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  • Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

    Swine flu reaches into the lungs and gut

    Studies of ferrets reveal details of disease.
    Katharine Sanderson
    <!-- --> The swine flu virus was found in the lungs and intestines of infected ferrets.CDC


    The swine flu virus can reach deep into the respiratory system and even as far as the intestines ? findings which could explain why the disease's symptoms are different from those of seasonal flu.


    Two separate groups have been using ferrets to investigate how harmful A(H1N1) influenza virus is and how easily it is transmitted. One of the studies was by Terrence Tumpey at the Centers for Disease Control and Prevention in Atlanta, Georgia, and his colleagues, and is published in Science<sup>1</sup>. Tumpey's team put droplets of three different swine flu viruses, and one 'seasonal' flu virus into the noses of ferrets. Some ferrets shared cages with other uninfected ferrets and some were placed in cages next to other ferrets, sharing nothing but the air they breathed.


    The experiments showed that the ferrets with swine flu strains lost more weight than those with normal flu, and that the swine flu reached lower down into the lungs of some of the ferrets than normal seasonal flu, penetrating the intestines in some cases. This tallies with observations in humans that some patients suffered vomiting and diarrhoea. A second study by Ron Fouchier at the Erasmus University Medical Center, Rotterdam, the Netherlands, and his colleagues also showed that the virus penetrated the lungs. "This is the first indication of how pathogenic [swine flu] really is," says Fouchier. "In the field that conclusion is hard to draw."
    Transmission riddle

    Ferrets have long been used as an animal model for flu because they show similar symptoms to humans, and symptoms tend to last the same amounts of time in both species.


    Tumpey's studies showed that the virus wasn't transmitted between animals as efficiently as the seasonal flu, but Fouchier's results, also published in Science<sup>2</sup> suggest that the virus was transmitted just as efficiently as seasonal flu.


    The disagreement could be because Fouchier used a different sample of swine flu, or that the ferrets are slightly different, says Fouchier ? his ferrets sneezed a lot whereas Tumpey's didn't. Fouchier's experiments were also a little different ? he didn't have any ferrets in direct contact with other ferrets, for example.


    Tumpey says that the virus's failure to transmit 100% of the time shows that it is still changing to suit its new hosts. "We don't think it's fully adapted to humans yet," he says.
    Changing threat

    The virus has not caused serious illness in the majority of cases but this might change. Both studies emphasize the need to keep an eye on swine flu, particularly into the Northern Hemisphere's winter, says Tumpey. "We're worried that the virus could increase its disease-causing ability," he says.

    Flu viruses in different species are continually swapping genes among themselves in a process called reassortment. Fouchier says that the swine flu virus he tested has the avian version of a particular flu gene, which may mean the virus can currently only thrive in warm conditions. If that gene mutates to a more cold-tolerant human version, the virus could grow in the nasal passage and so spread more easily. He has now made a version of the virus to include this mutation and is using his ferret model to see how it affects the animals.


    These two studies will help scientists to monitor the swine flu virus in future, says John McCauley a virologist from the National Institute for Medical Research in London. "It's a very useful thing to provide the baselines," he says, to compare mutated versions against as they emerge. "We need to keep doing these studies," McCauley adds.


    http://www.nature.com/news/2009/0907...tml?s=news_rss

  • #2
    Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

    Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds


    By Simeon Bennett

    July 2 (Bloomberg) -- Swine flu caused more-severe illness in ferrets than seasonal flu, according to two studies in the journal Science that help explain why the H1N1 virus causes symptoms not seen in regular flu such as nausea and vomiting.

    The H1N1 swine flu virus went further into the ferrets? lungs, and also penetrated the gastrointestinal tract while seasonal flu stayed in the nasal cavity, researchers from the U.S. and the Netherlands found. Ferrets are affected by flu viruses much as humans are, the researchers said.

    Swine flu has struck at least 77,201 people in 113 nations worldwide, killing 332, according to laboratory-confirmed reports compiled by the World Health Organization, which has declared the first flu pandemic since 1968. While the virus causes little more than a fever and cough in most people, a previous study showed that about 40 percent of those infected have developed symptoms such as diarrhea, vomiting and nausea.

    ?These data suggest that the 2009 A(H1N1) influenza virus has the ability to persist in the human population, potentially with more severe clinical consequences,? wrote the Dutch study authors, led by Ron Fouchier at the Erasmus Medical Center in Rotterdam.

    The two studies were published online today. Both groups found that ferrets infected with swine flu lost more weight than those exposed to seasonal flu, and that the swine flu virus was more widespread in the animals? bodies.

    When they examined the transmissibility of the virus, the two groups found conflicting evidence. Fouchier and colleagues, who used a strain of swine flu taken from the first person infected in the Netherlands, said ferrets passed it to each other through the air as easily as seasonal flu.

    Efficiency Finding

    The U.S. researchers, led by Terrence Tumpey at the Atlanta-based Centers for Disease Control and Prevention, said the ferrets in their study didn?t transmit the swine flu strains they used, taken from patients in California, Texas and Mexico, as efficiently as seasonal flu strains.

    Swine flu doesn?t latch on to healthy cells in the human respiratory tract as easily as seasonal flu because of a genetic mutation, the CDC researchers said.

    Inefficient transmission suggests the virus would need to mutate to become as transmissible as seasonal flu or the 1918 pandemic virus, they said.

    To contact the reporter on this story: Simeon Bennett in Singapore at sbennett9@bloomberg.net

    http://www.bloomberg.com/apps/news?p...d=abAA7cQlO4Nc

    Comment


    • #3
      Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

      5-10 reports about this study now, none shows the viruses used.

      why not make this headline:


      Swine Flu Is More Severe in Ferrets Than Seasonal Flu, Study Finds
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #4
        Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

        Margaret Chan and company has told us that there are no important mutations in the new flu yet. However, two studies from credible scientists using samples from different countries get different results regarding the transmissibility of the new flu. Is this just a normal situation when studies of this nature vary or are there differences in the geographical strains that may not be obvious in the sequences or is this just spinning the information?
        Last edited by sharon sanders; July 6, 2009, 10:32 AM. Reason: typo
        Absence of evidence is not evidence of absence

        Comment


        • #5
          Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

          It may be more than a difference in geography. I wonder if the California, Mexico and Texas strains are much earlier in time than the Netherlands strain. If so, the Netherlands strain just may have changed.

          I believe Dr. Chan has said the virus has not mutated in any important ways. But, we only think we know what mutations are important. Perhaps, we're in for a surprise...

          Snick

          Comment


          • #6
            Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

            My understanding (and don't shoot me if I'm wrong) is that the two groups used subtly different tests of transmission. One group housed the ferrets apart from each other, thereby permitting only airborne transmission. The other group housed the ferrets together, thereby permitting both airborne and contact transmission. The first group found that swine flu transmits as well as seasonal flu, whereas the second group found that swine flu does not transmit as well.

            This suggests that swine flu transmits efficiently via the airborne route, but less efficiently via direct contact. However, the two groups of ferrets didn't have identical symptoms, so that conclusion isn't yet robust - and the answer is in any event presumably changing all the time as swine flu adapts to the new host.

            Comment


            • #7
              Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

              Swine flu transmission studies suggest new virus is here to stay:experts
              By Helen Branswell ? 18 hours ago

              TORONTO ? Swine flu viruses are missing at least two key features seen in all flu viruses present and past that transmit well among people and yet the viruses are spreading quite efficiently, two new studies suggest.

              The research groups which produced the work differ slightly in their views of the degree to which the novel H1N1 virus is spreading, with one finding transmission isn't yet as efficient as with human flu viruses while the other finding transmission rates are in lockstep with those of seasonal flu cousins.

              There is no disputing the evidence, though - the virus is spreading around the globe, claiming at least 332 lives so far. And it is doing this without all the tools scientists would expect a flu virus to need to become a successful human pathogen.

              "The take-home message is that a virus that does not have some of the features that we have previously recognized as hallmarks of adaptation of flu in humans was able to establish itself in humans and cause disease," said Dr. Daniel Perez, an influenza virologist with the University of Maryland.

              "Regardless of what the virus might do, I believe it is here to stay either as a whole virus or with some of its gene. It may be able to outcompete and-or co-circulate with seasonal flu strains."

              Perez was not involved in the studies, both of which will be published Friday in the journal Science. He is, however, familiar with the work; his lab has completed a similar study.

              The transmission studies were done by research groups at the U.S. Centers for Disease Control with colleagues from the Massachusetts Institute of Technology and at Erasmus Medical Center in Rotterdam, the Netherlands.

              Both groups tested spread in ferrets, which are considered an excellent model for flu infection in humans.

              The CDC's work suggests the virus isn't yet completely adapted to spread among humans. When healthy ferrets were housed in cages adjacent to and sharing feeding dishes with experimentally infected animals, only two-thirds of the healthy animals became infected in the CDC research.

              By contrast, the group in the Netherlands found all healthy ferrets caught the new virus when housed next to animals infected with the virus. Perez's work also saw this 100 per cent transmission rate.

              In both the CDC and Erasmus studies, ferrets that were infected with human flu viruses transmitted infection to all their healthy neighbours.

              Dr. Terrence Tumpey, senior author of the CDC study, said variation in the air flow setups between the CDC's ferret cages and those used in the other studies may explain the differing findings.

              But based on what they saw, his team believes this virus may still be getting used to its new human host.

              A key piece of evidence supporting their conclusion relates to the virus's ability to infect cells in the human respiratory tract. The CDC-MIT scientists showed the novel H1N1 virus's hemagglutinin - the surface protein that locks onto a cell it is about to invade - currently makes a connection that is weaker or less efficient than that made by regular flu viruses.

              That suggests the virus has room for improvement. And if it mutates to bind more efficiently, it would become even more adept at spreading from person to person.

              "I mean, it's transmitting. But we think it could potentially transmit even better," Tumpey said from Atlanta.

              He suggested with better transmission could come more severe disease - not just in sheer numbers, but in the proportion of infected people who develop serious illness.

              "A lot of cases have been mild. But if it was adapted more towards humans, it could be more severe. More consistently severe," Tumpey said.

              His counterpart on the Dutch paper, Dr. Ron Fouchier, shares his concerns.

              "I do agree that the virus might still pick up mutations to improve infection and transmission in humans. But in our opinion, it is already good enough to beat the seasonal flu viruses," he said via email.

              The CDC scientists also reported that the virus is missing a feature in an internal gene called PB2 that is known to relate to transmissibility.

              All seasonal flu viruses and the past three pandemic viruses - in other words, all flu viruses which have successfully made the jump from other species into humans - have had this feature. The swine H1N1 virus does not.

              They don't know how the virus achieved transmissibility without this mutation or how likely it is to acquire it. But Tumpey said the mutation is also linked to increased virulence or disease severity and the flu community is watching closely for this change.

              Both groups studied tissues from the infected ferrets. They found swine flu viruses triggered infections that went deep into the lungs of the animals. Human flu strains infect the animals' upper airways.

              That ability of the virus to spread to and proliferate deep in the lungs could help explain what doctors caring for severely ill swine flu patients are seeing: aggressive viral pneumonias that incapacitate the lungs.

              "Certainly, the lesions we noted in our ferrets are consistent with the disease in humans," Fouchier said.

              "It seems that due to more extensive virus replication, the virus does more damage, and spreads deeper down the airways as compared to seasonal viruses."

              Those findings are concerning, suggested Dr. Malik Peiris, a virologist and flu expert at the University of Hong Kong.

              Peiris, who was not involved in the studies, said that while the swine flu virus is not as virulent as H5N1 avian influenza or the virus that caused the 1918 Spanish flu, its ability to infect the lower respiratory tract "is clearly cause for caution in regard to the pathogenic potential of this virus in humans."

              Both H5N1 and the Spanish flu virus infect tissues deep in the lungs.

              Fouchier said he is concerned the novel H1N1's ability to invade deep lung tissue could lead to more severe disease when the virus is spreading in true winter conditions, which are better suited to spread of flu.

              A study in guinea pigs - also a good animal model for flu - published a couple of years ago found that at lower temperatures flu viruses replicate more and for longer durations.

              If that holds true for humans and for this virus, the severity of swine flu infections in winter could be greater, Fouchier warned.

              Copyright ? 2009 The Canadian Press. All rights reserved.
              Add News to your Google Homepage

              Schematic presentation (A) and a photograph (B) of transmission cages. The ferrets are housed in clear Perspex transmission cages, in which each inoculated animal was housed individually with a naive ferret. The two cages of the inoculated and naive transmission pair were separated by two stainless steel grids (1). Negative pressure within the isolator cage is used to direct a modest flow of high efficiency particulate air (HEPA) filtered air (2) from the inoculated to the naive ferret. The outlet airflow (3) is HEPA filtered to prevent continuous circulation of infectious influenza A virus particles and to prevent crosscontamination with other transmission cages placed in the same isolator cage. Arrows indicate airflow. THE CANADIAN PRESS/ HO -Science/AAAS

              http://www.google.com/hostednews/can...ax7Aq5u2hlkpVw

              Comment


              • #8
                Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

                Originally posted by Dark Horse View Post
                Margaret Chan and company has told us that there are no important mutations in the new flu yet. However, two studies from credible scientists using samples from different countries get different results regarding the transmissibility of the new flu. Is this just a normal situation when studies of this nature vary or are there differences in the geographical strains that may not be obvious in the sequences or is this spinning the information?
                I have no opinion on the other possibilities you mention, but yes, it's normal to see some differences in results between similar studies.
                Last edited by sharon sanders; July 6, 2009, 10:32 AM. Reason: typo in quote

                Comment


                • #9
                  Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Study Finds

                  Originally posted by gsgs View Post
                  5-10 reports about this study now, none shows the viruses used.

                  why not make this headline:


                  Swine Flu Is More Severe in Ferrets Than Seasonal Flu, Study Finds
                  Do you use your cell phone to type messages?

                  Can you please type full sentences, I don't understand your puzzle talk half the time, thanks

                  Comment


                  • #10
                    Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

                    There are 5-10 threads about this study now here at FT.

                    There are also many reports in newspapers.

                    But none of them lists the viruses which were used.


                    The headline suggests, that
                    swine flu were more severe in humans than seasonal flu.
                    But they only tested it in ferrets.

                    So, the headline of this thread is misleading.

                    Apparantly swine flu is much milder so far than seasonal flu in humans.
                    I'm interested in expert panflu damage estimates
                    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                    Comment


                    • #11
                      Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

                      There are two ferret studies that addressed this issue.

                      One tested seasonal flu in ferrets as compared to Netherlands/602 (CDC variant ii, similar to CA/05). The virus titers 3 days post innoculation were higher in the Swine Flu infected mammals than the seasonal flu based on nasal samples.

                      The second study tested seasonal flu in ferrets as compared to the following three Swine Flu viruses:

                      CA/04 (CDC variant v)
                      TX/15 (CDC variant i)
                      MX/4482 (CDC variant iii)

                      The weight loss in the ferrets were higher in the Swine Flu infected mammals than the seasonal flu animals by a substantial margin. There was no virus detected in either the lungs or intestines of the seasonal flu infected ferrets, but almost all of the Swine Flu infected animals showed titers in the lungs, and some in the intestines as well. With the MX/4482 infected ferrets, half died.

                      All of these results are consistent with the fact that the Swine Flu virus lacks the E627K mutation in the PB2 gene segment.

                      The only variant that was not tested against seasonal flu in ferrets was CDC variant iv, the strain that most affected New York.

                      Comment


                      • #12
                        Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

                        thanks for the summary.

                        is there any indication that some of the strains are worse
                        than others in ferrets ?

                        what's the reason that it causes fewer deaths in humans
                        than seasonal flu despite ferrets suffering worse ?
                        Children are preferrably infected and they rarely die from flu ?
                        Humans are different from ferrets ?
                        It's not so bad in summer ?
                        ...
                        I'm interested in expert panflu damage estimates
                        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                        Comment


                        • #13
                          Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

                          Originally posted by gsgs View Post
                          thanks for the summary.

                          is there any indication that some of the strains are worse
                          than others in ferrets ?
                          MX/4482 appeared to be more virulant in ferrets. That variant has the following unique characteristics:

                          NA: V106I coupled with N247D
                          NP: V100I

                          The large grouping of NY viruses in variant iv also have these mutations, but in addition have:

                          HA: S206T
                          NS1: I123V

                          So the NY strain may or may not show similar health issues in ferrets, or for that matter humans.
                          Last edited by AlaskaDenise; July 6, 2009, 04:15 PM. Reason: fix html

                          Comment


                          • #14
                            Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

                            Thank you Mamabird.

                            Comment


                            • #15
                              Re: Swine Flu Is More Severe Than Seasonal Flu, Ferret Studies Find

                              Full Free PDF Document is available previous registration at: http://www.sciencemag.org/cgi/rapidpdf/1177238v1.pdf


                              Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice

                              Taronna R. Maines,1 Akila Jayaraman,2 Jessica A. Belser,1 Debra A.Wadford,1 Claudia Pappas,1 Hui Zeng,1
                              Kortney M. Gustin,1 Melissa B. Pearce,1 Karthik Viswanathan,2 Zachary H. Shriver,2 Rahul Raman,2 Nancy
                              J. Cox,1 Ram Sasisekharan,2 Jacqueline M. Katz,1 Terrence M. Tumpey1

                              ...

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