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  • Novel UK White Chapel Neuraminidase Hybrid from animal H3N8 and Human Seasonal H1N1

    Neuraminidase (NA) Review

    UKWhiteChapel4880374_2M_2010_11_28

    Six of the seven polymorphisms on the Neuraminidase (NA) for UKWhiteChapel4880374_2M_2010_11_28 have now been confirmed with matches to various seasonal human H1N1 (S9, S8, S7). The seventh change, a T->C (T235C) SNP, coding for 79P, is found extensively in the zoonotic reservoirs across multiple species.

    This first base donor for the UK PF11 NA 79P codon (cCA) occurs at least 19 times in H3N8 from 2009 to 2005, spanning a wide range of mammal species:
    • Horses
    • Dogs
    • Swine
    Geographic significance is found in Sydney, Australia where the SNP is found in the following 2007 H3N8 animal sequences.
    • H3N8 canineSydney6692_2007_10_15
    • H3N8 canineSydney6525_2007_10_14
    • H3N8 equineSydney6085_2007_10_10
    This fact becomes of higher interest when we inspect the similarity of the dates and sample identification numbers. The possibility exists that these 3 animals were in a transmission chain on a ranch that may have included undetected or unsequenced human infection.

    Note that the HA of UKWhiteChapel4880374_2M_2010_11_28 is most closely matched to an Australian sequence. The three H3N8 sequences from Sydney also carry the HA syn474C found in a separate sub-clade within the 4 UK sequences on UKCambridge118_4F_2010_11_19. Evidently, pH1N1 is moving toward homology with non-human mammal H3N8 on the HA AND the NA gene segments in two separate genetic backgrounds within the UK.

    Sub-segment genetic recombinations from H3N8 onto human backgrounds are considered of interest in relation to severity.

    Furthermore, the SNP coding for the NA 79P is also demonstrated in two other zoonotic Influenza serotypes. In 2009, the change appears in Eastern Europe on an Avian H7N7 sample, mallardPolandM446_2009. Recall that the UKWhiteChapel4880374_2M_2010_11_28 HA 188T may have also originated from H7N7. Furthering the animal connection, the NA 79P SNP appears on a domestic poultry, lab-derived vaccine strain on the H9 background.

    This NA 79P from the animal reservoirs may have accumulated onto a very human-adapted NA in Australia / UK, generating a novel gene segment with a combination previously unknown in humans.

    . . . . UKWhiteChapel4880374_2M_2010_11_28 (
    . . . . . . . . 79P [SNP H3N8 (cAA), H7N7 (cTG), H9 Vx (cAt)],
    . . . . . . . . . . . [PF11 12 Instances, None with syn240T or 241I],
    . . . . . . . . 100H mix wt [S8, S7, WSN33 with syn240T & 241I],
    . . . . . . . . . . . . . . . . . . [Avian H5N1, H11N1],
    . . . . . . . . syn109G [S7],
    . . . . . . . . syn240T (ACc) [S7, tn],
    . . . . . . . . 241I (aTA) [1918, S7],
    . . . . . . . . 369K [swIndiana17311_2010_03_17]
    . . . . . . . . . . . . . [S9, S8, S7],
    . . . . . . . . syn377P (CCa) [WSN33 (CCt), S7 (CCt)])

    Comment


    • Re: UK: Reports of Approximately 31 Deaths and 460 Patients in intensive care (27 deaths confirmed by HPA as for Dec. 23 2010) due to influenza

      Source: http://www.thisissomerset.co.uk/news...l/article.html


      Thursday, December 30, 2010, 09:00
      Pregnant woman with swine flu is fighting for life

      A pregnant mother-of-four is fighting for her life in a medically-induced coma after contracting swine flu.

      Gemma Escott, 27, is on life support with kidney failure after husband Martyn, 33, took her to hospital on Christmas Day when she could not breathe properly...

      Comment


      • Re: UK: Reports of Approximately 31 Deaths and 460 Patients in intensive care (27 deaths confirmed by HPA as for Dec. 23 2010) due to influenza

        http://www.bbc.co.uk/news/uk-scotland-12093409 For more info

        30 December 2010 Last updated at 13:00 GMT

        Winter flu claims two more lives in Scotland
        Since the start of the flu season 23 people have required intensive care treatment

        Two people have died from seasonal flu in the last week, bringing the total number of deaths in Scotland this winter to four.

        Twelve people were also hospitalised in the last week, bringing the total so far to 23.

        The NHS in Scotland said the figures were to be expected at this time of year....

        Comment


        • Re: UK: Reports of Approximately 39 Deaths and 460 Patients in intensive care (27 deaths confirmed by HPA as for Dec. 23 2010) due to influenza

          Source: http://www.bbc.co.uk/news/health-12094135

          30 December 2010 Last updated at 10:25 ET

          Flu deaths continue to increase
          swine flu virus The majority of deaths were in people infected with swine flu

          Thirty-nine people in the UK have now died with flu-like illnesses this winter, figures show.

          All but three of them were infected with the H1N1 swine flu virus, while the remainder had influenza B, the Health Protection Agency data shows...

          Comment


          • Re: UK: Reports of Approximately 39 Deaths and 738 Patients in intensive care (27 deaths confirmed by HPA as for Dec. 23 2010) due to influenza

            Denis Campbell, health correspondent

            guardian.co.uk

            Thursday 30 December 2010 16.45 GMT

            Flu deaths continue to rise


            The government has been forced to take new steps to tackle seasonal flu after new figures showed there were 12 more deaths in the past week, and 738 people seriously ill in hospital.

            The total number of deaths from this winter's outbreak now stands at 39, up from 27 last week, the Health Protection Agency confirmed.

            Of those, 36 died from H1N1 swine flu, which is the most virulent of the two main flu strains circulating this winter. The other three died from Influenza B. All but one of the 39 was under 65, and four were under five years old.

            The government will now reintroduce a media campaign to help tackle the outbreak. Labour, which earlier this week claimed the campaign had been axed, accused the government of a U-turn.

            Some 61% of this year's victims were in one of the "at risk" groups who qualify for a free NHS seasonal flu jab, which include pregnant women, those with breathing conditions such as asthma and those whose immune systems are weak.

            But just two of the 23 individuals had received the jab, which for the first time this year includes protection against swine flu, which claimed hundreds of lives when it began circulating in the UK in early 2009.

            The figure serves to underline doctors' concerns that millions of people run the risk of infection, with potentially serious effects, because they have not been vaccinated.

            The number of people with known or suspected flu being treated in critical care units in hospitals has jumped from 460 to 738 - a rise of 278 in a week.

            (...)

            Number of victims of this year's outbreak up to 39 from 27 last week, forcing government to adopt new preventative measures

            Comment


            • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

              First, thanks to everyone for keeping the public informed, and thanks especially to Sharon for your heads up. I've been severely incapacitated this year as far as computer use is concerned, am only catching up to bits and pieces, so the following comments are only based on what's on this thread the the links that you all have so kindly provided.

              Such caveats aside, here're my thoughts, FWIW. The rate of increase in ILI in recent weeks may seem dramatic but is actually typical for UK, because of high degree of population mixing simply from daily routines. Someone mentioned the recent travel chaos as opportunity for extra mixing - I don't even think we need any extra reason, quite simply the degree of mixing from 'normal' life is sufficicent for very efficient transmission, as evidenced by the difference in pandemic experience in summer 2009 between the UK and the US http://www.newfluwiki2.com/diary/4115/are-we-done-here

              The outbreak is also seemingly dramatic compared to last year, but only because there was an out-of-season outbreak in the summer with the new H1N1, such that the winter outbreak in 2009 was somewhat dampened, but if you look at longer time trends (see <a href="http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1284475036543" target="_blank">HPA Influenza Surveillance graphs</a>), it hasn't reached the 2008/09 peak yet. Note that the ILI outbreaks in UK tend to peak very quickly, so I suspect the peak is either already reached or almost reached, by now.

              Also, given there is a new virus for whom a portion of the population is still immunologically naive, I would be surprised if we didn't see a bigger seasonal ILI epidemic this year compared to the same time-point in recent years, even if we exclude last year for the above reason.

              With all the in mind, personally, all I'm seeing is a 'big' flu outbreak that is still within the range of 'normal' seasonal flu, and, given the number of infected people, I'm not seeing any reasons for concern with the mortality figures so far, granted that anything that affects younger populations is always of more concern (on both compassionate and public health levels) than what affects the elderly. Note that the HPA charts show a very small increase in all cause mortality, but still within normal variations, but mortality for respiratory causes remains flat.

              Comment


              • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                Originally posted by SusanC View Post
                Note that the HPA charts show a very small increase in all cause mortality, but still within normal variations, but mortality for respiratory causes remains flat.
                Susan, the chart I see shows a large increase in all cause mortality which is outside expected range. This week's report repeats the same figure for Week 49 as last week's report with no explanation when it should have had the week 50 data. Hopefully this is just a Christmas late data issue as I'd really like to see what happened after this

                In week 49, an estimated 11,193 all-cause deaths were registered in England and Wales (source: Office for National Statistics), an increase from the previous week and now above the upper limit of expected levels for this time of year (figure 8). Potential factors for this increase include recent cold weather and circulating respiratory viruses.


                Figure 8: Observed and predicted all-cause mortality

                Comment


                • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                  Originally posted by Hogweed View Post
                  Susan, the chart I see shows a large increase in all cause mortality which is outside expected range. This week's report repeats the same figure for Week 49 as last week's report with no explanation when it should have had the week 50 data. Hopefully this is just a Christmas late data issue as I'd really like to see what happened after this

                  In week 49, an estimated 11,193 all-cause deaths were registered in England and Wales (source: Office for National Statistics), an increase from the previous week and now above the upper limit of expected levels for this time of year (figure 8). Potential factors for this increase include recent cold weather and circulating respiratory viruses.


                  Figure 8: Observed and predicted all-cause mortality
                  You have to look at the actual mortality charts from previous years (ie the 2 charts above the one you posted, sorry, can't post pics, too many clicks needed). Look at the all causes chart from previous years, and you'll see that every year, there's a peak starting around this time that breaks way out of the so-called 'prediction' chart that you're showing (which renders the prediction chart almost totally useless for this period, IMHO). Then look at the actual mortality chart for respiratory causes.

                  The caveat is this is still early days, so the respiratory deaths can still shoot up, just that so far I'm not seeing any signal for concern from these charts, that's all.

                  Comment


                  • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                    Originally posted by SusanC View Post
                    You have to look at the actual mortality charts from previous years (ie the 2 charts above the one you posted, sorry, can't post pics, too many clicks needed). Look at the all causes chart from previous years, and you'll see that every year, there's a peak starting around this time that breaks way out of the so-called 'prediction' chart that you're showing (which renders the prediction chart almost totally useless for this period, IMHO). Then look at the actual mortality chart for respiratory causes.

                    The caveat is this is still early days, so the respiratory deaths can still shoot up, just that so far I'm not seeing any signal for concern from these charts, that's all.
                    Thanks for the explanation. Still would be nice to see the data for the following week though.

                    Comment


                    • UK Severe Influenza Cases in ICU Percentage Update

                      ** Please note that the figure of 738 ICU Influenza patients has been defined by RoRo as being only for England. Figures for Wales, Scotland and Ireland will be produced as they are available. **

                      Total case count officially increased by 44.9&#37; in the UK, but ICU beds with Influenza (HPA Week 52) appear to have risen at the substantially higher rate of 60%.

                      The December 23rd official report (latest) showed that 1 of 7 ICU beds (~13%) were Influenza cases. Compare that figure to the 2009 pH1N1 Pandemic peak of roughly less than 1 of 12. The 738 ICU cases reported today demonstrate that UK hospitals are utilising 1 of 5 ICU beds for Severe Influenza cases.

                      GeneWurx_UK_ICU_Categories_v1.xls

                      These extrapolations suggest a severe wave that is continuing.

                      GeneWurx and the concerned public would like like to thank the officials who released the data today. Additional information is, however, required, including more frequent updates on cases, ICU cases and fatalities, alongside genetic sequences tagged according to mild, severe and fatal cases with clinical progression meta-data.
                      Last edited by NS1; January 1, 2011, 07:28 AM. Reason: RoRo Category Definition

                      Comment


                      • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                        what is the point, of giving millions of people adjuvanted vaccines of uncertain safety in a mild pandemic, when the worst may be over??


                        The worst was not over, as we can see this year.
                        if last year a greater number of people in England had been vaccinated, this year the performance of' outbreak might have been different.
                        Pandemics usually have different waves, the last may be worst than the first one, like in 1968-69

                        In this season we have normal level of ILI, compared with previous seasons, but ICU are stressed disproportionally

                        Graphs may be at low level, but you have to consider that elderly are largely spared

                        Comment


                        • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                          Originally posted by tetano View Post
                          what is the point, of giving millions of people adjuvanted vaccines of uncertain safety in a mild pandemic, when the worst may be over??


                          The worst was not over, as we can see this year.
                          Well, my original comment referred to the use of vaccines in a timely manner in a breaking pandemic. I wrote that comment in mid-November 2009. Now that we have 1 year of hindsight, we can look at the stats again.

                          Here's a paper analyzing H1N1 2009 mortality in the UK, up to March 2010. By mid-November, we were already on the downward slope of the second wave (see figure here, the line chart for outbreak which peaked in mid-October, mortality lags behind by a couple of weeks http://www.eurosurveillance.org/imag..._H1N1_Fig1.jpg )

                          At the same time, let's look at what actually happened with the vaccination program. Here's a report on the pandemic vaccine uptake . On page 19 of that pdf, you can see a chart of vaccine uptake over time. By mid-October, which was the peak of the second wave, <5% of target groups had been vaccinated. Suppose someone got vaccinated in mid-November, the date when I wrote that comment. Assuming, optimistically, 2 weeks for immune protection to occur, then they would have been protected from early December onwards, at which point the epidemic was well on the wane. Even so, only 20% of the target groups had received their vaccine by that mid-November date.

                          Another way of looking at this, in reference to this year, is that from June 2009 - Feb 2010, there were 436 deaths. For the current season, we're looking at double digits still, <50 so far. Any death is tragic, but I'd say, comparing 400+ to <50, the worst still was over by November 2009.

                          Of course, intuitively, I'd agree that if more people got vaccinated last year, we might have less deaths this year. OTOH, intuition is not science, and I'd say we probably should wait for the statistics (perhaps from different countries?) to actually see whether more vaccinations last year resulted in fewer deaths this year.

                          So, things are still evolving. I'd just stay tuned...

                          Comment


                          • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                            Originally posted by tetano View Post

                            In this season we have normal level of ILI, compared with previous seasons, but ICU are stressed disproportionally
                            FYI, ICUs are always stressed, if there's a big flu outbreak, which there is, this year. Put in another way, we have so little margin in the NHS that the degree of stress to ICUs is IMO overly sensitive (ie too easily triggered) to be useful for our interpretation of the severity of the disease ie a high-ish AR is enough to overwhelm ICUs even if the CFR remains low ...

                            Comment


                            • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                              Thank you to everyone who is participating on this thread.

                              Comment


                              • Re: UK: Reports of Approximately 39 Deaths and 700+ Patients in intensive care (39 deaths confirmed by HPA as for Dec. 30 2010) due to influenza

                                we have so little margin in the NHS that the degree of stress to ICUs is IMO overly sensitive

                                beds in the ICU must be tailored to the needs of a particular country. Maybe in UK are below requirements, but I do not think that every year there is evidence of overwhelming cases. From what referred by English doctors , you have to go back to the 1999-00 season to have a stress so great, in that case determined by the admissions of the elderly

                                At the height of the swine flu outbreak in July 2009 there were 63 people critically ill, while in November 173 people were in intensive care

                                Now there are 700 people in ICU, four times that number

                                As you say, we have to stay tuned and to wait and see

                                Comment

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