Rhiza Labs FluTracker Forum

Opinion: H5N1 flu is just as dangerous as feared, now requires action





Contact:
Barbara Hyde. bhyde@asmusa.org
Garth Hogan. ghogan@asmusa.org





WASHINGTON, DC—February 22, 2012--The debate about the potential severity of an outbreak of airborne H5N1 influenza in humans needs to move on from speculation and focus instead on how we can safely continue H5N1 research and share the results among researchers, according to a commentary to be published in mBio®, the online open-access journal of the American Society for Microbiology, on Friday, February 24.


H5N1 influenza has been at the center of heated discussions in science and policy circles since the U.S. National Science Advisory Board for Biosecurity (NSABB) asked the authors of two recent H5N1 investigations and the scientific journals that planned to publish the studies to withhold crucial details of the research in the interest of biosecurity.




In the mBio® commentary, Michael Osterholm* and Nicholas Kelley, of the Center for Infectious Disease Research and Policy at the University of Minnesota, present their case that H5N1 is a very dangerous virus, based on their analysis of published studies of the seroepidemiology of H5N1 in humans. H5N1 flu infections have exceedingly high mortality, they say, and current vaccines and antiviral drugs will not pull us out of a global H5N1 pandemic. "We believe that the assertion that the case-fatality rate of H5N1 influenza in humans may be overestimated is based on a flawed data analysis,”Osterholm said.




Analysis of reports of H1N1 seroprevalence that include data from the 1997 Hong Kong outbreak as well as data from 2004 to date will give a misleading impression because the 1997 outbreak was a very different “biologic event” that is recognized as such by the WHO, because the 1997 H1N1 virus has a significantly different genotype from that of later H5N1 viruses. This is why the WHO does not include the Hong Kong H1N1 virus data in any analysis of H5N1 transmission, and the 1997 Hong Kong virus is not recommended for inclusion in H5N1 vaccines, Osterholm explained.




Seroepidemiologic studies that have examined the exposure of various groups of people to H5N1 viruses only from 2004 onward indicate that only a small segment of the population has ever been exposed to H5N1, and that among those that have been exposed, many become seriously ill or die.




"The available seroepidemiologic data for human H5N1 infection support the current WHO reported case-fatality rates of 30% to 80%," Osterholm says. In the event of an H5N1 pandemic, they point out, if the virus is even one tenth or one twentieth as virulent as has been documented in these smaller outbreaks, the resulting fatality rate would be worse than in the 1918 pandemic, in which 2% of infected individuals died.




Vaccines will not head off an H5N1 pandemic either, the authors say, since the time required to develop and manufacture an influenza vaccine specific to new outbreak strain has resulted in “too little, too late” vaccine responses for the 1957, 1968, and 2009 influenza pandemics, and not much in the process has changed since 2009.




"The technology behind our current influenza vaccines is simply not sufficient to address the complex challenges associated with an influenza pandemic in the 21st century," Osterholm and Kelley say.




This is the heart of the matter, they say: there has been enough discussion about how severe an H5N1 pandemic might be. Moving forward, the current controversy has provided a valuable opportunity for scientists and public policy experts to discuss influenza research and preparedness and create "a roadmap for the future." The discussion among scientists and policy makers needs to move on from whether H5N1 poses a serious international threat - as it clearly does - and begin discussing how we can prevent these viruses from escaping labs and how scientists can share their flu-related results with those who have a need to know.




There are critical questions that need to be answered, the authors say. For instance, how can scientists conduct virus-transmission studies in mammals safely and how can scientists share research methods and results with those who have a need to know? We also need to come to agreement on how to ensure that strains of H5N1 viruses created in the lab don't escape those controlled environments, the authors say. And new, more effective vaccine technologies are needed that can enable substantially faster production. Resolving these issues could allow H5N1 research and preparedness to serve as a springboard for solving similar problems with existing or emerging pathogens.




*Michael Osterholm is a member of the National Science Advisory Board for Biosecurity.



# # #



mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.



The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Last Updated on Wednesday, 22 February 2012 23:06
http://www.asm.org/index.php/news-room/ ... 22212.html

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Not convincing. because the recipe is already PUBLISHED by the CDC (Fouchier used 3 of the 4 chnages used by the CDC and there is likely similar overlap in the Kawaoka paper). Moreover, the three papers show that MULTIPLE H5 tragets will yield transmission in ferrets.

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Commentary
http://www.recombinomics.com/News/02231 ... NSABB.html

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EPI153757 A/egret/Egypt/1162-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI136747 A/chicken/Egypt/06553-NLQP/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI124612 A/Egypt/902786/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI122751 A/Egypt/2992-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI122749 A/Egypt/2991-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI116414 A/turkey/Israel/365/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI116412 A/turkey/Israel/364/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI116410 A/turkey/Israel/345/2006 (A/H5N1) segment 4 (HA) 2968.7 0.000000e+00 1607/1607 (100%)
EPI318206 A/chicken/Egypt/RIMD9-2/2008 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI318200 A/chicken/Egypt/RIMD2-6/2008 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI259645 A/duck/Egypt/D1Br12/2007 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
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EPI127760 A/chicken/Egypt/06207-NLQP/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI127752 A/chicken/Egypt/9397NAMRU3-CLEVB188/2007 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI125642 A/turkey/Egypt/F2/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI124608 A/chicken/Egypt/3/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI116416 A/chicken/Israel/397/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI115422 A/chicken/Egypt/12378N3-CLEVB/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI115081 A/chicken/Egypt/1081-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI106348 A/chicken/Egypt/2253-1/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI103018 A/chicken/Egypt/960N3-004/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI58638 A/turkey/Egypt/2253-2/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI58619 A/chicken/Egypt/2253-1/2006 (A/H5N1) segment 4 (HA) 2963.1 0.000000e+00 1606/1607 (99%)
EPI127750 A/chicken/Egypt/9396NAMRU3-CLEVB187/2007 (A/H5N1) segment 4 (HA) 2959.5 0.000000e+00 1605/1607 (99%)
EPI318205 A/chicken/Egypt/RIMD8-14/2008 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI259644 A/duck/Egypt/D1Tr335/2007 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI225076 A/duck/Egypt/2253-3/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI225068 A/duck/Egypt/2253-3/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI156731 A/duck/Egypt/452-1VIR07/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI136749 A/chicken/Egypt/06612-NLQP/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI124636 A/chicken/Egypt/2/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI124634 A/chicken/Egypt/1/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI124610 A/Egypt/902782/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI116460 A/Egypt/2256-NAMRU3/2007 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI116422 A/chicken/Israel/625/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI116418 A/turkey/Israel/446/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI115430 A/duck/Egypt/12380N3-CLEVB/2006 (A/H5N1) segment 4 (HA) 2957.6 0.000000e+00 1605/1607 (99%)
EPI259646 A/duck/Egypt/D1Li4/2007 (A/H5N1) segment 4 (HA) 2952.1 0.000000e+00 1604/1607 (99%)
EPI136751 A/quail/Egypt/07120-NLQP/2007 (A/H5N1) segment 4 (HA) 2952.1 0.000000e+00 1604/1607 (99%)
EPI125644 A/chicken/Egypt/F3/2006 (A/H5N1) segment 4 (HA) 2952.1 0.000000e+00 1604/1607 (99%)
EPI115424 A/chicken/Egypt/12379N3-CLEVB/2006 (A/H5N1) segment 4 (HA) 2952.1 0.000000e+00 1604/1607 (99%)
EPI115079 A/chicken/Egypt/1080-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2952.1 0.000000e+00 1604/1607 (99%)
EPI259570 A/duck/Egypt/D3Li12/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI255357 A/Egypt/7021-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI182330 A/chicken/Egypt/07480S-NLQP/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI168662 A/chicken/Qalubia/1/2006 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI156786 A/duck/Egypt/5169-6/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI156784 A/chicken/Egypt/5169-5/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI136779 A/chicken/Egypt/07125-NLQP/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI127766 A/chicken/Egypt/06541-NLQP/2006 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI127720 A/chicken/Egypt/3049NAMRU3-CLEVB75/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI125646 A/chicken/Egypt/F4/2006 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI125640 A/turkey/Egypt/F1/2006 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI115434 A/duck/Egypt/1888N3-SM25/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI115426 A/chicken/Egypt/1889N3-SM26/2007 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1603/1607 (99%)
EPI103091 A/Egypt/2782-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2946.5 0.000000e+00 1601/1604 (99%)
EPI231114 A/duck/Mellach/335/2006 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1602/1606 (99%)
EPI231112 A/duck/Leibnitz/243/2006 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1602/1606 (99%)
EPI171701 A/Ardea cinerea/Slovenia/185/06 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1602/1606 (99%)
EPI153487 A/chicken/Egypt/1709-4VIR08/2007 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1602/1607 (99%)
EPI115083 A/chicken/Egypt/1300-NAMRU3/2007 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1602/1606 (99%)
EPI115019 A/swan/Austria/216/2006 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1602/1606 (99%)
EPI110247 A/chicken/Egypt/10845-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1594/1594 (100%)
EPI110235 A/Egypt/2786-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1594/1594 (100%)
EPI110233 A/Egypt/2783-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2944.7 0.000000e+00 1594/1594 (100%)
EPI224963 A/chicken/Gaza/714/2006 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1602/1607 (99%)
EPI224961 A/chicken/Gaza/713/2006 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1602/1607 (99%)
EPI156776 A/duck/Egypt/5169-4/2007 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1602/1607 (99%)
EPI127774 A/chicken/Egypt/2628-1/2007 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1602/1607 (99%)
EPI127768 A/chicken/Egypt/06959-NLQP/2006 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1602/1607 (99%)
EPI115420 A/chicken/Egypt/1129N3-HK9/2007 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1602/1607 (99%)
EPI106175 A/Chicken/Egypt/5612NAMRU3-S/2006 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1594/1595 (99%)
EPI106173 A/Chicken/Egypt/5611NAMRU3-AN/2006 (A/H5N1) segment 4 (HA) 2941.0 0.000000e+00 1600/1604 (99%)
EPI314342 A/duck/Egypt/D2br10/2007 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI259567 A/duck/Egypt/D2Br210/2007 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI231237 A/swan/Mellach/215/2006 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI171711 A/Anas acuta/Slovenia/470/06 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI171696 A/cygnus olor/Slovenia/156/06 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI115017 A/cat/Austria/649/2006 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI110243 A/Egypt/5494-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1593/1594 (99%)
EPI110237 A/Egypt/2947-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1593/1594 (99%)
EPI47732 A/swan/Slovenia/760/2006 (A/H5N1) segment 4 (HA) 2939.1 0.000000e+00 1601/1606 (99%)
EPI233772 A/chicken/Nigeria/08RS848-6/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI182328 A/chicken/Egypt/07118-NLQP/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI153485 A/chicken/Egypt/1709-1VIR08/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI152329 A/chicken/Nigeria/228-5/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI152321 A/chicken/Nigeria/228-6/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI136765 A/turkey/Egypt/07444S-NLQP/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI127708 A/duck/Egypt/3043NAMRU3-CLEVB56/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI116454 A/Egypt/1604-NAMRU3/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI115085 A/duck/Egypt/1301-NAMRU3/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI115077 A/chicken/Egypt/1079-NAMRU3/2007 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI115075 A/chicken/Egypt/1078-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)
EPI114792 A/Egypt/14725-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1599/1604 (99%)
EPI114790 A/Egypt/14724-NAMRU3/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1599/1604 (99%)
EPI14168 A/chicken/Nigeria/SO227/2006 (A/H5N1) segment 4 (HA) 2935.4 0.000000e+00 1601/1607 (99%)

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Commentary

http://www.recombinomics.com/News/02241 ... or_MM.html

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Nature News Blog

Canada confines mutant flu to maximum-security facilities

23 Feb 2012 | 14:50 GMT | Posted by Declan Butler | Category: Health and medicine, Policy, Swine flu


Canada this month announced that any research on mammalian-transmissible strains of the H5N1 avian flu virus in the country’s labs would need to be done at the strictest level of biocontainment, biosafety level 4 (BSL-4). It’s the first country to issue a biosafety rating following the creation of such H5N1 strains in two recent controversial studies (see Nature News Special: Mutant Flu).

The question of which biosafety rating is appropriate for research on the new strains was highlighted as crucial by an expert meeting convened in Geneva last week by the World Health Organization (WHO). The new, modified H5N1 strains are held at Erasmus Medical Center in Rotterdam, the Netherlands, and at the University of Wisconsin-Madison, in two BSL-3-enhanced facilities (the second highest biocontainment level), and the WHO described these as “well-established research facilities with high security and high safety“. But it also recommended that regulators “urgently” review the biosafety and biosecurity conditions under which further research on such strains is conducted, and that until that’s done, the strains should stay where they are and not be shared with other labs.

In biosafety assessment, pathogens are classified in terms of their ‘risk group’ (RG) on a scale of 1–4, where 4 is the highest, on the basis of an assessment of the relative threat they pose to people. They are also classified in terms of the biological containment levels needed, again on a scale of 1–4. What can be a bit confusing is that although required biocontainment levels for various research on a pathogen largely mirror the risk-group rating, they don’t necessarily equate with it. Some types of research may be permitted at a lower biocontainment level than their risk group, if it’s assessed that the research can be done safely with less-restrictive precautions. As the WHO explains, biocontainment level designations are “based on a composite of the design features, construction, containment facilities, equipment, practices and operational procedures required for working with agents from the various risk groups”.

Barry Bloom, a researcher and former dean at the Harvard School of Public Health in Boston, Massachusetts, also emphasizes the importance of training. “Security in handling dangerous pathogens is, in my view, less a function of the physical containment facilities than the training, experience and competence of the scientists working with them,” he says.

Some flu researchers are concerned that work on mammalian-transmissible H5N1 viruses will be severely hampered if it is restricted to BSL-4 laboratories, because BSL-4 conditions are much more constraining than BSL-3 labs, and because there are only a few dozen BSL-4 labs worldwide. Other experts feel that such high containment is essential, given the risk that any escape of the viruses could cause a H5N1 pandemic (see Fears grow over lab-bred flu.)

Whatever biocontainment levels are eventually decided as appropriate by the relevant authorities, many researchers are concerned about the proliferation of such mammalian-transmissible avian flu strains: as more labs work on them, the risk of release — accidental or intentional — goes up. Bloom says that he hopes that the number of labs allowed to work on them “would be limited, transparently identified, and monitored for safety under the aegis of an international body such as WHO”.

Declan Butler asked Sandra Fry, director-general of the Public Health Agency of Canada’s Pathogen Regulation Directorate, and Marianne Heisz, head of the directorate’s Office of Biosafety Programs and Planning, how the agency reached its decision to classify work on the new lab strains as requiring BSL-4 (note that Canada uses the term ‘CL’ in place of BSL) facilities.

Read the Q&A under the fold.


What prompted Canada to review the biosafety level of the new flu viruses and give them the highest RG4/BSL-4 rating?
The Public Health Agency of Canada (PHAC) is the national authority for human pathogen oversight, and administers and enforces the Human Pathogens Importation Regulations and the Human Pathogens and Toxins Act, which require any person in Canada importing or working with human pathogens to follow national biosafety requirements, specifically, the Laboratory Biosafety Guidelines. PHAC routinely reviews the scientific literature and conducts risk assessments on human pathogens, and assessments of new or emerging pathogens that result in new or altered biosafety requirements for working with that pathogen lead to the issuing of a Biosafety Advisory. Communicating the outcome of the risk assessment through a biosafety advisory raises awareness among PHAC’s regulated parties of the containment level requirements for biosafety and biocontainment for these specific viruses. Transmissible forms of the highly lethal H5N1 virus clearly meet the definition of an RG4 human pathogen, and should thus be handled under CL4.

How did you weigh up what was an appropriate biosafety rating?
The Human Pathogens and Toxins Act states that RG3 human pathogens pose a high risk to the health of individuals and low risk to public health. RG4 human pathogens are pathogens that pose a high risk to the health of individuals and a high risk to public health. These pathogens are likely to cause serious disease in a human and there are generally no effective treatments or preventative measures available. The risk of spread of disease caused by RG4 human pathogens is high.

PHAC completed a risk assessment on the H5N1 viruses that were engineered in the Netherlands and the United States taking into account their transmissibility in ferrets, which involved careful consideration of specific pathogen characteristics including pathogenicity, route of infection, and communicability. Although the H5N1 virus circulating in nature poses a serious risk to human health, human-to-human transmission of H5N1 occurs inefficiently, and this limited transmissibility has restricted the spread of H5N1 and is the main factor that distinguishes this pathogen as Risk-Group 3. By modifying H5N1 to be efficiently transmissible, including via aerosols, the risk to public health would increase vastly, as every primary infection could potentially lead to multiple secondary infections.

PHAC decided that, based on the severe impact on human health, high risk to public health, and uncertainty about the availability of effective preventative and therapeutic measures, the engineered H5N1 viruses should be rated as RG4 viruses.

One of the criteria in designating a pathogen as requiring BSL-4 facilities is that effective drugs and vaccines are not available. How do you apply that criterion to these new flu strains, given that although some H5N1 vaccines and drugs do exist, in practice there wouldn’t be remotely near enough of them should the virus escape from the lab and spread in the community?
The availability of effective preventative or therapeutic measures is a factor considered when conducting a pathogen-risk assessment. Although H5N1 vaccines have been developed, the research in question involves the deliberate modification of H5N1, and we have not yet determined how effective existing vaccines would be against the modified viruses. In considering the potential impact of a release of transmissible H5N1 into circulation, the availability of effective medical intervention and the capacity of the health-care response system will need to be determined. PHAC considered these and other factors, and they weighed into the conclusion that this pathogen is to be worked at in CL 4.

Did you consult with researchers, and what was their opinion?
Several experts in the field of biosafety were consulted in the development of the engineered H5N1 viruses Biosafety Advisory. As part of our standard Biosafety Advisory development process, the risk assessment is conducted in collaboration with researchers at the PHAC National Microbiology Laboratory (NML), and with our colleagues from the Canadian Food Inspection Agency (CFIA) for expertise on the animal pathogen component. Additional rigour was added by consulting with public-health experts through the Canadian Public Health Laboratory Network (CPHLN). There was general agreement that transmissible H5N1 should be handled at the highest level of containment.

The two studies that created these strains used ‘BSL-3-enhanced‘ labs, and some researchers say that this is adequate. What particular aspects of BSL-4 containment do you feel are most important with respect to ensuring the safety of these viruses?
In Canada the assigned levels of containment of human pathogens range from CL1 to CL4, with no ‘enhanced’ designations. Facilities meeting the ‘BSL-3-enhanced’ design generally include features that the Canadian Food Inspection Agency requires for CL3 containment of animal pathogens such as avian H5N1. These features include requirements such as the laboratory being the primary containment barrier, to name just one.

CL4/BSL-4 containment is the maximum level of containment available, and the features addressing protection against the potential for airborne transmission of the engineered virus to lab personnel, the environment and general public are key. CL4 ensures maximum containment through the complete sealing of the containment zone, isolation of personnel from the pathogen through the use of positive pressure suits, double-HEPA (high-efficiency particulate air) filtration of exhausted air, HEPA filtration of supply air, and decontamination of all effluents. This type of containment provides the maximum protection for laboratory personnel who handle the pathogen as well as the maximum protection to contain the pathogen from release into the environment. This level of containment was considered the appropriate containment level based on the extensive risk assessment done for this pathogen.

Did you consider biosecurity aspects in your assessment as well as biosafety?
As biosecurity is a subset of biosafety, the crucial aspects of biosecurity are always taken into account when completing our biosafety risk assessments and subsequent biosafety advisories. The specific requirements for CL4 include secure access to the CL4 lab and supporting facility and stringent controls on pathogen inventories, storage and access, to name just a few.

Did you liaise with the United States and other governments or the WHO on your assignment of RG/BSL level, and is there any emerging consensus?
As part of our Biosafety Advisory development process, our colleagues at the CDC and the WHO were contacted to determine their organizations’ intentions with respect to a given emerging pathogen. At the time of consultation, both organizations had not made the determination as to whether or not to develop a biosafety advisory.

How does the PHAC track lab-safety incidents? Do you have a list of all accidents or incidents in recent years at BSL-3 and BSL-4 facilities?
Under national regulations, the PHAC has a mechanism in place that captures the reporting of biosafety accidents or incidents for high-security CL4 facilities. For CL3 facilities, persons importing risk-group 3 human pathogens are required under the Laboratory Biosafety Guidelines to report biosafety accidents or incidents to their institutions. At present, there is no mandatory reporting requirement to inform PHAC, although voluntary reporting is a practice that the PHAC encourages.

The reporting and tracking of biosafety incidents or accidents in all Canadian labs is now being developed for all levels of containment under the development of the PHAC’s new Human Pathogen and Toxins Regulations through a stakeholder-consultation approach. The PHAC is now comparing international-reporting mechanisms to improve its monitoring programme and to influence evidence-based biosafety interventions both domestically and globally.
http://blogs.nature.com/news/2012/02/ca ... ities.html

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U.S. panel asked to take another look at bird flu studies

The Canadian Press

Date: Wednesday Feb. 29, 2012 1:42 PM ET

A panel of U.S. biosecurity experts is being asked to review its recommendation that two controversial bird flu studies shouldn't be published in full, a biosecurity conference was told Wednesday.

The group, the National Science Advisory Board for Biosecurity, will be given revised versions of the manuscripts of the studies, said the senior U.S. official who revealed the information.

One of the revised manuscripts in particular will clarify that an H5N1 virus made in a Dutch laboratory was not as lethal as has been suggested publicly to date, the meeting was told.

Ron Fouchier, the Dutch virologist who led one of the two research projects, told the conference the virus his lab created did spread easily among ferrets housed in adjacent cages.

But none of the ferrets infected that way died, Fouchier said. Only ferrets that were directly infected -- with high doses of virus dripped into their trachea -- were killed by the lab-made virus.

Those results have not been made public to date and actually contradict much of the information that has circulated about Fouchier's study since the NSABB recommended against its full publication last November.

Previously Fouchier has been quoted as saying all the ferrets in his study died after being infected by the mutant H5N1 virus. He was not immediately available Wednesday to explain how the misconception about his work arose.

The other study, led by virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison, reports on the creation of a different lab-made virus, a hybrid of H5N1 and human H1N1 viruses. Kawaoka has already revealed that the hybrid his lab produced spread easily among ferrets, but did not kill the animals.

Dr. Anthony Fauci, head of the U.S. National Institute for Allergy and Infectious Diseases, told the conference -- staged by the American Society of Microbiology -- that the NSABB will be reconvened to review the clarified data.

In an interview after the meeting, Fauci said he cannot prejudge what the group will decide, though he hopes a decision can be taken "within weeks."

The chair of the NSABB, virologist Paul Keim, told the meeting he cannot say what impact the revised information will have on the opinions of the advisory body.

The group, set up in the wake of the 2001 anthrax attacks in the United States, recommended last fall that the U.S. government ask two leading journals not to publish the full studies, saying they are recipes for making transmissible H5N1 viruses.

The journals and the researchers reluctantly agreed, but only on the proviso that a system be set up to share the withheld information with other scientists and public health officials who have a legitimate need to see it.

But that system still has not been devised. And a recent closed-door meeting on the controversy that was hosted by the World Health Organization concluded it could take years to develop such a system.

The WHO meeting, which was predominantly made up of influenza experts, concluded the studies should be published in full, but not immediately.



Read more: http://www.ctv.ca/CTVNews/Health/201202 ... z1no1uSLvR

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Two controversial studies on bird flu will once again be reviewed by an expert committee that advises the government on what to do with biological research that could pose potential dangers.

The move is just the latest development in a fierce ongoing debate about genetically altered flu viruses created in laboratories at Erasmus Medical Center in the Netherlands and at the University of Wisconsin-Madison.

The announcement came today at a scientific conference attended by about a thousand biodefense experts in Washington, D.C., that was organized by the American Society of Microbiology. One of the scientists who did the work, Ron Fouchier of Erasmus Medical Center, spoke at the conference and presented data suggesting that the mutant virus created in his lab was not as dangerous as has been presented in media reports.

"Certainly, this would not be a virus that would kill half of the world population, as we've seen in the lay press time and time again. That is clearly, clearly wrong," said Fouchier.

The experiments involved the potentially lethal H5N1 bird flu virus and showed which genetic changes could make the virus spread through the air between ferrets — the laboratory stand-in for people.

Late last year, in an unprecedented move, the National Science Advisory Board for Biosecurity reviewed the work and recommended not publicly publishing the details of how these altered viruses were created, so as not to publish a recipe that could be misused by someone seeking to create a dangerous, contagious virus.

But earlier this month, the World Health Organization convened a different panel, mostly composed of international flu experts, that came to the opposite conclusion. It said the experiments were important for public health efforts to prepare for a possible future pandemic, and that they should be published openly.

Fouchier emphasized that in his studies, ferrets did not die after getting the virus from the sneezes and coughs of other ferrets. "Certainly, if the ferrets receive virus via aerosol route, we have never seen severe disease in the ferrets," he said, although the virus could be highly lethal if administered at high doses directly into the respiratory tract of ferrets. He added that pre-exposure to seasonal flu seems to offer protection from severe disease.

Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said the government will ask the NSABB to review new versions of both scientific manuscripts in a meeting that could happen as early as March, depending on people's schedules. He said the discussion would cover new data and "re-clarification" of old data, so that the members of the NSABB would have the opportunity to see the same information as the WHO panel.

Paul Keim, acting chairman of the NSABB, said "new data is always good. We're scientists; we love data." But he said until the committee has seen the data, it's impossible to say if it could change their views on whether to publish the work.

"The board has always said that our recommendations were the first step in this process and that we were, if anything, just putting out an alert that this is an area of great concern that needs to be looked at very closely by a broad spectrum of people," Keim noted.

Another member of the NSABB, Michael Osterholm of the University of Minnesota, said the committee's initial recommendations came after hundreds of hours of conference calls that took place over two months. "To say that this was in-depth would not do it justice," said Osterholm, who noted that the recommendations were unanimous.

He noted that one of the primary concerns of the committee was the ability of the researchers to change a flu virus in ways that made it readily transmissible between mammals.

"As we've tried to make clear from the very beginning, the virulence of virus, the ability of it to kill, is not central to our deliberations," said Osterholm. "Because we know that what happens in ferrets may not predict what will happen in terms of virulence in humans."

The committee had recommended that sensitive details of the experiments be made available to legitimate scientists around the world through some sort of secure communications process. Government officials have been working hard to create such a system, but it's proving legally to be no easy matter. And some researchers say any attempts to keep the information under wraps would be futile anyway.

http://www.npr.org/blogs/health/2012/02 ... econd-look

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The battle over bird flu continues. As you may recall, researchers in Rotterdam, the Netherlands, have answered the two biggest questions about H5N1 bird flu: yes, a few mutations can make it readily transmissible between mammals; and no, the transmissible virus is not less deadly than the H5N1 we have now, which is hard to catch. New Scientist had the story when it was first reported at a scientific meeting in Malta last year.

Now, there are reports that Ron Fouchier, leader of the Rotterdam team, has told a meeting in Washington DC that the transmissible H5N1 wasn't all that deadly after all. What's going on?

What's going on is the continued dispute about whether the work can be published. The US National Science Advisory Board for Biosecurity (NSABB) advised against publishing details that an evildoer could use to make a nasty bioweapon. The journal involved, Science, agreed to the advice, but only if those details could be confided to public health agencies and other flu researchers. Last month, a group of flu specialists - including the chair of the NSABB - met at the World Health Organization and decided there was, unfortunately, no way to arrange that.

So what happens now? Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, which funded the work, has found a way through the impasse. He explained to a meeting on defence and biosecurity in Washington DC this week that there is now new information about the study that the NSABB should consider. A revised paper will be given to the committee soon.

Fouchier presented the new information at the Washington meeting. Nothing in his talk contradicts the story I heard in Malta, although it may refute some of the more hysterical interpretations of it. You just have to listen carefully.

Fouchier says the seven ferrets that caught the mutant H5N1 via aerosol transmission from other ferrets got sick, but didn't die. Moreover, only one of eight ferrets that had a large dose of the mutant actually put up their noses died. In contrast, ferrets which got the ordinary, wild-type, pre-mutation H5N1 in their noses all died. This certainly makes the mutant seem a wimp.

Actually, though, it's the wild-type virus that's odd. In general, when you give ferrets most kinds of H5N1 in their noses, said Fouchier, "they don't get sick at all". The strain he used, collected in 2005 in Indonesia, is known for causing unusual brain-related disease when put in ferrets' noses. Perhaps the mutant has lost this: the ferrets who got it in their noses, either by breathing it in or because it was put there, just got flu.

It's what H5N1 does in lungs that matters for us, because that's how it kills us. The Rotterdam group says putting flu viruses in the ferret's windpipe, or trachea, is the "appropriate model of infection in humans". And there the mutant, transmissible H5N1 was just as deadly as the wild one - just as Fouchier said in Malta. All the ferrets died.

Evidently the few ferrets so far exposed via aerosol didn't get enough virus in their windpipes to kill. But the virus has done the hard part: it's a shorter jump from nose to throat than from ferret to ferret. And we don't know how any of this plays out in people. So this still means H5N1 is a threat.

Fouchier also argues that his mutant virus wouldn't sweep the world if it escaped, as it doesn't spread as efficiently as the swine flu that went pandemic in 2009. That's not surprising: swine flu was fully adapted to mammals, H5N1 is a bird flu with a few mutations - that it can spread via aerosol at all is news. But such a virus would spread, and adapt, given a chance.

Finally, he says we're safe because ferrets first exposed to ordinary flu don't later die of wild H5N1. This is actually really important work, which we reported when it had still only been done in mice: it means having the flu gives you immunity to more kinds of flu than flu vaccine does. Most people have had flu. So are we safe from this thing after all?

Hardly. If having had flu protects you from wild H5N1, why have 348 people (at last count) died of it? Had none of them ever had flu? Unlikely. That cross-reaction may have protected some experimental ferrets from H5N1, but apparently it isn't enough for all of us.

If transmissible H5N1 wasn't worrying, we wouldn't be continuing the moratorium on research until, as Fauci also said in Washington, we've seen to the "fortification" of lab safety. That's welcome news - as long as the research resumes, safely, soon.

http://www.newscientist.com/blogs/short ... nline-news

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The above comments indocate the Fouchier transmission studies used A/Indonesia/5/2005, the WHO pandemic vaccine target for clade 2.1.

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