Since I started cogitating on the apparent dominance of H1 subtypes this flu season instead of the more common H3, I've continued to look at some previous papers on the subject. The take home message I am getting is that there is quite a bit we don't know about this disease, influenza, despite its long history and the interest of the medical and scientific community. We've commented on this before. Some problems are like that. Cancer is another example. A particularly interesting paper that illustrates the point by Hay et al. was published in 2002 (hat tip to a loyal reader who sent the link along). It reviewed the evolution of H3 and H1 seasonal flu viruses.
The question is of a great deal of practical importance. Since 1952 WHO has been running a network of Influenza Surveillance laboratories, encompassing 116 institutions in 87 countries. These laboratories take specimens sent by physicians in various areas and isolate influenza virus, subtype it (give it the H and N designation) and also determine different strains or variants within subtypes. The idea is to have an alert if a novel subtype were to suddenly appear and to specify the predominant variants of the circulating subtypes so that a properly matched vaccine can be prepared for the next flu season. This determination is done twice a year, once for the northern hemisphere and once for the southern, since the flu seasons in the two halves of the globe are 6 months out of phase with each other. The data we gave in the last post about which years were H3 and which H1 or B were from this network.
Only a few subtypes of the many possible H and N combinations seem to have established themselves in humans. From 1918 to 1957 it was H1N1, between 1957 and 1968 it was H2N2, and after 1968 H3N2. Each time the new influenza A subtype replaced the previous one. Then in 1977 H1N1 reappeared and began to co-circulate with H3N2. The resurrected H1N1's origin is mysterious. It was quite similar to the H1N1 circulating in the 1950s before H2N2 replaced it. Since 1977 it has been possible to compare the rate of significant change in the H3 and H1 subtypes over the same period and this comparison shows that while the mutation rates in the hemagglutinin protein of each virus seems about the same, the antigenic variation is quicker for the H3N2 virus.
H3 has evolved as a single lineage and one variant seems to succeed another rather quickly and to spread widely, often within the space of 1 or 2 years. Hence the H3 component of the seasonal flu vaccine has to be changed fairly often. Most of the variation is on the surface of the H3 protein spike and involves sites near the antigenic site, that is, the part the immune system "sees" and makes antibodies against. When antibodies attach to these sites they make it more difficult for the virus to infect, since it is the H3 protein that docks to the cell. The variations are not just amino acid substitutions in the protein chain but also involve glycosylation, the attachment of sugars at various points along the protein chain (see your explanation of glycoproteins starting here). It should be mentioned that variations in the H3 protein is not the only thing that produces variants. So do variations on the N2 and so do reassortments of one virus with the internal segments (PB2, PB2, M2, NS, etc.) of another. We now believe that there is continual and promiscuous reassortment of internal proteins with various make-ups going on and this may be related to the periodic emergence of one strain or another. While the H3 strains differ from year to year, they are still relatively similar, however.
The sudden replacement of one strain of H3N2 with another similar one is apparently not mirrored by the behavior in H1N1. Significant changes in the way H1N1 reacts to the immune system occur less frequently, occur more slowly and eventually produce viruses that are less alike. During this slow evolution from one strain to another, there may be several H1N1 strains co-circulating in contrast to the sudden changes in H3N2. It may be that H5N1 is more like H1N1 in this regard.
As with many papers I discuss here, I have left a lot out and only concentrated on things of special interest to me. In this case, it is the mysterious behavior of the familiar seasonal influenza, which we are still trying to decode even as we are anxiously looking over our shoulder at the specter of H5N1. In some ways we seem to be repeating the history of the HIV/AIDS catastrophe, where the urgency of the situation stimulated a tremendous amount of new research and science. The result was a treasure trove of new knowledge of the immune system and retroviruses and real progress in treating the disease, although not until it had killed untold numbers and infected tens of millions. And we still have much to learn about that fearsome disease.
Let's hope that the part about tens of millions being infected won't also be repeated. I have to laugh at whackos like Michael Fumento who are telling us not to worry about bird flu because we have vaccines and antivirals now we didn't have in 1918.
The fatuity of their arguments aside, if we listened to people like that we'd have nothing.
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Still have a whole lot of "nothing" around here; I am beginning to loathe my local government and other officials.
My tax dollars at work, to play russian roulette with panflu year; get us all killed. No thanks.
The take home message I am getting is that there is quite a bit we don't know about this disease, influenza, despite its long history and the interest of the medical and scientific community.
However, there is a whole lot that we do know about humans and how they interact with influenza (in the very stupidest possible way imaginable).
I was out walking the other day and noticed an advertising poster at one of the corner markets, for one of those ridiculously marked-up "vitamin water" concoctions. It said, verbatim, "LESS PAINFUL THAN A FLU SHOT".
Words fail me.
How many target customers will see that and decide to decline an immunization this year?
Underimmunization kills. Literally and specifically. Even in the context of a mere non-avian influenza. Lack of immunity may not kill the young and healthy individual who buys a useless "vitamin water" instead of having a shot, but it may well kill an elderly or immunosuppressed individual to whom that youngster later actively transmits influenza.
In a sane and competent world, where public health had the teeth necessary to bite where a bite would be salubrious, a firm like that would have its advertising pulled, and would be hit with the sort of massive punitive fine which would have the Board of Directors dubiously eyeing the CEO.
We do not live in a sane or competent world. Nothing has been done. Nothing will be done.
I also travelled by air just before the holiday season. One of the TSA (Thousands Standing Around) security supervisors was visibly and severely ill with some sort of respiratory bug. Shaking, blanched, barely able to stand, deep racking coughs, eyes streaming. And this guy was at work! At work IN AN AIRPORT. At work in direct contact with thousands of boarding passengers.
Those are things about which something could, theoretically, be done before a potential pandemic break. Once again, nothing *will* be done, but I don't want to belabor the point.
On the subject of things about which nothing really can be done, where I was flying to was to Europe, where I made it a point to ride the local mass transit even when there were other options.
It is always a sharp reminder when I do that of how high urban core population densities are in some places. Where I live, even at peak rush hour crowding, interpersonal space is a linear measurement, i.e., in centimeters of distance between you and the other people around you. That distance is sometimes small, but never zero.
In many places in Europe (and especially in Asia), interpersonal space is instead an areal measurement, in square centimeters, reckoning how much of your body surface has the bodies of others smashed up against it with the unavoidable relentlessness of a hydraulic press.
This has complications beyond merely providing a pleasant environment for pickpockets and gropers to ply their trades. I kept mentally reckoning how many people around me would have been immediately and unavoidably contacted on facial mucous membranes by a single cough or sneeze from me. In some cases it would have been as many as seven or eight of them at one go.
N95 masks aren't going to do the job of isolating people in that kind of a rugby-scrum crowd. It would take a full face respirator.
I have always been uncomfortable in crowded megacities, whether here in the US or abroad. Much of that is driven by the knowledge which I have, and which those around me lack, of the enormous logistical effort required to run even the most basic life-supporting functions of such a place, like putting food on shelves every day.
And what I further realize, and what those around me again fail to, is the fragility and lack of redundancy in those efforts, and just how fast things could get very bad were those efforts to for any reason stop.
I'm wondering now if it makes sense to move further out into the countryside and to amplify self-sufficiency efforts. That was not a comforting experience.
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marquer: As usual, good and valid points. For another point of view on megacities and disase, see Steven Johnson's new book on cholera in Victorian London, The Ghost Map. I tend to be cleave more toward his point of view, but no one knows what the future will bring.
"pump handle"? think I saw a PBS show including that; first public health sleuthing.
Hey; here's Steve Johnson on YouTube:
http://www.youtube.com/watch?v=3P8shnNEXb4
cr: Yes, pump handle. Last month we started a new public health blog called The Pump Handle. It was a soft launch and we are still getting our sea legs, but check it out.
"Since I started cogitating on the apparent dominance of H1 subtypes this flu season..."
True in the US but not everywhere. Europe is different.
"In contrast to the United States, where the predominant subtype is A(H1N1) (>95% of subtyped type A viruses since 1 October 2006 [click here]), the predominant subtype in Europe has been A(H3N2) [A/Wisconsin/67/2005 (H3N2)-like viruses] so far this season."
http://www.eiss.org/cgi-files/bulletin_v2.cgi?display=1&code=208&bullet…
Ottawa Guy: Thank you for that link. Extremely interesting. Does anyone know how often this happens? H1 drifts and spreads more slowly than H3, so maybe this is what will be in store for Europe next year. Or maybe not. Nothing much clear about any of this.
My daughter's fiance went to work with the flu, after two days off. Why? Partly because he needed the money, but more because he was afraid they'd fire him if he didn't show up. Figured he'd show up with a raging fever and cough, and they'd see he wasn't lying and send him home. But no, they made him stay and work. Where does he work? A fancy Japanese restaurant. What is his job: Salad Chef!!!!
(I will never eat out again!)
If we are lucky enough not to bite the bullet this time, and the pandemic threat goes away, then we need not only to set up a universal health care system of some kind, but it seems to me it needs to include "sick day" pay so that people who are ill (or who have sick children to care for)can miss a few days of work without losing pay. As a salaried employee, I've enjoyed those benefits for 20 years. I get 10 full pay sick days a year, but seldom have to use more than half of them. If you are out more than 2 days you need a doctor's note, but aside from that it's on the "honor system". Sure, some people would take advantage of it for extra days off (teachers do that all the time) but the maximum you get is 10, so the cost to the organization would be limited to that. Yes, it would cost the government (us taxpayers) money, but my guess is that in long term the costs might be offset by the overall health of the workforce.
New question, Revere and others:
have there ever been counted more deaths by subsequent flu-waves in one season? I remember to have caught a flu in 1983, and as soon I was recovered I caught another one.
I've feeled very tired for months.
When forms of H1N1 and H3N2 are both circulating, although one especially in America and the other one at the European continent, I do expect both will follow their own pathway. H1N1 has been signalled in Norway already, so maybe it's coming slowly to Europe, while at the same time H3N2 is crossing the ocean and going to the United States.
I 'd expect very young and very old people to be at a greater risk of getting pneumonia or other complications if they get two blows instead of one.