Effect Measure

Figuring out how flu gets around

One reason Helen Branswell is such a good flu reporter is she has the best contacts. Of course this is a chicken-and-egg proposition, because she has the best contacts because she is the best flu reporter. She gets it right and she explains it the way it was told to her. [By the way, I am not on her payroll. In fact she is uncomfortable about being praised. But I don't do it for her sake. She doesn't need it anyway. My motive is to show other reporters what good flu reporting is and encourage them to do the same. And there are a number of other excellent reporters, which I try to acknowledge when I can. They are one of our most important sources of information.]

This doesn’t mean everything told to Branswell is correct, but at least you know it didn’t come over a noisy communication channel. One of her recent stories I liked least (and didn’t discuss here) was also one of her more popular, the one about flu virus in mucus remaning viable for up to 17 days on banknotes. Why didn’t I like it? Because I had no idea what it meant. Is a virus you can scarf up off a dollar bill and test to see if replicates in cell culture one that can make me sick? If it’s going to infect me it has to be picked up from the currency, presumably on my hands or fingers, and then be transferred, still viable, to some cells where it can replicate. We have known for a long time that replicable virus will last a long time on hard, dry surfaces like currency or doorknobs or arm rests, but there is also evidence that a flu virus only remains viable on a human finger or hand for a few minutes. This shouldn’t be a surprise. Skin is a biological tissue with lots of defenses against microbial invaders.

Unfortunately and as we have pointed out here too many times to count or even link to, we know very little about how flu virus is actually passed around in the community. Except here at Effect Measure, you wouldn’t necessarily know this from reading most of what’s printed about flu. Maybe you didn’t even believe it when we said it. Well now this surprising piece of ignorance is the subject of more conversation in the flu community:

“It is gobsmacking in a way that we’ve got to the 21st century and we still don’t properly understand how influenza is transmitted,” admits Dr. Jonathan Van Tam, an influenza expert with Britain’s Health Protection Agency.

Is flu often or even occasionally spread by clouds of aerosolized viruses, which can waft through the air and infect people metres removed from an ill person? Or is it mainly transmitted by viruses contained in sneezed and coughed mucous droplets which travel only short distances before gravity pulls them out of play?

And what of viruses that land on surfaces? A study, presented at a major influenza conference in Toronto in June, suggested flu viruses in mucus could live on bank notes for up to 17 days. But does contact with viruses found on money or bus poles or elevator buttons actually lead to infection? And if so, is it common or rare?

There are plenty of firmly held opinions on these questions but little science to back them. Better proof is badly needed, experts agree. (Helen Branswell, Canadian Press via Medbroadcast)

The problem is how to figure this out. When I was in medical school we knew how to do it. Human volunteers. Much of what we do know comes from experiments on people conducted in the 1960s and before. But for very good reasons this is much more difficult to do now. Ethics boards must approve these studies and they reluctant to do so when a healthy volunteer is given a virus that could make him extremely sick or even kill him. So we have been relying on animals studies.

But the information is critical, so researchers have been trying to think of ways around doing the most obvious things like challenge studies, where volunteers are deliberately exposed to controlled amounts influenza virus via various modes.

Dr. Robert Couch, a virologist at Baylor College of Medicine in Houston, did flu challenge studies in the 1960s and 1970s, exposing volunteers to virus-laced nasal drops.

Couch says he would not be willing to do the type of study that would be required to answer the key question about flu transmission – whether aerosolized viruses play a major role in disease spread. That would involve trying to infect volunteers with viruses that could get deep in their lungs and could cause severe disease.

On the other hand, he believes it would be ethically possible to conduct trials where healthy, susceptible volunteers are exposed to people who caught flu naturally and to trace under which circumstances influenza spreads among them.

“I think that would be the way to do the studies, but they would be very difficult,” Couch says. “Very difficult and very expensive.”

I’m not sure exactly why this avoids the ethical questions of a challenge study, however. It has a different “look and feel,” to be sure, but ethically it seems qualitatively the same. Ethics boards take a dim view on coercing people to volunteer for studies. They consider payment, especially to people who really need the money, a form of coercion. As for using prisoners, that’s been an ethical no-no for decades. Would I volunteer for such a study as a way to advance science? Maybe. But I’m not sure. I could get a normally mild case or even be asymptomatic, but this can also be a very, very nasty disease. Even if you don’t die from it (which most people don’t), it can knock you out for weeks or months. Do I need that?

So meanwhile we are telling people to wash their hands or cough into their elbows or caution them that surgical masks don’t work but N95 masks might — whatever. And we do all this without really having a firm basis for our recommendations. Most of these things won’t hurt and may be useful for other diseases like the common cold, even if they don’t work for flu (and they may well work for flu; we just don’t know).

So what we need is some clever way of getting this information. Any ideas? I warn you. It is a lot harder than it looks at first.

Comments

  1. #1 The Doctor
    July 31, 2007

    There is probably a lot more known about how influenza can be spread intentionally which is different that how it actually is transmitted naturally person-to-person. The use of influenza as a bio-weapon has been discussed and analyzed by the US military from to standpoint of its being used against that country (at the very least). The good folks at Ft. Derrick probably have considerable data on this subject but are not likely to share much of it.

    A recent blog here focused on the possibility for a universal influenza vaccine. One aspect of this that was discussed was how this vaccine could be delivered quickly and efficaciously assuming that it could be produced. This is an important consideration because IMO our best hope in preventing the coming pandemic is to establish herd immunity in at least 40% of the population in the areas around outbreak and very quickly. Many think outbreak will occur in a remote place in Africa or Asia. Even if an efficacious vaccine could be produced in sufficient quantities getting it to enough people in the path of the virus quickly enough to slow or halt it long enough to get most of the rest of the world vaccinated it is tall order. The logistics alone of keeping the vaccine refrigerated properly while delivering it the ‘last mile’ is almost insurmountable.

    One rather outlandish notion broached by a wag who occasionally lurks and posts here was that aircraft could be used to spray the vaccine over large geographic areas very quickly. To work, the pandemic vaccine would need to be either a live attenuated strain of influenza or some other live attenuated virus that carried an immunogenic flu antigen on its surface and would be capable of immunizing people exposed to it by this delivery method.

    Like the good folks at Ft. Derrick who consider these sorts of things, it is probable scientists the EU, Russia, and the PRC have similar interests. It is probable that between them, they might have a pretty good idea how to get a live virus dispersed over a large geographic area in such a fashion that it has a high probability of infecting a high percentage of the population.

    It is ironic to think that the knowledge of our friends at Ft. Doom and its sister facilities worldwide on how to use and defend from attacks of this nature might actually already include know how to ‘immunize’ large numbers of people in a very short time. What’s more it is likely they also have the technology to do so ‘on the shelve’. If this guess is true, all we would need to prevent the coming pandemic is a viral candidate that would world well for this purpose.

    Of course the other thing we would need is a miracle given the political and military sensitivity of this area of government research and progress and the likely reluctance for any of the stakeholders to be willing to share information with their outside colleagues. Yes divided we are and divided we shall fall.

    It is a nice thought though and it would probably work very well and lot more effectively than the WHO’s plan to ‘blanket the outbreak region with oseltamivir used prophylactically. Trying to do anything on the ground anywhere will be exponentially slower than from the air.

    Another virtue of this adaptation of this criminal wartime technology into a plowshare of public health would be the ability to produce the candidate virus very quickly in just a few places, possibly remarkably enough at Ft. Derrick and its sister facilities located in other countries. The combine ‘vaccine’ manufacturing capacities of these fine government agencies is probably more than adequate to rapidly whip up a few billion effective doses in a month or two after outbreak. They are likely to even have the proper packaging required for transport and special delivery. It would come as no surprise to discover that these same agencies have wonderful technology for keeping the vaccine properly refrigerated (not too cold or to hot!) that I am sure they would love to employ for the benefit of humankind rather than letting it get all moldy down in the bunker.

    I will keep my fingers crossed but won’t hold my breath.

    The Doctor

  2. #2 revere
    July 31, 2007

    The Doctor: I consider it highly unlikely flu has been much discussed or investigated as a bioweapon. It would be a very bad one with much opportunity for blowback and uncontrollable. I also doubt that broadcast spraying of live virus vaccine would be feasible, either from achieving sufficient dose or the survival of virus from photlysis and photochemical oxidants. Just my opinion, of course.

  3. #3 Tom DVM
    July 31, 2007

    What do you think of by choice, deliberate, controlled self-innoculation of communities-groups with an attenuated live virus, once the pandemic is in full flight?

  4. #4 Tom DVM
    July 31, 2007

    Sorry…obviously this approach would not be used in a mild pandemic (1957 1968)…

    …I was thinking in the case of a pandemic that was emerging with a 10% Mortality rate and a 65% attack rate or as bad or a little worse than 1918.

    Thanks.

  5. #5 M. Randolph Kruger
    July 31, 2007

    The Ruskies, ChiComs, Iraqi’s, Iranians, Norko’s, Bulgarians, Czechs, Cubans and others all tried to get into the flu market but not as an incapacitating bug but as a killer one that they would only have the vaccine for. Problems encountered was that the stuff simply was ineffective or if it did get loose, it would mutate beyond control and make a superbug.

    Revere, re: UHC the Cubans Biocen facility is still rolling hard and strong. Part of what I dont know about Cuba. There is a lot of evidence that they used prisoners for guinea pigs. We did the same but we got caught and paid for it. They just kept right on. Still do. A lot of the Mariel boatlifters were products of this and had birth defects, active diseases, and physical deformations caused by it.

    http://www.globalsecurity.org/wmd/library/news/cuba/oagmc028.htm

  6. #6 marble
    July 31, 2007

    Is it still possible to get disqualified for military service on grounds of things like bad knees, poor eyesight, etc.? In the current environment it seems like the armed services probably can’t be too picky about who they allow to enlist, but if there are enough who can’t join, maybe some would like to serve the cause of humanity by putting themselves in harm’s way via viruses instead of bombs.

  7. #7 Herman
    July 31, 2007

    Many diagnosed as having bird flu, may have had tuberculosis, since the symptoms are similar.
    There are 500,000 who have contacted multiple drug resistant tuberculosis per year, and thousands more who are ill with extreme drug resistant tuberculosis.
    If tuberculosis becomes resistant to all durgs, it could cause a pandemic. Many of those diagnosed as having Spainish Flu in the pandemic of 1918, may have had acute tuberculosis.
    If you tell me tuberculosis cannot pass H2H, I will laugh,since it is an airborne disease, and easily passes human to human.
    Bird flu only rarely infects human to human.
    Bird flu is not the threat. The threat is drug resistant tuberculosis.
    If you are preparing for a bird flu pandemic, you are fighting the wrong war.

  8. #8 Tom DVM
    July 31, 2007

    Herman.

    I certainly agree that Tuberculosis is a major problem at the moment and a real threat in the future…

    …but it is not even a fraction as infectious-transmissible as pandemic influenza…and that is what makes the threat of an H5N1 pandemic singularly unique with potential losses similar only to that of a massive asteroid.

  9. #9 ssal
    July 31, 2007

    Relative to aerosol transmission, I’ve been wondering if there might be any useful information to be mined from nursing home records. In particular, from the records of patients confined to bed in the the non-ambulatory wings of nursing homes — patients that were essentially also confined to their rooms.

    Was there a lower incidence of flu in such patients in nursing homes which provided better protection from aerosol transmission — say, by using HEPA filters in their HVAC’s or even both HEPA filters and UVC lights in their HVAC’s? For all I know, though, all the states may require HEPA filters in all nursing home HVAC’s.

    But if I ran a nursing home I think that I might supplement HEPA filter protection in HVAC’s with powerful individual room air purifiers, most models of which seem to provide both HEPA filters and internal UVC lighting. (It would seem that the managers of at least some upscale nursing homes would consider doing this.)

    Also, are there nursing homes that require their personnel to wear any sort of masks while in the presence of patients (for patient protection) during the flu season? If so, do patient records show a lower flu incidence, and does it make any difference if an N95 or ordinary surgical mask is used?

  10. #10 Alan
    July 31, 2007

    Two ideas:

    1. Rather than deliberately trying to infect, what about approaching the problem from the other side and trying various additional preventative strategies under everyday circumstances. One difficulty would be that since important factors like whether the subjects were even exposed to virus would not be controlled, the experiments would need to be on a pretty large scale to give enough data to be useful. Perhaps something like having all federal employees working in office buildings over a certain size be recruited and then randomly assign half of those buildings to be ‘mask zones’ where all employees would wear masks during the annual flu season. Students in public schools might be another population to work with. Of course lots of things in the real world would complicate this simple idea- but is an approach of this type possible?

    2. Can any of this be hinted at through epidemiological studies of how various populations in different countries deal with flu, disease, and infection? Have such studies been done? For instance, here in Japan people tend to wear a mask if they are coughing or sneezing, whether due to colds or allergies. Could comparisons in patterns of infection between Japan and the U.S. yield interesting information? Of course, again there are lots of other factors involved, like differences in tendency to go to work when feeling ill, that would complicate this. But in a world with so many different populations with distinct differences in living patterns one would think there would be some data to be found in comparisons.

    Are these already used or already discredited approaches?

  11. #11 revere
    August 1, 2007

    Alan: Both good ideas but probably not senstive enough to tease out the answers. At this point we probably have learned as much as we can from obswrvational studies and will need experimental ones (those where the researcher controls the independent variable, viral exposure).

  12. #12 anon
    August 1, 2007

    only since a few years can we follow the evolution and spread of flu by extensive sequencing , collection
    in databases and analysis. IMO this bears the potential to solve how flu spreads.
    With the viruses they should also upload the exact date of sequencing, disease onset , coordinates of location.

  13. #13 Bob, DVM
    August 1, 2007

    I agree: dwelling on how long influenza virus can remain alive in snot on banknotes is missing the target. (I sigh every time I read Charles Gerba’s research cited in USA Today: the value of repeatedly investigating the bacterial contamination levels of toilet seats and subway handrails is questionable at best. All people need to hear is “wash your hands regularly”.)

    Note to The Doctor: it’s Fort Detrick, not Derrick. And the suggestion that there’s some being-sat-upon technology there to “rapidly whip up a few billion effective doses” of influenza vaccine (and various other secret capabilities)–well, this really strains credulity.

    Marble: bad eyes, knees, and other body parts are sometimes disqualifying conditions for military service, depending on the specific problems, how bad they are and what the potential military member wants to do (e.g., pilot wannabes obviously need better vision than payroll clerks). Too many variables to answer that one concisely. Regarding the idea that “…maybe some would like to serve the cause of humanity by putting themselves in harm’s way via viruses instead of bombs”, it’s a plausible idea, but I don’t think repeating this approach today would ever pass muster (see the story of the Seventh-Day Adventists who volunteered for infectious disease research in WWII and beyond; sorry, don’t have a link for it, but it’s a well-known chapter of military history.).

  14. #14 M. Randolph Kruger
    August 1, 2007

    And Tom/Herman, we have a better chance of getting out of the way of an asteroid than we do with Panflu.

  15. #15 the Doctor
    August 3, 2007

    Revere I am pretty sure the use of flu as a bioweapon has been discussed extensively including the problem of blowback and how to prevent it by vaccination of the protagonist’s population. I have two Power Point presentations on this that were given at the US Army’s Chemical Corps Annual Worldwide Chemical Conference in June 2000 at Ft. Leonard Wood. I am not advocating the use of bioweapons in the least. However, if there is data or good research that has been done in this area that could be made good use to fight pandemic flu then I would like to see the stakeholders share it.

    One of the presentations given at the WWCC discussing the use of flu as a bioweapon specifically referenced spraying it from a low flying aircraft. This could be done at night to prevent photolysis and if sprayed from a low enough altitude would also obviate freeze damage. If the inoculate was sufficient, enough virus would survive in shaded surfaces to vaccinate quite a few folks who came into contact with it. Secondary transmission would cause others to become vaccinated.

    Bob DVM; thanks for the correction on the name of Ft. Doom. Who knows what lurks there? It is one of the country’s deepest darkest secrets. They have been active for a long time. BTW, President Roosevelt began the program during WWII and the first director with Dr. George Merck, the president of a then small pharmaceutical company. No wonder some of the first big products produced by what was to become Merck Sharp and Dome after the war were vaccines including those for influenza.

    The Doctor

  16. #16 R.S. McNall
    August 3, 2007

    Seasonal FluMist is a group of three highly attenuated live viruses. Those vaccinated have a tendency to innoculate others around them inadvertently.

    Pre-pandemic herd immunity could be safely achieved by connecting some of the surface antigens from H5N1 to FluMist, but without the lethality (or morbidity) genes. If there is herd immunity, there is, by definition, no pandemic.

    Immunity acquired by flumist innoculation is much broader and longer-lasting than immunity from shots. Even without H5 or N1 surface antigens, the broad immunity conferred by FluMist innoculation (mucosal and cellular, as well as humoral immunity) may confer some unknown degree of immunity to all other flus, including H5N1.

    A study suggested that the N1 in the seasonal H1N1 influenza A shots (or something else in those shots) confers at least some immune protection against H5N1.

    The H5 or N1 antigens from H5N1 could be added to the current seasonal Flumist, and if they were, herd immunity would begin to be acquired in the process of routine seasonal vaccination itself, and thus at very low social cost and far in advance of an actual pandemic.

  17. #17 revere
    August 3, 2007

    RSMcNall: Yes, there may be some cross subtype protection against H5N1 through N1 or other antigens. We’ve discussed it here several times. Regarding your other points, however, I am not aware of any data on FluyMist providing community immunity. This occurs with polio (Sabin) vaccine but I know of no data on live virus flu vaccine. If you have a cite I’d be interested. However remember this is a live virus, cold adapted virus. You can’t just “add H5 antigen.” You need an attentuated H5 virus and that is a totally different matter. The ethics of this is also a real question since you would be involuntarily and unknowlingly vaccinating the population, possibly with adverse effects.

  18. #18 kiwi
    August 4, 2007

    At a less lofty level for a moment re the flu…the culture of work-places seems to be,cough,hack and splutter over your colleagues until you become too ill to work.Then,having passed the virus on,you take a couple of days off.

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