Announcement

Collapse
No announcement yet.

mBio: Pandemic Paradox - Early Life H2N2 Infection Enhanced Mortality From H1N1pdm09

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • mBio: Pandemic Paradox - Early Life H2N2 Infection Enhanced Mortality From H1N1pdm09

    mBio: Pandemic Paradox - Early Life H2N2 Infection Enhanced Mortality From H1N1pdm09


    18 known HA subtypes divided into 2 groups


    #13,074



    A little over a year ago, in Science: Protection Against Novel Flu Subtypes Via Childhood HA Imprinting,we looked at a study that strongly suggested the first HA Group type influenza virus an individual is exposed to makes the biggest, and most lasting, impression on your immune system.
    And that the resultant immune response may carry over to other - similar - subtypes within that HA group.
    This has some pandemic planning implications since - if your first influenza exposure was to H1N1 or H2N2 (group1) - you may carry some degree of immunity to the H5 viruses (H5N1, H5N6, etc.). If, however, your first exposure was to H3N2 (group 2), you may carry some protection against H7N9 instead.

    Today, however, we have a new study in the open-access journal mBio that suggests there is more to this first life exposure to influenza than previously thought.

    During the 2009 H1N1 pandemic, and its subsequent return for the 2013-14 flu season, those born during the 1957 H2N2 pandemic saw the highest mortality (see mbio chart below).


    This is doubly unexpected.

    H1N1 and H2N2 are both group 1 HA types, and some cross protection might be expected. Also, the mortality rate dropped for those born after 1957 - when H2N2 was still circulating - and didn't spike for those born during the 1968 pandemic when H3N2 (a group 2 HA type) was the only influenza A game in town.

    There is some historical precedent for this, as during the 1918 pandemic those born prior to 1890 appear to have been at least partially protected by (an assumed) H1Nx virus that likely circulated prior to the H3Nx pandemic of that year.



    Those born in 1890, during the H3Nx pandemic, would have turned 28 in 1918, and as the famous W Curve Chart above illustrates, that is the precise age that saw the highest number of deaths.
    While none of this invalidates the previously described HA Group type cross-protection theory, it does suggest there are exceptions to the rule.
    Since I can't possibly do this highly technical and intriguing study justice in the space I have allotted, I heartily suggest you find a quiet corner, turn off your phone ringer for an hour, and immerse yourself in:
    Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic

    Alain Gagnona,b, Enrique Acostaa, Stacey Hallmanc, Robert Bourbeaua, Lisa Y. Dillona, Nadine Ouellettea, David J. D. Earnd,e, D. Ann Herringf, Kris Inwoodg, Joaquin Madrenash, Matthew S. Millere,i

    ABSTRACT

    Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity.
    For example, during the 2009 H1N1 “swine flu” pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population.
    Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 “Spanish flu.” Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 “swine flu” pandemic and during the resurgent 2013–2014 H1N1 outbreak for those born at the time of the 1957 H2N2 “Asian flu” pandemic.
    We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.

    IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918—when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality.
    Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013–2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 “Asian flu” pandemic.
    These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect.
    (Continue . . . )


    Although I'm coming up on my 12th anniversary of full-time flu blogging, I am humbled by how much less I know about influenza than I did when I started.

    http://afludiary.blogspot.com/2018/0...life-h2n2.html
    All medical discussions are for educational purposes. I am not a doctor, just a retired paramedic. Nothing I post should be construed as specific medical advice. If you have a medical problem, see your physician.

  • #2
    Excellent find.

    Comment


    • #3
      I'm not yet convinced ... checking the data ... I don't have Mexican data by month but most countries
      by age5 and year P+I from WHO

      they have an agenda ... see earlier papers about 1918 and discussion here.
      It's likely that they are cherrypicking from the data to support their claim.

      Yes, I do see peaks at birth cohorts from ~1957 in some countries - including USA-monthly
      but it's less clear.

      And even then - why are there no peaks in 1969 or other severe H3-seasons like 1971f,1972f,1974f,1975f,1984f,1989f,1993f,1999f
      vs. H1-swasons or B-seasons like 1976f-1983f



      more later

      first trying to match their fig.1A :

      OK., that looks pretty good.
      How unusual is it , is it the same in other countries ? Why 1957 and not 1968 ?

      I just noticed, that they use influenza-deaths in their subsequent figures.
      Very unusual, usually one take P+I deaths, influenza deaths are
      only a small fraction of these. What makes a flu-death-cause rather than
      pneumonia and why is it special for pH1N1 ?
      From fig1A you could also conclude that the excess mortality in 2009
      mostly involved ages 47-58 , those were born 1951-1962 - just
      the agegroup which had no contact in school to H1N1, which mostly
      attacked schoolchildren after 1977.

      Germany : by age5groups,year,disease,region
      www.gbe-bund.de search Todesursachen Tabelle gestaltbar

      Europe : by country,month,(not by age , disease, though)
      eurostat.eu

      my mortality statistics data links :


      ---------------
      > Taken together, the findings reported herein firmly establish that exposure to a
      > pandemic virus during the first years of life served as a susceptibility factor during later
      > heterosubtypic influenza virus pandemics or intense seasonal outbreaks

      this is just their final "conclusion" . Shown was only that those cohorts had a
      somehow matching mortality peak by some specific restrictions.
      I wonder, what probability(age at infection) you can choose to get such _symmetrical_
      peaks in later heterosubtypic pandemics. I mean, born x years before a pandemic
      should be different from born x years after a pandemic here.

      A really good method to test their hypothesis would be data by month of birth,
      which exists for some groups. There should be a difference in birthmonths
      before and after a severe outbreak

      ----------------------------------------
      from Mexico’s Instituto Nacional de Estad?stica y Geograf?a (INEGI)
      http://www.beta.inegi.org.mx/proyect...ult.html?init2
      I'll check this
      http://en.www.inegi.org.mx/contenido...5_2009_dbf.zip
      75 MB , 2005-2009

      They have indeed available the digital death certificates since 1990
      with cause,age,sex,and most even with day of death,day of birth.
      Although the month of birth is only filled >90% for 2002,2009,2014-2016

      First data that I find with day of birth, thanks Mexico.
      Why wasn't this mentioned and used in the paper ?


      --------------------------------------
      Last edited by gsgs; October 4, 2018, 01:15 AM.
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #4
        USA-Influenza-deaths by age for 2014 give indeed a surprisingly clear chart with
        a peak at age 55-56

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

        WHO has deaths by age5,sex,year,country,disease-code (with holes) since 1950 at
        http://www.who.int/healthinfo/statis...ty_rawdata/en/

        direct Influenza deaths are rarely reported, usually those people finally die from pneumonia
        or cardiovascular causes (H3N2, elderly) as official cause . It's a bit different for new H1N1

        So I grouped them by continent for 2009-2014 to get more datapoints than by country :


        the picture is not so clear as the above one , there are 3 peaks at 30-35,50-55,65-69
        In Europe we usually had all 3 , H1N1 and H3N2 and B , but for H3N2 there
        are no peaks, it increases towards age
        I'm interested in expert panflu damage estimates
        my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

        Comment


        • #5
          The peaks correspond to pandemic years because afterwards the signal is less clear and more obscured. Pandemic years experience vastly increased transmission morbidity and therefore synchronized immune imprinting to a particular strain. Afterwards you could have similarly synchronized events, but this is the same year-to-year and very reduced in impact since it's not nearly as many affected at once. We would expect such bias in response to various strains based on birth cohort, which is reflected in age-biased morbidity season-to-season. So we do see it annually. It's just not as pronounced. Pandemic years offer very convenient and clear case studies.

          Comment


          • #6
            ----------------------------8 citations at google-scholar :-----------------------

            Immune history and influenza vaccine effectiveness
            J Lewnard, S Cobey - Vaccines, 2018 - mdpi.com
            -.-.-.-
            Influenza, evolution, and the next pandemic
            DS Fedson - Evolution, medicine, and public health, 2018 - academic.oup.com
            -.-.-.-
            Original antigenic sin: how first exposure shapes lifelong anti?influenza virus immune responses
            A Zhang, HD Stacey, CE Mullarkey? - The Journal of ?, 2019 - Am Assoc Immnol
            -.-.-.-
            Influenza vaccination and the 'diversity paradox'
            CP Thompson, U Obolski - Human vaccines & ?, 2018 - Taylor & Francis
            -,-,-,-
            The Effects of Birth Year, Age and Sex on HA Inhibition Antibody Responses to flu Vac
            E Plant, A Eick-Cost, H Ezzeldin, J Sanchez, Z Ye? - Vaccines, 2018 - mdpi.com
            > The first exposure to influenza is thought to impact subsequent immune
            > responses later in life ... antibody response is associated with, among other factors,
            > the influenza strain that circulated following birth.
            -.-.-.-
            Historical and clinical aspects of the 1918 H1N1 pandemic in the United States
            B Jester, TM Uyeki, DB Jernigan, TM Tumpey - Virology, 2019 - Elsevier
            -.-.-.-
            Public Health?Driven Research and Innovation for Next-Gen flu Vac, EU
            A Navarro-Torn?, F Hanrahan, B Kersti?ns? - Emerging infectious ?, 2019 - nih.gov
            > Although the idea seems counterintuitive, recent studies point to a so-called pandemic paradox (19),
            -.-.-.-
            Reporting and evaluating flu virus surveillance data: An argument for incidence by single year of age
            A Gagnon, E Acosta, MS Miller - Vaccine, 2018 - researchgate.net
            > The observation that past exposures to influenza virus shape the outcome of subsequent
            [not just year, but month of birth. The yearly statistics unfortunately cuts the flu-seasons and makes
            research more difficult - on diseases with seasonality of deaths = the majority]
            -------------------------also-------------------------------------------------

            Cobey, S.; Hensley, S.E. Immune history and influenza virus susceptibility.
            Curr. Opin. Virol. 2017, 22, 105?111. [Google Scholar] [CrossRef] [PubMed][Green Version]
            > so far there is little indication that hosts with pre-existing immunity are more susceptible
            > to viral infections compared to na?ve hosts.
            -.-.-.- From original antigenic sin to the universal influenza virus vaccine
            C Henry, AKE Palm, F Krammer, PC Wilson - Trends in immunology, 2018 - Elsevier
            https://www.sciencedirect.com/scienc...71490617301643
            > Although this model has been challenged since its discovery, past exposure,
            > and likely one?s first exposure, clearly affects the epitopes targeted in subsequent responses
            -.-.-.- In a recent study by Skowronski et al., they noted lower vaccine efficacy
            for the pdmH1N1 virus in the birth cohort for the years 1957 to 1967,
            that were likely primed with an A(H3N2) antigen rather than an A(H1N1) antigen [20].
            Similarly, lower A(H1N1) antibody titers in subjects born prior to the re-emergence of
            A(H1N1) viruses in the late 1970s were observed in this study.
            In another study, Skowronski et al. reported differences in the percentage of B/Victoria
            and B/Yamagata infections by year of birth [59].
            When information about the viruses that circulated following the birth year of the subjects
            in this study was included, we observed differences in HI antibody titers that appear to be
            due to the antigenicity of the virus circulating in the first years of life,
            not just the presence or absence of a virus.
            These differences support the notion that the environment plays a significant role in
            priming and shaping the immune response [60] and the recommendation
            that antigenic sin be considered in the development of immunization strategies [23].
            -.-.-.-.-
            from 2019/04/04 = today ?!?
            HI-negative group showed a significantly higher vaccine-specific response
            https://www.frontiersin.org/articles...019.00593/full
            [upon vaccination in the HI-positive group ] influenza-specific helper T-cells are
            predominantly recruited from the pre-existing cross-reactive memory and not the naive repertoires.
            [But in case of antigenic drift and shift the recruitment of naive T- and B-cells can be necessary
            for the efficient eradication of mutated viruses.]
            [But later they write :]
            " While naive vaccine-specific T-cells could be detected prior and after vaccine application
            independently of serological status, these cells were not recruited in the formation of
            vaccine-specific cellular memory as demonstrated by NGS and multiparameter flow cytometry.
            Our findings suggest that T-cell memory from previous encounters with close influenza strains
            provides sufficient help to naive B-cells specific to previously unseen viral strains and that
            the extent of previous encounters is beneficial in terms of vaccine-induced antibody titers."
            [similarly in the abstract, so my summary : -- no sin -- ]




            =======================================

            (human-)evolutionary it doesn't make sense , IMO.
            Why should it be better to boost lifelong immunity towards first encountered viruses
            rather than to subsequent ones ? One's birthdate does not influence the likelyhood
            of future circulating viruses.
            Last edited by gsgs; April 4, 2019, 01:01 AM.
            I'm interested in expert panflu damage estimates
            my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

            Comment


            • #7
              Originally posted by Eight View Post
              The peaks correspond to pandemic years because afterwards the signal is less clear and more obscured. Pandemic years experience vastly increased transmission morbidity and therefore synchronized immune imprinting to a particular strain. Afterwards you could have similarly synchronized events, but this is the same year-to-year and very reduced in impact since it's not nearly as many affected at once. We would expect such bias in response to various strains based on birth cohort, which is reflected in age-biased morbidity season-to-season. So we do see it annually. It's just not as pronounced. Pandemic years offer very convenient and clear case studies.
              the baby who gets it doesn't know whether it's pandemic or seasonal.
              It's the same virus. E.g. in Massachusetts (and probably in the whole
              NE-USA , but we only have data from MA) it was worse in Jan 1892
              than in Jan 1890 .And in other years there was also great variation,
              some years may even have had influenza B or a rest-recurrence of H1 - if it was
              indeed H1 before 1890. We saw this after 1957 and 1968.
              And in the babies, toddlers (those with the peak in 1918) it's also different ,
              flu usually spreads in school, at work, in trains, trams, shops, public places.
              And the special about pandemic strains is, that people have no immunity to it.
              H1 -if it was H1- before 1890 caused very few flu deaths but I would
              assume that the infection in babies was as high as in 1890.

              those aged 35 in fall 1918 went much better than those aged 34 in waves 2,3,4 in New York.
              Born in Dec 1882-Sep.1883 they caught the flu 1883/4 season, which those aged 34 didn't.
              But 1883/4 was apparently mild, while 1884/5 was more severe.
              Maybe you better get it aged 1 than 0. Maybe they were in school in 1890 already while
              the 34s weren't. 1878/9 was severe , corresponding to age 40 .
              -.-.-.-
              Week ended January 18. [1890]
              Many cases of influenza.
              Very young persons, under two years, practically exempt.
              weekly abstract of sanitary reports , 1890/4
              https://www.ncbi.nlm.nih.gov/pmc/jou...llpublichealth
              although in the mortality data from the 1890 census, respiratory deaths at age<5
              increases ~75% in Jan.1890 (vs.Dec.1890) while at all ages it increased ~120%,
              no big difference.

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

              Comment

              Working...
              X