and it should be given only to children with transplants or severe long diseases.

    Comment


    • #3
      Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

      Originally posted by ironorehopper View Post
      WHO. Recommended use of antivirals (August 21, 2009, edited)
      [INDENT]Recommended use of antivirals - Pandemic (H1N1) 2009 briefing note 8

      21 AUGUST 2009 | GENEVA


      WHO is today issuing guidelines for the use of antivirals in the management of patients infected with the H1N1 pandemic virus.

      ...

      The pandemic virus is currently susceptible to both of these drugs (known as neuraminidase inhibitors), but resistant to a second class of antivirals (the M2 inhibitors).
      No, that is not the case. Tamiflu resistance in pandemic H1N1 viruses is now a well established FACT. The only uncertainties remain around their frequency, the rate of change in resistance frequency, and geographic distribution of resistant viruses among host populations?

      As Niman and others have indicated before, it seems highly likely that current sampling and sequencing strategies are highly biased and thus presently incapable of determining these freuqnecies and rates with any degress of accuracy.

      BUT such data are critical if RESPONSIBLE advice is to be provided on antiviral usage. IRRESPONSIBLE advice on antiviral use (ie. in an environment of IGNORANCE) will continue to cost lives.

      ...

      Worldwide, most patients infected with the pandemic virus continue to experience typical influenza symptoms and fully recover within a week, even without any form of medical treatment. [B]Healthy patients with uncomplicated illness need not be treated with antivirals.

      ...

      At the same time, the presence of underlying medical conditions will not reliably predict all or even most cases of severe illness. Worldwide, around 40% of severe cases are now occurring in previously healthy children and adults, usually under the age of 50 years.

      ...

      Some of these patients experience a sudden and very rapid deterioration in their clinical condition, usually on day 5 or 6 following the onset of symptoms.


      Studies show that early treatment, preferably within 48 hours after symptom onset, is strongly associated with better clinical outcome.

      Does anyone spot a fatal flaw in the WHO advice?

      If a clinician cannot reliability predict whether an otherwise healthy infected patient might develop a rapid, life-threatening condition up to 5 or 6 days after the onset of symptoms, and knowing that in order to be of much use, antivirals need to be administered within 48 hours of symptoms, how does this add up?

      It doesn't. The entire purpose of administering antivirals post infection is to reduce the risk of a severe outcome. Advising clinicians against treating people with no underlying health conditions is extremely FOOLISH. Pandemic H1N1 IS the only underlying health condition for 20-50% of deaths that have occurred!!


      ...

      Where oseltamivir is unavailable or cannot be used for any reason, zanamivir may be given.

      This recommendation applies to all patient groups, including pregnant women, and all age groups, including young children and infants.

      ...

      Clinicians, patients, and those providing home-based care need to be alert to warning signals that indicate progression to a more severe form of illness, and take urgent action, which should include treatment with oseltamivir.

      ...

      In cases of severe or deteriorating illness, clinicians may consider using higher doses of oseltamivir, and for a longer duration, than is normally prescribed.
      I don't know about you but I get a strong sense that the WHO is very keen to push Tamiflu. You would be forgiven for thinking that the ONLY remaining effective antiviral, Relenza, was very poor second choice.

      After reading this rubbish, one would be forgiven for being more confused than ever. Not only does this advice ignore the clinical evidence that itself presents but if it were followed it is clear that many needless fatalities will occur that would otherwise not occur.

      Government Purchasers should note that Tamiflu now has a VERY limited life-span that cannot be extended simply by using it less frequently. This is the lesson the WHO should have learned from the rapid, silent, ubuiquitous spread of the H274Y resistance polymorphism in seasonal H1N1 populations in 2007/08...IN THE ABSENCE OF TAMIFLU USE.

      Governments wishing otherwwise are living in a fools paradise and will thoroughly deserve the contempt of its population.

      Comment


      • #4
        Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

        Given the relative scarcity worldwide of anti-virals, do you have any opinion about this:

        Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents

        David S. Fedson




        also - Can you comment on the possibility of novel H1N1 09 becoming more virulent? What might happen when this virus becomes endemic in areas that are also experiencing widespread H5N1 infections in the environment, including a history of human infections?


        Thank you.

        Comment


        • #5
          Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

          This is the lesson the WHO should have learned from the rapid, silent, ubuiquitous spread of the H274Y resistance polymorphism in seasonal H1N1 populations in 2007/08...IN THE ABSENCE OF TAMIFLU USE.
          Is there ANY official source relating this fact?

          Even one????

          Prior to the emergence of H1N1, I believe official explanations about the resistance without tamiflu, were "baffling", "mysterious", etc. It implied that what was occuring was abnormal, rare, anything but something to be considered as SOP for influenza.

          .
          "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


          • #6
            Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

            Originally posted by Florida1 View Post
            Given the relative scarcity worldwide of anti-virals, do you have any opinion about this:

            Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents

            David S. Fedson




            also - Can you comment on the possibility of novel H1N1 09 becoming more virulent? What might happen when this virus becomes endemic in areas that are also experiencing widespread H5N1 infections in the environment, including a history of human infections?


            Thank you.
            Florida

            I do have some opinions and thoughts on the Fedson paper (which I think is insightful - though perhaps not entirely accurate) which I will be happy to post but will need to return to this a little later...

            Comment


            • #7
              Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

              Originally posted by AlaskaDenise View Post
              Is there ANY official source relating this fact?

              Even one????

              Prior to the emergence of H1N1, I believe official explanations about the resistance without tamiflu, were "baffling", "mysterious", etc. It implied that what was occuring was abnormal, rare, anything but something to be considered as SOP for influenza.

              .
              As I recall, the only country that extensively administered Tamiflu for seasonal flu was Japan. But buried somewhere here, most likely in a Niman post, there was evidence of worldwide resistance of seasonal flu to Tamiflu that was not linked to over prescription in Japan or anywhere else. I leave to the genetics guys to explain it, but it certainly wasn't magic. In any case, as I understand it, certain strains of last year's seasonal flu were almost 100% resistant to Tamiflu and ARR_309 suggests that it won't be very long until Tamiflu is no longer useful in battling the novel H1N1 virus.

              Comment


              • #8
                Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

                Al - thanks for filling in the blanks that those following this issue for 2-3 years have taken for granted.

                Just for clarification.....

                I believe ARR_309, myself, & Al are all on the same page, which is:

                Tamiflu usage is being discouraged with the explanation it will lead to resistance, when in fact, the increasing resistance is mostly (but not entirely) due to the fact it picked up the applicable gene (NA/274Y) from old seasonal H1N1.

                The unfortunate outcome of this ill-advised policy is avoidable deaths.

                And as Al points out - "it won't be very long until Tamiflu is no longer useful in battling the novel H1N1 virus" - probably more due to gene-acquisition, rather than tamiflu-usage.
                Is the above a fair statement?

                .
                "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


                • #9
                  Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

                  I think you have stated my position clearer than I did. I think we all agree that Tamiflu resistance in novel H1N1 will not result from over prescription and use, it will result from the acquistion or changes of H274Y or Pro453Ser.

                  The bottom line here is that these two genetic changes -- in NA and Pro453Ser -- are associated and seem to be related to the unexpected fitness of Tamiflu resistant seasonal H1N1.
                  http://www.flutrackers.com/forum/sho...71&postcount=1

                  Comment


                  • #10
                    Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

                    I beleive it will be aquired by recombination and not reassortment.

                    Comment


                    • #11
                      Re: WHO. Recommended use of antivirals (August 21, 2009, edited)

                      Since to get Reassortment you have to get to similar viruses in the same cell. Then they exchange genetic material. The RNA of a influenza virus has eight genome segments. H274Y is in the neuraminidase (NA) portion. To get recombination you have to have a strand of genetic material from the DNA or RNA broken down and then it joins to a DNA molecule. So therefore I believe that Recombination is a more likely scenario to get H274Y, the Oseltamivir resistance.

                      Comment

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