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  • Bird flu 'still a major threat'

    Source: http://news.bbc.co.uk/2/hi/health/7457054.stm

    Bird flu 'still a major threat'
    By Fergus Walsh
    Medical correspondent, BBC News
    Video

    The world is still at risk from a new pandemic strain of flu according to leading scientists.

    The H5N1 strain of the bird flu virus has been out of the headlines for some time but experts say it still poses a potential threat.

    I have been taking part in a vaccine trial against the virus and have just received my latest jab.

    It is two years since I volunteered for a clinical trial in Oxford for a vaccine against H5N1.

    In 2006 bird flu was a major news story in the UK following the discovery of a dead swan with H5N1 in Scotland.

    In January that year there had been the first human deaths in Turkey and the threat to Western Europe seemed palpable.

    Since then, although there have been further outbreaks among poultry in the UK, there have been no human fatalities in Western Europe.

    The level of media interest in bird flu has subsided - but has the threat disappeared? Not really.

    Still killing people

    It is very hard for humans to be infected by H5N1 - it requires very close contact with the virus.

    The virus is endemic in poultry and bird stocks in south-east Asia - and 241 people have died after being infected, 24 so far this year.

    However, bird flu, as the name suggests, still poses its biggest threat to poultry.

    Earlier this month there was an outbreak of H7N7 bird flu at a farm 30 miles north of Oxford, forcing the slaughter of 25,000 chickens.

    Pandemic inevitable

    Robert Newbery, poultry adviser at the National Farmers' Union, said avian flu was still a serious economic and animal welfare concern - but the level of risk was quite different compared to that in countries like Indonesia and Vietnam.

    "The systems in which poultry are kept in south-east Asia are completely unrecognisable compared to the UK," he said.


    But he went on: "Having said that, while the theoretical risk to human health exists, we as a farming community and the government will continue to take the disease very seriously."

    The threat may be theoretical at present - but all of the infectious disease experts I have spoken to over recent years agree that it is not a matter of if but of when the next flu pandemic will occur.

    H5N1 might not eventually be the virus responsible but the pandemic will almost certainly start in animals and then mutate into an infectious human disease.

    We simply don't know when that will happen - which makes it hard for the media to maintain interest.

    Millions at risk

    Nick White is a leading expert on infectious disease and professor of tropical medicine at Mahidol University in Bangkok and Oxford University.

    He spends most of the year in Thailand where there have been 17 deaths from H5N1 but was in Oxford the day I had my third jab.

    "We did not overreact to the threat from bird flu and we should still be worried," he said.

    "It is fortunate that nothing has happened so far but a flu pandemic could be cataclysmic for the human race.

    "If it became as infectious as Spanish flu in 1918-9 it could kill hundreds of millions of people."

    Dr Alan Hay, director of the World Health Organisation Collaborating Centre at the National Centre for Medical Research in the UK, says no-one is writing off the threat from H5N1.

    "We are in a state of stasis. There are plenty of infections in birds and there have been isolated human cases in Africa which is worrying.

    "Thankfully, H5N1 does not readily infect people but when it does it can have disastrous consequences."

    Currently, for every 10 people who get infected, six will die.

    No regrets

    I have no regrets about volunteering for the vaccine trial.

    Just because bird flu is not on the front pages any more doesn't mean that the potential threat has gone.

    As for the injection itself, some people expressed surprise that I volunteered for the trial and concern for my well-being.

    In fact the technology used to create the prototype vaccine is very well-established and any threat to my health was vanishingly small.

    I have had no ill-effects from any of the three doses I received.

    The first two contained a vaccine against the Vietnam strain of bird flu and the most recent was against the Indonesian strain.

    So if and when the next pandemic happens, will I and the other trial volunteers be better off than everyone else? That is a difficult question to answer.

    It is possible that H5N1 pre-pandemic vaccines may offer some protection but no one can be sure until it happens.

    The real point of the trial is to help scientists understand the best way of creating a vaccine when a pandemic occurs.

    Only when scientists know the exact pandemic strain will they be able to tailor-make a vaccine against it and know what the right dose should be.

    Let's hope that day is a long way off.

  • #2
    Re: Bird flu 'still a major threat'

    That's just it the threat of a influenza pandemic will never ever go away as long as there is humans. That is just the unfortunate thing.

    Comment


    • #3
      Re: Bird flu 'still a major threat'

      This from 2006

      'I am testing new bird flu jab'

      <!-- S BO --> <!-- S IBYL --> <table border="0" cellpadding="0" cellspacing="0" width="416"> <tbody><tr> <td valign="bottom"> By Fergus Walsh
      Medical correspondent, BBC News
      </td> </tr> </tbody></table>

      <!-- E IBYL --> <!-- S IBOX --> <table align="right" border="0" cellpadding="0" cellspacing="0" width="208"> <tbody><tr> <td width="5"></td> <td class="sibtbg">


      <!-- S IMED --> Fergus gets his jab
      <!-- E IMED -->
      </td> </tr> </tbody></table> <!-- E IBOX --> <!-- S SF --> The first medical trial in Britain of a vaccine against the bird flu virus H5N1 has begun in Oxford.

      This is an experimental vaccine against a virus with deadly potential.
      To see how well it works the Oxford Vaccine Group needs 150 volunteers.
      Having witnessed the progress of the virus - H5N1 - from Asia to Europe, it seemed right for me to take part.
      <!-- E SF -->
      That meant a medical check-up and some blood samples before getting the vaccine.
      Over the coming months I will get several blood tests.
      These will show how my immune system has reacted to the vaccine - crucially whether it has produced enough antibodies in my blood to protect me from H5N1 in the future.
      The trial is trying to find out what is an effective dose of the vaccine. It will monitor side effects in volunteers.
      It is all part of a global effort to create an H5N1 vaccine.
      Different doses
      The trial is testing two different doses. Only by scratching off a panel just prior to receiving the jab did the research team know which one to give me.
      I was selected to receive a 30 microgram dose with added adjuvants which are designed to enhance the immune response.
      I will get a second dose of vaccine three weeks after the first, and another top up shot in six or 12 months time.
      <!-- S IIMA --> <table align="right" border="0" cellpadding="0" cellspacing="0" width="203"> <tbody><tr><td> Dr Pollard says their work is a "dress rehearsal"

      </td></tr> </tbody></table> <!-- E IIMA -->

      The researchers will compare the results of the people in my group with a second receiving a less powerful dose.
      It was just a scratch, and so far there have been no ill effects.
      Even in South East Asia the immediate threat to humans from the H5N1 virus is very low.
      More than 100 people have died in the region, but in almost every case we know they have caught the virus directly from birds.
      H5N1 would need to mutate into a new infectious strain to transmit between humans.
      Dr Andy Pollard, who leads the Oxford Vaccine Group, said: "It is very important that we start to develop vaccines at this point that could allow us to save millions of lives in the future.
      "We don't know the exact strain that is going to be there, but we have to have all the processes in place so we can make a vaccine quickly. It is like a dress rehearsal."
      Huge demand
      The Oxford team are trying to establish the minimum dose needed to protect people, because that will mean there is more to go round.
      <!-- S IBOX --> <table align="right" border="0" cellpadding="0" cellspacing="0" width="208"> <tbody><tr> <td width="5"></td> <td class="sibtbg"> The potential for influenza to kill very large numbers of people is enormous


      Professor Nick White

      </td> </tr> </tbody></table> <!-- E IBOX -->

      But the figures don't add up. If a flu pandemic happens the UK wants 120m doses of vaccine, enough for everyone to have two injections.
      But currently only 90m doses of seasonal flu vaccine are produced for the whole of the EU each year.
      So why not just stockpile experimental H5N1 vaccines?
      That might help, but we don't know if this prototype vaccine will give any protection once a pandemic begins. The volunteers in Oxford may not be any better off than anyone else.
      Only a vaccine made after a pandemic starts will guarantee protection, because then we will know the exact strain of the virus.
      History tells us it could be a global killer.
      Professor Nick White, an expert in tropical medicine who is also working on the trial, said: "We have to look back at probably the worst infection ever of human beings in terms of pandemic.
      "That was the Spanish flu of 1918-1919 to which this virus bears a chilling resemblance.
      "That killed between 20m and 40m people, and probably infected a third of the people on the planet.
      "The potential for influenza to kill very large numbers of people is enormous."
      Vaccine trials are a crucial part of the preparations against a flu pandemic - a health emergency we must hope won't hit us for many years.


      http://news.bbc.co.uk/2/hi/health/5011534.stm

      Comment


      • #4
        Re: Bird flu 'still a major threat'

        Commentary

        Comment


        • #5
          Re: Bird flu 'still a major threat'

          April 17, 2007
          Our STN: BL 125244/0
          Sanofi Pasteur Inc.
          Attention: Gary K. Chikami, MD
          Director, Vaccines Establishment
          U.S. Regulatory Affairs
          Discovery Drive
          Swiftwater, PA 18370
          Dear Dr. Chikami:
          We have approved your Biologics License Application (BLA) for Influenza Virus Vaccine, H5N1, effective this date. You are hereby authorized to introduce or deliver for introduction into interstate commerce, Influenza Virus Vaccine, H5N1, under your existing Department of Health and Human Services U.S. License No. 1725; however, we acknowledge your statement provided in your submission of April 5, 2007, that Sanofi Pasteur Inc. does not intend to license this product for commercial distribution, since it was produced under contract to the U.S. Department of Health and Human Services as part of national pandemic preparedness initiatives. Influenza Virus Vaccine, H5N1, is indicated for active immunization of persons 18 through 64 years of age at increased risk of exposure to the H5N1 influenza virus subtype contained in the vaccine.
          Under this authorization you are approved to manufacture Influenza Virus Vaccine, H5N1 at your Swiftwater, PA facility. Final product filling, labeling, and packaging will be performed at your above facility. The vaccine will be supplied as a suspension in 5 mL multi-dose vials.
          The dating period for Influenza Virus Vaccine, H5N1 shall be 18 months from the date of manufacture of the final container vaccine. The date of manufacture shall be defined as the date on which this monovalent vaccine is filled; thus, the 18-month shelf life is inclusive of the time that the product is held in filled final containers at 2-8<SUP>o</SUP>C prior to packaging.
          We note that you have submitted samples and Batch Release Protocols for Influenza Virus Vaccine, H5N1, bulk Lots U2148, U2149, and U2150. For any other bulk lots that you may have produced or will produce in the future, please submit final bulk samples of the product together with lot release protocols in the proper format showing results of all applicable tests. You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologics Evaluation and Research (CBER).
          You must submit information to your BLA for our review and written approval under 21 CFR 601.12 for any changes in the manufacturing, testing, packaging or labeling of Influenza Virus Vaccine, H5N1, or in the manufacturing facilities.
          All applications for new active ingredients, new dosage forms, new indications, new routes of administration, and new dosing regimens are required to contain an assessment of the safety and effectiveness of the product in pediatric patients unless this requirement is waived or deferred. We have reviewed your submission dated February 9, 2007, and we deny your full waiver request for pediatric assessment. However, we grant a deferral of your pediatric studies for Influenza Virus Vaccine, H5N1, in children less than or equal to 16 years of age.
          Postmarketing Studies subject to reporting requirements of 21 CFR 601.70
          We acknowledge the postmarketing clinical commitments outlined in your submission of April 5, 2007. These commitments, along with any completion dates agreed upon, are listed below and will provide additional clinical data for the Influenza Virus Vaccine, H5N1.
          1. You agreed to submit data to assess safety, reactogenicity and immunogenicity of Influenza Virus Vaccine, H5N1 administered in children.
            Protocol submission: Study DMID 04-077: "A randomized, double-blinded, phase I/II, study of the safety, reactogenicity, and immunogenicity of intramuscular inactivated influenza A/H5N1 vaccine in healthy children aged 2 years through 9 years."
            Final study report submission: September 30, 2008.
            Please note that although your pediatric studies required under section 2 of the Pediatric Research Equity Act (PREA) are deferred, the deferred status of these required postmarketing studies should be reported as such annually according to 21 CFR 314.81. We will reassess the deferred status of your pediatric studies upon review of the data from the completed pediatric study which you have agreed to submit as a postmarketing commitment listed above.
          2. You agreed to provide the final study reports on or before June 30, 2008, as additional data to support immune responses and safety of the Influenza Virus Vaccine, H5N1.
            1. Study DMID 04-076: "A randomized double-blinded, placebo-controlled, phase I/II, dose-ranging study of the safety, reactogenicity, and immunogenicity of intramuscular inactivated influenza A/H5N1 vaccine in healthy elderly adults."
            2. Study DMID 05-0043: "Revaccination of healthy subjects with intramuscular inactivated subunit influenza A/Vietnam/1203/2004 (H5N1) vaccine representing a drifted variant."
            3. Study DMID 05-0090: "Evaluation of a booster dose of A/Vietnam/1203/04 (H5N1) vaccine administered at 6 months to healthy adult subjects after a two dose schedule at 0 and 1 month."
            4. Study DMID 05-0129: "Open label evaluation of H5N1 vaccine at vaccine manufacturing facilities."
            5. Study DMID 05-0130: "A single center, open label, phase I/II study of the safety and immunogenicity of two 90 ?g doses of intramuscular inactivated influenza A/H5N1 vaccine in healthy adult subjects."
          Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70
          We acknowledge the postmarketing commitments outlined in your submission of April 5, 2007 to submit updated stability data as follows.
          -------------------------------------------------------------------------------------------------------------------------------------------
          -------------------------------------------------------------------------------------------------------------------------------------------
          -------------------------------------------------------------------------
          -------------------------------------------------------------------------------------------------------------------------------------------
          -------------------------------------------------------------------------------------------------------------------------------------------
          -------------------------------------------------
          -------------------------------------------------------------------------------------------------------------------------------------------
          -------------------------------------------------------------------------------------------------------------------------------------------
          ----------------------------------------------------------------------------------------
          Please submit non-clinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA, STN BL 125244. Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:
          • Postmarketing Study Protocol
          • Postmarketing Study Final Report
          • Postmarketing Study Correspondence
          • Annual Report on Postmarketing Studies
          For each postmarketing study subject to the reporting requirements of 21 CFR 601.70, you must describe the status in an annual report on postmarketing studies for this product. The status report for each study should include:
          • information to identify and describe the postmarketing commitment,
          • the original schedule for the commitment,
          • the status of the commitment (i.e. pending, ongoing, delayed, terminated, or submitted), and
          • an explanation of the status including, for clinical studies, the patient accrual rate
          • (i.e., number enrolled to date and the total planned enrollment).
          As described in 21 CFR 601.70(e), we may publicly disclose information regarding these postmarketing studies on our Web site (http://www.fda.gov/cder/pmc). Please refer to the April 2001 Draft Guidance for Industry: Reports on the Status of Postmarketing Studies - Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997 (see http://www.fda.gov/cber/gdlns/post040401.htm) for further information.
          Please submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and distribution reports as described in (21 CFR 600.81). Under 21 CFR 600.80(c)(2) [Periodic Adverse Experience Reports], you must report each adverse experience not reported under paragraph (c)(1)(i) of this section at quarterly intervals for the first 3 years following approval, and then at annual intervals. Since your product is characterized as a vaccine, you must also submit these reports to the Vaccine Adverse Event Reporting System (VAERS) using the pre-addressed form VAERS-1. Furthermore, we acknowledge your agreement stated in your pharmacovigilance plan and submitted on April 5, 2007, to work with U.S. federal government agencies to design epidemiological studies to assess safety and efficacy of the vaccine and to collaborate to fill gaps in the collection and analysis of important safety, and possibly effectiveness, data in a pandemic situation.
          You must submit reports of biological product deviations under 21 CFR 600.14. You should promptly identify and investigate all manufacturing deviations, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.
          Please submit all final printed labeling and implementation information on FDA Form 356h. Please provide a PDF-format electronic copy as well as one original paper copy.
          Since, as stated in your April 5, 2007, submission, you do not intend to market this product for commercial distribution, we understand that you will not be distributing promotional advertising or promotional labeling materials. However, should you develop any advertising and/or promotional labeling related to this product (for example, educational brochures), we request that you submit two draft copies with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448.
          If you have any questions, please contact Dr. Rakesh Pandey at 301-827-3070.
          Sincerely yours,
          --- signature ---
          Norman W. Baylor, Ph.D.
          Director
          Office of Vaccines Research and Review
          Center for Biologics Evaluation and Research


          <!-- InstanceEndEditable --><!-- #################################### END MAIN DIV #################################### --><!-- #################################### END CONTENT DIV #################################### -->

          Comment


          • #6
            Re: Bird flu 'still a major threat'

            Sanofi to give WHO 60 million doses of H5N1 vaccine

            Robert Roos News Editor

            Jun 16, 2008 (CIDRAP News) ? Sanofi Pasteur pledged today to give 60 million doses of H5N1 influenza vaccine over 3 years to the World Health Organization (WHO) for a planned stockpile to help poor countries in the event of an influenza pandemic.
            Sanofi Pasteur, the vaccines division of French-based Sanofi-Aventis, is the second company to make a specific pledge for the WHO stockpile. A year ago, the United Kingdom's GlaxoSmithKline (GSK) promised to provide 50 million doses of H5N1 vaccine. At two doses per person, the combined total of 110 million doses would be enough to vaccinate 55 million people.
            "The H5N1 virus is currently circulating in some of the poorest regions of the world and an outbreak of pandemic influenza would most likely hit populations living in areas with limited access to vaccines," said Wayne Pisano, Sanofi Pasteur's president and chief executive officer, in a news release. "This donation of H5N1 vaccine aims to address the needs of those most vulnerable populations."
            Sanofi Pasteur makes an H5N1 vaccine that is being stockpiled by the US government. It became the world's first licensed H5N1 vaccine when it was approved by the US Food and Drug Administration in April 2007. The European Union approved an H5N1 vaccine made by GSK last month.
            Sanofi did not say when it would turn over the first doses to the WHO. A month ago, the WHO reported that work on the stockpile was under way, but no doses had been acquired yet.
            In that report, the WHO said the contemplated uses of the stockpile were to help contain the initial, localized emergence of a potential H5N1 pandemic and to provide vaccine to countries that would have little access to it.
            Besides Sanofi and GSK, Omnivest of Hungary and US-based Baxter have expressed a willingness to contribute to the stockpile.
            WHO member countries called for the establishment of a global H5N1 vaccine stockpile when they met for the World Health Assembly in May 2007. The idea of a global stockpile emerged after complaints by Indonesia and other developing countries about lack of access to commercial H5N1 vaccines.
            In its news release, Sanofi said it is "committed to producing as many doses as possible of its most advanced vaccine in the shortest possible time frame should a pandemic be declared by WHO. Under such circumstances, Sanofi Pasteur's seasonal influenza vaccine facilities would globally be able to switch to pandemic vaccine manufacturing."
            See also:
            Jun 16 Sanofi news release
            http://www.vaccineplace.com/docs/H5N1_WHO_160608_ENG.pdf
            May 16 CIDRAP News story "Launch of WHO H5N1 vaccine stockpile still awaited"
            May 2008 WHO report "Options for the use of human H5N1 influenza vaccines and the WHO H5N1 stockpile"
            http://www.who.int/csr/resources/publications/WHO_HSE_EPR_GIP_2008_1d.pdf
            Jun 13, 2007, CIDRAP News story "Glaxo to give 50 million doses of H5N1 vaccine to WHO"

            Comment


            • #7
              Re: Bird flu 'still a major threat'

              Commentary

              Comment


              • #8
                Re: Bird flu 'still a major threat'

                <TABLE id=Table11 style="BACKGROUND-IMAGE: none; HEIGHT: 87px" cellSpacing=3 cellPadding=1 width=605 bgColor=#c1d0d5 border=0><TBODY><TR vAlign=top><TD>
                Session:
                </TD><TD>Influenza in Animals and People
                </TD></TR><TR vAlign=top><TD>
                Date/Time:
                </TD><TD>June 20, 08
                </TD></TR><TR vAlign=top><TD></TD><TD>10:15-12:15
                </TD></TR></TBODY></TABLE><TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD align=middle><TABLE id=Table10 style="BACKGROUND-IMAGE: none; HEIGHT: 171px; BACKGROUND-COLOR: transparent" cellSpacing=3 cellPadding=1 width=615 border=0><TBODY><TR vAlign=top><TD width=80>
                Title:
                </TD><TD width=521>Progress on Pre-pandemic/Pandemic Influenza Vaccine
                </TD></TR><TR vAlign=top><TD></TD><TD>
                </TD></TR><TR vAlign=top><TD>
                Author(s):
                </TD><TD>M. Tashiro
                </TD></TR><TR vAlign=top><TD>
                Affiliation:
                </TD><TD>National Institute of Infectious Diseases, Japan, Tokyo, Japan
                </TD></TR><TR vAlign=top><TD>
                </TD><TD>
                </TD></TR><TR vAlign=top><TD>
                Abstract:
                </TD><TD>As pandemic influenza is a matter of global crisis management, WHO has urged to increase international production and supply of pandemic vaccines. For this, each country should establish influenza vaccination policy depending on annual health burden and economical situation. In Asia, while only Japan and China produce seasonal influenza vaccines, several countries including India, Indonesia, Singapore, South Korea, Taiwan, Thailand, and Vietnam, are planning to establish local production of pandemic vaccines. However, pandemic vaccine policy should be based on sustained annual vaccine measures. WHO started to support these countries to implement their local vaccine production of pandemic vaccines. Technical transfer to these facilities by vaccine manufactures in developed countries is essential, but it is conflicting with business and profits of the manufactures.
                To develop human H5N1 influenza vaccine, Japan experienced a low immunogenic property in humans of split-type vaccines derived from A/Hong Kong/156/97(H5N1). The Japanese project of H5N1 vaccine development aimed to develop a pandemic vaccine with highly immunogenic and to spare antigens to provide larger population with the vaccines in a short period of time. The WHO prototype vaccine strain, NIBRG-14, propagated in eggs was fixed with formalin. Based on animal experiments, alum-adjuvanted, inactivated whole virus vaccines were prepared. Phase 1 clinical studies followed by Phase 2+3 studies were conducted with 1.75, 5, and 15 mcg HA/dose in one or two doses, and subcutaneously or intramuscularly. Results of the clinical studies showed that the vaccine with 15 mcg HA was tolerable and did not cause severe adverse event. Serum antibody responses were induced efficiently by one or two shots with the high (15) or medium dose (5) , respectively, of the vaccines, meeting all of the three EMEA criteria. There results indicated that the inactivated whole virus vaccine conjugated with alum adjuvant is a practically suitable formulation of H5N1 pandemic vaccines. The serum antibody induced by the Clade 1 vaccine cross-reacted significantly with three subclades of Clade 2 viruses.
                Based on the data, the Government has introduced national stockpile policy of prepandemic vaccines, now with 20 million courses. Stockpile is to scale-up annually. Before expiration of each batch, vaccination to volunteers of the prioritized groups and then general population is under discussion.
                http://www.x-cd.com/isid08/prof2265.html

                </TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>

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