Effect Measure

One of the enduring scientific mysteries about influenza is what causes its marked seasonal pattern. A new paper in the Journal of Virology provides a useful mini-review of the many theories. [PubMed says its free online, but it seems to be behind a subscription firewall; maybe that will change. Here's the cite: Lofgren E, Fefferman NH, Naumov YN, Gorski J, Naumova EN., "Influenza seasonality: underlying causes and modeling theories", J Virol. 2007 Jun;81(11):5429-36. I have a print copy only.] The most surprising thing to most people who don’t follow this is that this is still a mystery. We’ve known that there is a predictable “flu season” for a very long time. We just don’t know why. The new paper confirms this and remarks on how often seasonality is taken as a given, not as something to be explained. Over the years many explanations have been advanced, hypothesized or speculated, although few have been tested epidemiologically.

A number concentrate on the host, that is, us. Maybe our resistance or susceptibility to influenza virus varies seasonally. Among the possibilities are seasonal variations in immune function, perhaps mediated by sunlight (or its lack), diet or differences in behavior and hence frequency and intimacy of person to person contact. Crowding, air travel, the school year and other seasonal differences in behavior are frequently invoked, especially in the lay press, but as some have pointed out, large international conventions in the summer or other occasions that produce crowding don’t seem to induce outbreaks “out of season.”

Maybe the season affects the virus. The most frequent factors mentioned are temperature and humidity, both known to affect the survivability of the virus. One possibility not mentioned by Lofgren et al. is that the lower humidity in the fall increases the proportion of aerosolized material with infective virus that is of small aerodynamic diameter. But I speculate (like everyone else). Included in their catalog of suggested causes are effects of indoor heating systems, air travel and a variety of other things. One of the more bizarre ideas they report from the literature (a paper in 1989) is that the virus exists as a huge aerosol cloud in cities in China and the viral miasma is carried by upper level wind currents to Europe and transoceanically to North America. They are politely skeptical of the idea. I’ll be less polite: dumb.

Finally, Lofgren et al. mention the possibility that the periodic nature is an inherent property of disease dynamics. I know two of the five authors and they are both mathematical modelers, and good ones, too. So I was especially interested to hear what they had to say. They divide the models into two piles, those that produce periodic patterns by some external driver (e.g., letting R0 to vary periodically) and those where the periodic pattern emerges from the operation of the system, much as a weight on a spring will oscillate up and down without any external force. The former is just a mathematical description of the unknown factor in the world that causes the seasonality, but the latter is quite different. It says, in effect, that seasonality might be produced without any “ouatsie” factor in the world, like temperature or host variation, causing it. We know that systems that have different strains interacting can do this, and two of the authors, Fefferman and Naumova show previously unpublished data that fairly small differences in social interactions between groups of people in the community (e.g., between the elderly and children) can produce startlingly different patterns, some showing periodic behavior and others showing none.

The authors conclude, naturally but somewhat unhelpfully, that the actual situation is complex and seasonality likely results from many different factors. That kind of conclusion is always a safe bet, but I am still hopeful the answer will be simpler. My interest in mathematical modeling makes me sympathetic to the emergent behavior idea, but if I had to guess (and I do have to guess), I’d say it was a combination of inherent disease dynamics (the emergent idea) combined with a simple external phase resetter from the environment. This is like what happens with our body’s inherent circadian rhythm, which operates on a cycle longer than 24 hours, but gets “reset” by the day light cycle. We are still trying to puzzle out how that resetting occurs for circadian rhythm, but the goal is to figure out the mechanism so we can do something about sleep disorders and other derangements of the cycle. If we can do the same for flu — that is, identify the mechanisms — we might also be able to damp out the huge increase in disease incidence each winter.

Why there is a flu season: just one more thing you thought we knew but don’t.

Comments

  1. #1 Tom DVM
    May 21, 2007

    Where does it spend the summers?

  2. #2 traumatized
    May 21, 2007

    American Society for Microbiology says full text available for free after 4 months.
    Someone give ‘em a citizenship medal!
    Even better, lets let them advertise as free full text on pubmed!

    wtf

  3. #3 revere
    May 21, 2007

    Tom: Excellent question. There are two broad schools of thought. The first is that it is absent from the West and is reintroduced yearly from China and environs. The second, more favored idea, is that it is present year round but at very low levels in the summer and undergoes sudden increases during “flu season.” Why? you might ask. Yes, you might.

  4. #4 Lofgren
    May 21, 2007

    Revere,

    PubMed says that it’s free online because they have only archived the “JVI Accepts” version, which *is* freely available online in pre-editorial draft form until its formally published.

  5. #5 revere
    May 21, 2007

    Dr. Lofgren: Thanks. If you have a link, send it on and I will post here.

  6. #6 Lofgren
    May 21, 2007

    *digs about the internet*

    Unfortunately, the JVI accepts portion is now whittled down to an abstract which, amusingly, was cut for the final publication. Feel free to drop an email to the address listed for the corresponding author and I’ll send you on a digital copy.

    And in the interest of full disclosure, there is no “Dr” before “Lofgren”.

  7. #7 Lofgren
    May 21, 2007

    As to Tom’s more flu-based and less nuances of published papers based question, the question of “where does it spend summers” is yet another unknown.

    One school, as Revere mentioned, holds that it emerges out of China/East Asia each and every year, and that the rest of the time we are “flu free”. This viewpoint is especially handy in explaining why “crowding” (many people in a confined space due to cold) is a legitimate theory for flu seasonality, as crowded summer areas, such as conventions and cruise ships, do not give rise to flu epidemics – because the virus isn’t there.

    The other is that it *is* sitting around in the environment, but lacks the potential to cause seasonal flu. This could be a more robust summer immune system, some “internal clock” in the form of accumulating viral mutations, or a switch in the environment…temperature, humidity, etc.

    Unfortunately where flu spends its summer vacation is intrisically tied to what its doing the rest of the year.

  8. #8 Dorman
    May 21, 2007

    Doesn’t it spend its “summer” vacation (our summer) in the Southern Hemisphere where it’s winter? What is the seasonality there?

  9. #9 phytosleuth
    May 21, 2007

    How would vitamin D deficiency during winter factor into this question?

  10. #10 revere
    May 21, 2007

    phytosleuth: Vit D is in the explanation mix. It’s a crowded field.

  11. #11 Lisa the GP
    May 21, 2007

    I think that it anti-phases the surfers. Surfers follow the endless summer, flu follows the endless winter.

    I bet you could find a statistically significant correlation between the number of surfers in a region and the absence of flu. In which case we should just force surfers to remain local and surf year round as a matter of public health.

    (This is a joke, of course.)

  12. #12 traumatized
    May 21, 2007

    Lisa,
    Also a statistically significant correlation with the number of pirates.
    http://www.venganza.org

  13. #13 revere
    May 21, 2007

    . . . or sunblock.

  14. #14 Lisa the GP
    May 21, 2007

    Yes, that solves the bird flu problem, all we need to do is distribute massive quantities of sunblock and the population will be protected.

    Ar! Flu comes from China, and there are still pirates in the south china sea. Bad news for Pastafarians.

  15. #15 M.Randolph Kruger
    May 21, 2007

    Any comment on that Bloomberg report that BF is at the end of its cycle according to the FAO. That was about 10 hours in advance of the news that the Chinese had to kill 54,000 chickens in four days and that India was bracing up for BF and that Bangladesh and others were reporting kills and culls?

    Seems kind of stupid to make those kinds of statements when people are actively dying from it, chickens and poultry in general are dying. Its a novel virus, designed to be adaptive and it also is kind of following 1918 flu in its workings.

    Believe me I would like not to have to talk about it. I would much rather fight over other things but I cant believe its “coming to the end of its cycle”

    http://www.hindu.com/2007/05/22/stories/2007052209550100.htm
    http://www.hindu.com/2007/05/22/stories/2007052213921100.htm
    http://www.thedailystar.net/2007/05/22/d70522014524.htm

    and the winner …..http://www.bloomberg.com/apps/news?pid=20601202&sid=af5SEQC7m8hw&refer=healthcare

  16. #16 revere
    May 21, 2007

    My reaction tomorrow a.m., with my own selection of storie (interestingly, only overlap is the Bangladesh story).

  17. #17 Racter
    May 21, 2007

    This is one of the questions that’s always interested me the most. I guess I just like puzzles. Here are some of my questions:

    We don’t actually see ZERO cases of influenza off-season, do we? During summer outbreaks, is international travel identifiable as a common factor among index cases? During winter, are there fewer cases among those who, for whatever reason, get significantly more sun exposure than others? If influenza hangs around off-season, but lacks the potential to cause seasonal flu due to a more robust summer immune system, how can it maintain the chains of continuous transmission it needs to survive? And wouldn’t we expect to still see cases among the immunocompromised? Do we?

  18. #18 Interrobang
    May 21, 2007

    Yes, that solves the bird flu problem, all we need to do is distribute massive quantities of sunblock and the population will be protected.

    Ouch, no, don’t you guys ski? Lemme tell you, there are plenty of skiiers who use sunblock. *waves* A winter sunburn might be a bit less likely to happen than a summer sunburn, but not impossible. I’m seriously melanin-deprived, live at 43N latitude, and have definitely had my share of winter sunburns (and influenza). So it can’t be the presence or absence of sunblock. Maybe of goofy sunshading hats, however…

    I got it, string bikinis. Yeah, that’s my story, and I’m stickin’ to it.

  19. #19 Ron
    May 21, 2007

    Hmm. I was taught that it had to do with migratory birds, especically waterfowl, well-known reservoirs of all strains of flu, as they head south for the winter. I thought that was the accepted explanation. And since I am very wary of accepted explanations… Learning everyday.

  20. #20 M. Randolph Kruger
    May 22, 2007

    Racter-As we get it, this stuff can live for about 4 days in the dirt at 98 degrees, poop too. Big possibility you might catch a load of flu from a load of doo. It also does well at about 35 degrees for about 30 days. As for the zero cases of flu during the off season, no a lot of cases were reported both N and S. Hemisphere for birds and humans in summer and winter, spring and fall. There was a hemmoraghic something or other that they called “ebola flu”

    http://yaleglobal.yale.edu/display.article?id=6077

    back in July 2005. It almost sounds like what those pigs got from the Newsweek article. Was it a sub-clade of BF? I sure as shit dont want to find out. You have heard Revere talk about ultraviolet bug killers and whether they would work or not. Dont know if they would or wouldnt. You could expect that if a bug got loose and could survive at 98 degrees (human temps) that baring sunlight in the factors it would be easily transmissible. Revere could cover that better of course along with Lisa. Bottom line is that until I see no birds dying, no one reporting H5N1, H3N2, H7N7 or any of the others I will consider BF of some sort to be standing at the door waiting for us. Pandemics dont just happen. They signal for a bit before they come. Herald waves preceded just about all of them. This is a novel virus and it means it will do strange shit and baffle the best of them. So far its doing that and no one can come up with a vaccine. If it swings in on a moderately pathogenic note, then better for the vaccine production. If not, better for the body bag people.

    I sent almost a year ago a personal E to Revere telling him about 50,000 body bags that were sent to SE Asia. Since then another 200,000 have been sent. Thats a sizeable investment in death at about 10 bucks per pop. So do they think its coming? I cant tell because of the mixed signals. Its not gone high path, doesnt mean it will …. or wont. One group noted above says its at an end of a cycle. Another alumnus of a university says that its one antigenic recombination or reassortment away. Dr. Webster says he thinks its coming. How hard and fast is his question. Osterholm thinks so and its his imperitive right now. So there aint no ghost busters on this one.

    Ron-Dead on bubba. Its taken me nearly three years to be able to read the stuff off of GenBank. Still dont understand most of it but I can see patterns that are there when sequences are posted for human deaths and infections. I can see Nimans work and where he is headed with it. Recombination or reassortment? Still dont know enough. The more you know if it comes the more chance you will have if it does along with the people around you. Chicken Littles is all we are until it happens, then we are going to be in the fight of our lives if its a high path flu. I like a fight, but not one where there is nothing but pyrrhic victory. Thats what we have now. We live and win, well whats going to be left if this has even a 15% CFR, let alone the current 60?

    Its all rhetorical for now. Post up, learn from Revere and others. Throw stuff out there because we will have already come to some conclusion(s) and possible remedies while everyone else will be trying to get out of the gate if it happens. Fact that you are here means you are smarter than the average bear.

  21. #21 Racter
    May 22, 2007

    RK, I tend to make whatever effort is necessary to keep a fair distance between me and doo, especially loads of it (and ESPECIALLY loads of it that have been at 98 degrees for 4 days), so I’d say the possibility of me (personally) catching flu that way are actually rather small, despite the fact that loads of doo are anything but scarce these days. I’m a little OCD when it comes to handwashing, so that probably helps, too.

    I take it that the “this stuff” you refer to is H5N1. I’ve actually seen it stated as 6 days at 98.6 degrees, and up to 35 days at 39 degrees. But that’s H5N1, and the same sources also indicate that this is longer than with seasonal flu, which is probably the kind to start with if you want to understand why seasonal flu is seasonal, even if your main reason for wanting that is the hope of finding some trick for minimizing the impact of a pandemic flu. Not that the notion of seasonal flu spending its summers hiding out in dung heaps is necessarily any crazier than some of the others I’ve seen.

    My comment on that Bloomberg report that BF is “at the end of its cycle” is that, like so much of what we’ve seen, this is easily subject to over-interpretation. All Vallat (Director General of the OIE) was saying is that the thing ebbs as susceptible hosts are depleted, rebounding when they are replaced with fresh batches. Hardly an earthshaking revelation, IMO.

  22. #22 M. Randolph Kruger
    May 22, 2007

    Racter-I agree. Revere is covering our friends from FAO/OIE with a pretty borad paintbrush this morning in another post. As of this morning there are unconfirmed 15-29 familial possibilities in Hungary. The Romanians also have to come clean why they isolated 60,000 people in their houses last year. Then there was that deal with the old hospital with the crematorium that was reopened for “a military exercise”.

    If BF breaks it wont be a question once it gets past say 100 cases. You’ll see it broach onto every media outlet there is including the bathroom walls in the public johns. I just want them to quit talking out of both sides of their mouths, and making contradicting statements. How can a disease be at the end of its cycle when there are fewer deaths of wildfowl when they know full well that the birds are becoming endemic carriers? And I pay money for this kind of drivel to come out of a world organization. Who are we going to appoint to that group? Supari is taken, how bout that guy from Grenada that saw UFO’s?

  23. #23 anon
    May 22, 2007

    http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030089

    http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030121

    it should be easy to figure this out …

    host ? what’s with swine ?
    also seasonality in birds,I think.
    But they rarely have (human) H3N2.

    crowding,airtravel,school year – we don’t have this in 3rd world countries, nor centuries ago.

    humidity, temperature, UV-light – these can all be easily tested. Has it been done ?

    flu-season in South-Africa is March-May, doesn’t fit so well.

  24. #25 revere
    May 22, 2007

    John: Everyone is entitled to their opinion. This is not well accepted, however.

  25. #26 anon
    May 22, 2007

    also, why do pandemics not follow this pattern ?

  26. #27 John Cannell, MD
    May 22, 2007

    As far as influenza and seasonality and vitamin D goes, here is another link:

    http://vitamindcouncil.com/newsletter/2006-oct.shtml

  27. #28 revere
    May 22, 2007

    anon: You mean flu pandemics? They mostly do.

  28. #29 Racter
    May 22, 2007

    I would REALLY like to believe the sunlight hypothesis. In fact, I CHOOSE to believe it, even though the available evidence doesn’t yet seem to adequately support it — and I almost never do that sort of thing. My thinking is that if production of vitamin D, a hormone, is stimulated by sunlight (which we do know for sure), and seasonal affective disorder is lessened by it (which also seems pretty clear), then surely there are other effects that we simply haven’t identified — or perhaps secondary effects of those two (for example, that depression negatively impacts immunity also seems fairly well supported). I’m taking the same approach to statins; I’ll take them to lower cholesterol, and if I (a COPD’er) get better survival odds out of the deal due to some mysterious anti-inflammatory effect or whatever, then hey, bonus.

    Last fall, I began trying to get at least 10-15 minutes of sun every day, when available (which is most days, where I live). I have reasons for doing this other than boosting immunity; it dovetails with a regimen of diet and weight-bearing exercise intended to counter accelerated bone loss from corticosteroid therapy, to which end calcium uptake (and hence vitamin D) is critical. This past winter is the first in years to have passed without my having to do battle with some bug; I wasn’t sick more than a couple of days all told, and never bad enough to keep me off the stationary bike. So there’s a sample of one. Gotta say I still don’t like my chances against any kind of flu, tho — in fact, pandemic or no pandemic, I’ll most likely be long gone before all the evidence on these things is in, so I’m going with what looks like a decent risk/benefit ratio on the preliminary findings.

    Go Doc Cannell!

  29. #30 Lofgren
    May 22, 2007

    Anon-

    “crowding,airtravel,school year – we don’t have this in 3rd world countries, nor centuries ago.”

    You certainly do. Crowding is everywhere, and is arguably worse, in the 3rd World or a century ago.

    “humidity, temperature, UV-light – these can all be easily tested. Has it been done ? Easily tested?” Yes. Easy to establish robust biological plausability? Not so much. Remember, correlation =/= causality.

    “flu-season in South-Africa is March-May, doesn’t fit so well.” March to May is early/mid-winter in the Southern Hemisphere

  30. #31 anon
    May 23, 2007

    much summer panflu in history ,
    https://www.singtomeohmuse.com/viewtopic.php?p=25126

    leave out crowding : remains air-travel, school year.
    (crowding while traveling – mixing with people from other regions)

    the connection with weather – not just seasonality,
    but periods of sunshine, rainy weeks, temperature
    has it been tested ?

    South Africa : April
    Europe : February
    (difference should be 6 months)

  31. #32 anon
    May 23, 2007

    hey, are you the Lofgren from the paper ?
    Very good. Also Cannell from the vitamin D -paper,
    revere , racter … are interested.

    Shouldn’t we put the discussion to a forum with
    better formatting, management of new posts,
    more space for posting tables, graphics, papers ,
    easier access with one click…

    let’s a start a public “seasonality of influenza” – forum !

  32. #33 anon
    May 23, 2007

    also a recent paper about Brazil:

    Influenza circulation and mortality impact in tropical areas have not been well characterized. The authors studied the seasonality of influenza throughout Brazil, a geographically diverse country, by modeling influenza-related mortality and laboratory surveillance data. Monthly time series of pneumonia and influenza mortality were obtained from 1979 to 2001 for each of the 27 Brazilian states. Detrended time series were analyzed by Fourier decomposition to describe the amplitude and timing of annual and semiannual epidemic cycles, and the resulting seasonal parameters were compared across latitudes, ranging from the equator (+5°N) to the subtropics (–35°S). Seasonality in mortality was most pronounced in southern states (winter epidemics, June–July), gradually attenuated toward central states (15°S) (p < 0.001), and remained low near the equator. A seasonal southward traveling wave of influenza was identified across Brazil, originating from equatorial and low-population regions in March–April and moving toward temperate and highly populous regions over a 3-month period. Laboratory surveillance data from recent years provided independent confirmation that mortality peaks coincided with influenza virus activity. The direction of the traveling wave suggests that environmental forces (temperature, humidity) play a more important role than population factors (density, travel) in driving the timing of influenza epidemics across Brazil.

    Brazil; climate; geographic locations; influenza, human; mortality; pneumonia; seasons

  33. #34 anon
    May 23, 2007

    I doubt my South-Africa data : March-April now.
    I found it somewhere on the web.
    Here is a paper about France,USA,Australia
    showing a 6 months-difference N-S :

    http://www.medscape.com/viewarticle/466481_3

  34. #35 Lofgren
    May 23, 2007

    As JVI allows authors to publish the full text of their papers on university hosted websites, with all the sundry copyright information included:

    http://www.tufts.edu/med/informid/pub/2007-01-Lofgren.pdf

  35. #36 M. Randolph Kruger
    May 23, 2007

    Lofgren-Nice work on the link. I am dealing with people here in Memphis that are in the ER that are being told that a ordinary N-95 will protect them if BF comes. No provisions are beiing made for full faceplates, or shields for the eyes. I was actually told by the head of one of the ER training departments that the USGovt said they wouldnt need them and that the masks were resuable! Uh, hmm, uh, what? Come again? Who told you that? I was stunned when I heard it. I wonder if they actually ever read this stuff that you guys like Revere and yourself put out. How they couldnt is beyond me. It also ensures that there are going to be one hell of a lot fewer patients and HCW’s if it comes.

  36. #37 anon
    May 23, 2007

    I looked at the paper. Sounds as if the problem
    could be solved with appropriate effort.
    How much money and time is needed ? Give your estimates !
    Just some thoughts,ideas,remarks.
    No airtravel needed, flu spread faster than h2h even in
    1789 or 1792 when fastest were horses. (R.Johnson)
    flu-B mutates slower and has no avian hosts, still
    shows the same seasonality. RSV peaked 5 weeks earlier
    in Europe the last 3 years, is it typical ?
    Other viruses might cooperate with flu as seen in pigs.
    As nutritient let me mention polyphenols from berries.
    Remarcable that those exposed in summer develope better immunity, maybe we should vaccinate in summer ?
    Crowding was given as possible reason for seasonality,
    but the 1918 examples involved summer-crowding.
    How far back goes seasonality in history ?
    Temperature, indoor heating should have had larger
    effects in cold winters or just cold weeks – was it
    measured ?
    Bulk aerosol transport, why is it unlikely ?
    To escape UV use clouds or dust-particles.
    Maybe not intercontinental but by wind.
    Use birds as transport, no replication necessary,
    or in feathers.

  37. #38 anon
    May 23, 2007

    or the virus survives summer at hidden places in the body
    without replication, escaping immunity

  38. #39 Racter
    May 25, 2007

    G:
    >>No airtravel needed, flu spread faster than h2h even in 1789 or 1792 when fastest were horses.

    Historically, it has often been noted that flu appears to be able to travel faster than humans can. One assumption is that epidemic spread does nonetheless evidence spread of the virus itself, in continuous chains of transmission from one human to another. The alternative is that it evidences broad, concurrent shifts in susceptibility to a virus already widely present. Both seem to have their own problems.

    >>flu-B mutates slower and has no avian hosts, still shows the same seasonality

    Not quite as much seasonality.

    >>Remarcable that those exposed in summer develope better immunity, maybe we should vaccinate in summer ?

    And water our lawns when it’s pouring down rain?

    Those exposed during summer are less likely to develop infection, but I wouldn’t be quick to assume that this indicates “better immunity”; what hasn’t been established is the extent to which it’s the result of a stronger defense by the host versus a weaker attack by the virus. (Frustrating, isn’t it? You’d at least think somebody would have a good handle on that most basic of questions.) If it were clear that vaccination with LAIV during summer resulted in lower antibody titres than during winter, that would seem like an important clue, suggesting that viral replication is strongly influenced by some host factor, in turn perhaps influenced by ultraviolet, or temperature, or what-have-you, but most of what I can find indicates that there is little or no difference.

    >>or the virus survives summer at hidden places in the body without replication, escaping immunity.

    As far as I know, no one has yet been able to show that influenza is capable of a latent phase, much less that this is the commonly occuring phenomenon it would have to be in order for this to fully explain the seasonality.

  39. #40 Marissa
    May 25, 2007

    I think the UV factor is important, particularly in the case of virus reservoirs, such as bird poop, or other areas out in the open air. Wintertime, less UV exposure coupled with lower temps enables the virus to persist longer in the outside air with potential for infection.

  40. #41 anon
    May 25, 2007

    Racter:

    >>No airtravel needed, flu spread faster than h2h even
    >>in 1789 or 1792 when fastest were horses.
    >Historically, it has
    >often been noted that flu appears to be able to travel faster
    >than humans can. One assumption is that epidemic spread does nonetheless
    >evidence spread of the virus itself, in continuous chains of transmission
    >from one human to another. The alternative is that it evidences
    >broad, concurrent shifts in susceptibility to a virus already
    >widely present. Both seem to have their own problems.

    we do observe flu traveling from location to location.
    Just faster than it should.

    >>flu-B mutates slower and has no avian hosts, still shows the
    >>same seasonality
    >
    >Not quite as much seasonality.

    I can see no difference:
    http://magictour.free.fr/eiss.JPG

    >>Remarcable that those exposed in summer develope better immunity,
    >>maybe we should vaccinate in summer ?
    >And water our lawns when it’s pouring down rain?
    >
    >Those exposed during summer are less likely to develop infection,
    > but I wouldn’t be quick to assume that this indicates “better
    >immunity”; what hasn’t been established is the extent to which
    >it’s the result of a stronger defense by the host versus a weaker
    >attack by the virus.

    I thought, I read it, that immunity _development_ is better
    in summer but now I can’t find it. (and doubt it a bit)

    >(Frustrating, isn’t it? You’d at least think
    >somebody would have a good handle on that most basic of questions.
    > If it were clear that vaccination with LAIV during summer resulted
    >in lower antibody titres than during winter, that would seem like
    >an important clue, suggesting that viral replication is strongly
    >influenced by some host factor, in turn perhaps influenced by
    >ultraviolet, or temperature, or what-have-you, but most of what
    >I can find indicates that there is little or no difference.

    should have a look at Dowell[25]

    >>or the virus survives summer at hidden places in the body without
    >>replication, escaping immunity.
    >As far as I know, no one has
    >yet been able to show that influenza is capable of a latent phase,
    >much less that this is the commonly occuring phenomenon it would
    >have to be in order for this to fully explain the seasonality.

    can’t we strictly isolate some island-country or region or
    town or village for one season and see whether people there
    still get the flu ? Would also be interesting to know wrt. panflu.

    Marissa:
    >I think the
    >UV factor is important, particularly in the case of virus reservoirs,
    > such as bird poop, or other areas out in the open air. Wintertime,
    > less UV exposure coupled with lower temps enables the virus to
    >persist longer in the outside air with potential for infection.

    but still consideral amount of flu all year long in Hongkong.
    Birds rarely get H3N2 and no flu-B.
    And see H5N1 in Indonesia, which is almost on the equator.

  41. #42 Racter
    May 25, 2007

    >>should have a look at Dowell[25]

    Perhaps here: http://www.cdc.gov/ncidod/eid/vol7no3/dowell.htm

    Frankly, I didn’t learn anything from Lofgren that I hadn’t already seen in that article. I see you’re on this on your site, and tried a bunch of times to post replies, but keep getting gonged on the confirmation codes (my eyesight’s fine, and my keyboard too; looks like the applet is broken?)

    This is from the CDC link you put up to the article by Viboud et al addressing influenza in the US, Australia, and France:

    “We used codes 470-474 and 480-486 from the International Classification of Diseases (ICD) 8th revision, before 1979, and codes 480-487 from ICD-9 from 1979 onwards to select deaths due to pneumonia and influenza.”

    I thought of you when I read that. Any chance you might be interested in trying to access that data in order to apply your data sifting skills to answering some of these questions? One I’d like to know is whether there is a correlation between latitude and excess mortality; in other words, do more people become infected at higher latitudes, and do those that become infected experience more severe illness?

  42. #43 Tom DVM
    May 25, 2007

    Why do pandemics tend to hit in the summer rather than the winter?

  43. #44 Racter
    May 25, 2007

    G:
    >>can’t we strictly isolate some island-country or region or
    town or village for one season and see whether people there
    still get the flu ?

    That approach seems a little… Teutonic. How about looking for communities that were already isolated for some other reason (“experiments of nature”) and see what can be gleaned from whatever records exist. That’s been done. I’ve found some of the results for sale, but nothing very recent, and unfortunately, none for free. Not even an abstract.

    Tom, I’m not sure the sample is large enough to justify the generalization that pandemics tend to hit in summer rather than winter. I’m not sure that “when they hit” is the most important thing anyway; why not “when they peak”?

    My question regarding latitude and severity is a tricky one. As revere notes above, seasonality is often “taken as a given, not as something to be explained”. Where there IS no flu season, “excess mortality” is hard enough to define, much less measure; where’s the baseline? The lack of seasonality makes it more difficult to estimate the number of genuine cases of influenza, too. In temperate regions, the arrival of flu in an area tends to be hard to miss, and diagnosing it often consists mostly of a clinician noting that a patient has the symptoms, same ones as most of the others he’s seen that day — but in the tropics, all bets are off (and as if that weren’t bad enough, laboratory confirmation of influenza is probably less likely to be performed than in more affluent temperate regions).

  44. #45 anon
    May 26, 2007

    HK is 22° latitude with 37% flu-hospitalization
    USA is 38° latitude with 45%
    no big difference due to latitude.

    genbank now has exact date and >100 H3N2 genomes
    per season , but only from USA,NZ,AUS,(TW).
    It should be possible to determine how the
    viruses travel per season, or whether they
    spend the summer in USA.
    Presumably it has been done…

  45. #46 Lofgren
    May 26, 2007

    As for the seasonality of Influenza B, I assure you it is both later and much less pronounced…the term I use is pseudoseasonal. A great deal of time series analysis has gone in to figuring that out.

  46. #47 anon
    May 27, 2007

    I found this:
    http://www.tufts.edu/med/informid/pub/2006-01-Lofgren.pdf

    61 pages, pdf. Lofgrens thesis ,2006, about flu-seasonality ! (haven’t yet read it)

    Now I’m even more eager, to get your estimate, when this problem might be solved… (Cannell:is already solved)

    also found papers about flu in Taiwan,HK1997,Dakar

    wondering whether correlation with weather has been examined, time series of flu and weather (temp.humid.
    rain.sunshine..)should be available

  47. #48 anon
    May 27, 2007

    Lofgren thesis, page 36:
    “The use of viral genomics may very well be the key to establishing biologically plausible
    causation for the statistical relationship established in this work.”

  48. #49 Lofgren
    May 29, 2007

    Anon-

    Quick answers to both your previous posts. First, the relationship between temperature and flu seasonality has been examined, and is indeed what is commonly cited as the “why” of flu seasonality. The problem being we lack a causal link to back up the numeric correlation. Revere above suggested it might take form as enhanced survival for aerosolized particles. It may manifest itself as increased use of indoor heating, or in increased crowding. Or it may simply be a extraneous correlation with some *other* factor that also accompanies a decrease in temperature, such as lower Vitamin D intake.

    As for *when*? That depends on a great many things. Funding, reseach interest, competion for limited resources/researchers between pandemic and endemic flu, etc. Best I can do is “someday”.

  49. #50 anon
    May 30, 2007

    just assume same funding, research interest,competition
    etc. as in the previous years. Say average of the last 3 years continues for 10 years. What’s your subjective
    estimate of the probability that it’s solved within the
    next 10 years ? I somehow feel this should had been solved centuries ago…

    What about rain ? In the tropes it seems to depend
    on rainy season more than temperature. It could be
    different for different strains… actually we have
    H7N2 in summer in Wales.

    Such problems could be researched in worldwide public
    internet discussion, with free data uploaded
    to webpages – the concept of Universities
    is somehow “expired” …

  50. #51 qbsmd
    April 27, 2009

    I thought I had learned (I don’t recall where) that influenza wasn’t endemic in humans, and people were reinfected by birds (I think waterfowl) every year, related to the birds’ migrations.
    Am I thinking of a different disease? Is influenza endemic, or is it even known?

  51. #52 revere
    April 27, 2009

    qband: Possibly you are thinking of West Nile? Where flu goes “in the summer” we don’t know. Presumably the southern hemisphere.

  52. #53 Earthborn
    April 29, 2009

    Maybe it has something to do with the seasonal migration of some birds? Just thinking out loud here…

  53. #54 John Gable
    April 29, 2009

    I beleive humidity has a lot to do with seasonality. Does the water content of air block the virus because there is no room between the molicules, does it wet the virus so that it drops down to the groung, does the water cause the virus to break down or does the water cause the virus to starve by activating it without nutrients like dropping a seed into a glass of water?? I know that since we started running a humidifier the family doesn’t get colds. With this new outbreak, I’m running the humidifier, taking Vitamin D and getting a tan.

  54. #55 revere
    April 29, 2009

    John: I’m traveling at the moment, but if you search this site for Nicaragua you’ll find our post on seasonality in that country, which comes during the hottest time of year and the rainy season (July). The humidity work has been done in guinea pigs. Real life seems to be different.

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