Indonesia full of infected birds

Points well taken as usual, especially liked the Bellagio Principles (we're definitely all in this together).

I find the additional mammalian reservoir palatable from an epidemiology standpoint as well as the mentioned possible sequence problem. It's always seemed strange to me how hard it is for people to get it considering the huge exposure to poultry and I find it difficult to completely embrace a genetic difference in those infected. If we add an additonal step such as cats or dogs getting it from eating dead poultry and then the virus doing some more mammalian adaptation and then passing it on to a family group that would seem like a possibility.

Revere, Back in May you had given some pandemic hallmarks to watch for. I think you included sick HCWs, more clusters, and larger clusters.

We are definitely seeing more clusters in Indonesia. They are testing HCWs, classmates, and extended family members of some of the patients.

If any of these tests come back positive, do you think that the "bubbling pot" may have moved from simmer to boil and we just don't know it yet?

I know this is an unfair question, but your perspective is a valuable beacon for me and lots of other people.

kent: I'm guessing there are other reservoirs. The main question is whether they are significant for transmission to humans or not. I still see this as a virus that is not very transmissible to humans, whatever the source, so it doesn't seem required to me that people are getting it easily from a hidden reservoir that is mammalian adapted because then they would plausiby pass it between themselves more easily than seems to be the case. Of course I am just making educated guesses here. There is the question of whether there has been significant underascertainment, too. Which brings me to Nancy's question.

Nancy: You would have a point if we could be sure things have changed. It could be that ascertainment has changed which would make it look like there are more clusters. The seroprevalence surveys that have been done have been limited and in some cases of retrospective diagnosis we have found antibody rises that weren't visible at first. So I don't think the data on mild or inapparent infections being absent (and hence transmissibility being historically low) are that good, but they are still data points and we have nothing much to the contrary. So I see the pot as bubbling and I think it is bubbling more because there is more and more virus there. I don't have a view as to whether it has changed appreciably in the direction of becoming more likely to be a pandemic strain. There are all sorts of things that can happen in a situation like this.

Think of the virus as wanting to climb a fitness hill to get as high as possible via natural selection. If the landscape has many hills and it climbs one of the smaller ones (because it started out near the foot of that hill) it has moved to a more fit condition, true, but it may have isolated itself on at a local maximum that is not a pandemic position for humans, just the fittest point in the local area (genetically speaking). We expect this virus to change genetically and move to be more fit. But that might not be the global maximum with respect to fitness with respect to humans. If there are other reservoirs this might even be good news, because its most fit position might be adapted to the most animals in ways that make it not very transmissible to humans. Is this clear?

kent nickel,
"If we add on an additional step such as cats or dogs getting it from eating poultry and then the virus doing some more mammalian adaption and then passing it on to a family group, that would seem like a possibility."
I think you are exactly correct. The scientific evidence shows there is no direct link from poultry infections to human H5N1 infections. It is that simple.
If someone has scientific evidence to contradict the above statement, please immediately post it here.
To say poultry is a vast reservoir of H5N1 is obvious. What is false is to conclude humans are being directly infected by this vast poultry reservoir. There is no scientific evidence to prove the latter statement. And to insist this reservoir is directly infecting humans is equilivant to concluding bleading patients will cure them, or to conclude that since the horizon appears flat, the world is flat. It is a barbaric conclusion that will regress science to the stone age. Anyone that maintains that position is a neanderthal idiot.

william: Grow up. You talk like George Bush: "Either you are with us or against us." Scientists disagree all the time. It is normal. We argue, we talk things through, we keep examining the evidence, we look at alternative interpretations. Your position is, "It's true because that's how I interpret Henry Niman's opinion." I doubt that you even know what a phylogenetic tree is or how it is determined (or that different methods or different settings for the same method can give you different trees). Henry can be pretty forceful in his opinions but he doesn't hold a candle to your pronouncements: ("It is a barbaric conclusion that will regress science to the stone age. Anyone that maintains that position is a neanderthal idiot.").

I'm glad to have you contribute to the argument as long as you make an argument instead of wild assertions unfounded by understanding and you don't contribute to anyone's else's understanding of the science here. If it is your position that you agree with everything Henry Niman says that's your privilege, but not even Henry agrees with everything Henry Niman says because he's a scientist and he looks at the evidence and he leaves possiblities open and can change his mind as the evidence emerges. He doesn't just go on Authority.

You are becoming extremely tiresome. Maturity is called for. Get some.

Yes, Revere, that is clear. And helpful. Thanks.

Revere,
Rather than attack me and Henry Niman, why don't you have the decency to give me specific answers to my questions?
You said: "But the poultry reservoir is gigantic and probably the source of most human contact with the virus"
It is obvious poultry is the source of much human contact with the virus. But you infer from this statement that humans are being directly infected from poultry, do you not? Where is your evidence to support that conclusion? If you have none, please admit it. If you have evidence, present it. Otherwise stop making the statement, because this implication is probably false.
Now please respond to my post from last night, where I responded to your questions, but you never gave an anwer. Why? Only you know why.
Now please respond to Niman's statement of September 8, where he said as follows regarding the 47th Indonesian victim.
"Although there were dying poultry in the proximity of the confirmed case, the link to domestic poultry remains weak.
"In 2006, all human H5N1 isolates, other than the cluster from Karo, have had a novel HA cleavage site, RESRRKKR. This change is associated with a number of additional changes in HA as well as the other seven gene segments which are not present in poultry H5N1 isolates."
Just for a moment, please assume Niman's statement is correct and factual. If there is no match between the poultry sequences and the human sequences, how can chickens be infecting humans directly? Please answer my question, instead of responding with a personal attack on me.
Tell us your opinion. This is important. You certainly have more knowledge of this subject than I do, and I want a direct answer.
My position is that it is very difficult for chickens to infect humans. It has probably happened, but it is rare. But it may be possible that cats and dogs eating, raw poultry, are an indirect souce of infection to humans. Of course I have no evidence to support this position. But this should be investigated, instead of being ignored. Or there may be another reservoir we do not know about.

The Fat Lady began her concert in 2003...she's hoarse now.

"The lesson of the bubbling pot in Indonesia is not to beat up on them to do better, but to get ready in your own community. That's called prudence."...Exactly!!

william: I responded to you. I didn't attack Henry, so please be accurate.

This virus changes rapidly and if you take isolates from the same person you won't get a "match." The question has always been what is a significant change or most likely changes and which ones can be reliably used as markers for source. The odd cleavage site seen in Indon is something to ponder, but there are human cases all over (including Indon) without that cleavage site. Nor do the E627K mutations reliably distinguish human and avian. We are learning that there is cooperation between gene segments required, not just specific changes on one segment.

The question remains what changes can be used as reliable markers of human or avian viruses. Chen's EID article from September listed about 50 possible differences where the entropy of particular locations was low, although even that classification is sensitive to the underlying dataset (as you can see in that article where the entropy of E627K used as the cutoff changed markedly when the dataset was enlarged with new additions to the database).

This is a complicated problem and you are trivilizing it. "A little knowledge is a dangerous thing" is something to keep in mind. I could be wrong about any of this, as can Henry or others. We are talking about it to each other, not shouting at each other with slogans.

I told you my opinion. I think most of the cases have a poultry origin but that might change, be changing or be wrong. I have pointed out many times here that we need to worry about non-poultry reservoirs. I am not rejecting it, in fact I was one of the earliest to raise it. As for poultry, I don't think evidence has been adduced to rule it out and from the epidemiological perspective it remains the most tenable hypothesis. If and when other kinds of evidence (and make no mistake, this is an area where the gaps in our knowledge are much huger than our knowledge and we are trying to put together puzzle pieces that don't have the intervening pieces available yet; many of us will do this differently depending on our disciplinary perspective.), I'll consider it, in the context of other evidence, not just sequence data.

I don't think we know enough about the relationship between the genetics and the biology (and even further from there to the epidemiology, which is what we are talking about here) to make the jump from the appearance of the cleavage site to where you are going. Like Henry and everyone else I am looking at the evidence and trying to fit the pieces together in various ways, rearranging and shifting the pieces as new evidence comes available. It might turn out that what Henry thought or I thought was an important piece in the center of the picture is really on the periphery as we learn more or isn't even part of the same picture, or it might be that Henry was right or I was right all along. Or that he was right before but things have changed or vice versa.

We are all struggling with this and your shouting isn't going to help. It just adds to the noise. Your position that it is difficult for chickens to give this to humans? Fine. That is the same as mine, expressed here often, and also the same as WHO's and everone else's. Big deal.

These viruses don't "match" with each other, even when one is the direct result of a replication from the other. If they did, they couldn't evolve. There are lots and lots of differences. The trick is to figure out which differences are important, important in what way, what do they tell us about a whole host of questions like transmissibility, virulence, source (host range), etc. "Non-matching" viruses don't preclude transmissibility or anthing else and which parts of the non-matches indicate host range is an open question. Henry has a position, as do others, and he states it. We'll have to see if it is well supported by the evidence or if there are alternative intepretations given other things. That's called science.

You started this, so please take responsibility for it and not accuse me of launching an unprovoked personal attack on you.

william:

"It is a barbaric conclusion that will regress science to the stone age. Anyone that maintains that position is a neanderthal idiot."

That kind of rhetoric differs sharply from your rhetoric a few weeks ago:

"These are very complex issues, and there are no black and white answers...It is good we can dialogue here and learn from each other. Have a good day."

The calm and civil approach to discussion is the one everyone will benefit from. The name-calling never adds anything valuable.

My own layman's view is the increase in human cases in Indonesia is a consequence of the increased exposure to the same not-very-tranmissible but very lethal virus. The overall human exposure in Indonesia must be vast; even if H5N1 fatalities are under reported by a factor of 10 they must be a tiny fraction of those exposed.
Again a layman's view but the idea of differences in host susceptibility makes sense to me. The clusters that do occur are nearly always linked genetically. That's relevant whether the infection was acquired from a common source or H2H.
An unknown mammalian reservoir acting as a vector has some contradictions I have difficulty with. If we postulate the existence of mammal 'X', then either H5N1 does not cause significant mortality in 'X', or said mortality is not noticed, perhaps because 'X' does not live in close proximity to humans. To be a significant vector, humans would need to have regular contact?
If 'X' is an asymptomatic host of H5N1, then we postulate a virus lethal in fowl is harmless in 'X' but again lethal when transmitted to humans. Not impossible, of course, but fails Occam's razor.
What alarms me about Indonesia is the repeated human exposures. Clearly bad news, and opportunities for adaptation.

Doing the math, if 80% of Indonesian households have poultry, and 27% of these poultry flocks are infected, then of the 55 million people in Indonesia, about 12 million are in constant daily contact with H5N1. Based on that, the virus isn't highly infective to humans yet, chickens or no chickens. As a matter of fact, considering the preponderance of chickens around humans in the outbreak areas, I think the evidence points to the fact that, based on laws of probability, sick chickens do NOT infect humans, at least not directly. So what unique set of circumstances make humans catch the virus? If one were to study the correlation between dogs and infected humans, or cats and infected humans, would the ratio change? If sick chickens are pretty much everywhere there is an outbreak of Human infections, and yet are also everywhere there is not, one needs to start putting some other variables into the line up. In other words, yes...chickens are the initial pool, but there must be some other link or factor which causes their virus to infect humans. Is it another interim carrier or vector, or a human genetic predisposition, as has been suggested before based on familial cluster data?

Another thing in the article above makes me wonder about the lethality of this virus: ""The survey of hotspots in the backyard sector showed almost every flock has been previously infected,'' though not all birds show symptoms of the disease, he said."

So, in these spots where there have been bird flu outbreaks, virtually every bird was infected but they didn't all die or get sick. Why? Were they given vaccines, or are they naturally resistant? Are they now carriers? Or could they possibly be used as a source of antiserum?

On another note, on those occasions when the ducks and geese in North America have been tested and shown to be infected with H5N1, we are told they are "pretty sure" it is the "non-lethal" or mild type, and not to worry because the birds aren't sick. But from the above, it appears a lot of the birds in Indonesia that have or have had the virus also do not appear to be sick, so this doesn't seem to be a good criteria. Since I am not a geneticist, I would really appreciate someone who is knowledgeable explaining to me what criteria they are using to tell a high pathogenic H5N1 from a low path one in these birds.

Edmond,
I have no excuse for the name calling and I apologize.
Revere,
Thank you for answering my question. I apologize to you for the argumentative tone of my previous posts.
In general, I just want to add that I keep seeing government officials in Indonesia insisting that people are being infected with bird flu, and some are dying, as a result of contact with sick poultry. Of course they may be correct.
But what happens if they are wrong, and people are being infected by contact with dogs, cats, or some other animal?
This is not some theoretical issue. There are increasing numbers of human clusters in Indonesia. These people are getting sick and dying at an increasing rate. This is a life or death issue. If, for example, people are getting sick through contact with their dogs, and we know this, then something can be done about it. And government officials in Indonesia will hopefully act to stop this vector from infecting people.
But what I have been very slow to realize is the profound ignorance of the scientific community in regard how H5N1 is transmitted, and how difficult it is to identify the vector.
There is a vast amount that is not understood.
I fear time is running out for the scientific community to find the anwers that are needed to slow down the spread of the human H5N1 infection. The clusters in Indonesia are growing rapidly, and the clusters we know about are probably only the tip of the iceberg.
I greatly admire what Revere and Henry Niman are doing.
Now I want to quote from Revere, from a post yesterday.
In comments regarding the study on the human immune response to H5N1 infections Revere said:
"There is a lot of work being done on this and I think if we are still around, that we will know much more within a year. If we are still around, that is (that is a joke--sort of.)"

Thank you for your math, MIH.
What I do understand from 'non-lethal' or 'low pathogenic type' is that it is so for the chickens tested on it in a laboratory, but that doesn't have to mean it's also Low Path for humans. It usually is, but since ducks can have H5N1 without symptoms and still be dangerous to other fowls or mammals I wouldn't be reassured by some message like this.
When it takes some time before they conclude it is low path they maybe have done the laboratory tests on chickens.
If they conclude it right away within one or two days it maybe just an inference made by their not being able to find masses of dying birds in the neighbourhood of the index case.
Also a LP could mutate to a HP, as you and I are knowing.

I think you are right in questioning how they concluded about low path in North America. Some well informed reporters could be questioning the source or maybe the government could announce some official information desk where all questions will be answered?

For who's interested in the differentiation between HP and LPAI (Low path avian influenza):
The level of pathogenicity is measured by infecting the fowls in a laboratory (usually chickens) and observe the onset of symptoms, occurrence of death, and percentage of death within about 10 days. Revere wrote about it in an earlier posting at the old Effect Measure site.

A more precise description of the procedure I found in a newspaper during my holidays. I will look it up in the coming days.

willliam: Apologies are not necessary here, but I am happy to accept although not required for you to tender it.

MiH: Given the exposure, it is not highy transmissible form chickens, true. But consider that the probability of transmission may also be very small, either because the transmitted viruses have some factor allowing it to happen with some people, the risk factors for people getting infected (unknown) may be rare or something else.

Yes, there may be another reservoir and people are checking cats and I presume dogs, if some investigation has shown this may be a risk factor. And if I had to guess a mammal where it is hiding I'd guess bats. Don't know if they've been looked at. However if it has adapted to some mammal it still isn't very transmissible between humans.

I am not at all surprised that for an infectious disease, the rate of really serious cases is small. That's normal. The thing I can't understand about this is that there seems to be so little mild and inapparent infection. This is not like any other kind of influenza virus in that regard. There just isn't any evidence to indicate it exists, but I can't help but think we are missing it, that it is around a lot in humans and we aren't seeing it.

That's the hunch of an epidemiologist, but just a hunch.

From tan06: "The level of pathogenicity is measured by infecting the fowls in a laboratory (usually chickens) and observe the onset of symptoms, occurrence of death, and percentage of death within about 10 days."

Is it just me, or is anyone else feeling these days like we have fallen through the rabbit hole and back into 1952 here with pathogenicity tests that need live chickens and take 10 days, and vaccine production methodologies that use football fields full of actual eggs instead of bio-technology? In this world, are they still using those poor fuzzy little live rabbits to test whether a woman is pregnant? It's 2006!

I know, funding, funding...

Pixie: Not just funding, timing. We didn't start this until it was on top of us. This is one more casualty of the War on Terror which sucked the oxygen out of priorities. If we throw all sorts of money at it now, it would still take time because science takes time.

Mary First let me disclaim by stating that I have no idea what a phylogenic tree is. And I agree with you that we need more data on cats, dogs, etc. But I'm not quite sure that quite adds up to there necessarily being an intermediary host between chickens and humans.

The way I understand it from reading EM this last year or so, the small number of human infections could be explained by the virus not being well adapted to humans. That doesn't mean it necessarily is explained, but it could be. I don't know enough about diseases to make a disease analogy, so let me try a homier one.

Say H5N1 in chickens is represented by lentils. The species barrier of the virus not being well adapted to humans is a sieve whose holes are too small to allow the lentils through. And the little pieces of lentil skin or small broken bits that do make it through the sieve are the human cases.

You're saying, this sieve is too small to let any lentils through, or else there would be far more bits coming through. There must be a grinder somewhere dogs or cats or another intermediary that is allowing these lentil bits to fall through the sieve.

There may be a grinder (intermediary) or there may just be the random chance and rare confluence of circumstances that allow the bits to come through. The holes in the sieve may be getting bigger (the virus getting better adapted to humans), or we may just be watching more carefully or sifting more lentils (more infected flocks). Revere, does this analogy work for you?

To abandon that conceit, if there were an intermediary such as dogs or cats, to me that would raise additional questions. Particularly, are cats and/or dogs that much rarer than chickens that they would explain the human cases but not also raise the question of why there aren't more? You see, I'd have the same question about them as you do about chickens: why the relatively small rate of human infection? There might be good cultural/epidemiological reasons for that, I don't know... or it could just be that sieve.

Caia: I like your analogy, and do understand the premise. But it seems like once a human does get the virus, there has been an increasing tendency for it to spread in human clusters rather easily and rapidly (and then die out rapidly as well) compared to the ratios involved in the initial B2H spread. This is another oddity. First it's extremely tough to get, even when there are infected chickens all around you daily, (your lentils and sieve premise) but once you do get it, it's fairly easy to pass on. Remember the Garut cluster, where WHO hypothesized that the family members were infected by sleeping in close proximity to the female index case...I believe for just one night? WHO didn't even say those who became ill were necessarily tending to her, just in the same room. That screams airborne to me. Chickens don't cough much, nor are their human caretakers likely to nuzzle up to chickens, so that might explain why B2H is so rare. If we can for a minute stick with the hypothesis that the respiratory tract is the point of entry in H2H, how is it getting into the lungs in B2H cases? Possibility 1: airborne dried feces with virus particles attached enter lungs as a woman sweeps her house. How to check? See how many of the victims kept chickens right in the house. Possibility 2: Perhaps bird mites carry virus to lungs. They live on the poultry host until it dies, and then jump off looking for a new host. They could go airborne (they're small enough) or could simply climb onto the human who is handling the dead carcasses, who then scratches his nose or mouth and there you go. I recall there is also evidence of blood to blood transmission, in which case a bird mite could work quite well. I am more inclined to guess that if there is an intermediary between poultry and humans, poultry and cats, poultry and dogs etc it is not a mammal but some kind of lowly invertebrate who sucks blood...but if guesses were dollar bills we'd all be in Vegas. None the less, has anyone been checking mites (or the correlation between people who let their birds poop in the house and cases of bird flu?) Might be worth a look.

I'm never sure what is meant, precisely, by airborne, but I agree that family cluster indeed looks like spread by coughing.

And I hadn't considered the apparent tendency to cluster. I can see several possibilities. One is that this has something to do with the clade of H5N1 that is spreading in Indonesia... it may be more apt to produce clusters than other clades at other times. (Split lentils that cook faster?)

Or it could be that there are more situations which do end with a single infected human that are never recognized. Think of the pattern we keep seeing: person is suspected of bird flu. A person near to them has recently died (supposedly of pneumonia, denge, etc.) but was never tested. So when, if ever, would we hear about a single case? If the person recovered, no one would look twice at them. If the person died, but no one around them took ill, then still no one would look twice. We've seen that it can be long into treatment of the second victim before the families will even admit they'd had sick birds.

We might look askance at overall rates of pneumonia or denge, but we'd have no way of knowing which, if any, were actually H5N1. Maybe H5N1 is getting more cluster-prone, either in an intermediary or by some other means, or maybe we're just missing a lot of cases. Neither of which is very comforting.

There may well be another mammalian reservoir, but let's put this in perspective. In the long run, (a) H5N1 has to evolve to become highly infective, and (b) a pandemic will only be sustained through h-2-h transmission, not infection from some unknown source. If there were another mammalian source, it might increase the potential for further evolution, perhaps toward inceased infectivity in the HA subunit, but as Revere points out, this also might increase the chances for differentiation into species adaptation.

I asked Henry if he would publish his sequence and match findings, but he declined to answer this time. That's a pity. We need a paper published in the peer-reviewed literature to open debate on the subject.

If we looks at SARS, it is likely that the civet secondary source was important in the very early stages in increasing the chances for human infection, but after a while h-wh infection dominated. The ultimate repository of bats in the case of SARS probably made the new coronavirus strain possible (a long-term mixing vessel model), but it did little else. We might expect H5N1 to follow SARS here, and if it does, identification of other repositories is important, but whether there is a pandemic will depend on changes to the virus that will increase infectivity and then sustained h-2-h transmission. For the last 3-4 months I haven't seen any significant changes that would make me change the current phase status of H5N1.

Marissa, re your last statement.
Granted, B2H transmission is still extremely extremely low. From the statistics in the article above, 12 million Indonesians are daily in contact with H5N1 infected birds, and only about 60 got it so far, and of those maybe half caught it directly from birds and half from the first human in the chain to get it. A simplification, but not all that far off for the sake of the math. So, the odds are .000005 to 1 that you will get H5N1 from your sick chicken. However, if one out of two cases got it from another human who was infected by chickens, then it would appear once your brother in law gets it, the odds are .5 to 1 that you will catch it from him. That's a huge difference in orders of magnitude for infectivity H2H compared to B2H.

Is that right? If so, it's pretty scarey. It means we already have efficient, very efficient H2H with this virus. The inefficiency, the thing that needs to change for it to take off like a rocket, is increased B2H transmission. So looking at the situation in that way, shouldn't we be at phase 4 or 5.....?

Mary: I'm not sure what you mean by 0.5 to 1 chance... I think you mean 0.5 chance, (where 0.0 is impossibility and 1.0 is certainty). At least that's how I dimly remember my stats class. In order for you to have a 0.5 chance of getting H5N1 from an immediate family member who had it, i.e., a coin flip 50/50 chance, we would have to observe that the average index case gave it to half his/her immediate relatives/close contacts. The curve would probably encompass index cases who gave it to no one, and index cases that gave it to everyone in their household, but the average in this case would be half their relatives.

i.e., this would be different from half of all index cases giving it to someone, because then the chance would be the one person who got it divided by however many members of the household (or other close extended contact) there are... which could be 1 or 2 or 8 or 10. So what looks like a 0.5 probability (p=0.5, IIRC), when half of all indexes give it to someone could really be a quarter, sixth, or twelfth chance (0.25, 0.125 or 0.1). We might actually have clusters now where it seems like half the household members get it, but like I mentioned above, we may not be seeing all the cases where the index gave it to no one, so the actual percentage of relatives who get it is probably lower.

If you're talking about the average number of people each index gives it to independent of how many are around them, or reproductive number, Ro (don't know how to make the subscripts appear here, sorry), then an Ro of 0.5 is not really that high. As Revere recently explained, anything with an Ro less than 1 will peter out. And the Ro for the second or third generation cases appears to be pretty small, with the 3rd gen Ro approaching zero (as we've had no confirmed 4th generation cases yet that I know of). Plus, again, the index Ro is probably not 0.5, because of all the cases we don't see.

So no, I don't think the hurdle H5N1 needs to get over to go pandemic is increased B2H. I think the hurdle is more efficient H2H. Sure, the clusters look scary, and each new human case gives the virus another chance to learn the efficient H2H trick. Increased B2H is worrisome for that reason. But even if we had twenty clusters in Indonesia right now, if the Ro of the index stays below 1, and the Ro of the later generations stays even lower, we'd still not be at pandemic.

That said, I think the clusters now do look like phase 4, but then, I'm pretty safe saying that, since Revere did months ago. *g*

Mary, to reach Phase 4 using the new WHO definitions, we need a few clusters greater than 25 people. This implies an R of slightly > 1. Again, the limited h-2-h transmission we have seen is still very limited, otherwise we should be seeing large clusters of over 100. So my opinion still stands. The new criteria might seem arbitrary, and they are, but they're still good guides as to what is going on. Bottom line: when I see clusters of 50-100 with intervals of 2-4 days between infect dates, then I'll be a lot more concerned.

The key is the R (reproductive number). Click on this link and read the section on R--it will help you understand h-2-h transmission better. Might also be a good science lesson for your students. Note in the article the differences in R between the first and second waves.

Something new to look at is the total number of cases as of the 25th of last month. We are now getting a case roughly every 3 days for 06. The outcomes, well you know what most of them are. This has gone from only about 1 a week in January to this rough rate starting in March. If we use the WHO criteria and because of surveillance there will be approximately a one month lag before they make the call. In fact Marissa I am with you on this and re: "When I see clusters of 50-100" I will be a lot more concerned"

That IMO would indicate that it would be out of the Indon petting zoo or someplace like it and coming. The surveillance is so very weak and it takes way too long for them to call a case a case. So it would be about a month before they called it and likely would be into Pan 5 by then-possibly higher. The great big badassed plan that the WHO would throw up unless implemented much earlier by local governments would be worthless. It looks good on paper but getting someone to make the call is way too difficult.

Arguably, one person could infect as many as 68 people a day if he was motivated to do so and wanted to remain inconspicuous-(Joint Services Bio-Warfare Tranining Manual). So figure half of that for Johannes J.Ginting. One person in an H2H kind of way would be able to do 30 without any motivation, who would do another 30 each and then so on. I dont think it will move that fast but its a fair estimate to say from looking at the models that it will be on us super fast and in a month if it comes. Doesnt matter, they'll just call it ordinary pneumonia to preserve the tourist season.

William: you wrote:

"But what I have been very slow to realize is the profound ignorance of the scientific community in regard how H5N1 is transmitted, and how difficult it is to identify the vector.
There is a vast amount that is not understood."

The scientific community is anything except ingnorant. There is an extreme amount of knowledge in each area of science that a person must learn in order to become a specialist.

The more we learn... the more we realize how much more there IS to learn. I would liken your comment to the thought many people have in their view of the medical field. Expectations of the public are for us to "fix" them.... "cure" them.... make them better. Sometimes it is just not possible...... Why? Because we do NOT know it all....... Although most nurses and doctors will not give up trying.

Yes, I agree with the part of your comment " There's a vast amount that is not understood" . This is frustrating for the scientists, epidemiologists, public health persons, nurses, doctors,, and many more specialists who are working to try to stop any potential pandemic. But, we acknowledge it, and then try to figure it out.... methodically....... by using science as a tool.

I posted a thread on Fluwiki I would like you to read. The title is "Pandemic, as it unfolds." The link is below...

The content is all from WHO updates, and it shows a true progression of information we might see in an H5N1 Pandemic. I won't tell you more than that...... But, it represents how our lack of knowledge progresses to better understanding...... But, it doen't lessen the fear that is generated by the reporting of facts.

http://www.fluwikie2.com/pmwiki.php?n=Forum.PandemicAsItUnfolds

In the tropics there are not just microbats, the cute little things that catch insects at night. There are also megabats, the Flying Foxes.

Various species of these weigh up to 1.5 pounds with up to a 5 foot wingspan. They eat fruit during the day and operate by sight, not echolocation. They hang out in "camps" in trees. If you harvest the fruit also, you have a major bat feces exposure.

This story brings to mind a question I've wondered about for some time. There's extensive discussion, in the news and in flublogia, of the H5N1 case fatality ratio in humans, down to some fussing over the next decimal point. There's also discussion of whether a potential upcoming H5N1 pandemic would of necessity have a substantially lower case fatality ratio than the current one. But I don't recall ever seeing any estimate of the H5N1 case fatality ratio in chickens. Does anyone know what a range for this is? Obviously, we're only beginning to get a grip on the lower end of the range for this, as the above story on asymptomatic H5N1 positive chickens points out. But, for instance, when H5N1 goes through a chicken farm, what's an approximate maximum percentage of chickens that develop symptoms, and what percentage of those die? Obviously these numbers will vary strongly with the type of poultry operation (e.g., with how the chickens are housed). But how many die? Does anybody know what happened last year on poultry farms in southern Russia, for instance?

Part of my motivation for asking about this is just curiosity. The other part, though, is that I believe this question has some bearing on what we might expect if H5N1 becomes a pandemic virus for us. As you all know, the argument has been advanced that for a flu virus to turn pandemic in humans, the case fatality ratio "should" or "must" drop to a fairly low level, from its present level of ~60%. Others, including the reveres, have argued that such a drop in the case fatality ratio is by no means required. Well, what about the chickens? H5N1 has been going around in chickens for a number of years now, and my impression is that it still kills an awful lot of them. My impression from news reports from southern Russia (sometime within the past year...), based on calculations using numbers provided in those news reports, was that H5N1 was killing ~70% of all chickens on farms where infections developed. Does anyone have any better information? And isn't it interesting that H5N1 does seem to spread rampantly among domestic poultry, and it still manages to kill an apparently large percentage of them, for years on end? Granted, the lifespans of chickens are shorter than those of humans, so the year-to-year dynamics of infection are different in such short-lived birds vs. humans. Probably things will take longer to settle out for the birds than they would for us, too. But why isn't the apparently high death rate in chickens ever mentioned as evidence for why the case fatality ratio in humans doesn't absolutely need to decrease in order for H5N1 to "go pandemic"? In the biological world, things can take a while to settle down to a stable equilibrium.... Don't the chickens give us some strong evidence for this? The chicken H5N1 pandemic developed with a high case fatality ratio; doesn't this alone provide evidence that the same could happen for us?

L: High path H5N1 strains have been essentially 100% lethal in chickens. That is the usual case. If they are vaccinated, they may still become infected, shed virus (but to a much less extent) and appear healthy. For an unvaccinated bird and most strains, however, infection with H5N1 means death. They are packed together in factory farms and the virus travels quickly and can kill a bird and still be easily transmitted. We still don't know what the dynamics of virulence will be in a human population. As I noted in my long post on the evolution of virulence, the dynamics can be complicated and counterintuitive. The maintenance of high virulence in chickens is an indication that there is no "must" about this.

revere: Thanks very much for your response. I appreciate it, as I do all of your work here.