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  • EM 2006 - H1N1 in Liverpool 1951

    http://scienceblogs.com/effectmeasur...e-flu-in-1951/


    [Given our posts (here, here) on the particularly severe flu season in Australia, we thought it useful to remind ourselves that a bad flu season can be really bad -- worse than the 1918 pandemic in some locations. Here is a post we did back in April 2006 about an interesting paper (see link in post) by Cecile Viboud and her colleagues at NIH that looks at historical records on flu mortality. Flu is a bad disease, pandemic strain or not. Why some flu is worse than others we don't know.]

    Originally posted Friday, April 7, 2006:

    We talk frequently about the H5N1 virus mutating to a form transmissible between humans, although we acknowledge we don’t know the factors that make that transmissibility possible. There is also the possibility that the virus, if mutated, will modify its current virulence. The case fatality rate (proportion) now is hovering around an extremely high 50%. However we don’t understand the factors that affect these factors in any influenza sub-type, including the current seasonal variety, H3N2. Even within the yearly H3N2 seasons there is a four-fold variation in mortality.

    We are now realizing that in some years there are extraordinary mortalities that exceed those seen in pandemics, including the pandemic of 1918. Our relative ignorance about these variations is emphasized dramatically in a fascinating paper in CDC’s Emerging Infectious Disease journal by NIH’s Cecile Viboud and her co-authors.

    Viboud et al. detail a new investigation of the 1951 H1N1 epidemic:

    Anecdotal accounts exist in the literature of historical influenza epidemics associated with unusual numbers of deaths, such as occurred in the 1951 epidemic in England in the midst of the first era of A/H1N1 viruses (1918 – 1957). In Liverpool, where the epidemic was said to originate, it was “the cause of the highest weekly death toll, apart from aerial bombardment, in the city’s vital statistics records, since the great cholera epidemic of 1849″. This weekly death toll even surpassed that of the 1918 influenza pandemic. (Viboud et al.; all cites omitted)

    The authors compiled monthly pneumonia and influenza (P&I) and all-cause death numbers between 1950 and 1999 in Canada, England and Wales and the US and used additional data for Liverpool where the disease seemed particularly severe. Using the monthly data they fit seasonal variation in a 20 year span to be able to compare the 1951 epidemic with the 1957 and 1968 events, controlling for differences in population, healthcare and socioeconomic status, all factors that affect P&I deaths (age-adjustment and mortality in the summer of 1960 were used to adjust the seasonal estimates for this purpose). A shift toward younger age groups was used as a pandemic signature.

    The results are striking:

    Influenza activity started to increase in Liverpool, England, in late December 1950. The weekly death rate reached a peak in mid-January 1951 that was ~40% higher than the peak of the 1918-19 pandemic, reflecting a rapid and unprecedented increase in deaths, which lasted for ?5 weeks (see figure). Since the early 20th century, the geographic spread of influenza could be followed across England from the weekly influenza mortality statistics in the country’s largest cities, which represented half of the British population. During January 1951, the epidemic spread within 2 to 3 weeks from Liverpool throughout the rest of the country.

    For Canada, the first report of influenza illness came the third week of January from Grand Falls, Newfoundland. Within a week, the epidemic had reached the eastern provinces, and influenza subsequently spread rapidly westward.

    For the United States, substantial increases in influenza illness and excess deaths were reported in New England from February to April 1951, at a level unprecedented since the severe 1943-44 influenza season. Much milder epidemics occurred later in the spring elsewhere in the country.

    Local disparities were found in all 3 countries, with a consistent pattern of higher numbers of deaths in locations affected earlier. In England, influenza-related death rates were ~3-fold higher in Liverpool than in the rest of the country. In Canada, death rates were ~2.4-fold higher in the eastern seaboard provinces than in the rest of the country. Similarly, in the United States, rates were ~2.3-fold higher in New England than in the rest of the country.



    Figure 1 from Viboud et al. paper: Liverpool P&I deaths (A) and all cause deaths (B)

    In Canada this was the most severe influenza epidemic in the second half of the 20th century, including both pandemic years of 1957 and 1968, by a factor of 50% and 200 – 300%, respectively. Similar results were seen in England and Wales. In the US, by contrast, the flu season was mild, except in New England.

    The suspicion that England and Wales and Canada may have experienced an epidemic with a novel sub-type was not confirmed by an examination of the age distribution, which was typical of interpandemic years. 1957 and 1968, by contrast, did exhibit the age shift thought to be a characteristic pandemic signature. The Canadian data for 1951, the only one where detailed age breakdowns were available, showed that the death rate in the younger age groups was almost as high as in the 1957 pandemic, but the death rate in the over 65 age group was double that of the 1957 pandemic. Thus the age distribution wasn’t shifted to the younger age groups but markedly increased across the age groups. Additional analyses suggested it was not transmissibility that characterized the 1951 outbreak but the virulence of the virus, although data are not sufficient to establish this with certainty. The subtype circulating at the time was H1N1, the same subtype as the 1918 pandemic and the predominant seasonal form until the H2N2 pandemic of 1957.

    But what about the markedly lower death rate in the US (except for New England)?

    These disparities are in part explained by laboratory surveillance reports by WHO, indicating that 2 antigenically distinct influenza A/H1N1 strains cocirculated in the Northern Hemisphere during the 1951 epidemic. The so-called “Scandinavian strain” was isolated in northern Europe and associated with mild illnesses. By contrast, the “Liverpool strain” was associated with severe illnesses and high deaths in Great Britain, Canada, southern Europe, and Mediterranean countries . As both strains cocirculated in some countries, intrasubtypic cross-immunity might have existed, with these 2 strains competing for susceptible hosts.

    No viral isolates or genetic sequences are available for the 1951 virus, so the source of the unusual virulence of the Liverpool strain remains unknown. This intriguing paper underlines once again how much we don’t know. The elderly seemed to do relatively well in the pandemics of 1957 and 1968, but suffered disproportionately in the non-pandemic year of 1951 where they did worse than in two of the three 20th century pandemics in England, Wales and Canada and worse in Liverpool than in any pandemic, including 1918.

    A well-known flu researcher said to me recently he thought he knew more about flu 20 years ago than he does now. With the publication of this paper, we might say we also know less about seasonal influenza now than we did last month.
    I'm interested in expert panflu damage estimates
    my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

  • #2
    Re: EM 2006 - H1N1 in Liverpool 1951

    http://www.ncbi.nlm.nih.gov/nuccore/CY077886
    VRL 15-DEC-2010

    A/Liverpool/1951(H1N1)


    2 papers by Vibaud et.al. :

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294686/
    http://www.ncbi.nlm.nih.gov/pubmed/16806596


    -----------------------------------------------------------------------

    distance to related viruses in the 8 segments :

    Code:
     41 >A/Liverpool/1951,1951//,
    
     18: 16, 37, 29, 25, 27, 63, 24, 16   A/Hickox/1940,1940//
      2: 36, 15,  7, 46, 14, 14, 13,  4   A/Index/1977(H1N1)
     35:  6,  6,  7, 34,  8, 11, 12,  4   A/Fort Worth/1950,1950//
     37:  0,  0,  0,  1,  2,  0,  3,  0   A/Albany/12/1951,1951//
     38:  0,  0,  0,  1,  1,  0,  1,  2   A/Albany/13/1951,1951//
     39:  2,  0,  0,  1,  0,  1,  3,  2   A/Albany/14/1951,1951//
     40:  0,  0,  0,  1,  1,  1,  1,  1   A/Albany/1618/1951,1951//
     41:  0,  0,  0,  0,  0,  0,  0,  0   A/Liverpool/1951,1951//
     43:---,---,---, 11,---,---,---,---   A/TF/15/1951,1951//
     44:---,---,---,  9,---,---,---,---   A/Tokyo/1/51,1951//
     46:  6,196,  5, 31,  8,  7,  8,  5   A/Netherlands/001R1/1953,1953//
     47:  7,  7,  5, 31,  8,---,  8,  4   A/Netherlands/002W1/1953,1953//
     51: 10,  8,  7, 35, 11, 13, 12,  3   A/Netherlands/001H1/1954,1954//
     49: 11,  9,  7, 13,  8,  8, 12,  4   A/Malaya/302/1954,1954//
     50: 11,  9,  7, 14,  8,  8, 12,  4   A/Malaysia/1954,1954//
     63: 14, 12,  9, 40, 14, 19, 12,  9   A/Kw/1/1957,1957,H1N1

    4 Albany genomes are very similar, Albany is in NY-state

    the HA is unusual and rare and wasn't seen the years before
    it has D239G(4) = D225G, but this is not so unusual for that time
    I'm interested in expert panflu damage estimates
    my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

    Comment


    • #3
      Re: EM 2006 - H1N1 in Liverpool 1951

      Nice find gs.
      Do you know how Fouchier came up with a sequence half a century later (permafrost, lead coffin etc) and why only PB2? An HA would be nice.

      Comment


      • #4
        Re: EM 2006 - H1N1 in Liverpool 1951

        we have all 8 segments and it's very similar to the Albany genomes from April

        I assume they did store some samples in labs, liquid nitrogene or
        paraffine or such


        here is a paper from 2008, when the sequences were not yet available
        They were released in 2010, after the new pandemic had emerged
        and there were concerns about the Norwegian D222G mutation
        and the severe early season in Ukraine


        http://www.plospathogens.org/article...l.ppat.1000012

        In addition, a virus likely associated with the 1951 epidemic also appears to have
        been generated by a reassortment event
        ....
        Based on the phylogenetic movement of clade E, a major reassortment event
        clearly occurred in the early 1950's to create a virus with novel PB1, PA, NP,
        NA, M, and NS gene segments in combination with older PB2 and HA genes
        that were closely related to those circulating in the 1940's. The extensive
        evolutionary change in six of the eight viral gene segments generated in
        this reassortment event may resolve the quandary over how a virus that
        displayed little antigenic drift in HA caused such a severe epidemic [11].
        ...
        it is not known whether the A/Fort Worth/1950 and/or A/Albany/12/1951 isolates
        contained within clade E were derived from the severe 1951 epidemic
        ...
        I'm interested in expert panflu damage estimates
        my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

        Comment


        • #5
          Re: EM 2006 - H1N1 in Liverpool 1951

          Thanks. I did not check but was the PB2F2 active, did you look?
          As that season has generated such interest, and multiple papers, it seems strange that if there were samples from the period no one else sequenced them earlier.

          Comment


          • #6
            Re: EM 2006 - H1N1 in Liverpool 1951

            semi-pandemic flu from 1977 was quite similar to the
            Liverpool virus in segments 3 and 8, while especially
            HA was quite different.
            Hmm, Fouchier should have asked NSABB before publishing ...
            I hope these viruses do qualify for highest security level


            That it appeared first in Liverpool lets me speculate it came from India

            A similar virus was sequenced in Malaya 1954 (now extinct)

            A/Malaya/302/1954 (H1N1); is also a common lab-strain,
            requires only biosafety 2



            -----------------------------------------------

            and indeed, it had been seen in India in August 1950, where this strain was common.
            Also in Australia two months before
            http://whqlibdoc.who.int/bulletin/19...6)_679-686.pdf

            ------------------------------------------------------

            http://afludiary.blogspot.de/2010/10...om-norway.html

            four main sub-types
            FMI virus, isolated in 1947,
            so-called A-prime virus of which FMl is generally taken as the reference strain.

            Our results so far indicate that it has been possible to transform a Liverpool
            type virus into a Scandinavian type virus.

            The principle of the method used is to passage the Liverpool
            virus in eggs in the presence of homologous antiserum.
            These conditions favour the
            multiplication of any variant virus particles which are not readily neutralized by anti-serum,
            and after three or four egg passages it was found that virus with the properties of the
            Scandinavian type was obtained. In the absence of antiserum, all the strains which we have
            tested have retained their serological identity on passage in eggs.

            Shope (1941) has shown
            that the virus of swine influenza can "go to earth"-in this case, literally-in the earthworm
            and in the pig lung worms which the earthworms harbour.

            The A-viruses which caused outbreaks
            everywhere between 1936 and 1946 seem to have vanished.

            http://www.ncbi.nlm.nih.gov/pmc/issues/154159/

            http://www.ncbi.nlm.nih.gov/pmc/arti...00580-0033.pdf

            the Sardinian virus from 1948/9: (--> "Scandinavian" from 1950/1
            A/Netherlands/001S1/1948(H1N1))
            http://www.ncbi.nlm.nih.gov/nuccore/CY077755
            A/Netherlands/002K1/1949(H1N1)
            http://www.ncbi.nlm.nih.gov/nuccore/CY077763



            ’ At that time avid and nonavid strains were re- ferred to as P-phase and Q-phase variants
            (6). Subse- quent studies with Asian influenza viruses suggest that P-phase and Q-phase
            viruses represent mixtures of two genetically distinct populations with an avid var- iant
            predominating in the former case and a nonavid variant predominating in the latter case ( 7)



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            >A/Index/early human                    ...........................................................................................................................................................
            >A/WSN/1933 TS61,1933//,                K..YFV..IFAR.......T........R....A......L.....--FN.VS.R........D..T.......SS.DE...S.GA.....K.H.............E......S.N........Y..R.........L................
            >A/WSN/1933,1933//,                     K..YFV..IFAR.......I........R....A......L.....--FN..S.R........D..T.......SS.DE...S.GA.....K.H.............E......S.N........Y....I.....G.L................
            >A/Wilson-Smith/1933,1933//,            K..YFV..I.AR.......T........R....A......L.....--FN..S.R....I...D..T.......SS.DE...S.GA.......H.............E......S.N........Y............L................
            >A/United Kingdom/1/1933,1933/04/16,    ........L...................R....A....T.L.......L..VS.G......T.D..N.......SS..E...H.V........P...L........................................L......D.........
            >A/United Kingdom/1-MA/1933,1933/06/01, ........L...................R....A....T.L.......L..VS.G......T.D..N.......SS..E...H.V........P...L........................................L......D.........
            >A/Puerto Rico/8-1/1934,1934//,         N.....A.....R...........P..VR....I..............N-....E.....E.E...K.K....I.N.KE.N...E.T..E.....K...N..M..........L...Y...A.......T.I.K...............V.I...
            >A/Puerto Rico/8-SV14/1934,1934//,      N.....A...............G.P..VG....I.......K...D..N-....E..N....ES.EK.K.RE.I-D.EE.N...E.T..E.KG..K..KN..M..........L...Y...A.......T.I.K...............V.I...
            >A/Puerto Rico/8-WG/1934,1934//,        N.....A.....R...........P..VR....I..............N-....E.....E.E...K.K....I.N.KE.N...E.T..E.....K...N..M..........L...Y...A.......T.I.K...............V.I...
            >A/Puerto Rico/8/1934,1934//,           N.....A.....R...........P..VR....I..............N-....E.....E.E..NK.K....ISN.KE.N...E.T..E.....K...N..M..........L...Y...A.......T.I.K...............V.I...
            >A/Puerto Rico/8/34/Mount Sinai,1934//, N..S..A.....R...........P..VR....I..............N-....E.....E.E...K.K....I.N.KE.NI..E.T..E.....K...N..M..........L...Y...A.T.....T.I.K...............V.I...
            >A/Alaska/1935,1935//,                  N.....A.....R...........P..VR....I..............N-....E.....E.E...K.K....I.N.KE.N...E.T..E.....K...N..M..........L...Y...A.......T.I.K...E...........V.I...
            >A/Melbourne/1935,1935//,               .I..........R...................KI...........K................ED....K.....SN.KE.T...E....E.........N....................KA..................I......K..P....
            >A/Phila/1935,1935//,                   ......A.....R.P.............R....A..N........K................ED..K.K.....SS.KE.T...E....E...T.....N.....................A.................................
            >A/bh/1935,1935//,                      ........L...................R....A......L.......-...S.R.Q......D..N.......SS..E...R.E........T...M........................................L................
            >A/Melbourne/1/1946,1946//,             .I..........R.......I...........KI...........KS...............ED....K.....SS.KE.T...E...IEEK..I....NV...................KA..................I......K.......
            >A/Henry/1936,1936//,                   ............R...........P...R....IA.............NI................K.K....ISN.K..T...E....EE......M.NV....................A.................................
            
            
            
            >A/Netherlands/001S1/1948,1948//,       ----........R.......I..E..SER................K...........C..E.D..NN.K.....SNIK..T..KE....E..G......N.......................................SIR.NK..........
            >A/Bellamy/1942,1942//,                 ....I...I...R.......I..E..SER..........T....TK...........C..E.D..NN.K.....SNIK..T..KE....E..G......N.........................................R.NK..........
            >A/AA/Marton/1943,1943//,               ............R.......I..E..SER.............S..K...R..........E.D..NN.K.....SNIK..T..KE....E..G..K.M.N...........D............................NR.NK..........
            >A/AA/Huston/1945,1945//,               ............R...R...I..E..SER......TN........K...R..........E.D..NN.K.....SNIK..T..KE....E..G..K.M.N...........D.......................I.....R.NK..........
            >A/Iowa/1943,1943//,                    ............R.......I..E..SER.............S..K--.G..........E.D..NN.K.....SNIK..T..KE....E..G.IK.M.N...........D............................NR.NK........A.
            >A/Weiss/1943,1943//,                   ........I...R.......I..E..SER.I....T.........K..AR..........E.D..NK.K.....SSIKE.T..KE....E.........N...........D.......................I.....R.NK..........
            >A/Hemsbury/1948,1948//,                -.F.........R.......I..E..SER....-........S..K...R..........E.D..NK.K.....SNTK..T..KE....E.........N...........D.............................R.NK..........
            
            >A/Roma/1949,1949//,                    K....S......R.......I..E.FSKKA....YA........RK.V.R....K.....E.D..N.K..E...SNIE.KT.RKE....E..G.I....N...H......DD.....................K.........NK..........
            >A/Index/1977(H1N1)                     K....S......R.....S.I..E.FSKKA....YA........RK.V.R..S.K.....E.N..N.K..E...SNIE.KTIRKE....E..G.I....N...H......DD.....................K.........NK..........
            >A/Leningrad/1954/1,1954//,             K....S......R.....S.I..E.VSKKA....YA........RK.V.R..S.K.....E.N..N.K..E...SNIE.KTIRKE....E..G.I....N...HN.....DD....................DE.........NK..........
            >A/Albany/4836/1950,1950//,             K....S......R.......I..E.FSKKA....YA........RK.I.R....K.....E.N..NKK..E...SNIE.KT.RKE..K.E..G.I....N...H......DD.....................K.........NK..........
            >A/Albany/4835/1948,1948//,             K....S......R.......I..E.FSKKA....YA........RK.I.R....K.....E.N..NNK..E...SNIE.KT.RKE....E..G.I....N...H......DD.....................K.........NK..........
            
            >A/Cameron/1946,1946//,                 KI...S......R.......I..E..SKRA...A.A.......GRE.IDI........K.E.D..NNKK.E.I..NIENKT.RKE....E..G.I....N....N.I...DD.......F......D......K......NR.NK.F........
            >A/Fort Monmouth/1/1947,1947//,         KI...T......R.......I..E..SKRA...A.A........RK.I.R........K.ETD....K..E...SNIE.KT.RKE....E..G.I....N.....D....DD........K.......W....K......NR.NK..........
            >A/Fort Monmouth/1-MA/1947,1947/06/01,  KI...T......R.......I..E..SKRA...A.A........RK.I.R........K.ETD....K..E...SNIE.KT.RKE....E..G.I....N.....D....DD........K............K......NR.NK..........
            >A/Netherlands/002K1/1949,1949//,       KI...S......R.......I..E..SKRA.....A........RK.I.R........K.ETK..N.K..E...SNIE.KT.RKE....E..G......N......L...DD........K............K......NR.NK..........
            >A/Netherlands/001G1/1950,1950//,       KI...S......R.......I..E..SKRA.....A........RK.I.R........K.ETK..N.K..E...SNIE.KT.RKE....E..G......N......L...DD........K............K......NR.NK..........
            >A/Hickox/1940,1940//,                  KI...S......R.......I..E..SKRA.....A........R..INI........K.E.D..NNKK.E...SNIENKT.RKE....E..G......N......L...DD.......F......A......K......NR.NK..........
            >A/Netherlands/002P1/1951,1951//,       K....S.Y....RK......I..E..SKRA.....A.........K...R.....R..K.EAN..N.K.QE...SNIE.RT.RKE....E..N......N......L...DD........K......M.....K......NRL.K.......R..
            
            >A/TF/15/1951,1951//,                   KI...S......R.......I..ET.SNRA.....A........RK.I.RG....K..K.EAN..N.E..E...SNIE.RT.RKE....E..G.I.K..N......L...DD..............-----------------------------
            >A/Tokyo/1/51,1951//,                   KI...S......R.......IT.E..SNRA.C...A........RK.I.R.....K..K.EAN..N.K..E...SNIE.RT.RKE....E..G.I.K..N......L...DD..............-----------------------------
            
            >A/Albany/12/1951,1951//,               .I...S......R.......I..E..SNRA.....A........RK.I.R.....K..K.EAN..N.K..E...SNIE.RT.RKE....E..G...K..N......L...DD...............V.....K......NR..K..........
            >A/Albany/13/1951,1951//,               .I...S......R.......I..E..SNRA.....A........RK.I.R.....K..K.EAN..N.K..E...SNIE.RT.RKE....E..G...K..N......L...DD...............V.....K......NR..K..........
            >A/Albany/14/1951,1951//,               .I...S......R.......I..E..SNRA.....A........RK.I.R.....K..K.EAN..N.K..E...SNIE.RT.RKE....E..G...K..N......L...DD...N...........V.....K......NR..K..........
            >A/Albany/1618/1951,1951//,             .I...S......R.......I..E..SNRA.....A........RK.I.R.....K..K.EAN..N.K..E...SKIE.RT.RKE....E..G...K..N......L...DD...............V.....K......NR..K..........
            >A/Liverpool/1951,1951//,               .I...S......R.......I..E..SNRA.....A........RK.I.R.....K..K.EAN..NIK..E...SNIE.RT.RKE....E..G...K..N......L...DD...............V.....K......NR..K..........
            >A/Malaya/302/1954,1954//,              .I...S......R.......I..E..SNRA...I.A.........K.I.R.V...K..K.EAN.LS.KDRE...SNIE.RT.RKE....E..GP..K..N......P...DD...............V.....K......NR..K...A......
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            ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ +++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
            
            >A/Fort Worth/1950,1950//,              KI...S......RK......V..E..SNRA...I.A........RK..IR........KVEAN..A.T.QE...SNIEERT.RKD....K...P............P.P.DD...............M.....K......NRL.K.......R..
            >A/Kojiya/1/1952,1952//,                KI...S......RK......V..E..SNRA.....A........RK...R........KVEAN..N.K.QE...SNIE.RT.RKD....K..GP............P.P.DD..............-----------------------------
            >A/Netherlands/001R1/1953,1953//,       KI...S......RK......V..E..SNRA.....A........RK...R.....R..KVEAN..N.K.QE...SNIE.RT.RKD....K...P............P.P.DD...............M.....K......NRL.K.......R..
            >A/Netherlands/002W1/1953,1953//,       KI...S......RK......V..E..SNRA.....A........RK...R.....R..KVEAN..N.K.QE...SNIE.RT.RKD....K...P............P.P.DD..........K....M.....K......NRL.K.......R..
            >A/Netherlands/001H1/1954,1954//,       KI...S......RK......V..E..SNRA.....A........RK..-R.....R..KVEAN..N.K.QE...SNIE.RT.RKD....K...P............P.P.DDA..............M.....K......NRL.........R.M
            >A/Taiwan/13/1954,1954//,               KI...S......RK...N..V..E..SNRA.....A........R...IR.....R..KVEAN..N.R.QE...SNIEERT.RKD....K...P.......G....P.PLDD..............-----------------------------
            >A/Denver/1957,1957//,                  KI...S......RK...N..V..E..SNRA.....A........R.--.R...P.R..KVEAN..N.R.QE...SNIEERA.RKD....K...S............P.PLDD............V..M.....KM.....NRL.K.......R..
            >A/Meguro/1/1956,1956//,                KI...S......RK......V..E..SNRA.P...TNK..L...RK...R.....R..KVEAN..T...QE...SNIEERT.RKD....K...P............S.P.DD......V.......-----------------------------
            >A/Yamagishi/55,1955//,                 KI...S......RK...E..V..E..SNRA.P...A.K..L...RK...R.....R..KVEAN..N...QE...SNIEERT.RKD....K..GP............S.P.DD..............-----------------------------
            >A/Saga/2/1957,1957//,                  KI...S......RK...N..V..E..SGRA.....A........R.--.R...P.K..KVEAN..N.R.QE...SNIEERT.RKD....K..GS............P.PLDD............V.-----------------------------
            >A/Netherlands/001B1/1956,1956//,       KI...S......RK...N..V..E..SNRA.....A........R.--.R...P.R..KVEAN..N.R.QE...SNIE.RT.RKD....K..GS............P.PLDD...............M.....K......NRL.K.......R..
            >A/Netherlands/002Z1/1956,1956//,       -I...S......RK.I.N..V..E..SNRA.....A........R.--.R...P.R..KVEAN..N.R.QE...SNIE.RT.RKD....K..GS............P.PLDD...............M.....K......NRL.K.......R..
            >A/Kw/1/1957,1957,H1N1                  KI...S......RK...N..V..E..SNRA.....A........R.--.R...P.M..KVEAN..N.R.QE...SNIE.RT.RKD....K..GSI...........P.PLDD............F..M.....K......NRL.K.......R..
            
                                                    00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000
                                                    00000000000000000000000000000001111111111111111111111111111111111111111111222222222222222222222222222222222222222333333333333333333444444444444444555555555
                                                    00011111334566667777788888899990001111222333344444455555556677777778888899000000001111222333344555666667777788999000001122334456999011344556677899001122234
                                                    47902356672304570135813568901792361349468257824567912467893601234790567826012346780129058368914268026890578989034025692557081392189556349371817978685747971
                                                    -----------------------------------------------------------------------------------------------------------------------------------------------------------
                                                    RVLCLATDVLTSKIALGKNALNEDSLPASVTSETDIDRSSFEPESNNTTKVAASAGKSRLKKGGSKSNNKGKVVPTSNDQSLQNAVSRTAKRDAMETIETIPWYSGFGSMHNTQASSFIVRTRIISTIGSVTNNLVEDSNSKIDRNYEEISVQVL
            
            
            4R,


            the Liverpool virus has S179I(4) [presumably S165I in WHO-numbering] ,
            that's basically the only amino-acid difference from the Albany viruses.
            It's also not seen in the other viruses.

            Could this one mutation make the difference ?




            there are 9 other human, old H1s ar genbank with S179I

            179 h1b09p 4932 -:59 E:6 F:1 G:5 I:10 K:61 N:25 R:13 S:4817 T:7 X:12

            E >A/Puerto Rico/8-CV1/1934,NON//,LAB,H1N1,4
            ...

            F >A/Milan/10/2006,2006/04/04,Italy,H1N1,4

            G >A/British Columbia/0017/2007,2007/12/31,Canada,H1N1,4
            G >A/Malaysia/33166/2005,2005/12/06,Malaysia,H1N1,4
            G >A/South Carolina/WRAIR1116P/2009,2009/03/01,USA,H1N1,4
            G >A/Taiwan/10092/2007,2007/11/14,Taiwan,H1N1,4
            G >A/Taiwan/1026/2009,2009/01/13,Taiwan,H1N1,4

            I >A/Guangzhou/1561/2006,2006//,China,H1N1,4
            I >A/Hawaii/1313/00,2000//,USA,H1N1,4
            I >A/Hokkaido/08H009/2008,2008/12/30,Japan,H1N1,4
            I >A/Illinois/10/2007,2007/12/12,USA,H1N1,4
            I >A/Liverpool/1951,1951//,United Kingdom,H1N1,4
            I >A/Michigan/2/2003,2003/02/05,USA,H1N2,4
            I >A/Michigan/4/2003,2003/02/01,USA,H1N1,4
            I >A/Nagano/92/1991,1991//,Japan,H1N1,4
            I >A/Nagasaki/142/1999,1999//,Japan,H1N1,4
            I >A/North Carolina/04/2008,2008/02/06,USA,H1N1,4

            K >A/Alaska/1935,1935//,USA,H1N1,4
            K >A/Albany/4836/1950,1950//,USA,H1N1,4
            K >A/Hemsbury/1948,1948//,USA,H1N1,4
            K >A/Henry/1936,1936//,USA,H1N1,4
            K >A/Mongolia/111/91 ,1991//,Mongolia,H1N1,4
            K >A/Mongolia/153/88,1988//,Mongolia,H1N1,4
            K >A/Phila/1935,1935//,USA,H1N1,4
            K >A/Puerto Rico/8-1-MA/1934,NON//,LAB,H1N1,4
            K >A/Puerto Rico/8-1/1934(H1N1)
            K >A/Puerto Rico/8-1/1934,1934//,Puerto Rico,H1N1,4
            K >A/Puerto Rico/8-9NMC1/1934,NON//,LAB,H1N1,4
            ...
            K >A/Puerto Rico/8/1934,1934//,Puerto Rico,H1N1,4
            K >A/Puerto Rico/8/34/Mount Sinai,1934//,Puerto Rico,H1N1,4
            K >A/Puerto Rico/8/34/PY102-V1,1934//,Puerto Rico,H1N1,4
            K >A/VM113-V1,1934//,Puerto Rico,H1N1,4
            K >A/Weiss/1943,1943//,USA,H1N1,4

            R >A/Canterbury/95/2000,2000/10/22,New Zealand,H1N1,4
            R >A/Gyeongnam/3062/2007,2007/04/13,South Korea,H1N1,4
            R >A/Hanoi/1892/2002,2002/01/06,Viet Nam,H1N1,4
            R >A/Kyoto/07K303/2008,2008/01/21,Japan,H1N1,4
            R >A/Malaysia/23582/2002,2002/11/13,Malaysia,mixedÞH1,4
            R >A/North Carolina/05/2008,2008/02/14,USA,H1N1,4
            R >A/Texas/25/2006,2006/12/20,USA,H1N1,4
            R >A/Thailand/328/2006,2006//,Thailand,H1N1,4
            R >A/Thailand/344/2006,2006//,Thailand,H1N1,4
            R >A/Thailand/501/2007,2007//,Thailand,H1N1,4
            R >A/Thailand/Siriraj-07/2000,2000//,Thailand,H1N1,4
            R >A/Vietnam/HN1892/2002,2002/09/15,Viet Nam,H1N1,4
            R >A/Weiss/1943,1943//,USA,H1N1,4

            S >A/1352/02,2002//,United Kingdom,H1N2,4
            ...
            I'm interested in expert panflu damage estimates
            my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

            Comment


            • #7
              Re: EM 2006 - H1N1 in Liverpool 1951

              nfluenza virus surveillance first began in Malaysia in 1954. Participants include
              Government outpatient clinics and private clinics, as well as student clinics
              In 1954, the first influenza A virus was isolated from throat washings of a patient
              http://www.ncbi.nlm.nih.gov/nuccore/CY009342
              Submitted (02-MAR-2006) on behalf of TIGR/Wadsworth-NYSDOH and
              NIAID, NIH/NCBI, National Center for Biotechnology Information,
              NIH, Bethesda, MD 20894, USA
              ------------------------------------------------------------------
              http://www.plosone.org/article/info:...l.pone.0035108
              We also obtained influenza A/Malaya/302/1954 H1N1 serotype from the American
              Type Culture Collection (ATCC, Manassas, VA) for Western blot analysis
              .... were infected with Influenza A/Malaya/302/1954 H1N1.
              NECs were exposed to air or ozone and 24 h post-exposure, cells were infected
              with Influenza A/Malaya/302/1954 H1N1.
              -------------------------
              NLF (50μg of total protein), was incubated with Influenza A/Malaya/302/1954 H1N1
              ------------------------------------------------------------------------
              http://en.wikipedia.org/wiki/Great_Smog
              http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3421718/

              annual influenza mortality-rates per 100,000 population.
              Deutschman (who types this into computer ? it should have been done long ago.
              So much effort had been done to collect the data, with so little additional
              effort the useability could be enhanced greatly, now that we have computers.
              Yet this is rarely being done with old statistics :-( )
              http://www.flutrackers.com/forum/att...1&d=1363417299
              I'm interested in expert panflu damage estimates
              my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

              Comment


              • #8
                Re: EM 2006 - H1N1 in Liverpool 1951

                see here, how it did spread:

                influenza deaths per 10000 population in weeks 49/50-10/51:
                Liverpool,-,1,10,58,140,94,39,16,12,6,3,2,5
                Wallasey,-,-,15,169,257,236,72,41,-,21,-,15,5
                Blackburn,5,5,5,5,9,19,89,154,51,23,23,5,5
                Birkenhead,-,4,-,51,154,84,40,22,4,-,-,4,-
                Bootle,-,-,7,52,37,163,44,22,7,-,-,-,-
                Southport,6,6,12,73,91,109,85,30,36,6,-,-,6
                St.Helens,-,-,5,135,232,107,42,28,14,32,14,5,-
                Wigan,12,-,6,-,98,153,79,85,31,12,6,12,18
                Cambridge,-,6,-,-,-,17,68,114,51,51,23,-,17
                Belfast,-,1,-,9,39,70,40,13,3,8,7,2,2
                London,2,3,1,6,12,16,19,22,12,8,3,3,2
                Newcastle,2,14,18,62,55,12,12,4,11,5,5,-,11

                it reached the peak from zero in just 3 weeks in those big cities
                in the Liverpool region ! (compute the R0 !)
                But then it somehow reduced the CFR a lot.
                It wasn't so bad in London, where it peaked just 2 weeks later.
                Maybe London got a different strain or maybe it did mutate/reassort
                (again). Or maybe there were multiple competing strains of different
                virulance, all very fast.
                Or maybe there was a particularly bad bacterium around in the
                Liverpool area (but not elsewhere) which made it worse.
                However, they had antibiotics in 1951.
                But it looks more as if the virus had mutated,reassorted in Liverpool.
                Now, almost the same virus appeared 3 months later in Albany
                and descendents were seen in Malaysia,1954

                Why did it suddenly disappear,reduce virulence ?
                And could it happen again ?

                -----------------------------------------------------

                influenza cases reported weekly in NE-USA , weeks 6-18

                CT,2,2,35,942,673,703,630,515,51,15,14,1,-
                ME,67,12,164,508,1925,-,1563,139,242,165,19,25,22
                NH,-,1,40,166,537,664,281,94,34,9,-,9,2
                VT,-,17,60,54,91,67,41,10,15,-,-,-,-

                2 weeks to peak in CT, 3-4 weeks in ME,NH,VT
                but not the Liverpool-virulence
                ~1100 deaths from P+I and 12000 reported cases
                in 1950 there were cases and deaths
                in USA 1951 there were ~100000 reported cases and ~50000 P+I-deaths
                in Liverpool week 2 there were 949 deaths, 430 of these from P+I

                ----------------------------------------------------------

                They began to increase in mid-December, 1950,
                in Tyneside and Aberdeen, also in the Shetlands and East
                Anglia-all areas
                be associated with a serologically different
                strain of virus,2 appeared on Merseyside.
                There was yet
                another plague-spot, in Cornwall, which seems not-to
                have led to much trouble.
                The spread all over
                Britain between the week ending January 2 and that end-
                ing January 9 was phenomenally rapid:
                it is hard to
                believe that any transference due to ordinary man-to-
                man contact could have proceeded with that speed
                ----------------------------------

                I cannot verify the Canada data.
                The link from the Apr.2006 paper is dead.
                Statistics Ontario gives no increase in death rates nor Newfoundland
                nor Prince Edward Island
                from all causes. Ontario no increase for P+I deaths in 1951.
                Statistics Canada gives no increase in deaths from all causes in 1951

                apparently the data was available in 2006, but no longer. Privacy issues ?
                As in USA, where no geographical data from online death certificates
                is available since 2005
                ----------------------------------------
                OK, I found something here:
                http://www.ncbi.nlm.nih.gov/pmc/arti...01231-0032.pdf
                -------------------------------------
                I'm interested in expert panflu damage estimates
                my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                Comment


                • #9
                  Re: EM 2006 - H1N1 in Liverpool 1951

                  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427756/
                  page 4

                  But the Liverpool
                  strain was also prevalent in Belfast and in some
                  parts of southern England and in a number ofcoun-
                  tries in southern Europe and in Turkey and countries
                  to the south of it. Six months earlier it had been
                  isolated in outbreaks in the southern hemisphere.
                  In none of these areas except Merseyside was it
                  associated with an unexpectedly high death rate.
                  Itwouldseem thatsomeadditional factormusthave
                  been operative in Merseyside. Semple (1951) pointed
                  out that immediately before and during the epidemic
                  period Merseyside experienced the coldest spell for
                  many years, the weekly mean temperature from mid-
                  December to mid-January being 4.4F to 7.5F
                  (2.5C to 3.6C) below the mean temperatures for
                  the corresponding weeks in the previous 20 years.
                  Over two-thirds of the deaths were in persons,
                  mainly women, 65 years of age or more and most of
                  these deaths were in persons over 75 years of age.
                  As long ago as 1885 Farr showed from statistics
                  of deaths in England and Wales that " the degree
                  down to which mean monthly temperatures fall in
                  December, January, or February determines, to a
                  great extent, the mortality of winter ", even when
                  epidemics of influenza are absent. He went on to
                  suggest minimum night temperatures for the bed-
                  rooms of the very old and very young.
                  In 1950-51, therefore, 2 explanations ofthe abnor-
                  mally high death rate in Merseyside were possible:
                  a more virulent strain, or an exceptional climatic con-
                  dition occurring as the epidemic developed. Perhaps
                  there were also other factors which were not
                  identified.


                  Andrewes, C. H. (1954) Epidemiology of influenza.
                  In: Influenza: a review of current research, Geneva, pp. 9-24
                  (World Health Organization: Monograph Series, No. 20)
                  Farr, W. (1885) Vital statistics, London, Office of the Sanitary Institute, p. 413-416
                  (increased mortality during 6 cold weeks in England 1855,1874/5)
                  https://archive.org/details/vitalstatisticsm00farruoft

                  Massey, A. (1951) Proc. roy. Soc. Med., 44, 790-792
                  Semple, A. B. (1951) Proc. roy. Soc. Med., 44, 794-796
                  Attached Files
                  I'm interested in expert panflu damage estimates
                  my current links: [url]http://bit.ly/hFI7H[/url] ILI-charts: [url]http://bit.ly/CcRgT[/url]

                  Comment

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