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Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

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  • Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

    [Source: Science, full page: (LINK). Abstract, edited.]


    <CITE>Published Online July 18 2013</CITE>
    <CITE></CITE>
    <CITE>Science DOI: 10.1126/science.1240532 </CITE>
    <CITE></CITE>
    <CITE></CITE>Report

    H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet


    Qianyi Zhang<SUP>1</SUP>,<SUP>2</SUP>,*, Jianzhong Shi<SUP>1</SUP>,*, Guohua Deng<SUP>1</SUP>,*, Jing Guo<SUP>1</SUP>,*, Xianying Zeng<SUP>1</SUP>,*, Xijun He<SUP>1</SUP>, Huihui Kong<SUP>1</SUP>, Chunyang Gu<SUP>1</SUP>,<SUP>2</SUP>, Xuyong Li<SUP>1</SUP>, Jinxiong Liu<SUP>1</SUP>, Guojun Wang<SUP>1</SUP>,<SUP>2</SUP>, Yan Chen<SUP>1</SUP>, Liling Liu<SUP>1</SUP>, Libin Liang<SUP>1</SUP>, Yuanyuan Li<SUP>1</SUP>, Jun Fan<SUP>1</SUP>, Jinliang Wang<SUP>1</SUP>, Wenhui Li<SUP>1</SUP>, Lizheng Guan<SUP>1</SUP>, Qimeng Li<SUP>1</SUP>,<SUP>2</SUP>, Huanliang Yang<SUP>1</SUP>, Pucheng Chen<SUP>1</SUP>, Li Jiang<SUP>1</SUP>, Yuntao Guan<SUP>1</SUP>, Xiaoguang Xin<SUP>1</SUP>, Yongping Jiang<SUP>1</SUP>, Guobin Tian<SUP>1</SUP>, Xiurong Wang<SUP>1</SUP>, Chuanling Qiao<SUP>1</SUP>, Chengjun Li<SUP>1</SUP>, Zhigao Bu<SUP>1</SUP>, Hualan Chen<SUP>1</SUP>,<SUP>2</SUP>,?

    Author Affiliations: <SUP>1</SUP>State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, People?s Republic of China. <SUP>2</SUP>College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730030, People?s Republic of China.

    ?Corresponding author. E-mail: chenhualan@caas.cn

    * These authors contributed equally to this work.


    Abstract

    A newly emerged H7N9 virus has caused 132 human infections with 37 deaths in China since 18 February 2013. Control measures in H7N9 virus?positive live poultry markets have reduced the number of infections; however, the character of the virus, including its pandemic potential, remains largely unknown. We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice. Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplets. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.


    Received for publication 15 May 2013. Accepted for publication 2 July 2013.


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  • #2
    Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

    While concerning, it remains difficult to assess the actual human health threat posed by the new H7N9 virus.

    Essentially, for a reason: it is almost impossible to believe that No One Individual currently entering in contact with farmed chickens or in other settings - through occupational exposure or consumption - is developing infection caused by this new H7N9 virus, even though during summer season avian influenza may be less active than in cold weather.

    We need desperately more data, more transparency and a clear picture of the events are occuring on the ground.

    Without these essential data, the most important step from a global public health perspective - namely the start of the H7N9 monovalent pandemic vaccine - will not be taken until it will be too late.

    Ferrets, mices, chickens: yes, but humans?

    No poultry farmers?

    Excuse me, but I cannot believe longer... GM

    Comment


    • #3
      Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

      Guiseppe - completely agreed.

      Comment


      • #4
        Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

        Relevance of the Science study explained in this article:

        Risk of Human-to-Human Spread of Deadly New Bird Flu Virus Higher Than Previously Thought

        Mounting evidence suggests lethal H7N9 bird flu poses ?worrisome? threat

        Before this year the H7N9 bird flu virus linked to 133 human infections and 43 deaths was never seen in people. All the available evidence suggests that an effective biological barrier apparently kept a pandemic at bay?humans only contracted the novel virus via direct contact with poultry or environments such as live bird markets rather than by human-to-human transmission. New analysis from the Chinese Academy of Agricultural Sciences (CAAS), however, suggests that the virus is closer to becoming a disease transmitted among humans than previously thought.

        Read more: Scientific American
        "Addressing chronic disease is an issue of human rights that must be our call to arms"
        Richard Horton, Editor-in-Chief The Lancet

        ~~~~ Twitter:@GertvanderHoek ~~~ GertvanderHoek@gmail.com ~~~

        Comment


        • #5
          Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

          Relevant is relevant.

          But from where these infected poultry were from?

          China poultry Sector is not a residual one, but a key industrial asset, providing meat to a 1+Bln people country.

          Since these infected live market poultry cannot be born from nothing, how many farmed chickens were actually infected and what is the actual number of workers exposed to the virus?

          The virus, itself, is able to grow at higher temperature, such as those recorded during summer?

          An enormous amount of litter was likely also be produced by all these farmed chickens and - thus - a quota of this mass contained the virus too.

          The manure ended surely in part to the ground or directly into river and canals.

          We are talking about huge figures and not a single human-derived virus.

          I have the clear impression that this is a game where players tend to increase their stakes (from a study to another and another) without discover their cards.

          A ferret cannot obscure the fact that without any reasonable doubt the virus is continuing to infect people (other than several species of animals, birds or mammals), but we continue to keep the sight on these d*** ferrets.

          I cannot believe that H7N9 IS NOT INFECTING PEOPLE because some live poultry market reduced for some weeks their activity, leaving intact the source of chickens - namely the large poultry industrial farms.

          GM

          Comment


          • #6
            Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

            Science: H7N9 Transmissibility Study In Ferrets




            Photo Credit Wikipedia


            # 7496


            While the welcomed lull in avian influenza cases in Eastern China over the past six weeks has taken H7N9 largely out of the daily headlines, history has shown that avian flu viruses often go `quiet? during the warm summer months, only to reappear again in the fall or winter.
            Complicating matters, we still don?t know the source of this virus, or exactly how it managed to spread across tens of thousands of square kilometers of Eastern China - and infect at least 132 people - in a matter of a few weeks.
            So over the summer researchers have continued to examine the H7N9 virus, trying to gauge its pandemic potential should it return with colder weather this fall.

            Last week we saw two studies in the Journal Nature(see Nature: H7N9 Pathogenesis and Transmissibility In Ferrets & Mice & CIDRAP NEWS article New studies on H7N9 raise pandemic concerns) that suggested the H7N9 virus might be better equipped to spark a pandemic than previously thought.
            Researchers determined that while the virus did not appear to transmit as easily as seasonal flu via respiratory droplets between ferrets, once acquired, the virus replicated at a much higher rate than one normally sees with seasonal flu.
            Today, we?ve a complex and fascinating new study by scientists from Harbin Veterinary Research Institute and the Gansu Agricultural University appearing in the Journal Science that gives us a detailed look at two critical issues; the pathogenicity and transmissibility of the virus (in mice & ferrets).
            Ferrets ? whose respiratory system (and susceptibility to flu) are reasonably close to that of humans ? are often used in transmissibility and pathogenicity studies of influenza.
            Today?s study tested several different H7N9 isolates (acquired from birds, and from humans) for transmissibility, and even though their HA and NA proteins were genetically quite similar, at least one H7N9 isolate transmitted readily via respiratory droplets among ferrets.

            The abstract (see below), only scratches the surface of research conducted in this study.
            H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

            <cite>
            Science DOI: 10.1126/science.1240532 </cite>

            Qianyi Zhang, Jianzhong Shi, Guohua Deng, Jing Guo, Xianying Zeng, Xijun He, Huihui Kong, Chunyang Gu, Xuyong Li, Jinxiong Liu, Guojun Wang, Yan Chen, Liling Liu, Libin Liang, Yuanyuan Li, Jun Fan, Jinliang Wang, Wenhui Li, Lizheng Guan, Qimeng Li, Huanliang Yang, Pucheng Chen, Li Jiang,Yuntao Guan, Xiaoguang Xin, Yongping Jiang, Guobin Tian, Xiurong Wang, Chuanling Qiao, Chengjun Li, Zhigao Bu, Hualan Chen
            Abstract (EXCERPT)

            We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice.

            Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplets. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.


            While I?m sure CIDRAP NEWS will have a more detailed look later today (I?ll post a link), a few of the high points in this study include:

            • Researchers tested more than 10,700 samples taken from poultry farms, live market birds, wild bird habitats, and even poultry and swine slaughter houses and only managed to find 52 samples that were H7N9 positive (all but 2 were found in live-markets)
            • Chickens intravenously inoculated with two early strains of the virus showed no signs of illness indicating the H7N9 is largely non-pathogenic in chickens
            • Isolates taken from humans appeared to be more pathogenic in ferrets and mice than those taken from birds, suggesting adaptation of the virus may occur after the virus jumps to humans.
            • All of the human isolates had either the 627K or 701N amino acid changes in their PB2 (both associated with increased virulence and transmission in mammals) - while the avian isolates did not - again suggesting that adaptive mutations may have occurred during replication of the virus in the human host.
            • Mice inoculated with avian H7N9 isolates showed no signs of disease signs or deaths.
            • Mice inoculated with human derived H7N9 isolates experienced significant weight loss & pathogenesis.
            • In ferret transmissibility studies, four of the five viruses tested could be transmitted between ferrets in direct contact with each other, and one transmitted with high efficiency via respiratory droplets.


            Being non-pathogenic in chickens, this virus has the potential to spread stealthily, and its rapid spread across multiple provinces in China suggests it transmits efficiently among poultry species.
            This research suggests that the H7N9 virus already binds pretty well to human-like (a2,6) receptor cells, and it replicates efficiently in a mammalian (ferret) host.

            Additionally, the H7N9 virus appears capable of accruing adaptive mutations that enhance both its virulence and transmissibility once it starts to replicate within a human host.

            And perhaps most worrisome of all, at least one isolate tested already demonstrates the ability to transmit readily via respiratory droplets in ferrets.
            Complicating matters, earlier this week we saw a study (see mBio: Antiviral Resistance In H7N9) suggesting that antiviral resistance may form quickly in patients infected with the H7N9 virus.

            All qualities that could help make the H7N9 virus a formidable foe should we see it return in the fall.

            Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.ca/2013/07/science-h7n9-transmissibility-study-in.html" rel="bookmark" title="permanent link"><abbr class="published" title="2013-07-18T14:37:00-04:00">2:37 PM</abbr>

            Comment


            • #7
              Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

              Originally posted by Giuseppe Michieli View Post
              While concerning, it remains difficult to assess the actual human health threat posed by the new H7N9 virus.

              Essentially, for a reason: it is almost impossible to believe that No One Individual currently entering in contact with farmed chickens or in other settings - through occupational exposure or consumption - is developing infection caused by this new H7N9 virus, even though during summer season avian influenza may be less active than in cold weather.

              We need desperately more data, more transparency and a clear picture of the events are occuring on the ground.

              Without these essential data, the most important step from a global public health perspective - namely the start of the H7N9 monovalent pandemic vaccine - will not be taken until it will be too late.

              Ferrets, mices, chickens: yes, but humans?

              No poultry farmers?

              Excuse me, but I cannot believe longer... GM
              I agree too.

              What is this? The Magical Market Disease?

              Comment


              • #8
                Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

                Harbin Institute is a key research centre and provides genetic analysis of many avian influenza viruses to the entire world.

                Clearly, Chinese are sending to the world a warning message: they have a big problem with a novel influenza virus with substantial pandemic potential, so the international community and health agencies have to start preparedness activities, including the preparation of vaccine stockpiles and antivirals, as they are saying that a community spread of the virus is anticipated if not imminent.

                What would also be the reason behind these stark conclusions from almost all Chinese written papers appeared since April?

                Comment


                • #9
                  Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

                  noone asks which strain was submissible in ferrets
                  noone asks whether they did the passaging

                  something has changed in flublogia
                  I'm interested in expert panflu damage estimates
                  my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                  Comment


                  • #10
                    Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

                    They challenged ferrets with viruses from environmental samples, chickens and humans.

                    Only the human isolate (from an Anhui patient) resulted in efficient airborne ferret-to-ferret transmission.

                    However, the other viruses demonstrated less efficient droplets transmission.

                    But, a part the strict science questions, we should take notice of the stern message from the authors, namely this new virus is quite dreaded by the Chinese authorities.

                    Why should we not be worried too?

                    Comment


                    • #11
                      Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

                      CIDRAP:
                      " Aerosol transmission studies involved placing uninfected ferrets in cages adjacent to those housing infected ferrets. The investigators found H7N9 in one ferret exposed to those infected with one of the bird strains and two human strains isolated from some of the first patients in Shanghai. However, the virus was detected in all three ferrets exposed to animals infected with a human H7N9 strain isolated form a patient in Anhui province (AH/1). "

                      that one is almost identical to the index
                      so apparently the ability of ferret transmission decreased during
                      subsequent evolution


                      A/Anhui/1/2013(H7N9) has just one amino-acid difference to the index
                      and that is E627K in PB2
                      I'm interested in expert panflu damage estimates
                      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                      Comment


                      • #12
                        Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

                        so, when this one transmits well in ferrets, than basically all the human ones do.
                        Except they mutated away so to reduce ferret transmission.

                        That one E627K mutation apparently has a big effect.
                        It could be that there are many human cases without E627K and they were asymptomatic or
                        low symptomatic and thus were not detected.
                        Serology should show it. Did we have serology ? I forgot

                        --------------------------
                        now I read they did serology in Japan (!) . negative, of course

                        in poultry workers _before_ 2013
                        I'm interested in expert panflu damage estimates
                        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                        Comment


                        • #13
                          Re: Science. H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

                          Kawaoka: (AH/1) transmitted through respiratory droplets in one of three pairs of ferrets.
                          CDC: (AH/1) transmitted to naive ferrets through direct contact but not by respiratory droplets.
                          Chen: (AH/1) was highly transmissible in ferrets by respiratory droplets.
                          I'm interested in expert panflu damage estimates
                          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                          Comment

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