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A Severe Pandemic is Likely, Part 6
In reviewing the US State Plans, I have come to the conclusion that there are many, including public health officials, who are apparently unaware of the facts pertaining to the risk of a severe pandemic. Since planning is heavily dependent on the assumptions made, it’s important that decision-makers, which includes the general public, understand why a severe pandemic is likely.
Definitions
I am defining a severe pandemic as a case fatality rate of at least 2%. I use the term very severe to mean a case fatality rate of at least 5%. I am only referring to virus, not to effect of the pandemic on society. I believe it is possible for society to survive a very severe pandemic, if adequate planning is done.
Clusters are becoming more frequent and larger.
Although we don’t know what the kill rate of a pandemic strain of H5N1 will be, there is no reason to think that it will be less than the 1918 pandemic strain and many reasons to think that it will be worse, much worse. Historical arguments are non-scientific and ignore basic virology. Risk assessments of the likely severity of an H5N1 pandemic should be based on the very substantial data that has been collected on this virus and not based on what has happened in previous pandemics with different viruses.
Given the available facts, failing to prepare for a severe pandemic is irresponsible and likely to result in the deaths of hundreds of millions of people.
Additional References
Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam
The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host
Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus
Monotreme - I can no longer remember which thread we discussed this on, but I finally got a reply from the DOE. I was routed to their website (which of course I had already reviewed and that is how you got Jacqueline Flood’s email address). But I do have a new contact name, Napoleon.Avery@hq.doe.gov, I emailed him back and have gotten a prompt and courteous reply. According to him, the DOE does indeed have a plan and they are working with the states for them to develop their own plans. He also suggested that I contact my local energy provider, which I did some time ago. He said that Ms. Flood is working with the Office of Environment, Safety and Health on plans to ensure safety of employees and is not doing pandemic planning overall for the DOE. Anyway, not much new news, but at least I got a response and again, he seemed very helpful, so maybe he would be willing to answer more technical questions from those who actually know what they are talking about;-)
WIT
This is from anon −451′s post last night — I was thinking about it all night but couldn’t get on again to post my question, maybe someone here can answer:
“I have been giving the numbers that I have worked out some additional thought, and I have run some additional numbers. What I have found is that an individual who remains infectious for 3 days and has an R0 of 0.9275, then a Pandemic with the possible world wide infection would happen. At 0.9 then the spread of infection would start to collapse at 154 cases. At 0.75 it would start the collapse at 5 cases. (What we saw in the Karo Cluster). “ (Anon_451)
Anon_451 — I realize you are just making guesses here. But I see you have assumed that an individual will remain infectious for 3 days. What about — what would happen if the indivuals infected were AIDS patients or otherwise immune-compromised? I recall reading somewhere that there was a concern that such patients, if also infected with another virus, would or could shed the virus i.e. be more infectious for a longer period of time. I believe that many countries in Africa in particular have great numbers of their population suffering from AIDS and I am wondering what would heppen in those countries with regard to a pandemic virus. Any thoughts, anyone?
Arg, so sorry, bump was me, average concerned mom
Hi Average Concerned Mom.
In biological systems (including pathogens and a populations response to them) we are talking about the average or the mean…
…if you remember Karo, they were talking about a ‘super-shedder’ being the cause of the cluster…
…the same thing happened with SARS in the Hong Kong elevator…one super-shedder (the doctor from Guandong) basically infected the rest of the world…so to speak.
If a person has aids or other immuno-compromising diseases, they would most likely die in short order…
…the super-shedder of carrier will come from the most unlikely sources…a doctor, a nurse, your postal delivery person etc…and they may not actually get sick themselves.
Hope that helps…just remember…nature is regularly irregular. /:0)
Average Concerned Mom – at 10:18 What Tom Said. Remember I took this as a pure math problem to find the points of collapse and the points of spread.
As I have said mother nature hates math and does what she wants.
The virables of AIDS, Super Shedder’s and others was not taken into consideration. Just numbers.
Listen more to the HCW’s on the site for the information you are looking for and then look at the numbers. You then will also understand why NO ONE can call this.
(I will save you spot by the river but you have to bring your own RWFK <Grin>)
Anon 451.
I’m there…
…and by the way…people like me also sometimes forget that nature is regular as well as irregular…
…I sometimes spend so much time out on the fringe, looking for the exception…that I forget there is a mean.
Thanks for the reminder. The numbers are important too.
Everytime I look at the Indonesian map—I think mosquitoes not chickens. Look at the maps and remember mosquitoes stay close to where they’re born unless they get transported somehow. Mosquitoes bite ducks and chickens,something unseen happens inside the skeeter, and then bite zero patient who incubates it and passess to others. I know this has been shot down numerous times, but skeeters have passed many plagues in the past. If viri are changing and adapting, why can’t the same be said for mosquitoes? Of course not all possible mammmals have been ruled out, but that map reminds me of the old yellow fever maps as does the incubation times between cases. Everyone go look at that map and tell me you don’t think mosquitoes. Is there a mosquito expert in the house? Or TomDVM?
Leo7-Don’t add to my nightmares. “Windblown” virus is bad enough. Skeeters delivering panflu would be the deathknell.
Leo7 -
Why not just consider flies? They have been shown to be infected.
JV:
The incubation times of mosquito transmissions fit better because the skeeter has been known to make changes to the virus,(in 1900 they used to say it ripened)but I will buy into flies. That map screams some sort of flying is involved in transmission that goes beyond just being in a wild bird fly over path. Ever since that map got posted I’ve bitten my tongue. Once they were clued in to mosquito vectors in yellow fever they would map out the residences of infection. Our map shows villages, but if there is a street house map it would be clearer, maybe Indo does it and keeps it private. But as our map stands it shouts “take a longer look at skeeters as incubators.”
MM: I know, but you’ve read the other threads—the sequences are strange. It also explains the family connection as much as the genetic one. It just might be in only one breed, which would not deliver the deathknell as you put it.
Leo7-I am sure I have antibodies for West Nile virus as do most of us now. I even have an inkling as to when I was exposed because of a several day bout of strange flu-like symptoms in the middle of July a couple of years ago. I had a headache which I never get, period.
I would just as soon be dead if I had to cover myself in Deet and netting every time I went outdoors for several years. There are some things I just won’t do. And that would be one of them.
MM:
You know I haven’t google this, but no one has ever explained to me the biological need for mosquitoes. Why do the exist? There are many types of mosquitoes and some are associated with disease like yellow fever. We search for mammalian mixing vessels, while true the search has been weak, mosquitoes can’t be argued out totally. In Yellow fever the skeeter would feed off the blood of someone with the disease. It couldn’t transmit infection to another person for at least 3 days, because inside the mosquito it incubated the virus. After 3 days it was considered infected and could and did bite at will, usually those in the house, those around the house, and those that visited the house. The YF studies proved that mosquitoes could convey the disease with one bite as easily as many bites. Mosquitoes can live up to 60 days. But you didn’t get YF through respiratory. But maybe the mosquito can keep a virus alive in this slow process until a mutation is reached inside the human mixing vessel and the RO goes greater than 1. Ergo, the purpose of a mosquito is to incubate disease.
I just came in from a run and during stretching I got bit—this is a huge mosquito season on the GC because of Kat. Anyway, I agree I probably have been exposed to WN. I admit I’m way off base until I see the map. Again, a street map marking infection house to house would totally rule this wild theory in or out. Unfortunately, we can’t to that from the US.
Leo7 at 12:43-“Ergo, the purpose of a mosquito is to incubate disease”.
Love that theory! The Skeeter-God’s little grim reaper, doing what is good for us in the long, long run-leveling the playing field and pushing evolutionary change.
Monotreme & anon_22: Can we categorically say that the mutations in Indonesia are not occurring specifically within the individual humans that have acquired H5N1 B2H – not within some large but unknown body of humans with low level infections - but that the mutation cannot be happening within the humans that acquire H5N1 B2H and in real time?
The chart that Revere highlighted at Effect Measure http://tinyurl.com/ has stuck in my mind. Using laymen’s terms, it looks as if H5N1 is a pitcher, winding up and letting loose a fastball each time we see a spike on that graph. If it is pitching directly from the chickens, it only makes sense that we would see more clusters simply due to the saturation of H5N1 in Indonesia. If H5N1’s job is to pitch to humans until it “sticks,” it has more opportunities to do so there than in other places that we are aware of. Why does it need an intermediate host? Can’t it keep pitching directly from birds to humans until it finally gets the job done (i.e. homerun)? If theoretically the mutations can occur in any host, can’t they occur right in the human host? Why couldn’t H5N1: - be pitching a brand new game every time it attempts human infection - achieve success due to 2.6 receptors in some genetically susceptible humans - with PB2 627 have no problem with the human host temperature - dead end because while the mutation happened in the host, the mechanisms leading to full efficiency are still not fully achieved (at the moment)
While an intermediate mammalian host is a possiblility, and a cross-species viral swapmeet is also possible, here are some of the posts in Monotreme’s “Final Adaptation to Mammalian Reservoirs” thread http://tinyurl.com/p3pf9 that lead me to ask if B2H with direct mutation within the humans themselves is impossible.
Anon_22: H5N1 at the moment preferentially binds to á2,3 receptors which are present in avian species. One of the barriers to becoming a pandemic virus is the ability to change this affinity to á2,6 receptors, the predominant type in the human upper respiratory tract, where replication and shedding would allow the virus to spread efficiently h2h. How can this change occur? Theoretically the mutations required can occur in the human, avian, or an intermediate host. As discussed on this thread overcoming species barrier, changes arising from a series of mutations require each intermediate mutation to be passed on ie transmitted host2host, otherwise it would be lost. Mutations happening in human hosts, before there is efficient h2h, would be lost or ‘dead-ended’ with the last case, unless there is a significant pool of asymptomatic hosts, which current data does not suggest.
Montreme – at 21:43: Each time the virus infected a human, it would have to start from scratch to adapt to humans. Hence, we should be no closer to a pandemic strain now than we were in 1997. Yet, larger and more frequent clusters and the recent finding of high viral loads in the nose and throat of members of the large Karo cluster clearly argue for adaptation to humans.
Beehiver: ..here is an article showing that the human airway epithelium (including the nasal passages), also contain both 2,3 and 2,6 types of receptors, depending on whether the cells are ciliated or non-ciliated. It is a free article, published in PNAS in 2004, the PubMed number is 15070767.
Dr. Nidom: The aim of the research to know whether the circulating virus in the field, only had the shape of the virus from the poultry that is had spesifisitas the receptor alfa 2,3 or that had spesifisitas the receptor alfa 2,6 that is the virus that could infect direct to the mammal (the pig and humankind, etc.. ) The sample that I the test came from the poultry, the pig, and humankind. From 100 samples, there is 20 that succeeded in being turned on and evidently 11 among them had spesifisitas the receptor 2,6. Meaning that, these viruses had the capacity immediately could infect humankind without must from the poultry before. Moreover, some of the samples had the amino acid lisin in the number 627 proteins PB2, that meaning that the virus could be stable in the temperature of the human body. Because of several matters above, the direct spread to humankind without through the poultry very possibly happened in Indonesia.
Thanks all for any input.
Pixie, there are many characteristic mutations for the Java-human viruses. Some are synonymous. It’s unlikely that exactly the same mutations happen each time again in the individuals.
Watching in Texas – at 09:51
I can no longer remember which thread we discussed this on, but I finally got a reply from the DOE. I was routed to their website (which of course I had already reviewed and that is how you got Jacqueline Flood’s email address). But I do have a new contact name, Napoleon.Avery@hq.doe.gov, I emailed him back and have gotten a prompt and courteous reply. According to him, the DOE does indeed have a plan and they are working with the states for them to develop their own plans.
The thread was Community Preps for the Worst Case Scenario. Maybe we should start a new thread on the GRID, one of these days. Given what Jumping Jack Flash has said about the interdepedence of power plants, I don’t think letting every state develop their own plan will work. It seems to me that keeping the Grid up is a federal responsibility, even if that means requiring action of private or state utilities.
Pixie – at 13:56
Can we categorically say that the mutations in Indonesia are not occurring specifically within the individual humans that have acquired H5N1 B2H – not within some large but unknown body of humans with low level infections - but that the mutation cannot be happening within the humans that acquire H5N1 B2H and in real time?
I wouldn’t say anything categorically, but if humans were getting infected by birds, the sequences isolated from humans should most nearly match nearby infected birds - they don’t. They either match infections of cats or other humans.
Once the virus enters humans it does come under selection and mutations that occur that favor human adaptation will be selected for. Thus, some of the similarities between different human isolates could be a result of convergent evolution. However, this would only apply to nucleotides that were subject to selection. My understanding is that at least some of the differences between birds and humans are in “neutral” areas of the genomic segments that are not expected to be under selection, although I confess I haven’t looked at this closely.
anonymous – at 20:23
You would be correct, absolutely correct, if what conventional wisdom calls random mutation were truly random.
But we know from looking at the sequences (observational evidence), that the genetic acquisition is not random and does recur.
Pixie -
Keep digging. You are in the right field.
I have no doubt that H5N1 will use a human host as the intermediate solution on the way to PF51. In fact, we may be the hidden mammalian host that Monotreme is pursuing. I’d like to see several genome segments of the human survivors, the human cadavers and the human HCWs on the cases in Indonesia. Not the Influenza genome . . . the host genome, post-exposure.
Now we just need better tools and a map with proper coordinates and an accurate legend.
Monotreme – at 22:21
Have you considered that the viral isolates we sequence from the hosts may have already overtaken the terrain of the host, acquired genetic material in vivo (adapted) and reduced the in vivo population of any other viral strains that may have caused the initial host infection?
I sometimes wonder if we caught the infection on day one if the viral isolates might match something we have on file because the infective strain would not yet have made significant changes? Or is it possible that the very first reproductions from the initial infective strain would show a multitude of genetic acquisitions?
See how much it matters how you focus the lens . . .
Leo7at 12:43:
In the (I think) early ‘90′s, Harper’s or Atlantic Monthly published a research article about HIV with finding of HIV virus, active and present in mosquito ovaries.
Monotreme - at 22:21 “My understanding is that at least some of the differences between birds and humans are in “neutral” areas of the genomic segments that are not expected to be under selection”
That would be a reasonable theory. I wonder what Taubenberger found there in the 1918 virus since he assumes no intermediary.
I’m just trying to get rid of the birds. We either have:
1. infection from birds - same sequences (this is not happening) 2. infection from birds - selection and mutation within humans 3. infection via the larger mamalian family (cats, rats, bats, goats, and those pigs)
So convergent evolution in humans would be far less likely to happen than optimal evolution in an intermediary? If that’s the mechanism, it may be more difficult to control anywhere than the birds have been.
What got me thinking about all this is the story of the beginnings of H1N1 in Haskell, KS, in the winter of 1918, and the first small family clusters that were found in humans on isolated farms which were strewn about a large geographic area.
TEP1 research on innate immune response in mosquitos to plasmodium (malaria) is becoming less conclusive as we learn more.
NS1 - at 22:37: “Now we just need better tools and a map with proper coordinates and an accurate legend.”
And a trowel. Or maybe a dental instrument.. We are like archeologists and our dirt is halfway across the globe, the already retreived fragments hidden behind laboratory doors.
NS1 – at 22:37
Sorry, if I understand you correctly, I don’t agree. It looks like the virus mutates, a SNP is observed, the mutant virus gets passed on to a relative, the virus mutates again, now their are 2 SNPs etc. I have looked at lot of sequences since my debate with Dr. Niman. I am absolutely convinced he is completely wrong about random mutations being rare with H5N1. But this probably not the thread to discuss that ;-).
Pixie – at 22:50
I wonder what Taubenberger found there in the 1918 virus since he assumes no intermediary.
The problem for Dr. Taubenberger is that he has very few cotemporaneous sequences to compare the 1918 virus with.
1. infection from birds - same sequences (this is not happening) 2. infection from birds - selection and mutation within humans 3. infection via the larger mamalian family (cats, rats, bats, goats, and those pigs)
Actually, I don’t see why all three couldn’t be happening.
So convergent evolution in humans would be far less likely to happen than optimal evolution in an intermediary?
It depends on how much “time” the various spends in humans. If only a single patient is infected, the virus has only a few days to come under selection, not much time. If H2H2H occurs, the virus has much more time to come under positive selection.
What got me thinking about all this is the story of the beginnings of H1N1 in Haskell, KS, in the winter of 1918, and the first small family clusters that were found in humans on isolated farms which were strewn about a large geographic area.
The apparent simultaneous explosion of H1N1 in 1918 in many cities is one of the great mysteries of that pandemic.
the “human” sequences do happen in birds, just not so often. the “bird” sequences do happen in humans, just not so often. The human sequences can hardly have evolved in humans alone without another reservoir. That reservoir could also be other birds IMO, which don’t mix a lot with the “bird-sequence-birds”. NS1, your sentences are too difficult for me to understand…
Monotreme, are you assuming the humans in Indonesia give the virus along to some other animals where it continues to evolve in a host’s-cycle ?? I don’t think so. Too few human infections. Animal infections are more likely to stay undetected.
‘ Have you considered that the viral isolates we sequence from the hosts may have already overtaken the terrain of the host, acquired genetic material in vivo (adapted) and reduced the in vivo population of any other viral strains that may have caused the initial host infection? ’
no. I don’t think so. Not worth considering. Unlikely. (IMO)
Monotreme – at 23:01
We each are absolutely convinced and you have my deepest respect, so I must believe that our language is getting in the way of our thinking and our communicating.
We certainly can avoid the discourse tonight.
I do agree that a SNP seems to be passed and then another added, then another two, et al. I interpret the additive effect to Niman’s idea of having better landing zones or a more perfect match for attractant or chaporone molecules like wetDirt hypothesized in July 2006.
anonymous – at 23:24
Do your homework and read the papers presented in the threads referenced in my NS1 Profile Cytokine Dysregulation section for more background on testing fallacies.
Especially note some of the shortcomings indicated in Gene Expression
Assume a mammalian host. If the host does not die from the infection, then the undiscovered animal host may stay in the geographic area. The cluster instances in this set of circumstances should repeat themselves. If we have such a host then, for example, Karo should have another cluster(s). Each cluster in an area should have another cluster(s). If we map the clusters over time, do we have the same locations repeatedly having cluster(s)?
Same circumstances, BUT =>if the host animal moves away from the site, then we should have a string of clusters that follow the animal(s) around. If we map the clusters over time and geography and look for a pattern…is there one?
If we have a bat as the host animal, the circumstances would allow for the “same” sequences to show up in differenct areas at about the same time. The host animal is covering a large area. If we map clusters and look for a corelation with sequences and time of outbreak, do we see that over time?
My point is we need to look at this problem with the data we know and see if we can then make any patterns that make sense. What we can know is date, place, some sequences, weather and the kind of animals. It is one level to the puzzel.
Re: 1918 and it’s breakout, the only answer I have to that is the wind and dry conditions and tiny virus particles. It would have to be a very infectious agent!
Leo7 – at 12:43 said “no one has ever explained to me the biological need for mosquitoes.”
There is no “biological need” for most species. There is only a niche which allows them to propagate.
The cases where there is a biological need, such as an orchid dependent on pollenization by a specific specie of bug may define a “need” for the orchid, but if you consider the two species as a pair, again there is no “need” that requires it exist.
Why is the mosquito so successful at transmitting disease ? It’s just like when junkies reuse the same dirty needle; replacing the needle between jabs is just not necessary for short term survival.
Monotreme – at 22:21 said “…similarities between different human isolates could be a result of convergent evolution. However, this would only apply to nucleotides that were subject to selection.”
Are you thinking only of the first two of a triplet which determines an amino acid ? I suspect that even the third may be under selection in certain viruses, specifically if the third nucleotide has some effect on how the RNA folds and is encased by virus coat protiens. We think of a successful virus as one which is capable of infecting a cell, but a successful virus is also one that assembles itself correctly.
So the idea that certain viral sequences are highly conserved over years is not sufficient evidence that random mutations do not occur (a la recombinomics). Only evidence that random mutations have not yet found another stable configuration.
Monotreme – at 23:09
The apparent simultaneous explosion of H1N1 in 1918 in many cities is one of the great mysteries of that pandemic.
Yep, and in China at the same time too, a milder spring wave in humans only, and a severe autumn wave in humans and pigs, mirroring what happened in the US. Really weird.
hmm, I didn’t know that. Is there a referrence ? We could explain the 2nd wave, in that the mutation 1st→2nd wave was only a small change and could happen independently, and that maybe summer-weather delayed its emergence.
But why the spring wave in China ?
Monotreme, for some time now I’ve been mulling over your theory that the virus is being carried in some unknown mammal reservoir(s), and I have a couple of questions for you. If the virus is being transmitted from mammals to humans and not birds to humans, then why does it seem that Vietnam’s aggressive bird culling operation seems so successful? Afterall, they have plenty of other mammals there but haven’t seen the virus resurface. 2nd question: Has it ever been proven that the virus can spread from asymptomatic pigs to humans? Even if the virus has been found in pigs, how good are pigs at efficiently transmitting it to humans? Why haven’t we found human cluster evidence around pig farms, in other words, if pigs were a significant vector? Lastly, it seems to me that perhaps there is a partially adapted H5N1 circulating in the human populations where there have been outbreaks, which would explain the sequence diffences between avian and human. It seems that the current tests are having trouble positively identifying the virus. Recent findings suggest it is more effective to make a positive determination from autopsies (lung tissue presentations), in my opinion due to the rapid mutation that this virus is undergoing. It seems harder to get these autopsy findings due to cultural and religious reasons in the countries that have been hit the hardest. Perhaps when seroprevalence studies are done to look for specific antibodies, the antibodies don’t show up because they are so different than the viral strain being tested? I don’t know. My professional training is not in such matters. It would seem to me to be a good idea to encourage all countries that have been hit by this virus to collect and test more autopsy samples (on both the victims and those who’ve died from “natural” causes). I suspect that if a very few people may be able to carry the virus asymptomatically (and shed the virus while doing so), then it would be very, very hard to detect with current seroprevalence studies.
anonymous – at 23:16
I think there are multiple things happening, some of which are relevant to pandemic onset, some of which aren’t. I’m sure some people have been directly infected by birds, but I think this is very rare. I think more people have been infected either by another mammal or by another person. Which sequences a particular human isolate matches gives a clue as to how they were infected. This is why it is so critical to tie sequences to specific patients, to sample every person and animal near that patient and to make it clear exactly where every infected animal is found and to describe the relationship between the sequences, regardless of source, to very specific geographical regions. This should have been done from the very beginning of the H5N1 outbreaks. I continue to be stunned that it is not being done today. I don’t know what they people who should be doing this are thinking.
anonymous – at 23:19
…are you assuming the humans in Indonesia give the virus along to some other animals where it continues to evolve in a host’s-cycle ??
I’m not assuming it, but I consider it a possibility.
I don’t think so. Too few human infections. Animal infections are more likely to stay undetected.
Human to pig transmission has been suggested for other flu viruses, so it’s a possiibility. The probability would depend on the what the real number of human infections are and how efficient human to mammal transmission is. I think this is much more efficient that bird to human or bird to other mammals. The high prevalence and clusters suggests that human to human during close contact is very high.
NS1 – at 23:26
So, I think we agree on the facts but not the interpretation. That’s OK. I have always had the highest respect for how you conduct yourself on Flu Wiki.
Dude – at 01:24
My point is we need to look at this problem with the data we know and see if we can then make any patterns that make sense. What we can know is date, place, some sequences, weather and the kind of animals. It is one level to the puzzel.
Yes, I agree this is important and I’d like to work on it, but there is never enough time.
de jure, we are only speaking of Java here. In Vietnam and elsewhere they probably did get it directly from the chickens.
a’Akova – at 01:54
Are you thinking only of the first two of a triplet which determines an amino acid ? I suspect that even the third may be under selection in certain viruses, specifically if the third nucleotide has some effect on how the RNA folds and is encased by virus coat protiens. We think of a successful virus as one which is capable of infecting a cell, but a successful virus is also one that assembles itself correctly.
There are a number of sequences under selection that don’t directly relate to coding of amino acids. I don’t think there is anything we really disagree about.
De jure – at 08:16
If the virus is being transmitted from mammals to humans and not birds to humans, then why does it seem that Vietnam’s aggressive bird culling operation seems so successful? Afterall, they have plenty of other mammals there but haven’t seen the virus resurface.
I don’t know the answer to your question, but here are some possibilities. 1. Vietnam was affected early in H5N1 outbreaks. H5N1 has evolved since 2003. Some of the new strains have different properties. Clusters may be growing more common than they were. 2. Maybe certain species of birds are necessary to be part of the mammal to mammal evolution. Quail have been suggested.
Has it ever been proven that the virus can spread from asymptomatic pigs to humans?
I’m not sure about this, maybe someone else knows.
Even if the virus has been found in pigs, how good are pigs at efficiently transmitting it to humans?
No-one knows. Every strain of virus is different.
Why haven’t we found human cluster evidence around pig farms, in other words, if pigs were a significant vector?
Some have suggested that this has happened in China, but was attributed to another disease, S. suis. Also,pigs and chickens are often on the same farm, at least in China. The fact that a farmer kept chickens is always emphasized in reports. The fact that he also kept pigs is usually not mentioned. Lots of pigs have been dying in China. Promed has requested that they be tested for a variety of pathogens including H5N1. To my knoledge this has not been done.
Lastly, it seems to me that perhaps there is a partially adapted H5N1 circulating in the human populations where there have been outbreaks, which would explain the sequence diffences between avian and human.
I don’t buy this. There is no evidence for it. This would not explain why the sequences from a human cluster more closely resemble a sequence from a cat than they do sequences from other humans. See my post on this on the previous thread. Also, if subclinical spread were occuring, it would be all around the world by now.
well, the synonymous mutations don’t seem entirely random when you look at it statistically. But I never saw an explanation why and how they change the properties of the virus ?
Monotreme at 8:57: “2. Maybe certain species of birds are necessary to be part of the mammal to mammal evolution. Quail have been suggested.” Hmmm…you’ve got me thinking. Let’s hypothesize that the Vietnamese strain required avian help while the new Indonesian strains don’t need this assistance. It would seem that you would be able to look at the differences between the strains and tell which polymorphisms were making the virus more adaptable to people. Just a thought. By the way, thanks for your response. Intriguing as always.
I’m thinking cats. Not pigs.
Why not rats or mice ?
“anonymous – at 14:13 Why not rats or mice ? “
Why not? That’s one reason that I am an advocate of stocking lots of d-Con among the preps.
Surely the spread has to be something that can travel long distances relatively quickly and achieve contact with some fairly remote areas. This means wild birds have a role rather than insects and mammals, or even the villager types who have been doing all the dying so far.
Call of the Wild – at 21:27 If the spread was by wild birds, then why don’t the wild bird sequences match the human sequences? I rather suspect the long-distance vector is two-legged, two-wheeled and two-stroke.
Monotreme: I may be totally off-base, but in trying to follow your theories, I have been reading about the mammals of Indonesia. Black macaques are found there (in particular, Sulawesi), they are endangered because of over-hunting for food as they are considered delicacies and are served at feasts or special occasions such as weddings, and they are mostly vegetarian but are known to eat nesting birds. Macaques are also found in China.
I’m sorry, I cannot make my link to Durrell Wildlife work tonight.
the special human sequences are only in Java, and different from most bird sequences, so they shouldn’t get it by hunting birds but rather spread it from member to member within that reservoir. And occasionally spread it to humans, but rarely to (other) birds. We have a duck in Indramaju and two chickens in Sumatra with that virus, but all other birds have a different strain. Some humans also got that different strain, e.g. Karo. Karo could also be viewed as such a special, isolated strain ,…, if they hadn’t happened to test the Dairi-chicken and some others. There can always develope some branches, which you can’t easily link, but with the humans in Java it’s more obvious and separated as usual.
De jure – at 11:51
It would seem that you would be able to look at the differences between the strains and tell which polymorphisms were making the virus more adaptable to people.
Yes, I think so, although the WHO doesn’t.
And thanks.
I’m going to add the following to the next iteration of this thread, but just to assure people that the title of this thread is not a fringe opinion:
The likelihood of an H5N1 influenza pandemic seems high, and the consequences could be catastrophic. Recent findings suggest that the 1918 “Spanish flu” pandemic may have resulted from a similar interspecies transmission event in which a purely avian virus adapted directly to human-to-human transmission without prior reassortment
From:
Authors:
H. Chen, G. J. D. Smith, K. S. Li, J. Wang, X. H. Fan, J. M. Rayner, D. Vijaykrishna, J. X. Zhang, L. J. Zhang, C. T. Guo, C. L. Cheung, K. M. Xu, L. Duan, K. Huang, K. Qin, Y. H. C. Leung, W. L. Wu,H. R. Lu, Y. Chen, N. S. Xia, T. S. P. Naipospos, K. Y. Yuen, S. S. Hassan, S. Bahri, T. D. Nguyen, R. G. Webster, J. S. M. Peiris, and Y. Guan
Published in the Proceedings of the National Academy of Sciences.
Call of the Wild – at 21:27
One of the interesting things about the H5N1 found in Indonesia is that it came directly from China. Not Viet Nam, not Thailand, not Malayasia. It came direct from China. Here’s a map of Southeast Asia. Now what was the species of bird that brought it there? Anyone know?
Reference
Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam
Swann – at 23:12
A perfectly reasonable hypothesis. The only question is how much contact to people in Jakarta have with monkeys? I’m guessing not a lot, but I don’t really know. OTOH, it’s certainly reasonable to suggest that they could be part of a complex mammal to mammal chain of infection.
likelyhood is “high” ? high = 10% ? 50% ? 90% ? and in which timeframe ?
“could be” became famous after Webster’s ABC-statement. Too imprecise.
anonymous – at 23:57
For a scientist, the language used was very strong. I would interpret “high” as over 50%. I think they are also implying that there is good reason to believe that an H5N1 pandemic would be as bad as 1918. JMO, of course.
some rare species of monkeys ? They should have noticed the connection if several human cases had monkey-contacts in common.
So, if the bird and human sequences don’t match well and cats are a possibility—why hasn’t the virus jumped to a major city? That elusive mammal would have to not be in the big, overcrowded cities wouldn’t it? How else can you explain the fact it isn’t in the big cities yet? I’m thinking cities with international airlines or seaports? I vote for a mammal, not avian, that a cat mingles with, but what?
Leo7 – at 00:06 - Cats like mice.
mono 00:04, I don’t read that from the statement. “could be” when Webster
said it, hardly meant more than 10% (?) , why should “could be”
in a similar context be more than 50% now ?
no one knows.
Also Webster said 50% for efficient h2h with H5N1,
which seems to be necessary for a pandemic. So less than 50% for a H5N1
pandemic for one of the Coauthors.
Ontario Health is now saying that 35% of population may become infected with AI -
or visit Canadian Preppers thread for other technicolour dreams!!
Monotreme— Where the chinese sequences came from:
ISDN184026 A/chicken/Hong Kong/947/2006 HA (4) 1706 2006 H5N1 ISDN207246 A/Chicken/Karo/BBPVII/2006 HA (4) 1703 2006 H5N1 ISDN138756 A/chicken/Malaysia/935/2006 HA (4) 1721 2006 H5N1 ISDN207245 A/Chicken/Padang/BBPVII/2006 HA (4) 1708 2006 H5N1 ISDN207244 A/Chicken/Pulau Rampang/BBPVII/2006 HA (4) 1738 2006 H5N1 ISDN184030 A/Common Magpie/Hong Kong/645/2006 HA (4) 1662 2006 H5N1 ISDN138780 A/duck/Laos/3295/2006 HA (4) 1719 2006 H5N1 ISDN140810 A/Indonesia/534H/2006 HA (4) 1679 2006 H5N1 ISDN140894 A/Indonesia/535H/2006 HA (4) 1703 2006 H5N1
Mainly it’s the ducks that are the long-range carriers, with songbirds as local carriers to chickens.
Leo7 - Cats like a varied menu---birds of any feather, mice, rats and even the occasional squirrel. Does anybody see a possible link? gina
from the news thread: The traffic in chickens and poultry cannot be controlled because the demand is so high, which traders will do anything to meet. Traders in Bogor confessed that they would bring chickens in from anywhere, such as Bandung and Sukabumi, and that sometimes their stocks would be bought by traders from Tangerang or Jakarta. Government officials are not empowered to interfere with this traffic, but at the same time they must campaign about how dangerous bird flu virus is.
I still think the vector is two-legged, and two-wheeled.
disgruntled - at 00:34: “Mainly it’s the ducks that are the long-range carriers”
Are we talking domestic ducks or wild ducks in these sequences?
Wild ducks, I think, but the sequence labels aren’t too specific.
Disgruntled: If human then why isn’t it in the big cities?
wild ducks do meet in Indramaju, where the human sequence was found in ducks. I assume they travel to/from Sumatra. But there are also farms with domwestic ducks in that area. How about parasites ? I was speculating about Freyana Anserina with these swans in Europe.
Hurricane Alley RN- Like them all, but which one hasn’t been sampled? Maybe, have been and they are in the sequences the CDC are holding back, as disgruntled commented on earlier.
we are getting off-topic. I start a new thred : Indonesian reservoir
There’s lots of rodents — many species of rats, mice, voles —
I did some internet searching for Indonesia + mammalogy and came up with Dr. Lance Durden. I sent him this at his university:
While reading discussion threads on fluwiki.com, I have come across several threads that insist that there must be a mammalian reservoir of H5N1 virus in Indonesia. The virologists feel this must be so because many of the H5N1 strains isolated from different people (in different villages) are similar to each other but are NOT similar to H5N1 strains isolated from local chickens.
I am wondering if any ma! mmalogists are studying H5N1 in Indonesian mammals (roof rats, ground mice, fruit bats, monkeys, etc) or if anyone is looking at recent blood samples drawn from such mammals from earlier collections. (If this is not being done, it seems like an interesting PhD problem for someone — complete with good opportunities to acquire funding —alas, a reality for biologists). So far, I only find reference to Dr. Nidom planning to look for H5N1 in cats.
Are you aware of any such work being done?
I very much hope you will have time to reply.
He replied: Thanks for your message. I agree that there could be one or more mammalian reservoirs for H5N1 but I don’t know of anybody looking into this. I assume somebody must be looking though. Have you tried asking Dr. Nancy Cox at CDC (Atlanta) about this? She would know more about this than I do. So, strike out on that one, so far. Anybody know Cox?
Leo7 – at 00:52
Disgruntled: If human then why isn’t it in the big cities?
Just give it a couple weeks. It still is taking a lot of direct contact to spread.
Leo7 - @ 00:55
Tom DVM and I have dicussed this situation at length. I think it was around the time Karo cluster. We tried to go back to Q. Lake in China, but with no sequences coming out of China we hit a major dead end.
Even with the sequences recently released by China, I’m not so sure I would believe them. After an eighteen month delay, China could have made up the sequences they sent in.
Don’t forget, China has much to lose. Hosting the Olympic’s for the first time in 2008 could be a major factor. They have also become a major exporter of goods to 1st world countries. One word of an AI outbreak and there goes China’s economy. Can you really blame them for wanting to keep this quiet. gina
Monotreme, Dude, FloridaGirl, I just updated the page with the graphs of cluster size and frequency over time, with the same text but now in a hopefully more readable layout. Please do check to see if this is not what you meant to write. I think the first paragraph can be simplified a bit.
Now, I’ve become a bit fixated with that chart these past days. If things are the way they look, then the virus is gradually becoming more H2H-capable. But we want to look into alternatives explanations - both because we want to get as close to scientific truth as possible, and because we want to make a case for the need to take preparedness action.
One alternative explanation is that detection has become better. Maybe because of clinical awareness, better tests or tests applied faster, etc. So it would be a good idea to look into how many tests are being done and plot that against the positives: if it’s both that there are more tests being done and the percentage of positives is increasing, then that’s really scary - the “better surveillance” hypothesis can’t be sustained if that’s the case (IMO).
What would happen to that other alternative (and others we should definitely look into) is of course another matter. What I mean to say is: what if surveillance is better? What if the real (unknowable) number of clusters is really the same year after year? It would mean sustained risk, but not increasing risk, wouldn’t it? The WHO says something to the effect that “more human cases means more oportunities for mutation and reassortment”, so even sustained risk means increased cummulative risk; but not as bad (a lower degree in the badness scale) as “really, more real clusters”.
This matter is not settled in my opinion. The only real way to be certain is to wait, and of course we strongly feel we shouldn’t wait. But what’s fact, what’s reasonable speculation, and what’s shakey opinion?
On the other hand, we all know, and doctors out there all know, that several grey points draw a clear line (there’s probably a mathematical way to formulate this). Each pixel may be challenged, and yet the picture is extremely clear. If you’re not fully sure there are more clusters and you’re not fully sure there’s this and there’s the other, you can still be fully sure a pandemic is getting closer.
At the very least, it’s not going away. And pandemics happen. And even if we can’t see small changes in the distance, things are different than a couple years ago.
If someone can help adjust the contrast in the image, please do so.
I still beleive it’s wild birds. Indo. is all islands. Yes, people travel around and birds are traded/sold, but not many poor villagers go island hopping. I have to beleive that on larger islands most trades/sales are on the island. Islands are very close together making it easy for wild birds to island hop:
From Monotreme at 23:39 link: study of wild and domesticated birds in China: Most of the ducks infected with MDk/JX/1653/05 and MDk/JX/1657/05 survived (seven of nine and five of nine, respectively) and continued to shed virus for up to 3 days postinfection (Table 3). All nine ducks infected with BH goose/QH/65/05 survived, and three ducks shed this virus for up to 7 days postinfection. All geese infected with BH goose/QH/65/05 died before day 7 (Table 3). Experimentally infected ducks shed virus throughout the experiment. Because these viruses, isolated from migratory duck, are not invariably fatal for ducks, there is a possibility that migratory ducks could harbor the virus and have the potential to transmit interregionally during migration.
If ducks and others can shed UP TO 7 Days - we all know how much ducks and especially geese cra** all over the place. The majority of chickens in Indo are free range, eating off the ground with said cr**.
I only hope and pray that if it goes H2H HUMANS don’t shed for 7 days - imagine how many more infected people that could mean?
hmm, but the chickens (almost) only have the other virus, not the human virus. Could it be that it’s because the human virus is often asymptomatic in chickens and thus missed ?
oops, wrong thread again
LauraB at 6:43,
I only hope and pray that if it goes H2H HUMANS don’t shed for 7 days - imagine how many more infected people that could mean?
From the 2005–2006 Fluzone vaccine literature:
“The incubation period for influenza is 1–4 days with an average of 2 days. Adults and children typically are infectious from the day before symptoms begin until approximately 5 days after illness onset. Children can be infectious for greater than or equal to 10 days, and young children can shed virus for less than or equal to 6 days before their illness onset. Severely immunocompromised persons can shed virus for weeks or months.”
could that be different with a pandemic virus? i hope flu surveillance allows us to know!
Have we ruled out asymptomatic humans? While it is true that poor villagers don’t ‘island hop’ in a touristy sense of the phrase; sometimes people work in the ports/seafaring hubs and go home to the villages/inland once a month or so.
Also, is there anyway we could overlay the Indo outbreak maps with roads?
What we currently have is an epidemiological mystery. Sure wish Dr. Snow were alive…
enza - is it possible to do as Nature’s Butler does with http://maps.google.com and pin-point each case? Coordinates? Links between them? Dates?
I would bet this has been done by WHO people and maybe others. But we have the hive-mind, and some collective time to pursue this kind of things.
I’ll ask my geek friends. We have the Excel files - we could have another two columns with the x and y. First thing is to have all the locations in a wikipage - then look for and add coordinates cooperatively. Small steps!
making the invisible visible
beehiver – at 14:27 The incubation period for influenza is 1–4 days with an average of 2 days
lugon – at 14:43 could that be different with a pandemic virus?
http://www.who.int/mediacentre/factsheets/avian_influenza/en/index.html
“The incubation period for H5N1 avian influenza may be longer than that for normal seasonal influenza, which is around two to three days. Current data for H5N1 infection indicate an incubation period ranging from two to eight days and possibly as long as 17 days. However, the possibility of multiple exposure to the virus makes it difficult to define the incubation period precisely. WHO currently recommends that an incubation period of seven days be used for field investigations and the monitoring of patient contacts.”
Dennis. The two to eight to seventeen days were quoted by the World Health Organization in an effort to make the data fit the theory…a theory that best served their self-interest…nad their self-interest, at the point these figures were used, was to relate every case to a sick chickent rather than assume human to human transmission with the built-in requirement to raise the alert level.
In my opinion, the common sense answer to your question lies in the observation in the laboratory etc. that H5N1 replicates at many multiples of a seasonal influenza and this is in part, the cause of the cytokine storm…
…therefore, it would make sense that with a multilied replication rate, the incubation period for an H5N1 pandemic influenza would be shorter rather than longer.
with a multilied replication rate, the incubation period for an H5N1 pandemic influenza would be shorter rather than longer.
better ask JKT - we probably don’t know.
but it does make sense, yes.
what happened with the other pandemics?
‘treme at 23:09 above-
The simultaneous expression of a pandemic strain argues strongly for your theory of a mammalian transfer species with wide access to both fowl and humans.
Lugon at 15:48-- I showed the maps to a couple pub hlth professors and the first reponase was, “It would help if we could see where the roads are.”
I like your idea. Lets try to find the patterns.
I sense that this is the time to ask this question: would GIS help? We have capability, I could call in a couple favors…
but the amount of the virus spreading through asymptomatic incubation time or through asymptomatic carriers is usually much lower
anonymous. There have been no identified asymptomatic carriers or incubation times in these asymptomatic carriers…so could you explain your point a little more…thanks.
There are exceptions to the rule as SARS did point out and Karo may have pointed out…
…the exception is super-shedders who may be asymptomatic but more often shed large numbers of virus for prolonged periods.
An example of this was the doctor in the Hong Kong Hotel elevator that was the index case for the worldwide distribution.
lugon – at 03:58
Thank you… You did a good job. The clusters represent what we know. I wanted to be certain I did not count anything that wasn’t “true”. You lose credibility that way. There were some differences between what WHO issued in their updates and what I found in the studies.
But, even working on it and going thru the studies, it was difficult to see the entire picture until after the fact.
But, truth being said. I do not feel that is all the clusters…. A good example would be to look at Michelle’s spreadsheet for September. There are 43 patients listed as suspect or confirmed. But only 4 tested positive, 3 died without testing, and the rest have tests pending.
Now, when you look at the spreadsheet, you can get a feel about “ does this patient really have AI?”
I am working on some graphs for individual patients…. And even, being conservative in the patient count I am using for September… I still came up with roughly 13 patients, who died or were admitted to the hosp with Sx, but had contact with someone positive… (Searching for [reliable]sources tomorrow on september patients; I may add more)
And then the question is…. Are we capturing them all? probably not. So if anything, The graphs represent what we can reliably count. There may be more… (now and in the past).
But, one thing I did learn…. the WHO updates are not complete with the information THEY have available. And that is frustrating…
Thanks again for straightening up the graph page.
I should add… The spreadsheet I was working fromwas the septemeber 29 spreadsheet…… I am quite sure it has changed with the amount of patients that are / were being located.
TomDVM, ..talking about normal flu, not h5n1. the dr. did he shed much virus or was it just unlucky circumstances that these few viruses could reach many other people ? The Karo people were symptomatic when they infected others, I think.
In order to present the data, we have to have a flash presentation of points on a large “Google Earth” type map with the roads included. To keep the visual perspective of when something happens we start at one end of the color spectrum for the dots and finish at the other. So, say we start with blue and end in red with the transition through the colors scaled to the total number of cases. We then start the “movie” and have each point add itself to the graph at it’s location and point in time. We use not the hospital, but the home address as close as we can get it. This, IMO, would show us if we are talking about cases being the results of roads. We then think about roads and then add streams and rivers etc. What do you all think?
I think the home addresses would add something to our spacial and temporal understanding of the outbreaks. Unless, most of the clusters are peopled with one address per cluster. Even so, that would tell us someting about them being in close proximity to each other.
Re wild ducks in SE Asia - cormorants - widespread coastal birds - often nomadic(some species migrate) - used for fishing by traditionalists - knwon to get H5N1 - just a thought
FloridaGirl, Dude, enza - all
Great ideas. Truth is a difficult thing to get at. We have information with different degrees of hardness. The hard-core info in the graphs already produced strikes a chord with everyone I’ve commented it with. Let’s add other layers if we can.
lugon, I missed you while you were gone, I love your “solve the problem” attitude. I was quite in dispose for a while with work, family, getting bird flu and then taking care of my family who got bird flu from me. We had no CFR, so I guess it wasn’t bird flu after all, but it was nasty stuff. Used a lot of preps and need to restock before the real thing hits. Good thing I had preps!!! Just taking a little time tonight to read, read, read and catch up on what’s going on and post a little. Don’t want to take up room here, but just wanted to say “hi”.
Reader, thanks but - you didn’t catch bird flu, did you? Give details if you did. :-?
Great discussion, but this thread is getting too long. Please continue here.