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  • China had bird flu case two years earlier than Beijing admits: researchers

    China had bird flu case two years earlier than Beijing admits: researchers
    17:06:03 EDT Jun 21, 2006
    HELEN BRANSWELL, The Canadian Press

    (CP) - In an extraordinary turn of events, Chinese researchers have contradicted Beijing's official version of the country's H5N1 human infection timeline, revealing a Chinese man died of H5N1 avian flu fully two years before China reported its first human case to the World Health Organization in November 2005.

    The eight researchers reported in a letter in Thursday's New England Journal of Medicine - a letter they attempted to withdraw Wednesday - on the genetic blueprint of H5N1 virus isolated from the man, who died in November 2003.

    That case predates any of the 228 confirmed cases that have been reported to WHO since the current outbreak of H5N1 virus began in late 2003. Officially, the first human cases in this outbreak occurred in Vietnam in December of 2003.

    Influenza experts outside China have long believed the country has hidden or missed human cases of H5N1. To date the country has reported 19 cases to the WHO; 12 of those people have died.

    "They were just so noticeable by their absence," influenza virologist Earl Brown of the University of Ottawa said of China's contention through 2004 and most of 2005 that it had found no human cases of the often fatal disease.

    A spokesperson for the WHO's China office said officials will be seeking answers from the Chinese Ministry of Health about the discrepancy.

    "I think it's safe to say that we will be asking for more information on this in the wake of the publication of this letter by the eight scientists," Roy Wadia said from Beijing.

    "We would certainly want much more information as to exactly what happened, who this case was, what the possible source of infection was, where he was infected, the treatment - all the standard questions.

    "There is information that needs to be shed on this by the Ministry of Health and we will be asking for that."

    Meanwhile editors of the New England Journal, one of the most prestigious scientific publications in the world, have questions of their own. They were caught totally off guard Wednesday when they received word the authors wished to withdraw their letter. No explanation was given.

    Spokesperson Karen Pedersen said the journal was trying to reach the authors to ask for their rationale and explain that the request came too late. Though the journal's official release day is Thursday, it has been in the hands of first-class subscribers for days.

    "The only option for them is to retract. But they have to do that. We can't do it for them," Pedersen said.

    The worrisome H5N1 virus was first isolated from a goose in the southern Chinese province of Guangdong in 1996 and is believed to have spread widely throughout the country's vast expanses.

    When country after country in Asia reported outbreaks in domestic poultry in late 2003 and early 2004, China maintained an official silence, insisting it was free of the virus.

    "I think they were probably part of it (the outbreak) and they didn't look hard or they didn't tell us when they found stuff," Brown said.

    The letter is signed by Dr. Qing-Yu Zhu, Dr. E-De Qin, Dr. Wei Wang, Jun Yu, Bo-Hua Liu, Yi Hu, Jian-Fei Hu and Dr. Wu-Chun Cao. The researchers are from a variety of well known Beijing-based scientific institutions, including 309th Hospital of the People's Liberation Army and the State Key Laboratory of Pathogens and Biosecurity.

    Cao, the corresponding author, did not respond to an e-mail from The Canadian Press seeking an interview or additional information.

    The eight wrote of the case of a 24-year-old man, apparently from Beijing, who had pneumonia and respiratory distress in November 2003. In that period, when the entire world was anxiously waiting to see if severe acute respiratory syndrome would re-emerge with the arrival of cold and flu season, doctors thought he was suffering from SARS.

    The man tested negative for the SARS coronavirus. But H5N1 was found in tissue from his lungs. The letter does not state when the testing was done or how long it has been known that the man died from H5N1.


    Nor does it make any reference to the fact that this case predates by two years the official version of when H5N1 cases first started occurring in China. Instead, it describes the molecular characteristics of the virus and compares them to earlier and later viruses.

    Flu watchers aren't surprised that China had cases as early as 2003. In fact, outside China it has been widely assumed, given that three people from Hong Kong became infected with the virus during a visit to Fujian province in February 2003.

    But those cases - only two were confirmed as one died without being tested - were shoved off the world's radar screens within days. That's because SARS exploded in the intensive care wards of hospitals across Asia and in Toronto.

    "It's clear that (H5N1) cases were occurring in China before they were reported and likely have occurred since - and were not reported," infectious disease expert Dr. Michael Osterholm said when told of the letter.

    "So I think it says that the idea that we have an understanding of the true magnitude of the current ongoing endemic disease in Asia is not correct."

    "I don't believe - and I think this is an important caveat - I don't believe that we're missing hundreds of cases," said Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

    "But I think that the idea that there are more cases, both in humans and in animals . . . is what we've all suspected all along."

    ...when you have eliminated the impossible, whatever remains, however improbable, must be the truth. - Sherlock Holmes

  • #2
    Fatal Infection with Influenza A (H5N1) Virus in China

    Anyone [Dr. Niman?] have access to the full article...?

    Fatal Infection with Influenza A (H5N1) Virus in China
    NEJM
    Volume 354:2731-2732 June 22, 2006 Number 25

    To the Editor: A 24-year-old man had pneumonia and respiratory distress in November 2003 and died four days after being hospitalized. Because the clinical manifestations were consistent with those of the severe acute respiratory syndrome (SARS) and occurred when sporadic cases of SARS were described in southern China,1 serum and lung tissue from the patient, as well as fluid aspirated from his chest, were examined for SARS coronavirus with the use of indirect fluorescence antibody tests and the reverse-transcriptase polymerase chain reaction (RT-PCR). All tests were negative for SARS.

    A virus was isolated from the lung tissue in Vero-cell . . .

    ...when you have eliminated the impossible, whatever remains, however improbable, must be the truth. - Sherlock Holmes

    Comment


    • #3
      Re: China had bird flu case two years earlier than Beijing admits: researchers

      <TABLE cellSpacing=0 cellPadding=0 width=640 border=0><TBODY><TR><TD vAlign=top align=middle><TABLE cellSpacing=0 cellPadding=0 border=0><TBODY><TR><TH vAlign=top noWrap align=right>Volume 354:2731-2732</TH><TD noWrap></TD><TH vAlign=top noWrap>June 22, 2006</TH><TD noWrap></TD><TH vAlign=top noWrap align=left>Number 25</TH></TR></TBODY></TABLE></TD><TD vAlign=top noWrap align=right>Next</TD></TR></TBODY></TABLE>
      Fatal Infection with Influenza A (H5N1) Virus in China

      <TABLE cellSpacing=0 cellPadding=0 width=200 align=right border=0><TBODY><TR><TD width=20> </TD><TD bgColor=#336699><TABLE cellSpacing=1 cellPadding=0 border=0><TBODY><TR vAlign=top><TD align=middle width=200 bgColor=#e8e8d1>

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      </TD></TR><TR><TD><TABLE cellSpacing=0 cellPadding=2 width="100%" bgColor=#ffffff border=0><TBODY><TR vAlign=top><TD colSpan=2></TD></TR><TR vAlign=top><TD vAlign=top align=middle width=15></TD><TD vAlign=center>Add to Personal Archive</TD></TR><TR vAlign=top><TD vAlign=top align=middle width=15></TD><TD vAlign=center>Add to Citation Manager</TD></TR><TR vAlign=top><TD vAlign=top align=middle width=15></TD><TD vAlign=center>Notify a Friend</TD></TR><TR vAlign=top><TD vAlign=top align=middle width=15></TD><TD vAlign=center>E-mail When Cited</TD></TR><TR vAlign=top><TD vAlign=top align=middle width=15></TD><TD vAlign=center>E-mail When Letters Appear</TD></TR><TR vAlign=top><TD colSpan=2></TD></TR></TBODY></TABLE></TD></TR><TR><TD align=middle width=200 bgColor=#e8e8d1>

      </TD></TR><TR><TD><TABLE cellSpacing=0 cellPadding=2 width="100%" bgColor=#ffffff border=0><TBODY><TR vAlign=top><TD colSpan=2></TD></TR><TR vAlign=top><TD vAlign=top align=middle width=15></TD><TD vAlign=center>Find Similar Articles</TD></TR><TR vAlign=top><TD colSpan=2></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE><!-- end of outer content box1 --></TABLE><!-- end of outer content box2 --><!-- <CENTER>Fatal Infection with Influenza A (H5N1) Virus in China

      </CENTER> -->To the Editor: A 24-year-old man had pneumonia and respiratory<SUP> </SUP>distress in November 2003 and died four days after being hospitalized.<SUP> </SUP>Because the clinical manifestations were consistent with those<SUP> </SUP>of the severe acute respiratory syndrome (SARS) and occurred<SUP> </SUP>when sporadic cases of SARS were described in southern China,<SUP>1</SUP><SUP> </SUP>serum and lung tissue from the patient, as well as fluid aspirated<SUP> </SUP>from his chest, were examined for SARS coronavirus with the<SUP> </SUP>use of indirect fluorescence antibody tests and the reverse-transcriptase<SUP> </SUP>polymerase chain reaction (RT-PCR). All tests were negative<SUP> </SUP>for SARS.<SUP> </SUP>
      A virus was isolated from the lung tissue in Vero-cell cultures<SUP> </SUP>and was characteristic of influenza A virus on electron microscopy.<SUP> </SUP>A serum sample collected on day 8 of the patient's illness was<SUP> </SUP>positive for IgM antibody against the isolated virus. Fragments<SUP> </SUP>of both the influenza A virus matrix gene (M) and the H5-subtype<SUP> </SUP>hemagglutinin gene (HA) were amplified from the infected Vero<SUP> </SUP>cells with the use of RT-PCR assay.<SUP>2</SUP><SUP>,</SUP><SUP>3</SUP> The nucleotide sequences<SUP> </SUP>of the fragments were identical to those amplified from the<SUP> </SUP>stored specimens of the patient's serum, chest fluid, and lung<SUP> </SUP>tissue.<SUP> </SUP>
      The genomic sequence of the virus (A/Beijing/01/2003) was determined,<SUP> </SUP>and its eight segments were genetically related most closely<SUP> </SUP>to corresponding sequences of influenza A (H5N1) viruses that<SUP> </SUP>had been isolated from chickens in various regions of China<SUP> </SUP>in 2004. The segments of the polymerase basic protein 1 gene<SUP> </SUP>(PB) and the nonstructural gene (NS) were most closely related<SUP> </SUP>to those from Guangdong Province (in southeastern China), with<SUP> </SUP>99 percent identity. The segments of the polymerase basic protein<SUP> </SUP>2 gene (PB2) and HA gene were closest to those from Jilin Province<SUP> </SUP>(in northeastern China), with 99 percent and 97 percent identity,<SUP> </SUP>respectively. The segments of the neuraminidase gene (NA), nucleoprotein<SUP> </SUP>gene (NP), and M gene were closest to those from Hubei Province<SUP> </SUP>(in mideastern China), with 98 percent, 98 percent, and 99 percent<SUP> </SUP>identity, respectively, and the polymerase acidic protein gene<SUP> </SUP>(PA) segment was closest to that from Japan, with 99 percent<SUP> </SUP>identity.<SUP> </SUP>
      These findings suggest that influenza A/Beijing/01/2003 may<SUP> </SUP>be a mixed virus. Phylogenetic analyses of the HA and NA genes<SUP> </SUP>of the representative influenza A (H5N1) strains have revealed<SUP> </SUP>that the viruses isolated from patients in Thailand and Vietnam<SUP> </SUP>in 2004 and 2005 belong to the same clade, and those obtained<SUP> </SUP>from patients in Hong Kong in 1997 and 1998 are from another<SUP> </SUP>clade (Figure 1 in the Supplementary Appendix, available with<SUP> </SUP>the full text of this letter at www.nejm.org). A sample of virus<SUP> </SUP>obtained from a patient in Hong Kong in 2003 seems to represent<SUP> </SUP>a transitional genotype, of which the HA gene sequence was close<SUP> </SUP>to the cluster from southeastern Asia (Figure 1A in the Supplementary Appendix),<SUP> </SUP>whereas the NA gene sequence was close to that of the cluster<SUP> </SUP>from Hong Kong in 1997 and 1998 (Figure 1B in the Supplementary Appendix).<SUP> </SUP>Phylogenetic analyses of the HA or NA gene indicated that the<SUP> </SUP>influenza A/Beijing/01/2003 strain was genetically distant from<SUP> </SUP>viruses previously isolated from humans, although it appears<SUP> </SUP>to have originated from a lineage similar to the influenza A/goose/Guangdong/1/96<SUP> </SUP>(Gs/GD) lineage.<SUP>4</SUP><SUP> </SUP>
      These findings have important implications for selecting viruses<SUP> </SUP>for the development of vaccines to prevent infection in humans.<SUP> </SUP>The genetic distance between the isolate reported and the strain<SUP> </SUP>currently proposed for vaccine development (A/Vietnam/1203/2004)<SUP>5</SUP><SUP> </SUP>implies that viruses from different regions may need to be considered<SUP> </SUP>in the development of an effective vaccine against influenza<SUP> </SUP>A virus.<SUP> </SUP>
      <SUP></SUP>
      Qing-Yu Zhu, M.D.
      State Key Laboratory of Pathogens and Biosecurity
      Beijing 100071, China
      <SUP></SUP>
      E-De Qin, M.D. <SUP></SUP>
      Beijing Institute of Microbiology and Epidemiology
      Beijing 100071, China
      <SUP></SUP>
      Wei Wang, M.D. <SUP></SUP>
      309th Hospital of the People's Liberation Army
      Beijing 100091, China
      <SUP></SUP>
      Jun Yu, Ph.D. <SUP></SUP>
      Beijing Genomics Institute
      Beijing 101300, China
      <SUP></SUP>
      Bo-Hua Liu, Ph.D. <SUP></SUP>
      State Key Laboratory of Pathogens and Biosecurity
      Beijing 100071, China
      <SUP></SUP>
      Yi Hu, Ph.D. <SUP></SUP>
      Beijing Institute of Microbiology and Epidemiology
      Beijing 100071, China
      <SUP></SUP>
      Jian-Fei Hu, Ph.D. <SUP></SUP>
      Beijing Genomics Institute
      Beijing 101300, China
      <SUP></SUP>
      Wu-Chun Cao, M.D., Ph.D. <SUP></SUP>
      State Key Laboratory of Pathogens and Biosecurity
      Beijing 100071, China
      caowc@nic.bmi.ac.cn<SCRIPT type=text/javascript><!-- var u = "caowc", d = "nic.bmi.ac.cn"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></SCRIPT>
      Supported by grants from the National Task Force of China (2004BA519A62<SUP> </SUP>and 2004BA519A71) and the 973 High-Tech Projects Plan (2005CB52300015).<SUP> </SUP>
      References
      1. <!-- null --><LI value=1>Liang G, Chen Q, Xu J, et al. Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China. Emerg Infect Dis 2004;10:1774-1781.<!-- HIGHWIRE ID="354:25:2731:1" --> [ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=2>Poddar SK. Influenza virus types and subtypes detection by single step single tube multiplex reverse transcription-polymerase chain reaction (RT-PCR) and agarose gel electrophoresis. J Virol Methods 2002;99:63-70.<!-- HIGHWIRE ID="354:25:2731:2" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=3>Lee MS, Chang PC, Shien JH, Cheng MC, Shieh HK. Identification and subtyping of avian influenza viruses by reverse transcription-PCR. J Virol Methods 2001;97:13-22.<!-- HIGHWIRE ID="354:25:2731:3" --> [CrossRef][ISI][Medline]<!-- /HIGHWIRE --><!-- null --> <LI value=4>Chen H, Smith GJD, Li KS, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A 2006;103:2845-2850.<!-- HIGHWIRE ID="354:25:2731:4" --> <NOBR>[Abstract/Full Text]</NOBR><!-- /HIGHWIRE --><!-- null -->
      2. Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med 2006;354:1343-1351.<!-- HIGHWIRE ID="354:25:2731:5" --> <NOBR>[Abstract/Full Text]</NOBR><!-- /HIGHWIRE -->

      Comment


      • #4
        WHO Asks China for Information on First Bird Flu Case (Update2)

        WHO Asks China for Information on First Bird Flu Case (Update2)

        June 22 (Bloomberg) -- The World Health Organization is asking China's Ministry of Health for information about a reported case of bird flu two years before the country disclosed its first human infection from the lethal virus.

        The case occurred in a 24-year-old man in November 2003, according to a letter in yesterday's New England Journal of Medicine written by eight Chinese scientists.
        The first human case reported to the WHO during the current avian flu outbreak occurred in Vietnam in December 2003, and China told the agency about its initial case in November 2005.

        "It's a very important issue that needs to be clarified urgently,'' Roy Wadia, a WHO spokesman, said today in Beijing. "It raises questions as to how many other cases may not have been found at the time or may have been found retrospectively in testing.''

        China was criticized by the United Nations health agency for its slow response to a 2003 outbreak of severe acute respiratory syndrome, or SARS. World health authorities are tracking cases of the H5N1 avian flu strain, which has infected at least 228 people in 10 countries since late 2003, killing 130 of them, the WHO said on June 20.

        International health agencies are trying to work more closely with China to detect and prevent infectious diseases faster, particularly in the densely populated southern region. Human H5N1 cases provide opportunity for the virus to mutate into a pandemic form that may kill millions of people.

        SARS

        The H5N1 virus, which has spread in birds across Asia, Europe and Africa this year, was first detected in a farmed goose a decade ago in Guangdong, where SARS may have first jumped to humans in 2002.

        SARS infected more than 8,000 people between 2002 and 2003, killing 774. The lung virus was originally suspected by doctors as the cause of disease in the 24-year-old man. The letter written by the Chinese scientists didn't say when samples from the man were analyzed.

        The authors of the letter asked editors at the New England Journal to allow them to withdraw it yesterday. Since the report was already printed in this week's issue, a withdrawal wasn't possible. The editors are still trying to uncover the problem and a future correction or retraction is possible, said Karen Pederson, a spokeswoman for the journal.

        Qing-Yu Zhu, from the State Key Laboratory of Pathogens and Biosecurity in Beijing, was the first author on the letter. The work was funded by grants from the National Task Force of China and the 973 High-Tech Projects Plan.

        Communication

        The authors, which include at least one medical doctor, are affiliated with a Chinese military institution, the WHO's Wadia said.

        "We don't know at this point because we are still awaiting clarification, but it may be that internal communication may have not been optimal'' between the researchers and the central government in Beijing, he said. "The communication between various branches hasn't always been the best. We knew during SARS, for example, that there were some instances when one wing of the government wasn't quite aware what was being done by another.''

        China has reported 19 human H5N1 cases, of which 12 were fatal. The most recent infection was confirmed on June 16 in a 31-year-old truck driver from the city of Shenzhen in Guangdong.

        Almost all human H5N1 cases have been linked to close contact with sick or dead birds, such as children playing with them or adults butchering them or plucking feathers, according to the WHO. Thorough cooking of meat and eggs kills the virus.

        Hungary, Romania

        In Hungary, scientists are examining samples from fowl in the community of Kulsogalambos to determine whether H5N1 has broken out there, Agriculture Ministry spokesman Andras Dekany said yesterday. Earlier this month, 500,000 poultry were culled in the southern county of Bacs-Kiskun to control the disease.

        In neighboring Romania, 80 H5N1 outbreaks have occurred in poultry this month, according to the World Organization for Animal Health.

        Romania first reported H5N1 in domestic poultry in October last year. An initial outbreak was reported in neighboring Ukraine two months later. Hungary's first outbreak was reported in February.


        To contact the reporters on this story:
        Jason Gale in Singapore at j.gale@bloomberg.net;
        John Lauerman in Boston at jlauerman@bloomberg.net.
        Last Updated: June 22, 2006 03:31 EDT

        ...when you have eliminated the impossible, whatever remains, however improbable, must be the truth. - Sherlock Holmes

        Comment


        • #5
          Re: China had bird flu case two years earlier than Beijing admits: researchers

          Commentart at

          http://www.recombinomics.com/News/06...jing_2003.html

          Comment


          • #6
            Re: China had bird flu case two years earlier than Beijing admits: researchers

            Yet again we see how China has failed the world. They can not handle the responsibility of being responsible.

            -hawkeye

            Comment


            • #7
              Re: China had bird flu case two years earlier than Beijing admits: researchers



              Human H5N1 From 2003 in Beijing

              Recombinomics Commentary

              June 22, 2006

              The genomic sequence of the virus (A/Beijing/01/2003) was determined, and its eight segments were genetically related most closely to corresponding sequences of influenza A (H5N1) viruses that had been isolated from chickens in various regions of China in 2004. The segments of the polymerase basic protein 1 gene (PB) and the nonstructural gene (NS) were most closely related to those from Guangdong Province (in southeastern China), with 99 percent identity. The segments of the polymerase basic protein 2 gene (PB2) and HA gene were closest to those from Jilin Province (in northeastern China), with 99 percent and 97 percent identity, respectively. The segments of the neuraminidase gene (NA), nucleoprotein gene (NP), and M gene were closest to those from Hubei Province (in mideastern China), with 98 percent, 98 percent, and 99 percent identity, respectively, and the polymerase acidic protein gene (PA) segment was closest to that from Japan, with 99 percent identity.

              These findings suggest that influenza A/Beijing/01/2003 may be a mixed virus.

              The above comments from today's New England Journal of Medicine paper on a 2003 human case in Bejing provide additional information on the diversity of H5N1 that can cause fatal human infections. The relationship to a variety of H5N1 bird flu isolates from poultry in China indicates the 2003 human isolate has undergone significant reassortment and recombination. The sequences summarized above are not yet available, but the HA and NA phylogenetic trees which include the isolate allow the new sequences to be positioned relative to other H5N1 sequences in the public domain.

              The HA tree shows the 2003 human sequence, A/BJ01/2003, which is most closely related to 2001 and 2002 H5N1 isolates from China. The current H5N1 isolates from humans are on a higher branch, which has Qinghai sequences (represented by Gs/QH/5/2005) at the bottom, Indonesian sequences (represented by Ck/Indonesia/2A/2003) in the middle, and Fujian sequences from China (represented by Dk/Fj/1734/2005) near the top of the branch. The top of the tree has human sequences from Vietnam and Thailand which represent clade 1.

              These new data raise questions on the number of unreported human cases in China. Earlier in 2003 a family from Hong Kong returned from a trip to Fujian province. They were infected with H5N1, listed as A/HK/212/2003 and closer to the top of the tree. Thus, it appears that at least two genetically diverse versions of H5N1 were in humans in China in 2003.

              This year all reported sequences from China are the Fujian strain, but the number of unreported cases in the past and present, remain unclear.

              Comment


              • #8
                Re: China had bird flu case two years earlier than Beijing admits: researchers

                Chinese scientists ask US journal to withdraw letter on human bird flu case

                1 hour, 55 minutes ago

                WASHINGTON (AFP) - Eight Chinese scientists have asked a leading US medical journal to withdraw a letter alleging that China knew about a human case of bird flu two years before the first case was officially announced.


                The latest news and headlines from Yahoo News. Get breaking news stories and in-depth coverage with videos and photos.



                ----
                maybe better to withdraw it.

                Comment


                • #9
                  Re: China had bird flu case two years earlier than Beijing admits: researchers

                  Bird flu may have been mistaken for SARS



                  By Maggie Fox, Health and Science Correspondent
                  WASHINGTON (Reuters) - A Chinese man who died of pneumonia in 2003 and was at first classified as a SARS victim might have in fact died of avian influenza, Chinese researchers reported on Wednesday.
                  But in a confusing development, at least one of the researchers asked that the letter reporting the case be withdrawn from publication in the New England Journal of Medicine. Editors of the medical journal said they were trying to find out why.
                  The letter was available to journalists before its withdrawal, and describes the case of a 24-year-old man who died from pneumonia and respiratory distress in November 2003.

                  "Because the clinical manifestations were consistent with those of the severe acute respiratory syndrome (SARS) and occurred when sporadic cases of SARS were described in southern China, serum and lung tissue from the patient, as well as fluid aspirated from his chest, were examined for SARS coronavirus," the researchers wrote. "All tests were negative for SARS."
                  The World Health Organization said it was asking China's Ministry of Health for clarification.
                  "This has been signed by eight scientists from very prestigious institutions. It certainly adds weight to the information," said Roy Wadia, WHO spokesman in China.
                  SARS first broke out in China's southern Guangdong province in 2002 and spread as far afield as Canada before it was brought under control in 2003. It killed close to 800 people out of the 8,000 known to have been infected.
                  Ironically, experts at the time assumed the then-mysterious illness making people sick in China was H5N1 avian influenza, which broke out in Hong Kong in 1997 and then disappeared. Continued...

                  Comment


                  • #10
                    Re: China had bird flu case two years earlier than Beijing admits: researchers

                    WHO seeks meeting with Chinese over report of unreported 2003 bird flu case

                    The Canadian Press
                    Published: Thursday, June 22, 2006

                    The World Health Organization has requested a meeting with officials of the Chinese Ministry of Health to ask about a startling admission in an academic journal that China had a human case of H5N1 avian flu two years before Beijing began to officially report cases.

                    The request, from the WHO's representative in China, was submitted Thursday, the day the report was published in the New England Journal of Medicine.

                    A spokesperson for WHO's Beijing office said the organization had to wait until the journal was published before it could formally ask for answers and a meeting. But WHO staff in Beijing began making informal inquiries a couple of days ago, when tipped to the pending publication by journalists.

                    "The Chinese government has indeed taken notice of this story,'' Roy Wadia said from Beijing.

                    "And what we're told is that they're making their internal inquiries and will get back to us as soon as possible. And so we are awaiting a formal answer from them.''

                    In a move that has taken the international influenza community by surprise, eight Chinese researchers submitted a letter to the journal describing the molecular characteristics of H5N1 viruses taken from the lung tissue of a man who died in November 2003, apparently in Beijing.

                    That's a full two years before China began reporting H5N1 cases to WHO. And it predates by a month the first confirmed human infections since the worrisome virus - which first attacked humans in 1997 in Hong Kong - re-emerged in Asia in late 2003.

                    Since its re-emergence, H5N1 has infected at least 228 people in 10 countries, killing at least 130. China, which only began reporting cases in November 2005, has admitted to 19 H5N1 cases with 12 deaths.

                    If Chinese officials knew of the case in November of 2003 and had alerted the world at the time, countries in the region may have been able to respond more quickly when they started to see avian flu within their borders, Wadia said.

                    "Lives could have been saved in Vietnam and Thailand,'' he said.

                    "So there are all sorts of implications here.''

                    Influenza experts outside China have long believed the country has hidden or missed human cases of H5N1 - but hadn't anticipated seeing proof in the pages of one of the world's most prestigious medical journals.

                    In the hours before the official release of this week's issue, corresponding author Dr. Wu-Chun Cao contacted the journal and asked to withdraw the letter. But it was too late. The hard copy of the journal was already printed; first-class subscribers had had the journal for days.

                    Spokesperson Karen Pedersen said Thursday the journal had sent an e-mail to Cao, a researcher with the State Key Laboratory of Pathogens and Biosecurity, asking for an explanation and asking if the authors want to retract the letter. Retraction would remove the material from the scientific literature.

                    "We have not received a response from the author,'' Pedersen said. "If we were to retract we would need an explanation. And they just have not responded.''

                    Cao also did not respond to an e-mail from The Canadian Press seeking an interview or additional information.


                    Wadia said WHO officials will ask about the attempted withdrawal.

                    "But I think for us really the focus is more on the case as to when it was known, who knew it, how it was done, all the testing protocols, all the technical information and also how it was communicated within the government, and to whom and at what time,'' he said.

                    "I think it's fair to say . . . that this story raises at the moment far more questions than there are answers. And we certainly hope to get at least some of these answers in the next few days.''

                    The WHO must follow strict protocol when seeking information from a country, a potentially time-consuming process that requires correspondence to be addressed through the ministry of health in the country.

                    "The way we work is through the MOH. And we can't at this moment in time at least pick up the phone and call these scientists ourselves,'' he explained.
                    ? The Canadian Press 2006

                    Comment


                    • #11
                      Re: China had bird flu case two years earlier than Beijing admits: researchers


                      Bird flu may have been mistaken for Sars
                      23 June 2006

                      WASHINGTON: A Chinese man who died of pneumonia in 2003 and was at first classified as a Sars victim might have in fact died of avian influenza, Chinese researchers reported on Wednesday.

                      But in a confusing development, at least one of the researchers asked that the letter reporting the case be withdrawn from publication in the New England Journal of Medicine. Editors of the medical journal said they were trying to find out why.

                      The letter was available to journalists before its withdrawal, and describes the case of a 24-year-old man who died from pneumonia and respiratory distress in November 2003.

                      "Because the clinical manifestations were consistent with those of the severe acute respiratory syndrome (Sars) and occurred when sporadic cases of Sars were described in southern China, serum and lung tissue from the patient, as well as fluid aspirated from his chest, were examined for Sars coronavirus," the researchers wrote. "All tests were negative for Sars." The World Health Organisation said it was asking China's Ministry of Health for clarification.

                      "This has been signed by eight scientists from very prestigious institutions. It certainly adds weight to the information," said Roy Wadia, WHO spokesman in China.

                      Sars first broke out in China's southern Guangdong province in 2002 and spread as far afield as Canada before it was brought under control in 2003. It killed close to 800 people out of the 8,000 known to have been infected.

                      Ironically, experts at the time assumed the then-mysterious illness making people sick in China was H5N1 avian influenza, which broke out in Hong Kong in 1997 and then disappeared.

                      Wadia said: "It reinforces what we have known for a very long time which is that the H5N1 virus has been in the environment of this part of the world for a while and it's therefore not surprising that you would have these sort of cases."

                      "This (case) was the same time that the virus had started taking human lives in some other countries, Vietnam, Thailand."

                      "In fact, WHO said in February 2004, when China was awash in poultry outbreaks at the time, that it would not be inconcievable that there could be sporadic human cases on the Chinese mainland that may not have been tracked or confirmed."

                      Influenza experts say flu viruses rarely just disappear and had been waiting for its return, which was reported in 2003.

                      In the case of the Chinese man, tests of his tissue were positive for influenza virus and genetic sequencing later showed it to be H5N1 avian influenza.

                      It genetically resembled samples of viruses taken from Chinese chickens in various provinces in 2004, the letter says. Parts of the virus also resembled Japanese samples.

                      The eight researchers who signed the letter include Dr Wu-Chun Cao of the State Key Laboratory of Pathogens and Biosecurity, Dr Qing-Yu Zhu of the State Key Laboratory of the Beijing Institute of Microbiology and Epidemiology, and Dr Wei Wang of the 309th Hospital of the People's Liberation Army.

                      They said the virus infecting the man had mixed lineages and that their findings were important for developing an eventual bird flu vaccine.

                      "The genetic distance between the isolate reported and the strain currently proposed for vaccine development implies that viruses from different regions may need to be considered in the development of an effective vaccine against influenza A virus," they wrote.

                      The H5N1 avian flu virus has swept across most of Asia, into parts of Europe and Africa. While it is mainly a disease of birds, it occasionally infects people and has killed 130.

                      Comment


                      • #12
                        Re: China had bird flu case two years earlier than Beijing admits: researchers

                        Archive Number 20060622.1729
                        Published Date 22-JUN-2006
                        Subject PRO/AH/EDR> Avian influenza, human (88) - China, Indonesia

                        AVIAN INFLUENZA, HUMAN (88) - CHINA, INDONESIA
                        **********************************************
                        A ProMED-mail post
                        <http://www.promedmail.org>
                        ProMED-mail is a program of the
                        International Society for Infectious Diseases
                        <http://www.isid.org>

                        In this update:

                        [1] China - identification of earliest Chinese case of H5N1 infection
                        [2] Indonesia - person-to-person transmission among family members

                        *****
                        [1]
                        Date: Thu 22 June 2006
                        From: Pablo Nart<PABLO.NART@terra.es>
                        Source: Pravda ru online, Thu 22 Jun 2005 [edited]
                        <http://english.pravda.ru/news/world/22-06-2006/82342-birdflu-0>


                        Beijing scientists said in a medical journal to be published Thu [22
                        Jun 2006] that a man in mainland China died of bird flu in November
                        2003, 2 years before the communist country reported any human
                        infections to the World Health Organization. On Wednesday, however,
                        the scientists asked without explanation to withdraw the report. But
                        it was too late.


                        The man's death was initially thought to have been caused by SARS,
                        the scientists wrote. That suggests some other cases attributed to
                        SARS may have actually been the deadly H5N1 avian influenza, and also
                        raises questions about how candid China has been about both diseases.

                        "It's hard to believe that this is the only person in all of China
                        who developed H5N1" that year, said Dr. John Treanor, a flu expert
                        at
                        the University of Rochester.

                        WHO was surprised by the report, which came not from the Chinese
                        government but from 8 scientists in a research letter to the New
                        England Journal of Medicine. "We will formally request the Ministry
                        of Health to clarify this," and why it has taken more than 2 years to
                        come to light, said Roy Wadia, a WHO spokesman in China.

                        At least one scientist e-mailed the journal on Wednesday morning [21
                        Jun 2006], asking that the report be withdrawn, but it was already in
                        print, a journal spokeswoman said.
                        The journal said it was waiting to
                        see whether the authors would now retract the paper.

                        The Beijing case does not necessarily mean the world faces any
                        greater danger of a pandemic; bird flu does not spread easily from
                        person to person, and nearly all human cases have involved close
                        contact with infected poultry. But the report raises questions about
                        the ability and willingness of scientists in China to study it.

                        Dr. Lindsey Baden, a New England Journal editor, said he does not
                        know what caused the delay in reporting the case but suspects it took
                        time for scientists to realize they had a novel H5N1 strain and to do
                        the genetic sequencing needed to analyze it. "It's to be praised
                        that they are doing this kind of work and sharing it," Baden said,
                        reports Associated Press.

                        --
                        Pablo Nart
                        <pablo.nart@terra.es>

                        [The report of an H5N1 human infection in China occurring in November
                        2003 is not surprising. During the early stages of pubic reports on
                        the outbreak of respiratory syndrome in Guangdong China (later on
                        being named the Severe acute respiratory syndrome (SARS)), there were
                        2 cases of H5N1 (in a father and son) diagnosed in Hong Kong in Feb
                        2003 with history of travel to Fujian province. There was also a
                        presumed 3rd case (a daughter from the same family) that became ill
                        and died in Fujian province, with no further diagnostic testing
                        done. The mother of this family also had a severe respiratory
                        illness but the final diagnosis on her was "thought to have been a
                        parainfluenza infection" (see ProMED-mail posting Influenza, H5N1
                        human case - China (Hong Kong) (04) 20030227.0491). Hence, one
                        surmises that there had been H5N1 activity in Fujian province
                        during the SARS outbreak as well. (see prior ProMED-mail postings
                        for 2003 listed below). - Mod.MPP]

                        [The pdf version of the New England Journal of Medicine letter
                        referred to above can be accessed at
                        <http://content.nejm.org/cgi/reprint/354/25/2731.pdf>. The reference
                        is: New England Journal of Medicine, volume 354 , No. 25, 2731-2732,
                        Jun 22, 2006.

                        The letter reads as follows:
                        "To the Editor: A 24-year-old man had pneumonia and respiratory
                        distress in November 2003 and died 4 days after being hospitalized.
                        Because the clinical manifestations were consistent with those of the
                        severe acute respiratory syndrome (SARS) and occurred when sporadic
                        cases of SARS were described in southern China (ref 1), serum and
                        lung tissue from the patient, as well as fluid aspirated from his
                        chest, were examined for SARS coronavirus with the use of indirect
                        fluorescence antibody tests and the reverse-transcriptase polymerase
                        chain reaction (RT-PCR). All tests were negative for SARS.

                        A virus was isolated from the lung tissue in Vero-cell cultures and
                        was characteristic of influenza A virus on electron microscopy. A
                        serum sample collected on day 8 of the patient's illness was positive
                        for IgM antibody against the isolated virus. Fragments of both the
                        influenza A virus matrix gene (M) and the H5-subtype hemagglutinin
                        gene (HA) were amplified from the infected Vero cells with the use of
                        RT-PCR assay (ref 2,3). The nucleotide sequences of the fragments
                        were identical to those amplified from the stored specimens of the
                        patient's serum, chest fluid, and lung tissue.

                        The genomic sequence of the virus (A/Beijing/01/2003) was determined,
                        and its 8 segments were genetically related most closely to
                        corresponding sequences of influenza A (H5N1) viruses that had been
                        isolated from chickens in various regions of China in 2004. The
                        segments of the polymerase basic protein 1 gene (PB1) and the
                        nonstructural gene (NS) were most closely related to those from
                        Guangdong Province (in southeastern China), with 99 percent identity.
                        The segments of the polymerase basic protein 2 gene (PB2) and HA gene
                        were closest to those from Jilin Province (in northeastern China),
                        with 99 and 97 percent identity, respectively. The segments of the
                        neuraminidase gene (NA), nucleoprotein gene (NP), and M gene were
                        closest to those from Hubei Province (in mideastern China), with 98,
                        98, and 99 percent identity, respectively, and the polymerase acidic
                        protein gene (PA) segment was closest to that from Japan, with 99
                        percent identity.

                        These findings suggest that influenza A/Beijing/01/2003 may be a
                        mixed virus. Phylogenetic analyses of the HA and NA genes of the
                        representative influenza A (H5N1) strains have revealed that the
                        viruses isolated from patients in Thailand and Viet Nam in 2004 and
                        2005 belong to the same clade, and those obtained from patients in
                        Hong Kong in 1997 and 1998 are from another clade (Figure 1 in the
                        Supplementary Appendix, available with the full text of this letter
                        at <http://www.nejm.org>). A sample of virus obtained from a patient
                        in Hong Kong in 2003 seems to represent a transitional genotype, of
                        which the HA gene sequence was close to the cluster from southeastern
                        Asia (Figure 1A in the Supplementary Appendix), whereas the NA gene
                        sequence was close to that of the cluster from Hong Kong in 1997 and
                        1998 (Figure 1B in the Supplementary Appendix). Phylogenetic analyses
                        of the HA or NA gene indicated that the influenza /Beijing/01/2003
                        strain was genetically distant from viruses previously isolated from
                        humans, although it appears to have originated from a lineage similar
                        to the influenza A/goose/Guangdong/1/96 (Gs/GD) lineage (ref 4).

                        These findings have important implications for selecting viruses for
                        the development of vaccines to prevent infection in humans. The
                        genetic distance between the isolate reported and the strain
                        currently proposed for vaccine development (A/Vietnam/1203/2004)5
                        implies that viruses from different regions may need to be considered
                        in the development of an effective vaccine against influenza A virus.

                        From: Qing-Yu Zhu, M.D., State Key Laboratory of Pathogens and
                        Biosecurity, Beijing 100071, China; E-De Qin, M.D., Beijing Institute
                        of Microbiology and Epidemiology, Beijing 100071, China; Wei Wang,
                        M.D, 309th Hospital of the People's Liberation Army, Beijing 100091,
                        China; Jun Yu, Ph.D., Beijing Genomics Institute, Beijing 101300,
                        China; Bo-Hua Liu, Ph.D, State Key Laboratory of Pathogens and
                        Biosecurity, Beijing 100071, China; Yi Hu, Ph.D., Beijing Institute
                        of Microbiology and Epidemiology, Beijing 100071, China; Jian-Fei Hu,
                        Ph.D.,Beijing Genomics Institute, Beijing 101300, China; and Wu-Chun
                        Cao, M.D., Ph.D., State Key Laboratory of Pathogens and Biosecurity,
                        Beijing 100071, China <caowc@nic.bmi.ac.cn>

                        References
                        ------------
                        1. Liang G, Chen Q, Xu J, et al. Laboratory diagnosis of four recent
                        sporadic cases of community-acquired SARS, Guangdong Province, China.
                        Emerg Infect Dis 2004;10:1774-1781.

                        2. Poddar SK. Influenza virus types and subtypes detection by single
                        step single tube multiplex reverse transcription-polymerase chain
                        reaction (RT-PCR) and agarose gel electrophoresis. J Virol Methods
                        2002;99:63-70.

                        3. Lee MS, Chang PC, Shien JH, Cheng MC, Shieh HK. Identification and
                        subtyping of avian influenza viruses by reverse transcription-PCR. J
                        Virol Methods 2001;97:13-22.

                        4. Chen H, Smith GJD, Li KS, et al. Establishment of multiple
                        sublineages of H5N1 influenza virus in Asia: implications for
                        pandemic control. Proc Natl Acad Sci U S A 2006;103:2845-2850.

                        5. Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M. Safety and
                        immunogenicity of an inactivated subvirion influenza A (H5N1)
                        vaccine. N Engl J Med 2006;354:1343-1351.

                        It remains to be seen whether this letter will be withdrawn, allowed,
                        or will remain unaltered. - Mod CP]

                        ******

                        Comment


                        • #13
                          Re: China had bird flu case two years earlier than Beijing admits: researchers

                          Has anyone heard what the reason was for the request for removal from publication? As I understand it, the New England Journal of Medicine is peer-reviewed before articles or letters are approved for publication. Is that correct?

                          Was it poor research?.... fears of persecution or reprisal?.... improper channels for release of classified or confidential state information?... other reasons?

                          The journal said it was waiting to see whether the authors would now retract the paper.
                          Hopefully, Dr. Qing-Yu Zhu, Dr. E-De Qin, Dr. Wei Wang, Jun Yu, Bo-Hua Liu, Yi Hu, Jian-Fei Hu and Dr. Wu-Chun Cao will be able to clarify their comments, research, and the implications at a future date, and whether they want to retract their research or further expand its significance to the world.
                          "Predictable is Preventable" by Safety Expert Dr. Gordon Graham.

                          Comment


                          • #14
                            Mystery thickens around report of early Chinese bird flu case

                            Mystery thickens around report of early Chinese bird flu case
                            16:14:27 EDT Jun 23, 2006
                            HELEN BRANSWELL

                            (CP) - The mystery surrounding a report by Chinese researchers that contradicts Beijing's official line on how long China has been having human cases of H5N1 avian flu took a twist Friday that suggests someone may have tried to block the report's publication in a prestigious medical journal.

                            Hours before the official release of this week's issue of New England Journal of Medicine, editors at the journal received a series of e-mails from someone purporting to be Dr. Wu-Chun Cao, one of the authors of the report which had been submitted by eight Chinese scientists.

                            But on Friday, editors at the journal spoke by phone with someone they believe to be Cao. He categorically denied having sent the e-mails and told the journal he and his co-authors stand behind their report.

                            Cao, of the State Key Laboratory of Pathogens and Biosecurity, later faxed the journal a letter reaffirming those claims.

                            "He has not requested withdrawal of the report, and so it stands as published in the issue of June 22," Dr. Jeffrey Drazen, editor-in-chief, said in a statement.


                            "We are continuing to investigate."

                            The eight researchers reported on the molecular characteristics of an H5N1 virus isolated from a Chinese man who died in November 2003.

                            The report has stirred up intense interest in the scientific world because that was two full years before Beijing first reported a human H5N1 case to the World Health Organization, in November 2005.

                            The authors made no reference to the discrepancy between their report and China's official H5N1 timeline. Nor did they indicate whether the testing that discovered H5N1 virus in the dead man's lung was actually done around the time of death or more recently.

                            When the report was published the WHO's China office formally requested that the Chinese Ministry of Health explain the discrepancy and provide information about the case.

                            On Friday, a WHO spokesperson in Geneva declined to comment on the latest development.

                            Influenza experts outside China have long believed the country has hidden or missed human cases of H5N1, but they hadn't anticipated seeing proof in the pages of one of the world's most prestigious medical journals. China has officially reported 19 cases and 12 deaths.

                            A spokesperson for the New England Journal of Medicine said the journal had received "multiple" e-mails asking to withdraw the report. From the e-mail addresses, some seemed to be from Cao; others claimed to be from all eight authors.

                            "It seemed very clear that they were coming from Dr. Cao and/or that institution," Karen Pedersen said from Boston. Copies of the e-mails were also faxed to the journal.

                            But editors could not immediately reach Cao to explore why he wanted the report pulled and to explain it was too late - the journal had been printed and mailed to subscribers days earlier.

                            On Friday someone identifying himself as Cao called the journal and said he hadn't made the request and didn't want to withdraw the report. Pedersen said the journal editors believe that call was legitimate.

                            The editors asked Cao to submit a letter reaffirming that the report should stand, and they received that letter. Pedersen said the journal was in the process Friday of getting the remaining seven researchers to sign similar letters.


                            ...when you have eliminated the impossible, whatever remains, however improbable, must be the truth. - Sherlock Holmes

                            Comment


                            • #15
                              Ministry: More tests needed to confirm possible 2003 bird flu death in China

                              Ministry: More tests needed to confirm possible 2003 bird flu death in China (Updated 05:30 p.m.)

                              2006/7/3
                              BEIJING (AP)

                              More testing is needed before China can confirm whether a soldier who died in Beijing in 2003 was an early case of bird flu, the Health Ministry said Monday.

                              The case, first disclosed last month in a letter by Chinese researchers to a U.S. medical journal, has raised questions about whether China failed to detect and report an early human infection of bird flu.

                              The 24-year-old man who died in a military hospital on Dec. 3, 2003, was first diagnosed with SARS. The Health Ministry said scientists in Beijing tested samples from the dead man in 2004 and last year and found "possible" infection with the H5N1 bird flu virus.

                              However, under World Health Organization and Chinese regulations, "confirmation still requires parallel testing" by another laboratory, the Health Ministry said. "Currently, work on a definite diagnosis on this case is under way."

                              The 2003 fatality came two years before China reported its first bird flu death but just a few months before the virus tore through Vietnam and Thailand.

                              Confirmation of early human bird flu infections in China would firm up theories that the virus originated in southern China.

                              The latest outbreak of the H5N1 bird flu virus has killed more than 130 people worldwide, 12 in China, and ravaged Asian poultry stocks since late 2003.

                              The bird flu outbreaks in late 2003 followed on the heels of severe acute respiratory syndrome, or SARS, which emerged in southern China in late 2002.

                              The findings by the Chinese scientists, whose letter was published in the June 22 edition of the New England Journal of Medicine, raised the possibility that other SARS cases might have been H5N1 infections.

                              ...when you have eliminated the impossible, whatever remains, however improbable, must be the truth. - Sherlock Holmes

                              Comment

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