Here are some questions raised in the Forum I can’t find answers to online, either at official resources like pandemicflu.gov, or through authoritative sites (like CIDRAP).
Not all these questions will have an answer (especially the last two) and there may be others I’ve left out. We’ve raised them repeatedly, and if anyone with more knowledge and expertise can answer any of them, that’d be a step forward. Especially on the last two, there’s plenty of material on the wiki (many opinions, although no one answer).
Feel free to add others. I’m going to be keeping a running list of the difficult-to-answer FAQ.
this is my seroprevalence + H5N1 search at PubMed.
The above articles appear to have looked at health care workers in Hanoi and poultry workers in Hong Kong, but afaik not the general population.
DemFromCt - Your question about official position on stockpiling Tamiflu is interesting, from what I’ve read the word put out is “No” , but then again, I don’t know if they have actually tken a stand anywhere. If people are lucky enough to have some in their personal storage, I think its a moot point for them. I wish I had some! I have looked for some on line, but feel that it is too late and that anything I could get now would be a “knock off”.
I also heard “no”. Tamiflu is apparently still available through pharmacies, but you need to have a prescription- hard to get unless you currently need it, I’m sure. Do you have a close relationship with a willing physician? Keep in mind he/she may have already been asked 1000 times or more and may be concerned about the ethics of prescribing it if it’s not needed right now. The price of Tamiflu has gone up alot in the last year- so expect it to be expensive if you can get it. Good luck!
seacoast, the stockpiling page is here. The states (well, some states) have taken positions, the feds have not. different countries have different advice.
I don’t think there is any ‘official’ position on the use of masks. The problem is that there is no evidence. I repeat, the operative phrase is ‘there is no evidence’ that masks make any difference.
I think the problem is that policy-makers want scientists to give them clear-cut answers ie make their decisions for them. Scientists are no fools (surprise surprise) and they will not provide such data simply because, well, such data does not exist. Policy-makers, aka politicians, at the moment are doing their favorite activity : when faced with difficult/embarrassing/unpopular decisions, either pretend the question does not exist (head-in-sand), or call for more data, without specifically making plans to set up studies to get such data, of course.
As one journalist recently enlightened me, “anyone can call for anything.” And perversely oftentimes the public (suckers all…well, at least some of them) shuts up and gives them another reprieve.
anon_22 – at 13:54 — “The problem is that there is no evidence.”
The problem is that there is no masks
“The problem is that there is no masks”
please define- as in, there are no masks at your store?
Pandemic is global event. Let’s assume that masks (N95) can reduce infection rate 99%. In order for global economic system to function we need people to go to work. There are billions of workers that will require billions of masks daily. We as a species can not produce that amount.
It gets worse. If a glass of clean water is a cure for pandemic, we can not provide that for 6.5 billion people.
ouch - very true. And speaks to the troubles of any nation’s effort to prepare.
N95 masks were initially recommended for health care workers caring for H5N1 patients because during the SARs epidemic there was some evidence that health care workers who used NIOSH approved masks had a lower rate of infection than those who used surgical masks. Influenza and the cornavirus that causes SARs are approximately the same size and both are thought to spread on relatively large droplets, usually. So, the initial recommendation was based on an extropulation of the SARs experience. Now that it has become apparent that there are nowhere near enough N95 masks for all health care workers, the recommendation regarding N95s is being revised. This does not appear to be because of new evidence regarding their lack of effectiveness has been presented, rather its because TPTB don’t want to tell health care workers that something that might save their lives is not available because they did not plan ahead. I include hospital administrators, especially, among TPTB.
DemFromCT: I would like to ask how many H5N1 viral sequences (whole genome or partial) do the WHO have? Why haven’t they deposited the sequences they have in GenBank? Would they be willing to adopt the Bermuda rules for sequence data given how important it is to get this information to the many scientists working on influenza who are NOT affiliated with the WHO?
Good question, and (as usual) beyond my capabilities to answer. But I’m hopeful someone will read the question and pass it on.
I wrote to some folks who passed this to the European Centre For Disease Prevention and Control (ECDC) in Stockholm. They were kind enough to send a reply.
HERE ARE THE REPLIES:
Q What kind of “testing” is done on patients in Turkey? Why are they sometimes negative when hospitalized but positive after the patient dies? What specific tests are they doing that are negative and which (RT-PCR?) are later positive? Have we seen that elsewhere outside of Turkey?
The tests that are being done in Turkey are essentially the same as those done in other parts of the world. It is not always appreciated how complicated ‘testing’ (as distinct from tests) is. Some of the steps in testing are:
For bird flu in a person who is not that ill we have to rely on testing the very surface of the patient (inside the nose, down the throat) when the virus may already be deep inside the person. That is why for one of the patients the nasal swab (not the best specimen anyway) was negative but a later specimen positive.
Also when a patient gets sicker more invasive tests become justified to get a firm diagnosis and then deeper tissue (like from the lung) can be tested and this is more likely to give a positive. Later the body may mount a response and the patient start to produce antibodies and then blood testing (called serology) comes into its own.
Finally if sadly a patient dies then an autopsy is performed which allows the pathologist to really find out what the patient had. Sometimes it is only then that a diagnosis is made.
Q Are there seroprevalence studies being done in SE Asia or Turkey to see how many people have mild illness? Why haven’t they been published if they exist? Why haven’t they been done if they don’t exist?
Seroprevalence studies are studies testing body fluids (usually blood but sometimes saliva) for antibodies that show a person has been infected in the past with a specific microorganism.
There is some published data. See Table 2 of the article in the New England Journal of Medicine – Sept 29th 2005 available at this link This found no evidence of mild infection among close contacts of cases of human H5N1 infection. It is unfortunate that there have not been any seroprevalence studies published from SE Asia as yet.
Also seroprevalence studies are not easy to do as unless they use ‘unlinked anonymous testing’ (e.g. link) they are difficult to do as researchers are asking well people to give blood. There are also often ‘political’ problems as the research will show the level of infection (usually an important one) in the population, hence it can be hard to get official permission to do the work and difficult to get permission to publish.
[editor’s note: see also link]
Q Do most virologists accept that recombination is necessary for a pandemic? Does a lack of acceptance affect pandemic likelihood predictions? The CDC FAQ, for example, implies reassortment is necessary for H2H, but the 1918 studies suggest otherwise.
The questioner is right. Though reassortment (two different influenza genes swopping genetic material to produce a novel virus) is one way that a pandemic virus might emerge it could also theoretically happen by genetic drift (the process of spontaneous mutation). Its probably incorrect to say that the 1918–19 pandemic virus emerged by recombination or drift – we simply do not know enough about what happened. See this link.
My deepest appreciation to the scientists and doctors who answered these questions. An informed public is a prepared public. It is my own opinion that field work such as is described above is underappreciated in terms of difficulty. Kudos to those who leave their homes to get it done.
Thanks for taking time to answer, ECDC.
Good luck in all your work.
(I wish it was easier to get seroprevalence studies, and places weren’t afraid of the truth. Playing politics isn’t going to stop a pandemic, but it could help a pandemic escape.)
Thanks DemFromCT for getting this information. It’s very helpful. And thanks to the ECDC for taking the time to answer your questions.
Monotreme, I put a Q&A link to this on the seroprevalence page you built.
DemFromCT: Good idea.
the ECDC-webpage is here: http://www.ecdc.eu.int/
Dem - perhaps it’s just having read too many carefully lwayer worded pieces of correspondence in my life, but I would like to take note of the wording of the reply to the question regarding Seroprevalence.
The questions was Are there sudies being done? and Why haven’t they been published? and Why aren’t they being done?
The answers you received are:
I will assume that one of two tactics are being employed by whomever answered the questions. The first is a non-answer that sounds alot like an answer. Most politically trained and astute individuals can pull this off. He has told you factual information which applies peripherally to the subject at hand, but doesn’t really give anything away. the second option is that by structurng the answer this way, the individual is telling you that such data exists, and that there are politically mandated gag orders in place.
Either way, the answer to the seroprevalence question does nothing to calm me and does much to increase my personal level of angst. This is because the person who answered the question did so in a fashion which strongly suggests to me that more information exists than has been released, and that it is a matter of someone’s policy that things run that way.
From an old Zen Koan: “Those speak do not know, and those who know do not speak”.
Eccles: I agree that the answers were phrased in diplomatese, but I think they relatively straight-forward to translate.
ECDC: “This found no evidence of mild infection among close contacts of cases of human H5N1 infection. It is unfortunate that there have not been any seroprevalence studies published from SE Asia as yet.”
What more do we need? Mulitple authoritative sources, Osterholm, Osterhaus, Taubenberger and now the ECDC have told us the same thing. No mild cases. Seroprevalence studies have been done in SE Asia, but not published. The virus is highly lethal. Case closed.
DemFromCt, having just read the link you provided on the last “question” made me feel even more uneasy. This most probably is not an event like 1918. It will be unique in its own way. I was not assured.
Just an addition to your discussion of recombination. There are really (t least) three mechanisms that people tallk about producing genetic variation in influenza: reassortment, random mutation and recombination. The influenza virus is unusual in that its genetic material is divided into segments, something akin to chromosomes in higher forms. Six of the segments code for single genes (viral proteins) while two code for two genes each. There may be an additional gene as well, so there are either ten or eleven viral genes.
Reassortment involves exhange of whole segments. It used to be thought this was necessary for a pandemic and gave rise to the notion of genetic shift, i.e., a genetic change so large that the virus appeared to “new” to the immune system. It now appears, however, that random changes in individual amino acides, perhaps caused by lack of faithful reproduction in the flu virus, can produce alterations that have large biological consequences. Many believe this is what happened in 1918 when a bird virus went to humans, and what is happening, step by step with H5N1 (e.g., the three Turkish virus mutations recently isolated)
Then there is recombination. This is where pieces of individual genes swap places. There are two kinds, homologous and non-homologous. In homoogous recombination, two different viruses that are co-infecting a cell exhange bits of genetic material in the same regions. Thus a section of the HA gene from a bird virus could exchange material with the corresponding section of the HA gene of a human virus. Henry Niman and the Gibbs’s in Australia have championed the idea that recombination is the major driver of genetic variation in flu virus. Non-homologous recombination involves the exchange of genetic pieces from entirely different genes, and can happen either with two different viruses or different genes of the same virus. It has been clearly established that this can turn a low pathogenic avian flu virus into a high pathogenic one, although it wasn’t an H5 virus as I recall.
In answer to Dem’s question, most flu virologists have discounted recombination as a major mechanism (they admit it happens but it is of minor importance). But they were wrong about reassortment being necessary for emergence of a pandemic strain and they may be wrong about this as well. If it comes down to the question of whether the final mutational nail in the pandemic coffin will come from random mutation or recombination it isn’t clear to me why I should care (except if that is my area of scientific expertise), i.e., what its practical significance is. Perhaps others would like to weigh in on that.
Medical Maven,
There is very little information which reassures. There is very little data. We prepare in the face of our best guesses.
If I were assured, I’d close down Flu Wiki. We’re still open for business, and we have work to do. But check out how local governments are responding. This is what’s needed at every level.
OTOH, hysteria and panic need not apply.
revere, thanks for rephrasing what i’ve not been able to articulate very well. The reason i asked the question (besides finding some experts talking about recombination and others never metioning the word) is I want to know if a lack of acceptance of three mechanisms changes the view of the likelihood of pandemic. For example, peter palese ( a real expert) has said in different venues that if it hasn’t happened already, why should it happen now? the virus has been around since 1997 Hong Kong. but such a view, imho, assumes reassortment is the driver. and, as you and ECDC points out, we really don’t know it can’t happen other ways. The CDC FAQ strongly implies you need reassortment for a pandemic. maybe you don’t.
And for those who read Henry Niman regularly, it’s helpful in interpreting him to know that recombination as the driver of viral evolution is not universally accepted, though it is seen as a possible contributor.
why can’t this be figured out with computer simulations ? We should have enough sequences already to decide how likely mutation,reassortment,recombination leads to new viruses and then just continue that experiment and see what future might bring…
Ah, gs, did you never dissect a frog in Gymnasium? The most sophisticated supercomputer in the world cannot model the function of one cell. The DOE hopes to be able to do this in 10 years. Virus host interactions are extremely complex. We have only a primivitive understanding of general mechanisms that may be involved. Even if we had a computer powerful enough, we would not know what algorithms to implement.
Dem,
It’s anecdotal, but points out the logical fallacy in Palese’s arguement: if I were standing on St. Charles St. in New Orleans on August 28 and said, “It never happened here before,” that wouldn’t be much of an argument in favor of yawning and turning over.
MASKS: At the very least they keep someone from putting a finger in the nose. If there is evidence that a finger to the nose can result in transmission then there is evidence that masks help. That has been proven, I believe, as a route whereby flu can be contracted. Why else the emphasis on hand washing? Masks MUST therefore provide that degree of protection. If accompanied with goggles that precludes those 2 possibilities from being effective routes. Where is the flaw in that logic? I don’t understand the debate about masks, eye protectopn if what I have said is true. Of course both would help otherwise the hand washing advice is bogus.
NW,
The handwashing advice is longstanding medical “best practice.” From the days of Semmelweiss, it works, it gets rid of the stuff on your hands that gets in your eyes and nose. All it needs is soap and warm water.
Actually, i don’t either. Surgical masks or a bandana (FLU WIKI bandana as a fashion statement) is better than nothing but not as good as an N95 which is not as good as an N100 or its euro equivalent. But are we protecting them or us?
“But are we protecting them or us?” If we are protecting “them” that is a good thing to because we are the other person’s “them” :)
You got it. It’s a community approach and a community benefit to wear a mask. Not now. You’d be looked at sideways and likely be made very uncomfortable, but the time may come when it’s the other way around.
>It’s anecdotal, but points out the logical fallacy in Palese’s arguement: >if I were standing on St. Charles St. in New Orleans on August 28 and >said, “It never happened here before,” that wouldn’t be much of an >argument in favor of yawning and turning over.
no fallacy in Palese’s argument. Your example-scenario is nonrandom.
My impression from Taubenberger’s presentation of the 1918 virus and its implication for the current outbreak is that he tends to think of (don’t want to use the word favor) recombination as the likely explanation for the 1918 virus. And because of the many similarities in behavior etc between the 1918 virus and H5N1, that is the mechanism to watch out for. This is not an exact reprodution of his position but just my take on it, but I think it is more ‘not reassortment’ than ‘has to be recombination’. In addition, he strikes me as a very unpretentious guy (for someone so famous) and doesn’t hesitate to say ‘I don’t know’ when that is truely the case.
masks: it is proven that flu spreads by droplet nuclei and droplet. It is proven that masks filter these. So it _should_ work. Heck, can’t they just test this ?
I suppose, but no one cared before now. You need to stay 3 feet away from people… that’s how far droplets go. That they know. The SARS experience led to some nice write-ups on masks, but it’s unclear for lay public not caring for ill people.
The social distancing cautions my group is working on right now says six feet for a “red zone” and ten feet for a “yellow zone.” I’m skeptical but willing to hear what others think.
anon_22: My impression is that Taubenberger favors random mutation with selective pressure, not recombination. Regarding gs’s question, it is not so easy to determine whether a genetic change is a recombination or not (Henry may have a different view, as his company is making proprietary software for predicting where flu sequences are going and it depends on recombination as a mechanism—at least as far as I understand it; a problem is that Henry doesn’t publish his stuff, so it is impossible to judge the validity—or the significance—of his contentions).
The number of differences between avian and the 1918 pandemic strain weren’t large and didn’t seem to be reassortment. IMO random mutation can easily explain it, although some years ago Gibbs proposed recombination as the mechanism (as I recall it was with a swine virus).
What isn’t clear to me is the practical significance of the difference between drift and recombination. The reassortment issue is another matter, as if this is the sole requirement then it is easy to see when it has happened (which is not yet) and it requires co-infection with bird and human viruses. We used to think that the latter required an intermediate host like the pig, but we now know this isn’t the case; humans can be co-infected with H3N2 and H5N1 because we have receptors for both in our respiratory tract (I covered the science of this on Effect Measure last week.
Masks: this is a question of mode of transmission. Three possibilities here: fomites (inanimate objects); large droplet transmission, which fall out of the air quickly but are a danger to those in the immediate vicinity of a cougher, sneezer or speaker; once fallen and deposited on a surface the question is how infective they are—i.e., the first mode of transmission0; and third, small droplets or nuclei. These pass easily through surgical masks and probably also N95s and N100s. In dry air, large droplets quickly become small ones by evaporation of the water. It has not been established that this form of transmission is important in influenza. The only agreement seems to be about large droplets. Even inanimate transmission has not been shown conclusively to occur (I think there is one paper that strongly suggests it but that’s all). It is a more complicated subject than would appear. Some data suggests that the viral particles remain replicable for considerable periods of time in feces, water and on hard surfaces, but paradoxically, only about 5 mnutes on human hands. Whether this is the general rule or not I don’t know.
The surprising thing is how little is known about flu transmission in the real world. And while masks probably don’t hurt (there is the question of cleaning them, etc., but that aside), if they don’t do any real good then they are an enormous expense and a practical and psychological hindrance. Remember that you can be infected through the eye (the conjunctivae or delicate tissue covering your eye which has sialic acid receptors of the α2, 6 variety) so in theory you are talking about a full face filtering respirator. I’m sorry, but this just isn’t practical for 24/7 use and might be dangerous because it restricts your vision and hearing (the sound of your breathing through the mask).
I don’t have masks and don’t intend to get them. But that’s just me.
thanks, again, revere. The above summary is why there were still questions. Not everything has an anwer.
Melanie – at 12:47
“The social distancing cautions my group is working on right now says six feet for a “red zone” and ten feet for a “yellow zone.” I’m skeptical but willing to hear what others think.”
More risk communication drift?
Typifies the need for some competent authority to maintain and keep public a concise approved solution. Last night I read a post about how viruses compete for living surfaces. It said, in effect, that wasted energy selectes for other stains. Fractal to our situation, imo.
dubina, that’s exactly why groups that don’t have consensus don’t usually talk at all. Yet we complain when WHO or CDC take that approach. So do I… I prefer transparency. But you really can’t have it both ways. It’ll result in nothing said until a definitive answer is rehearsed and vetted.
Sometimes, that’s a better approach (see the W VA coal mine disaster wherein first there were survivors, then there weren’t). sometime’s it’s not. And knowing the difference is very difficult.
revere, “What isn’t clear to me is the practical significance of the difference between drift and recombination. “ I agree, and I’m not sure that Taubenberger placed a lot of importance on the difference either. As I said, it was more like ‘not reassortment’ than actively stating whether it was recombination or drift.
Like you, I don’t see what is the point of the big fight about whether it is recombination or antigen drift. I’m sure there must be a point technically but it beats me whether that makes a difference to how the virus is going to behave or whether or when we are getting closer to a pandemic.
Hi Revere I think you should consider getting a rubber dust mask with exhale valves and goggles. Why?- because it sends a clear signal that you are not to be approached. The mask and goggles make us look alien. We don’t mention it much- except in regard to firearms- but no matter how meticulous our own behavior is- it can all be undone in a moment by an Andrew Weil who “refuses to give in to fear” and insists on hugging us or kissing us. If this flu arrives- people are going to confront it in a million different ways- most of which have not been discussed or considered on this wiki. You will be amazed by the dumb-assed behavior of a few of our friends, neighbors and family in the middle of a catastrophic flu. You won’t be able to shoot them!
clark: Well it is certainly a social distancing manuever. No doubt about that. I don’t know how seriously you wanted to make your point but it certainly is true that people will keep their distance. But the risk of dying in the 1918 flue was probably less than 1% (say 40% infected and 2% mortality) so I’m not sure I want to have the kind of soical effect we would cause by all of us walking around with full face masks. Of couse there aren’t enough masks to go around nor could most people afford it. Plus wearing it 24/7? No thanks.
anan_22:
I have only the most rudimentary understanding of this. It’s easy enough to see the potential consequences of reassortment; entire segments of RNA get swapped, so one virus has an opportunity benefit from something that already worked for another; saves the virus the trouble of hacking a favorable change one SNP at a time (to indulge a bit of teleology). Recombination then, I take to be something analogous to that, but at a higher ‘resolution’. For this to happen with any consistency would seem to me to require some mechanism; Niman’s “rules” (the “copy choice” method). This is mysterious to me; something like HOX genes in higher organisms is the closest I can come to grasping it at present. As for the significance, once it is accepted that such a mechanism exists (and I assume this is where the controversy lives) it’s really the same as with reassortment; instead of a long uphill grind, you get the sudden emergence of a new virus — so it would have a big impact on the amount of time likely to be involved before the virus aquires the changes needed to produce a pandemic.
Re “modes of appearance of a new virus”:
From a layman’s point of view, the change is either abrupt or slow or in noticeable steps. Which is which? How do we know? What must we (as a species) look for?
“I’m not sure I want to have the kind of social effect we would cause by all of us walking around with full face masks.”
I guess it depends on mortality. What would the effect be, after a few days? People travel touristically to places where women use burkas - culture shock to them? Sure, but they manage. “New normal” or at least “new accepted”.
While I’m here, in the subject of “masks” vs “no masks”, there may be other solutions, such as http://www.buff.es/
You just pull it up or down when entering a supermarket.
So it’s not 24/7 either.
And if eyes are exposed, then at least part of the exposure is avoided. R-naught should/might diminish. I hope.
Racter, I was talking about whether there is any need to distinguish between recombination and antigen drift, not recombination and reassortment.
Understood. If no such distinction is justified, any instances of recombination would essentially be flukes (secondary consequences of some particular instance of drift) and therefore of little significance in the long run. My take is that Niman (primarily) posits that such a distinction not only exists, but is at least as important as reassortment. I was using reassortment as sort of a metaphor for whatever mysterious mechanism would facilitate that.
The reason that Dr. Niman makes a big deal about recombination vs random mutation is that he believes that if one examines the existing sequences one can predict which recombinants are likely to result in a pandemic. Thus, with certain technologies, one could produce an effective vaccine prior to pandemic onset. He does after all, have a business.
Monotreme, that sounds good in theory, and I have a lot of respect for Niman’s work especially on gene sequences and now the clusters. But its a bit far-fetched to me how such predictions can be trusted to be accurate enough for policy purposes. I just don’t think that he has proven his case that this is a credible method on which to base such enormously important decisions.
So there is a mask shortage. In cold climates won’t an electric space heater fry viruses?
anon_22: I’m agnostic about recombination vs random mutation. Its all really a matter of statistics and data. Which is why Niman wants the sequences so bad. I hope he publishes his work at some point. At that time I’ll read it with great interest.
The idea of predicting what a lethal strain might look like in advance is interesting, although I don’t know how feasible. Looking at 1918 sequences might be more useful. In this paper some of the polymorphisms in polymerase genes that may be important in the adaptation of an avian virus to a human host.
A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.
Some vaccine technologies would permit the production of a “library” of potential vaccines. Thus, if the authors are correct, one could anticipate a range of possible epitope targets and be prepared in advance.
The problem with the recombination versus drift argument is that it is not just a matter of how “far apart” the sequences would be on the gene end but also on the phenotype end. Very tiny steps on the gene end, such as might occur with random mutation, are known to cause big changes on the biology side. We don’t have very good ways to predict that right now, but making recombination the driving for force doesn’t guarantee our ability to do that nor does random mutation prevent it. There have been some more or less successful attempts to predict where influenza virus evolution is going (e.g., there is a paper in <i>Science</i> by Robin Bush et al. in 1999 that does this for H3N2).
My bottom line here is that recombination versus random mutation has no obvious practical consequences at the moment. Perhaps if there is a successful way to predict viral evolution, one or the other of these propositions about the effective driving force of genetic variation will turn out to be the tool we need. But we aren’t there yet so I remain agnostic on the subject and only mildly interested in it. There are a lot of other scientific issues higher on my list at the moment (e.g., what is the main mode of transmission; is there a co-receptor for the virus; what restricts host range; etc.).
That’s just what I had in mind when I recommended Folding@Home to gs in response to one of his requests to see probabilities modelled in simulation.
Re: ECDC Reply to DemFromCT …”seroprevalence studies are not easy to do as unless they use ‘unlinked anonymous testing’ (e.g. link) they are difficult to do as researchers are asking well people to give blood. There are also often ‘political’ problems as the research will show the level of infection (usually an important one) in the population, hence it can be hard to get official permission to do the work and difficult to get permission to publish.
My responses:
1) Getting well people to submit to blood-testing in non-developed countries is not difficult, if they are given a small payment for their efforts. e.g. — for a relatively small bribe — $1 per patient — it would cost all of $40,000 in “bribe payments” to get 40,000 samples — which would result in 10x the seroprevalence data we have now.
2) The “political problems” clearly are more challenging. However, using a “carrot “-- such as money for public health, expertise and funds for pandemic planning, donation of tamiflu stockpiles, etc. could convince recalcitrant countries.
3) “Difficult getting permission to publish?” I’m sorry, once the data has been collected, you don’t need anyone’s permission to publish the analysis of such data. Is the ECDC seriously suggesting that censorship has occurred?
Bottom line, I have a hard time accepting the ECDC response that “seroprevalence studies are not easy to do” as an excuse for the lack of such studies. I have a harder time believing that WHO, ECDC and others haven’t used the “political” methodology suggested above to get better cooperation from affected countries in order to perform extensive seroprevalence testing. These guys (WHO, ECDC, etc.) are experts at surmounting obstacles like these.
So what is going on?!!!
These studies are urgently needed now and on an ongoing basis in the future. Maybe FluWikie users need to prod more!
These 3 r’s: random mutation, recombination and reassortment…Can’t they be going on in the variety of birds or other types of animals who could be infected with the virus? Every different “host” could offer the opportunity for the evolution of the virus. No?
Just less likely. Why should h2h-viruses be favoured in birdcell-mutations-evolution ? But why do we need life at all ? Let’s run the computer-simulations instead. Some reassortment,recombination,drift,random mutation, the exact amount of these will be adapted to the quality how the result matches with reality.We can ignore in first approximation how these proteins fold in 3d
That’s like saying “we can play around with random arrangements of letters, ignoring whether the results approximate meaningful passages in any known language”.
How long are RNA chains? Just to be able to imagine the power needed at the folding@home thing. We can make the “invitation to join folding@home” quite viral.
“eight negative-stranded RNA segments ranging from 2341 to 890 nucleotides in length for a total of about 13,588 nucleotides depending on the subtype”
The whole idea behind Folding@Home is distributed computing; as with Seti@Home, it emulates a supercomputer by having participants download software that utilizes idle time on their systems to process data (sort of like a trojan, only not malicious), the goal being: “To understand protein folding, misfolding, and related diseases”.
supercomputing is not so important IMO for simulating mutations. You only get slightly better data/results. I was searching google for recombination,reassortment,h5n1,simulation but found nothing useful. But I feel, that some people should be working on this somewhere…
Eccles: you think they know about unpublished seroprevalence studies from Asia ? If they know about this, others should too…
Again, that’s like saying you don’t need a supercomputer to generate random characters; the real challenge is in arranging those characters in a meaningful way. I’ve seen some interesting attempts at computer programs that generate prose, even some demented but amusing short stories. If you understand that challenge, you should understand the challenge in trying to predict what a virus will do. The protein folding is where the nucleotide sequences become ‘meaningful’ at the level of biological organisms.
You’re right that massive computing power doesn’t automatically lead to solutions. But it’s a start.
Its not just the virus that’s important. Any virologist will tell you that its impossible to talk about the lethality or infectiousness of a virus without also talking about the host. Most viruses are well-adpated to one species and utterly harmless to all other species. H5N1 is unique in that it can infect and kill a wide range of hosts. Still, the important thing to model is virus-host interactions, not just viral sequences. And these are very complex. We will not get the rules from simulation, sorry. I should point out that there are some experimentalists who are trying to figure out the rules empirically. They are generating H5N1 variants and testing to determine which variants, if any, could generate pandemic strains. Some experts think we will have the rules in a few years. Maybe we’ll be lucky and the pandemic won’t happen until after we’ve figured out the rules.
monotreme: any idea how to find something about this “empirically rules figuring” ? Some keywords to type into google, some names ?
Another quotable quote from the Nature Medicine article I linked above: “chance favors the prepared mind.”
I think I may have thrown this link at you before. Receptor Binding Specificities If nothing else, perusal of that article should serve to help you to better appreciate the depth of the waters here.
“A number of HA receptor binding studies have been reported previously, but these have primarily employed cell-based assays to probe sialic acid specificities among different influenza viruses. Such assays involve enzymatic removal of endogenous sialic acid from red blood cells using sialidases, followed by resialylation with linkage-specific sialyltransferases. While such assays approximate the natural binding of a virus to the host cell receptors, the results are subject to variation based on the quality of the cell preparations and degree of enzymatic modification, both of which are difficult to control. Use of whole viruses also introduces the uncertain effects of the viral neuraminidase on the binding assays. In other studies, competitive binding of viruses to synthetic natural analogs was analyzed, but again whole viruses were used here; we used recombinant HA protein as a probe to circumvent these problems.”
gs: Drs. Cox (CDC) and Osterhaus (Netherlands) are doing this work.
Now I’ve got one. From [[http://effectmeasure.blogspot.com/2006/01/background-science-for-turkish_19.html]|Effect Measure]
“It is still a bit unclear which cells in the respiratory tract have which surface markers, but it appears that the ciliated cells in the upper respiratory tract have a-2, 3 and the non-ciliated cells have a-2, 6.”
What the heck’s the holdup on that?
“What’s the official position on tamiflu personal stockpiling?”
I’d bet that the official (private) postion of most offficials is that they already have their personal and family stash of Tamiflu.
Ever wondered if the early announcements about Amantadine being ineffective against H5N1 (and the recent announcement that it’s no good against seasonal flu either) were just decoy maneuvers intended to divert attention toward Tamiflu, which they really knew wouldn’t be effective, so as to facilitate smoother distribution of the genuinely effective drug to the key people? Hey, you never know.
Who knows, but I’ve read and watched several articles/interviews, etc. with doctors who said they already had their supply of Tamiflu for their families. You know any politician or executive in an influencial position, and in the know, has done the same.
Could we model preparedness? How do we become alert, informed, willing to do something, and actually doing something? How do we influence each other? Who are better at getting others to act? In different countries and so on?
I’m more worried about us than about the virus. Well, not really. Or maybe. Dunno.
Lugon has been one of the more creative people here since the beginning. For newbies, don’t dismiss his questions just because there are no answers. We all have questions we don’t have answers to.
I am convinced many officials do not stockpile tamiflu and do not see the need. That doesn’t cover everyone. The tamiflu stockpiling page is here. Add or suggest additions.
re: lugon’s “Could we model preparedness? How do we become alert, informed, willing to do something, and actually doing something? How do we influence each other?”
This is the key question of our time. If the information gleaned from fluwikie and other sites is not taken off-site and acted upon locally, than these sites were just informational for US.
Tonight, in my township-Winslow Township NJ- there is a township meeting open to the public at 1900. Someone (?) from the public is going to ask the committee this: A request to form a Core Work Group for the purpose of fact-finding: how can the township prepare for, control and cope with an event causing mass casualties, including an influenza pandemic. Information on the initial results of the 2005 Tuft’s Hospital table-top exercise on pandemic flu and the latest info from the CIDRAP updated avian/pandemic overview will be made available to the mayor and committee.
Things have to move forward. It’s an experiment in managing,and saving, our own lives.
CIDRAP’s overview 1/23/06:http://tinyurl.com/9z763
Well, thanks, glad to be part of this team :), and there are “some clues to parts of tiny answers” to the questions above.
It may be a matter of looking at what has changed in real life and then look retrospectively at the chain of events that occurred before. We can look at ourselves - what got us here? And also look at other things that have happened already. After that, either do more of the same or try something different. I guess this calls for another thread, but let’s just chew it around for some time.
We may also want to look at the variety of people involved, try to cluster or sample them, and then try and be objective regarding what they really think. Not what they should think, but what they do think. Then, find ways to aproach them. Just like when someone on some other thread found it useful to talk about the Bible as an acceptable entry point for conversation with her older relative.
We should start meeting through IRC so that there’s less noise and more interaction. http://www.fluwikie.com/index.php?n=Forum.IrcChat
Has someone tried Open Space about flu? http://www.fluwikie.com/index.php?n=Forum.UseOfOpenSpaceTechnology
Dem, “What’s the official position on tamiflu personal stockpiling?”
From the U of Michigan symposium: It is not ethical for doctors to prescribe unless someone is currently suffering from seasonal flu.
“From the U of Michigan symposium: It is not ethical for doctors to prescribe unless someone is currently suffering from seasonal flu.”
I think a valid case can be made for the ethics of both points of view; hence, a dilemma. However, anyone with their own personal stockpile of Tamiflu who says this is completely unethical themselves.
MASKS? Lets bypass a double-blinded study on the subject and use some common sense. Crouched in your foxhole, a mortar shell can drop right in there with you and turn you to forensic evidence. Maybe a grenade. But standing up and waving would be really stupid. A flack jacket and helmet will probably afford you some protection, but that round right between the eyes will be the last thing going through your mind. I won’t ask for a guarantee that I won’t get sick caring for victims, but having reasonable protection I will demand, even if it’s just a theory.
You want a guarantee, buy a Craftsman wrench.
Me :)
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