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  • Expert warns of misunderstanding behind 1918 flu

    Expert warns of misunderstanding behind 1918 flu

    Updated Wed. Aug. 12 2009 11:40 AM ET

    The Canadian Press

    TORONTO -- Unproven assumptions about the course of the 1918 Spanish flu pandemic may be leading to misperceptions of what the swine flu virus has in store for the world, the scientist who decoded the genetic blueprint of the 1918 virus suggests in a newly published commentary.

    Virologist Dr. Jeffery Taubenberger, along with co-author and medical historian Dr. David Morens, argues there is no firm evidence that the 1918 virus ratchetted up in virulence in a fall wave - because there is no solid proof outbreaks of illness in the U.S. in the spring of 1918 were caused by the same virus.

    Their commentary, published in this week's issue of the Journal of the American Medical Association, suggested changes in virulence or transmissibility of the current pandemic virus are not inevitable. In fact, they wrote, there are reasons to hope for "a more indolent pandemic course and fewer deaths" than seen in many previous pandemics.

    "I think every pandemic is completely different," Taubenberger said in an interview from Bethesda, Md., where he and Morens work at the U.S. National Institute of Allergy and Infectious Diseases.

    "It emerges in a different way. Its genetics are going to be different. The population immunity by age is going to be different depending on what it is. So I think it's very difficult and perhaps a disservice to assume that a new pandemic is going to behave in a way like 1918."

    The scientific community is split about what happened in the opening days of the notorious Spanish flu pandemic, which is believed to have killed upwards of 50 million people in 1918-1919.

    The prevailing view is that spring outbreaks of largely mild disease in the United States and then in Northern Europe was actually the opening round - the so-called herald wave - of the pandemic. The received wisdom is that over the summer the virus mutated, making the disease it caused more severe.

    The concept that an initially mild pandemic virus could change into something nastier has featured prominently in the logic of public health officials as they have explained why the world needs to respond aggressively to the new H1N1 virus.

    But Taubenberger and some others have repeatedly noted that there are no virus samples from the spring wave, so there is no way to confirm that outbreaks were caused by the same virus or that the virus changed to become more virulent.

    "So that is an hypothesis. But it is one of several. And we don't know that that's really true," he said.

    Taubenberger and a team of collaborators excavated enough particles of the 1918 virus that its genetic code could be sequenced. The virus was then reconstituted at the U.S. Centers for Disease Control and remains the subject of ongoing research in select high-security laboratories.

    But the fragments of viral RNA used in the painstaking task were taken from tissues of people who died in the fall of 1918. To date no one has found samples of the virus or viruses responsible for illness in the spring of 1918.

    There is some high-profile support for the argument Taubenberger and Morens make.

    Dr. Walter Dowdle, a retired former head of the influenza program at the U.S. Centers for Disease Control, suggested so much has changed in the world since previous pandemics - the last was in 1968 - and so much is unknown about why flu behaves the way it does that it is impossible to predict the course of this pandemic based on previous ones.

    "I think what this article recognizes is that this is very, very complex," Dowdle said from Atlanta. "And in fact our understanding of the factors is so incomplete and so insufficient that I think we have to be very careful about coming up with any simple theories to explain any flu behaviour."

    One of Dowdle's former CDC colleagues, Dr. D.A. Henderson, thinks there is a model for the current pandemic, but it's not 1918.

    Henderson, an infectious diseases expert at the Center for Biosecurity at the University of Pittsburgh Medical Center, recently published a review article suggesting if authorities are trying to figure out how to gauge public health responses to the swine flu pandemic they should look to the lessons of the 1957 Asian flu.

    "I think that what we've seen in '57 and what we see now are very similar," he said in an interview.

    "And I think they (Taubenberger and Morens) feel the same way I do that we have really no evidence that this (virus) is likely to become more virulent ... or more infectious."

    But another researcher who has spent a lot of time mining records from 1918 believes there is good evidence the 1918 virus was responsible for the outbreaks of the herald wave.

    Dr. Lone Simonsen, an influenza epidemiologist at George Washington University in Washington, D.C., has studied medical data for a number of centres that reported outbreaks in the spring of 1918 - New York and Denmark among them.

    "There's always this discussion about 'If you don't have a virus, can you say anything about something?"' she said.

    Simonsen argued the answer is yes, if the pattern of disease bears the signature of flu pandemic - things like a shift in the age group in which severe disease is seen. That was observed in the spring of 1918 and in the spring of 2009 as well, she noted.

    "Absolutely there was a first wave that was milder. There's no doubt about it," she said.

    Simonsen said accepting that there was a herald wave of illness doesn't mean that the change in severity in the fall has to have been the result of viral mutations. There could be other explanations, she said, including concurrent spread of bacterial illness that combined to make the flu cases more dangerous.

    As to the path of the current pandemic, Simonsen suggested the best approach is a prudent one.

    "I just think we should keep our guards up. That's really my prediction."

    That is a point on which Taubenberger and Simonsen agree.

    "It's worth going through all of the effort to plan for a serious recurrence and to make vaccine and try to distribute vaccine as soon as possible," he said.

    "But we don't know what's going to happen."

    http://www.ctv.ca/servlet/ArticleNew...812?hub=Health

  • #2
    Re: Expert warns of misunderstanding behind 1918 flu

    Very good summary of the opposing theories in the virology community.

    Unfortunately, the "winner" of this debate will only be seen in hindsight.

    Comment


    • #3
      Re: Expert warns of misunderstanding behind 1918 flu

      Originally posted by St Michael View Post
      Very good summary of the opposing theories in the virology community.

      Unfortunately, the "winner" of this debate will only be seen in hindsight.
      Is it possible for someone to post the opposite view from experts so that we all can see the players in this debate? In other words, what experts are taking the position that will see another wave of much greater severity akin to the 1918 experience?

      Comment


      • #4
        Re: Expert warns of misunderstanding behind 1918 flu

        Here's something from the Reveres

        Swine flu this fall: turbulence ahead
        Category: Epidemiology ? Infectious disease ? Models ? Pandemic preparedness ? Swine flu
        Posted on: August 6, 2009 6:33 AM, by revere

        Making predictions about something as unpredictable as flu is foolhardy. I rarely (if ever) do it, but I'm going to do it now. I am predicting a bad and early H1N1 swine flu season in the northern hemisphere next fall and winter. The reasons for this departure from our usual custom is a paper in Nature from 2007 I just re-read. It's entitled "Seasonal dynamics of recurrent epidemics" by Stone, Olinkyl and Huppert from Tel Aviv University and it appeared in vol. 446, pp 533-536, 2007 (doi:10.1038/nature05638; html version here, if you have a subscription). The paper isn't specifically about flu and it is a mathematical modeling paper that presents an analytical condition for whether there will be a full epidemic or a minor "skip" in a seasonally forced SIR model. It's mainly concerned with childhood diseases like measles, not flu. But it seemed to us it was of immediate relevance to swine flu. We're going to try to explain why we were so struck by this paper (and if you want to know more about mathematical modeling for flu, you might try our 17 part series that takes a single paper and explains it, paragraph by paragraph and equation by equation at a level suitable for most educated readers; you won't need it for this post, though).

        It is an adage in the field of mathematical modeling that "all models are wrong, but some models are useful" (attributed to George Box). We think this is a model that is useful because it provides insights into what could be happening with flu. Not the whole story, but an important part of the story. Even relatively simple models for disease dynamics -- for example, ones incorporating crude assumptions like the probability of transmission is proportional to the rate of contact between infected and susceptible people -- can behave in very strange and counter-intuitive ways, especially when you include seasonal forcing in the equations. In simple terms, seasonal forcing says that some periodic environmental factor that varies throughout the year -- opening of schools or absolute humidity or temperature -- is altering the transmissibility of the virus. Many systems have their own inherent periodic behavior that don't require outside forces. A weight on a spring bouncing up and down or a child on a swing (i.e., a pendulum) are two examples familiar to any college student taking physics or differential equations. The rate at which the child swings back and forth after an initial push is characteristic of the swing apparatus and only depends on the length of the chains attaching it to the top bar (yes, I am neglecting damping and non-linearities from larger angles; so sue me). The reason a pendulum clock can keep time is because the period of swing is regular and fixed. Now, after the child is swinging back and forth in a regular, periodic way characteristic of the swing set-up, do some periodic forcing. What this means is that you start to give the swing an additional push but not at intervals corresponding to its inherent periodicity but some other period completely independent of the swing's inherent period. There are a huge number of behaviors of the swing that you can produce (including chaotic behavior) by different kinds of external forcing (pushing at odd intervals, say at the bottom of the path or as it is on the way up to you as you stand behind), and the mathematical analysis of inherently simple periodic systems with external forcing can quickly become intractable. But the authors of the Nature paper sidestep some of this analysis to see if there are some broad underlying regularities that might be useful:

        Theoretical studies have shown that seasonal forcing can be responsible for inducing similar complex population dynamics such as higher-order cycles, resonances and deterministic chaos. These complex responses can easily mask any simple underlying mechanistic processes that might otherwise help in forecasting future epidemics. The modelling framework used here helps uncover, and gives new insights into, these processes. (Stone et al., Nature [cites omitted])
        One of the innovations in this paper is that instead of trying to predict a specific outbreak, the authors concentrate on post-epidemic dynamics. In other words, they are looking at pairs or triples of outbreaks, not single outbreaks. It has been known for a long time that seasonal childhood diseases have really bad years, sometimes several in a row, and then suddenly a "skip" or year with a minor peak (the peak is there but its a mini-peak). Sometimes there will be several skips, then another bad year. Flu does the same thing. Last year was bad but the three previous seasons were "mild" but the one before that was also bad. Stone et al. tried to find a simple explanation for this behavior with the help of a mathematical model for seasonally forced infectious disease dynamics where there are just three kinds of people: those who are Susceptible, those who are Infected and those who are Recovered (or dead). It's called an SIR model for the three categories. Our series on modeling antivirals looks at a model very similar to this in concept.

        One of the main results in this paper is a mathematical formula for a threshold of the proportion of susceptibles in a population required at the outset of a season for it to be "bad" (have a high peak). If the number of people susceptible when the outbreak starts is above that threshold, then there is an epidemic that year. If it is below the threshold, there is a "skip." The exact formula isn't important for us, or even so much what goes into it (things like the size of the forcing function, the rate of entry into the population of new susceptibles, etc.). What is interesting is the insights it gives into what's going on.

        On one level the analysis just seems to confirm conventional epidemiologic wisdom: if there is a really bad year, most of the susceptibles are "used up" and the following year there aren't enough people left who aren't immune for the virus to get going. The virus confronts "herd immunity" produced by the previous bad year. But that doesn't always happen and the analysis shows why. It's not just how big the previous year's outbreak is, but its timing within the flu season (which they refer to as early phase or late phase). Instead of paraphrasing it, I'm going to quote directly from their paper. The two symbols used are S0 and Sc. The first is the minimum number of susceptibles left in the wake of the last year's outbreak, while the second is their threshold criterion. If S0 exceeds Sc then there will be a bad year:

        First, consider the case in which there are only two main seasons each year, a 'high' season (high disease transmission) and a 'low' season (low disease transmission). Suppose an infected individual is introduced into a population of susceptibles during the high season. It makes a crucial difference whether the individual enters the population relatively early or late.
        First, consider the scenario in which the infected individual is introduced early in the high season and proceeds to initiate an epidemic. This gives plentiful time for the development of a full-scale epidemic. These large protracted epidemics eventually die out, exhausting the susceptible pool (S0) in the process. If S0 < Sc, there are too few susceptibles to fuel an epidemic in the following year. Second, in contrast, should an infected individual enter the susceptible population very late in the high season, there may be little time available for the build up of a large-scale outbreak. Being late, the epidemic is more likely to be affected as the season changes from high to low. The smaller contact rate associated with the low season can act to curtail the epidemic, and cut it short. As a result, a large susceptible pool S0 remains. Should S0 > Sc, the number of susceptibles will be enough to trigger an outbreak in the following year.


        Stone et al. present very credible evidence that when the peak of the previous year occurs late in the season and is cut short by the "off season" factors (whatever they might be), then the following year is bad, because the aborted late appearance (aborted by the lack of seasonal forcing) leaves enough susceptibles to exceed the threshold for a bad year. While the insights here came from looking at the behavior of a mathematical model, the reasoning is fairly robust to its assumptions. I think you can see where I am going with this. I am not predicting a bad year because number crunching in a mathematical model said it must be so. On the contrary, through the use of the model, we are able to see some implicit logic about what goes on in systems like this.

        Here's how I see it applying to swine flu. This started late in the flu season. We're not sure when, exactly, but probably in March sometime. Because there was no natural immunity in the population and in other respects the virus transmitted with the facility of seasonal flu, it could spread pretty fast and widely before whatever factors involved in flu's seasonal forcing lowered transmission to the point it started to subside. It's true it is not subsiding everywhere but it is subsiding in many places in the north. However it is not the fact it is subsiding but the reasons why it is subsiding that are important. If it is starting to wane because it had burned itself out by using up the susceptibles, that would suggest next year wouldn't be so bad. But in fact, while there was a lot of flu around, most people didn't get it. If it is subsiding it is probably because whatever is involved in the seasonal forcing of flu (and we don't really know what that is) has started to cut it short before the "tinder" of susceptibles was used up. Everyone expected this to happen when the summer came and the fact it didn't happen right away was a surprise. It suggests this virus is quite transmissible and combined with the lack of immunity could overcome the extra push to transmissibility the seasonal forcing gives it. But it looks to be subsiding now. When the forcing starts again in the fall all the makings will be there for an early and big flu season if the threshold for it is exceeded. I feel pretty confident there are plenty of susceptibles around for the virus. True, I don't know how many are needed because I don't know what the threshold is. But I'm betting it's not too high. Meanwhile the vaccine won't be available to decrease the susceptibles before the virus can pick up a head of steam.

        I would dearly like to be wrong about this and making any prediction about flu is undoubtedly stupid. Doing so on the basis of a mathematical model may be even more foolhardy. But sometimes you just go on scientific hunches, and my hunch is that Stone et al. have this pegged right, even if they didn't intend it for this flu. We'll just have to see. But meanwhile, I'd keep your seat belts fastened because I see evidence of turbulence ahead.

        http://scienceblogs.com/effectmeasur...turbulence.php

        Comment


        • #5
          Re: Expert warns of misunderstanding behind 1918 flu

          Here is an interesting example of a recent herald wave from 2005-2006.

          Now, the virus is Chikungunya so it is not human-to-human but mosquito to human.

          Since this initial outbreak Chikungunya has now basically reached multiple WHO zones and infected millions.

          http://www.biomedcentral.com/content...4-8-99-2-l.jpg

          [ATTACH]3920[/ATTACH]

          Notice the Herald wave in May-June of 2005, then notice what happens about 6 months later.

          While not the same virus or the same transport mechanism it does give an example of Herald Waves.

          Comment


          • #6
            Re: Expert warns of misunderstanding behind 1918 flu

            Jeremy, are you suggesting the wave-like behavior is characteristic of infectious disease as a whole? A sincere question.

            Comment


            • #7
              Re: Expert warns of misunderstanding behind 1918 flu

              Originally posted by Snicklefritz View Post
              Here's something from the Reveres

              Swine flu this fall: turbulence ahead
              Category: Epidemiology ? Infectious disease ? Models ? Pandemic preparedness ? Swine flu
              Posted on: August 6, 2009 6:33 AM, by revere
              Yes, good post. But unless I'm mistaken, I think this model, and Reveres' position, is more about viral spread than virulence. I suspect there is significant agreement among all experts that this coming flu season will be challenging, to our schools, our clinics, hospitals, etc. simply because a whole lot of people are likely to get sick.

              But what about virulence? Do we have experts that take the position that the second wave of Swine Flu will be akin in virulence to the 1918 pandemic?

              Comment


              • #8
                Re: Expert warns of misunderstanding behind 1918 flu

                Originally posted by Snicklefritz View Post
                Jeremy, are you suggesting the wave-like behavior is characteristic of infectious disease as a whole? A sincere question.
                I think it would be incorrect to say wave-like behavior occurs for all infectious diseases.

                However, it is obvious that waves occur. The causes of some waves seems to be related to environmental factors (weather) and vectors.

                What happened in the case of Chikungunya is that it found a new vector (Aedes mosquitoes).

                You could argue that this new strain of H1N1 has also found a new vector, us.

                Comment


                • #9
                  Re: Expert warns of misunderstanding behind 1918 flu

                  From an empirical standpoint I understand their argument. They don't have the smoking gun and therefore can't compare the "phenomenon" that occurred in the spring to what arrived in the fall. I think there are plenty of examples where we can say that we might not have explicit evidence for something because no one thought to worry about it (i.e. take samples, record information, etc.) So they can slam down the trump card and say..."there doesn't appear to be any evidence linking."

                  I get it but isn't it unusual that something was amok during the late spring? Isn't the sickness in the spring of 1918, and how it subsided, consistent with less activity over the summer often common to flu? I once heard from a physician:

                  "If you hear hoof-beats in the distance, think horses not zebras."

                  While this may not be directly on point it raises the interesting question. When there is strong evidence in a particular direction, you should conclude the obvious (or what is most likely to have occurred). Is there a such thing as circumstantial evidence in science? (I know, such a concept is not very scientific but you get the gist)

                  Otherwise, we are left to believe that the fall virus in 1918 hit the scene brand new and was both highly transmissible and lethal all in one package....never before having been in the population in any identifiable or recordable way. (i.e. presenting in the population as sickness or had never infected the public prior to the fall)

                  I feel like based on the limited reports of the spring that it seems to have been somewhat "novel" for whatever it was.


                  P.S. If Dr. Niman is correct from earlier, that this is more political while resting on careers and reputations, then it looks like they are even trying to poo poo the theories they built their careers on just to salvage what is left. Kind of like saying, "Don't look hear, no reassortments etc. etc. this isn't even going to change and will likely die out. Stop looking for or modeling some theory from the past."

                  Comment


                  • #10
                    Re: Expert warns of misunderstanding behind 1918 flu

                    Originally posted by Jeremy View Post
                    Here is an interesting example of a recent herald wave from 2005-2006.

                    Now, the virus is Chikungunya so it is not human-to-human but mosquito to human.

                    Since this initial outbreak Chikungunya has now basically reached multiple WHO zones and infected millions.

                    http://www.biomedcentral.com/content...4-8-99-2-l.jpg

                    [ATTACH]3871[/ATTACH]

                    Notice the Herald wave in May-June of 2005, then notice what happens about 6 months later.

                    While not the same virus or the same transport mechanism it does give an example of Herald Waves.
                    Furthermore, I fully believe we will see something like this come this fall with H1N1, at least in terms of cases.

                    Will it have the same virulence as 1918? I have no idea. However, it is important to remember, most of those that died in 1918 did so because of the secondary bacterial infection (at least that is what some research says).

                    Comment


                    • #11
                      Re: Expert warns of misunderstanding behind 1918 flu

                      Originally posted by Jeremy View Post
                      I think it would be incorrect to say wave-like behavior occurs for all infectious diseases.

                      However, it is obvious that waves occur. The causes of some waves seems to be related to environmental factors (weather) and vectors.

                      What happened in the case of Chikungunya is that it found a new vector (Aedes mosquitoes).

                      You could argue that this new strain of H1N1 has also found a new vector, us.
                      I would also think that assuming that you could argue that all diseases have some identifiable "waves," waves of a certain characteristic and duration are indicative of a limited number of diseases possessing those characteristics. For example, airborne illnesses such as flu, for which we have data will act similarly. Such as those that spread quickly over a certain period of time.

                      Comment


                      • #12
                        Re: Expert warns of misunderstanding behind 1918 flu

                        Originally posted by Lurker View Post
                        I would also think that assuming that you could argue that all diseases have some identifiable "waves," waves of a certain characteristic and duration are indicative of a limited number of diseases possessing those characteristics. For example, airborne illnesses such as flu, for which we have data will act similarly. Such as those that spread quickly over a certain period of time.
                        I agree. Interestingly though, if H1N1 does outbreak in September/October it would have followed a very similar timeline to the Chikungunya outbreak even though the vectors were different (makes you wonder, how much do the seasons influence the time between waves...regardless of vector).

                        Comment


                        • #13
                          Re: Expert warns of misunderstanding behind 1918 flu

                          Got to land here,

                          I agree with Reveres analysis, but this I have against all those experts...

                          Doesn't virulence is link somehow to the condition of the individual?
                          You only focus on the virus, but this 'mild' virus with people with high level of arsenic in their blood or low selenium levels, or ashtma. or etc...

                          Aren't there the ones that define most what virulence in individuals is all about.

                          In Winnipeg, Manitoba, First Nations have become personna non grata socially, but when you daily drink arsenic, when you eat high levels of arsenic components, you can be sure that this virus is virulent.

                          Snowy

                          Comment


                          • #14
                            Re: Expert warns of misunderstanding behind 1918 flu

                            Originally posted by Jeremy View Post
                            However, it is important to remember, most of those that died in 1918 did so because of the secondary bacterial infection (at least that is what some research says).
                            That too is the subject of debate. More likely (IMHO) is that the lung pathology due to cytokine storm establishes a good petri dish for the growth of bacteria, and that secondary bacterial infection had nothing to do with the primary cause of death.

                            Again, we'll only know for certain in retrospect.

                            Comment


                            • #15
                              Re: Expert warns of misunderstanding behind 1918 flu

                              Originally posted by Mamabird View Post
                              ........But what about virulence? Do we have experts that take the position that the second wave of Swine Flu will be akin in virulence to the 1918 pandemic?
                              I believe the one factor that may impact virulence will be the acquisition of PB2/627K. Since it is circulating with seasonal flu, many have assumed the novel H1N1 will eventually acquire that change and increase virulence. But when? It may be happening as we speak, or this fall, or a year or more from now....or never. But given that all human flus have had that gene, including 1918, I think it's a reasonable assumption that this will occur.

                              As to the extent of virulence increase - it may not be more than a manageable small uptick.

                              I noticed recently that in some years, the elderly deaths occur more in a "second" wave, or at least during the January-March timeframe. That could be related to social customs, i.e., grandparents traveling to be with the younger generations for Christmas, getting sick after that and spreading it to their older friends.

                              .
                              "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

                              Comment

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