Forum: H 5 N 1 Spreads More Efficiently H 2 H Than B 2 H

This should have occurred to me some time ago, but it just struck me, H5N1 spreads more efficiently human to human than bird to human. We know from seroprevalence data that bird to human infections are very rare. Revere commented on this on Friday at Effect Measure. So, there is a very substantial barrier to bird to human infections. But, once it does infect a human, how often does human to human spread happen? Actually, human to human spread happens alot. As a proportion of all cases, clusters of H5N1 cases are very, very common. I have long thought that the separation of onset dates makes it likely that human to human spread was the most likely explanation for these clusters, rather than common environmental exposure. The mounting body of data regarding seroprevalence data supports this. If bird to human spread is so hard and uncommon, even among people with massive exposure to infected birds, how likely is it that members of the same family got separately infected by birds at different times? Not very, IMO.

People who are reassured by the barrier to bird to human transmission are mistaken, IMO. Because the converse is that the barrier to human to human spread is much lower than has been advertised. And after all, isn’t that what we’re really worried about?

Monotreme, couldn’t it also be possible that every now and then a bird will become infected with H5N1 and a mutation in the virus in that particular bird carries the ability to more easily infect a human or group of humans. In other words, that particular bird becomes a super carrier with a variant of H5N1 that is easily transmitted to humans and as the H2H occurence is still rare, it dies out when the one bird is disposed of? It would account for a variety of clusters where H2H transmission is not occuring, but where multiple humans are becoming infected. Just a thought.

Monotreme: Brilliant supposition! The only modifying factor might be the more constant intimate contact that humans engage in when a member of their family is sick. But that would seem to be only a slight modifier.

Every cluster is a prime opportunity for a “break-out”. And those opportunities will exist as long as the bird population harbors H5N1, and humans dare to live with their fowl.

Medical Maven, welcome back!

Note that the non-appearance of new cases in Turkey and rare cluster cases elsewhere is not to be ignored. Nonetheless, no one’s packing it in and saying ‘the worry’s over’. Not even Fauci and Gerberding.

Snowhound, no. Then the human sequences were different from the bird sequences. Well, they are in Indonesia - but not in the Qinghai-strain

Snowhound1: I think there are many H5N1 stains out there, some of which might be better at infecting humans than others, but that wouldn’t change my central thesis. If a given flock of birds had the B2H strain, then one would expect all the exposed villagers to get sick. That doesn’t happen. If only one bird had the B2H strain, then one would expect everyone who was exposed to get sick at the same time. In fact, the family members are often infected sequentially.

Medical Maven, thanks. I agree with you. Although I think H5N1 transmits H2H in a fairly high percentage of cases, I don’t think it’s being spread via respiratory droplets, yet. My guess is fecal-oral. This would require intimate contact, such as occurs between family members.

DemFromCT, flu season is over in Turkey, but not in Australia or Southeast Asia.

I don’t think h2h is fecal-oral. The virus goes into the lungs and hardly into the intestine. You can probably get it by eating but presumably it will infect you before it enters stomach. Do H5N1-patients sneeze ? I think it’s directly by breathing virus. Either by droplets or dust. Or by kissing, drinking from the same cup, using the same spoon or such.

gs: The virus goes many places in humans. One of the peculiar, and unusual for flu, symptoms of the H5N1 infections is severe diarrhea. I doubt very much that H5N1 is currently spread by respiratory droplets. If it was, the pandemic might well have already started. Also, the available studies on receptor binding don’t support this. btw, it spreads among birds fecal-oral.

Perhaps the family clusters represent a genetic predispoition or lack of a genetic predispostion to contract H5N1. Look at the fascinating work being done on descendents of the plague in Europe and the UK. Link:

http://www.thetech.org/genetics/ask.php?id=10

God, it feels so good to be back! Thank you all!

Grace RN: I have heard the family predisposition argument before, from Peter Cordingly, I think. Problem with that one is, sometimes spouses are affected. Also, nurses have been infected from patients as well. Also, if you accept the fact that there are not alot of asymptomatic cases, and the evidence now strongly supports this, then the clusters loom much larger. H2H is very common among the documented human cases. So, whatever role genetics plays, we can assume that the genotypes that allow for human infection via humans is quite common.

mono, there was an article recently from EF?? : how safe is food. Also the cat-studies etc., it is assumed that H5N1 goes into the lungs, see the alpha2–3 receptors. If it would bind to alphs 2–6 it would probably be more efficient and that’s assumed to be the reason why we have no pandemic yet. Not oral-fecal. Human stomach has PH=2, while (adult) birds have almost neutral PH in stomach. So H5N1 infects in the intestine in birds. The dead tigers and cats can have caught it by breathing through the mouth while eating or infecting the mouth-mucous or such. This is unclear, though, since just the 3 out of 7 cats who were fed the H5N1 had some signs (don’t remember which) in the intestine. But this is not yet seen as proof, it’s unclear.

Hi everyone. Grace, I agree. Just a thought. If we remove all the variables that we discuss every day in one way or another we can simplify things. In 1997 were there clusters….no. Are there more clusters today then two years ago…yes. Are the clusters bigger today than two years ago…yes. Are there known multiple strains of H5N1 circulating…yes. Are we seeing differences in clinical expression in humans…yes. Does this virus seem to be following the same pathway H1N1 used in 1918…yes. The source of the infection was China…yes. Has China done enough to eradicate this virus in the foreseeable future…no. Is H5N1 entrenched in several countries including Indonesia…yes. Has the WHO announced it is endemic in Asia…yes. Is H5N1 likely to continue radiating out from its source in China and now Asia…yes. Will H5N1 to continue its steady evolution into humans, birds and a variety of other mammals never seen before with other influenza’s…yes.

Therefore, we are one pig and one farmer with a big family who likes to travel away from a pandemic. Will this condition exist for the foreseeable future….yes and all other arguments must reflect this fact.

Tom - Thank you for an astute and succinct statement of the current situation. I think I may well make a poster of your “checklist” and use it as my source of continued motivation.

Thanks Eccles…coming from you it means a lot…I am embarassed and speechless.

Tom DVM - at 13:50 - sometimes graphs, posters and checklists, etc., are more effective in making important points with those that you are trying to teach. If you don’t mind Tom, I’d like to incorporate your list into emails to friends that remain unconvinced. This checklist is one that could be updated on a daily basis….unfortunately.

gs: H5N1 does infect lungs in humans, but many other tissues as well. The route of infection in mammals has not been established. Fecal-oral is my guess, but I’d like to see this tested explicitly. Cats fed infected chicks got it. I don’t think they got it by mouth-breathing, but that’s just my opinion.

Tom DVM: Nice summary of why all the variables that affect pandemic risk are going in the wrong direction.

There was a case in Indonesia where the mother and two (?) children were infected. In some later cases the father and one or two children. There seems to be something about bloodlines when one but not the other parent gets sick along with the some but not all children. I think there was a similar set of cirmstances in Turkey where sisters or cousins and their children but not spouses got sick. Seems to me that this needs to be looked at more closely. There are probably exceptions but my gues then (and now) is something in genetics is involved.

JoeW: If you check this link, you’ll find a number of examples of spread to unrelated people. Although infection of spouses may not be routine, I suspect this is due to one parent being the caregiver, usually the mother. In many of the clusters, the child gets sick first, then the mother. That being said, there could be genetic differences in susceptibility, there usually are with infectious diseases. However, keep in mind that clusters represent a very large percent of the total human cases. That means whatever the genetic susceptibility is, it’s common.

I would go with the waste products of the body. After all it is the poultrys waste products that seem to be the lethal agents, as well as the infected corpse. The mother would be cleaning up the childs diarhea and disposing of the fouled linens, or whatever they use as bedding.

I also agree that right now B2H transmission is likely body fluid/oral/extreme close contact. I remember reading about one case (Indonesia?) early on where the mother became ill after “kissing the ill daughter over and over again on the lips.” Some who got it got it were reported to have handled “dead” or “sick” birds, either chilren caring for the birds or older people killing the iinfected birds. There was also a story that in one village that had human illnesses- over 300 villagers were tested and none showed any trace of the virus, outside the immediate family (if I can find the link I’ll post it). This suggests that the virus has not yet made the mutation that makes airborne transmissable. But, as we all know, it’s likely not a matter of “if” this mutation happens but “when.”

Melody. Of course, you and anyone else can use anything I have written, anyway you choose.

Monoreme. Thanks.

The issues of susceptibility and transmissibility are interesting ones from two angles. One is just how unique H5N1 actually is and the second from evolutionary adaption.

In the case of transmissibility, H5N1 has demonstrated a unique ability, other than H1N1 in 1918, to cause respiratory, neural and digestive system clinical signs. I understand it is rare for influenza to be spread by the fecal-oral route but given its ability to infect the human digestive tract then it should also be transmissible in that fashion. Therefore, it is transmissible by bodily fluids and respiratory routes as in Iraq; an uncle who only went in the ambulance with his neice was also infected.

When considering the second issue, susceptibility, I think it wise to consider this from the approach of viral evolution to adapt to a new species. Don’t forget, it is attempting to do the same thing now to several mammalian species at the same time.

There are two groups to consider, children and adults. I believe that children are more susceptible to H5N1, not because they are in closer contact and recieve a higher viral load, but because they are physiologically more susceptible…could be any one of a number of variables…short respiratory system length, different receptors in childhood than maturity, different body temperature, different contents of respiratory inflammatory cells (immune system) or different respiratory secretions that favour viral entry…and as we discussed the entry could be respiratory or faecal-oral so the same argument would apply to the mouth environment etc.

With respect to adults, there appears to be a factor that make a few (at the moment) susceptible and most not susceptible. This could well be due to genetic factors or undetectable rare immunodeficiences or it could also be in a rare occurence of super-carriers or super-shedders.

I believe that the virus uses the young as a gate-way to get a toe-hold into a mammalian species and then directs further adaption through cycling in this small portion of the population. The adult infections maybe outliers from this toe-hold and represent small advances in adaption, in my opinion.

My toddler daughter and her peers are always putting thier hands in thier mouths (of course I do what I can to discourage it). That’s all I need to see to know kids will probably get hit harder than adults.

The Hand-to-mouth approach makes more sense than the Siegel/Orent/Others thought regarding the depth that the flu virus must go to harm.

Sorry. Do you ever notice that you start writing and lose your train of thought.

Anyway, If we look at H1N1 in 1918. Brian states that it was first identified in 1874. If we assume that the pandemic in 1918 was an intermediate evolutionary step then today is where it was headed from its emergence in 1918. It has been stated that H1N1 is involved, one way or another, in most seasonal flu outbreaks today…therefore H1N1 successfully accomplished its goal of adapting to humans as it is now endemic. It only kills the very young and very old, except in rare cases it does not kill the majority of the population.

H5N1 is at an intermediate stage of adaption. It could have been eradicated before it got a toe-hold but that did not happen. It has expanded its area of infection, increasing the opportunity for further mutation. If its goal is only to infect birds then it has already been successful, as it has been classified as endemic in the Asian region by the WHO. If that was the case then infections in mammals would be abberations. There appear to be too many infections in mammals for this to be the case….but only time will tell…just a few thoughts to expand the conciousness.

Satago. I agree with you about children but studies of handwashing have shown that adults cleanliness is often not quite what they think it is as well.

One last thought. If the infection only occured in toddlers than hand to mouth infections would likely be the cause, but H5N1 affects primarily the young and particularly non-toddlers and teenagers. Therefore, toddlers putting hands to mouth would not be the full explanation although could explain the susceptibility in that age group.

• **. Me again. If you assume that non-toddlers, teenagers and adults less than thirty years of age, have approx. the same handwashing efficiency, then there has to be another factor making the young more susceptible. Particularly interesting is its inability to infect the very old as they often demonstrate the same susceptibility to pathogens as the very young. This indicates that there is another unknown factor at play that makes the young more susceptible at this stage of H5N1 adaption.

There has been no evidence (yet) that H5N1 has adapted to be able to bind with the human alpha 2–6 receptors of the upper airway, which would be required for airborne transmission and pandemic levels of the disease.

Tom, The very young and the very old are always more susceptible to infectious disease. In the young this is because of an immature immune system, in the old it occurs because of a weakened immune system.

Tom DVM, yes I’ve become painfully aware of my hand washing habits in the past year or so and now make a serious effort to take better care. Still, I don’t put my hands in my mouth after I’ve just shared a banana with my co-worker. And I always wash up between picking my nose and licking my fingers.

I’m trying to teach my daughter better hand washing habits, but it’s a delicate line…you know how kids can rebel against things. And I don’t want to create some psychological issue about it, either (though I’m willing to accept it vs. the alternative)

LGCMA - Tom is highly educated and experienced. He knows the basics cold. If you check charts of the ages of people killed so far from H5N1, you will see the old are barely affected so something very untypical is going on here.

Monotreme, Tom DVM, gs, all - this is science at it’s best! I hope it’s being looked at, or forwarded to, people who can actually look at more raw data than we have.

Tom DVM - your list deserves a post on some blog, a link from the main page, or being turned into an email “meme” like what we’ve seen with the “rumsfeld and roche get rich so it’s a fake prepandemic” meme. How do we make it a successful meme? But i disgress.

Thanks Satago, LGCMA and Allquiet. The problem is that I am not explaining myself very well.

Okay, Monotreme will probably have a set of statistics on every case of H5N1 breaking it down to age ranges.

There are essentially two groups…those that are suceptible and those that are not. Monotreme can break down the age groups but for the sake of argument lets say those under forty years of age are susceptible and those less than forty years of age are not. The susceptible group breaks down into toddlers (Satago), pre-teens and teens and adults. If we assume that adults in the 20 - 40 yr age group wash their hands with the same efficiency as adults in the 40–70 age group then there has to be an unknown physiological factor making the 15 - 40 age group more susceptible. Satago is completely right about the toddlers. The question is why the other age groups are more susceptible.

This leaves the very old. As LGCMA states, for a wide variety of pathogens the target and susceptible group is the very young and the very old. Therefore, immunogenicity in the very young and the very old cannot play a substantial role in the differences in susceptibility.

The point being that H1N1 emerged in 1874, caused a pandemic at an intermediate stage of evolution and then fully adapted to humans such that it now kills the very young and the very old and only in rare circumstances kills the majority of the populations and that is how it has been so successful. Like H1N1, H5N1 is a pure bird virus that may be at one of H1N1’s stages of adaption and may be following the exact pathway to adaption. If that is the case then we should take no comfort from its limited infection range to this point.

The other point I unsuccesfully tried to make was that there has to be some unknown physiologic factor that is making H5N1’s specific age range susceptible…and again that is because it is gaining a toe-hold to adapt but is still a baby or immature at the adaption game.

If this is true we may have some time before it breaks out if you assume that evolution does not sometimes occur in jumps ie. all required mutations at once and leaps in transmissibility.

By the way, I completely agree with Monotreme’s first post heading this thread. It didn’t occur to me but upon reflection it makes good sense, especially given the clusters of the past six months.

Allquiet - thank you for letting me know Tom’s education and experience, not that I was suggesting he (or anyone here) is not educated. Sorry if I came off that way, Tom. Not to mention, I pretty much assumed Tom knows his stuff by the level of his writing, but I certainly don’t think that disqualifies me from putting in my two cents about it.

Also, I would like to know what has ever been “typical” about the flu, since you all are attempting to call the current adaptation of this strain “untypical.” “The basics” as you call them involve statistics from 16 HA and 9 NA subtypes of avian flu, all of which have very different chemical and pathogenic characteristics. Has there ever been a “typical” pattern of shifting or drifting among any of the strains throughout history?

LGCMA is right that H5N1 has not yet adapted to efficient spread via respiratory droplets, or else the pandemic would have already begun. My hypothesis is that it’s being spread fecal-oral, but is capable of infecting the lungs and many other organs as well. Once it acquires the ability to bind to alpha 2,6 receptors, that’s the ballgame, IMO.

Tom DVM is right about the age distribution for H5N1 cases and deaths not being typical of other infectious diseases, including normal flu. 70% of all H5N1 fatalities were 25 years old or less. More than half below 20 years old. Most deaths occur in individuals between the ages of 6 and 30, although there are some interesting differences in the pattern by country. Clearly something different is occuring with H5N1. Of course, we have to distinguish between transmission and lethality. I don’t have a chart for that, yet. However, here’s the breakdown on the ages of those who have died of H5N1.

There is anecdotal evidence that H5N1 symptoms are milder in older individuals and evidence for cytokine dysregulation which would cause more severe disease in the young. In addition, I think H5N1 has novel properties not seen in any other flu virus, including the 1918 virus. My guess at this point is that if H5N1 acquires alpha 2,6 receptor binding ability without significant changes in it’s other properties, we will have a very nasty pandemic on our hands, much worse than 1918. Let’s hope it becomes a lot more tame before it starts “meeting” us on a more frequent basis.

LGCMA. I agree with you about the atypical behavior of flu viruses. As you know, that is what makes them so successful.

The thing is that some are saying that we will not have a pandemic because it has not done so for the past decade…an argument that makes no sense to me whatsoever.

I am not making the argument that the current adaption of H5N1 is “atypical”. I am making the argument that it is typical: that we’ve seen this movie before in 1918. I hope this makes some sense.

Oops, wrong link above. Here’s the link to the H5N1 Fatality Table by Age and Country

Monotreme. Is there anyway to get a chart of the ages of all affected including the ones that did not die.

To summarize the discussion, H5N1 is a typical flu virus in that it is different from all other flu viruses ;-)

Tom DVM, I wanted to make a chart such as you suggest but the blankety-blank WHO doesn’t provide complete information on the survivors (age, gender, province, etc.), not in Vietnam, not in Turkey. And I had the devil’s own time getting all the info for the fatalities. This is one reason I sometimes descend into anti-WHO rants.

Monotreme. The more I think about your first post, the more it makes sense. Earlier there were few clusters, now there may be more cases in the clusters than index clusters. Could this be an indicator of one of those small adaptive steps.

However, your statement at 19.24…..I’m not too suuuuure about.

shoot, it should have said index cases.

Tom DVM, there was an influenza-report site somewhere - just can’t find it now. The charts were there.

Tom DVM, my comment at 19.24 was my attempt at a joke. Flu viruses are devil viruses to talk about. They share some common properties, but each subtype and strain do different things. I think H5N1 has some things in common with the 1918 virus, but I also think it may have some different properties. We’ll see.

Tom, in your comparison of H5N1 and the 1918 pandemic, I assume you are referring to the structural similarities between H1 and H5 within the globular domain of the trimer??

Mono, your comment at 19:34 is my point exactly… we could probably pick out similarities between strains until the cows (or perhaps the birds!) come home, but we would undoubtedly find as many differences along the way. I just don’t think we can pin this thing down, and as you said, “we’ll see.”

iran has sequenced the h2h and will be releasing it soon

LGCMA. I am a generalist. I just observe and record repeating patterns in nature.

By your post at 19:48, I can tell that you are a specialist or at least, what you said went right over my head…but I’m quite sure that you and Monotreme and our other resident experts in these matters, will have quite a conversation. I just won’t understand much of it.

I feel that H5N1 is ‘typically atypical’. It is atypical like all other flu viruses as you have said…but it is also in a sense typical and from my vantage point, it’s evolutionary behavior appears similar to what we know about the behavior and evolution of H1N1 1874–1918 (H5N1 1957–2006).

I appreciate your analysis and that of Satago and Allquiet. We are all friends here and often disagree ..Thanks.

rummy. Thanks for the information.

It saddens me to think how relatively easy it would have been to eradicate this virus before it implanted itself into so many countries; no one put their money in the right place at the right time. Penny wise, billions foolish. How typical. Now it’s endemic.

Monotreme, Eccles, Tom DVM-all good points. And is it good to “hear” from you again!

Here goes at a real layman’s comment regarding the appearance of H5N1 in the various age brackets.

As we are all well aware, to date, we cannot guarantee that each and every case of H5N1 infection has been tested and reported. In many of the countries (I hate to generalise but…) where human infections have occurred, the existing mortality rate in the very young and the elderly may mask these deaths as being ‘from an unusual source of infection’ - the death would be seen as a ‘not unexpected’ event. Within the data we do have, we hear of cases where family members had previously died and not been tested, so there is no evidence of H5N1 infection in those cases - we can only assume. These assumed cases are not in official statistics either.

Where, in virtually any country, deaths occuring in teens and early twenties are seen as unusual, these are receiving medical attention and, hence, are being tested.

I doubt we will ever move to the situation where each and every person, no matter what their age, running a fever and showing other symptoms of flu or H5N1 infection will automatically be tested - some will still not make it to a hospital or doctor prior to death or recovery - often because the illness or death will not be seen as ‘unusual’.

So, we can see the current prevalence of infection in the 5–30 age-group, but our data is dependent on those seeking medical attention and being tested.

I hope just a smidgeon of that makes some sense!

This thread turned into an age factor subject, and you have hit on something very odd, odder than just cytokine production in youth. Even if there is less cytokine production with age and higher survival rate, there should still be infection in people with exposure at different ages. I didn’t see it before, but now remember how the hundreds of people who had seroprevolence test, turned out to be negative of any antibodies to H5N1. There were 600 people who either did the chicken culling or farmers of sick chickens. It was expected that there would be asymptomatic exposure found. I know that young people can have filthy finger-licking habits, but — all these other adults living in likewise poor circumstances, can’t all be that uptight about hygiene. Are we to believe that at some certain late 20′s age, people suddenly change their habits? Children may play and feed the poultry, but wielding the killing knife would be a parent’s job. Why aren’t there more middle age people, who slaughter chickens, getting the illness?

Concerning the age issue relating to infection. I have to wonder if it is tied to rapidly growing tissues in young people. It seems like I read that the initial outbreak in birds in Russia was during the molting period of the wild waterfowl (a seasonal event). H5N1 appears to have a seasonal occurance. During molting there is a rapid growth of tissue. Could this aspect of the virus needing rapidly growing tissue not be the driving factor in H5N1 infecting young people? Just a guess and a shot in the dark, but I wanted to bring it up.

Annie B, NJ. Preppie, Okieman. All good comments and observations. One way to look at it. According to Monotreme, 7o% of fatalities are 20 years or less. As he explained, we do not know if survivor age distribution is the same because the WHO will not release the information, even anonymously as to country.

So the question is why are 15–25 year age group and the 30–50 yr. age group not. In my opinion, there is a physiologic predisposition in youth that we are currently unaware of…but that assumes the survivors have the same age distribution. The point NJ Preppie makes concerns me because most parents are over-protective and they would do the slaughtering etc. Okieman, I would agree with your point except the age distribution extends beyond the rapidly growing phase. AnnieB, I agree that there may be complicating factors on reporting in respect to age.

These are really interesting scientific questions and important to the analysis of the probability of this virus adapting to pandemic status.

It should have read…So the question is…why is the 15–25 yr. age group susceptible while the 30–50 age group is not?

What about the social asspects of this group?

let me clearify. Is this not the same group that STD’s are at it’s highest level of transmission?

mono: the lungs are infected first, other organs are affected later in the desease. The cats were infected by feeding,intratracheally and cat-to-.cat, they all died. There was also tiger-to-tiger transmission in a zoo. And I think some h2h which can hardly be explained by fecal-oral

here is the EFSA-document: http://tinyurl.com/hla7r

the question is: can H5N1 infect mammels through the intestine ? probably not, many observations are against this , although the 3 cats in the experiment who ate H5N1 got some damage in the intestine while the other cats had no damage. Human victims shed only few virus fecal and probably only late in the desease. I think, the clusters indicate that infection occurred early in the desease (?) [5 days difference of onset of symptoms]

maybe both happen : by breathing and fecal-oral. Also in birds, where fecal-oral is documented, when 100% of chickens are infected in a flock at the same day, can it be explained with fecal-oral alone ?

as for the age-distribution , is this also observed in birds ? Do younger birds get it more often ? They should have examined this

gs Birds would definitely be respiratory or faecal-respiratory.

Hurricane Alley RN. This may be a factor but then would H-H not have to play a role? The WHO is saying that this has not occurred except in I think two cases.

I think we would all agree with you that there is a lot more H-H then is being claimed…and I think that was the point of Monotreme’s starting post in this thread.

these data, how the people were infected are apparantly also being withheld in many cases. Why aren’t these patient’s reports published ? Some of them at least.

I feel, that they really should know by now, how the virus transmits.

Tom, do you have a source for fecal-respiratory in birds ? Is it through dried droppings, then dust, then bird’s nose ?

isn’t this typical. keep people in the dark. they might figure out what is really going on. gee they might even be able to prepare for it.

I don’t have any medical background. That stated it has occurred to me that the baby boomers and older may have inherited from their parents immunity to the virus and each generation after will have less and less. Or you may want to think about vaccines we did get in the 50′s, they protect us from TB for example but isn’t that on the rise now. Is it that these viruses have been lurking waiting for the next “weaker” generation.

to recall, this comment I just found about the cat-study earlier this year:

Researchers think that people mostly catch the disease by breathing in virus from contaminated bird droppings, but it has not been clear that it could spread between mammals by a faecal-oral route too. This suggests that avian flu might spread in water contaminated with people’s infected faeces or urine as well as in coughed-out droplets. Should a human pandemic begin, this could be a major problem in developing countries where poor sanitation would fuel spread of the disease. “We do need to be aware,” Kuiken says. The team also find evidence, for the first time, that the virus can directly attack nerve cells in the gut of cats fed infected chicken meat. This suggests the virus can directly attack the human intestine too, reinforcing current advice to avoid raw, infected meat. Kuiken says the finding could also explain two reported cases of human avian flu in which patients developed diarrhoea and encephalitis rather than the classic respiratory symptoms. Researchers already knew that the H5N1 virus, like other pathogenic avian flu viruses, spreads throughout the body of birds. But they are only beginning to identify the genetic tricks that allow H5N1 to march into so many tissues. Experts are still struggling to predict whether the virus will begin to spread swiftly between humans at all. “I think the greatest precaution we can take now is to control it in birds,” Brown says, “That’s the seething cauldron of the virus.” Cats are not expected to be a major reservoir for the disease.

apparently they are not sure here and recently published another message, why they start a project to examine cats more closely in Indonesia now.

I think the age breakdown of index cases can be easily explained by the social roles of the infected individuals. With the small children, it is undoubtedly hand to mouth. With the children and teens it is them that often care for the chickens as pets or as poultry to be consumed or bartered. The few older adults were all involved with raising or selling poultry and being in very close contact. I believe there are many many more cases that have not come to light and were easily dismissed as “something else” at the time. -especially in Africa, where we should be seeing many more cases by now.

Prepping Gal… now that’s some food for thought. i must admit it has crossed my mind as well. I keep thinking of all the people lined up to recieve thier “Swine Flu” injection in 1978.

There are some similarities here between H5N1 and another influenza that recently crossed the species barrier; H3N8, an equine influenza which now infects dogs and is easily transmissible between dogs.

As I understand it, H3N8 was present in horses for 40 yrs before jumping to canines; and then it jumped specifically to greyhounds, and from there it has been transmitted D2D into pet populations. There has been research involving H3N8, and there is plausible speculation, in my opinion, to believe that the way the virus crossed to greyhounds was because greyhounds were being fed raw horse meat which was infected with the equine influenza virus. The original H2D transmission was not by way of close physical contact between the horse and the dog. It was by ingestion of infected horse meat.

Once established among greyhounds, the virus is now easily transmitted D2D by aerosol airborne particles.

As to age correlation to infection, my guess (rank speculation) would be that the younger more susceptible victims have not been exposed to any agent from which they would build immunity, and that the older generation has been exposed to some closely related virus which has given them a measure of immunity. It would be interesting to research the prevalence of flu that may have been circulating in relation to the different years/ages to find if there was a specific flu that the older persons may have been exposed to which has given them a measure of immunity to H5N1.

Hi all- it is great to be back at the wikie with you all! I have missed this very, very human kind of unstructured discussion- which manages to inexplicably, lead to fruitful conclusions- following the most surprising pathways!

Just some comments which are also a question. Right now H5N1 is a bird virus that is higly infectious to birds- but not to people. My understanding is that the H5N1 which infects birds will never be a great threat to humans- (sort of like AIDS- if we behave carefully, the chances of getting AIDS are slim). The same with the bird flu. The H5N1 strain that is killing birds will not (never) easily infect humans.

However, if the H5N1 virus mutates to a strain or strains that is a human flu virus, we will be in a great deal of trouble- but not from birds, but from other people, who will be harbouring this new iteration (human) of H5N1. This would hold true of cats as well- a H5N1 that was contagious between cats would not pose a huge threat to humans who did not have intimate contact with cats- that strain of H5N1 would be cat specific.

This would go both ways. Birds would not be greatly threatened with getting H5N1 from humans- the strain in humans would mostly be human specific. The threat to us all is when the bird flu virus gets into a human, cat or pig and figures out how to change into a new cat, human or pig flu.

Is this correct, or am I completely wrong? My sense is that we don’t have to be inordinately afraid of sick birds or cats. Sick pigs (more human like) we should start feeling a bit queezy. Sick humans, we should be very worried about, indeed.

Possibly the reason that so few people are getting H5N1 is that 99.99% of the H5N1 out there is bird specific. Maybe 200 people had the extreme misfortune of encountering a bird which was infected with at least some H5N1 that was inclined towards humans? There will never be a great deal of that virus in birds. If it gets a foothold in humans, it would be another story.

clark:


yes, I also think panflu won’t be very infectious to birds
no, I think cats are not so different from humans
no, I don’t think those humans who catch it, are just unlucky to get a mutated bird-strain. Look at the sequences, they are similar (except in Indonesia) there are other reasons that it’s not (yet?) so infectious in humans. One of them are these alpha 2–6 cells. One other could be the acidity in human’s stomach.

petperson:
As I understand it, H3N8 was present in horses for 40 yrs before jumping to canines; and then it jumped specifically to greyhounds, and from there it has been transmitted D2D into pet populations. There has been research involving H3N8, and there is plausible speculation, in my opinion, to believe that the way the virus crossed to greyhounds was because greyhounds were being fed raw horse meat which was infected with the equine influenza virus. The original H2D transmission was not by way of close physical contact between the horse and the dog. It was by ingestion of infected horse meat.


same with the chicken-meat fed to cats,tigers,(humans ?) that it took 40 years could be because horses can’t fly and because there are fewer horses than birds, so the virus has fewer chances to spread. I haven’t heard about this H3N8, is it contageous in dogs as was panflu in 1918 ?

looking up the number of isolates in the database: any HA H3N8 1960–1969 5 any HA H3N8 1970–1979 10 any HA H3N8 1980–1989 24 any HA H3N8 1990–1999 52 any HA H3N8 2000–2006 19

Equine HA H3N8 1960–1969 3 Equine HA H3N8 1970–1979 6 Equine HA H3N8 1980–1989 19 Equine HA H3N8 1990–1999 44 Equine HA H3N8 2000–2006 9

Canine HA H3N8 1960–1969 0 Canine HA H3N8 1970–1979 0 Canine HA H3N8 1980–1989 0 Canine HA H3N8 1990–1999 0 Canine HA H3N8 2000–2006 4

Avian HA H3N8 1960–1969 2 Avian HA H3N8 1970–1979 4 Avian HA H3N8 1980–1989 5 Avian HA H3N8 1990–1999 8 Avian HA H3N8 2000–2006 6

grr, why does the forum-software ignore my newline-characters and I have to include these double-slashes ? That’s unpractical and uncommon.

Hurricane Alley RN, your “social aspects” and your mentioning STD (sexually transmitted diseases - I hope this doesn’t get blocked by the server - grin) makes me think - could there be some co-infection at work? Some other virus or condition which makes people more succeptible to catching H5N1?

Clark’s comments - have all infections been poultry-to-human (p2h), or are there many wild-bird-to-human (wb2h)? Are they any different?

Another hypothesis: could there be a link we’re missing? Bird-to-cat-to-human? This would be a confounding factor, just like when researchers found people who liked coffee had more lung cancer (just because coffee consumption and tobacco consumption were related: many people liked both).

We’re exploring this transmission issue (or maybe it’s more a succeptibility issue). I hope this atracts some attention. At some point in time (let’s not rush it?) there should emerge a few practical ideas on how to research this and what further data is needed.

Older cases may have non-recoverable information, but new cases are another matter. I can imagine getting information on the field is often difficult: done under stress, political circumstances, pressure to do things well, etc. We are not at the battlefront, and hoping this might help.

Please, if someone’s listening, please release any information you may have. Annonymize it as needed, but do count on the hive mind!

The problem with not turning up at the wiki forum for 24 hours is that every thought that you’ve had since has now been expressed by someone else, and spookily in the same sequence that you think them.

Are you guys for real out there or do you exist just in my head?

Or is it jet-lag?

i dont know about you Sybil…but i’m real ;) And so are the rest of the people in my head.

Tom, Monotreme, we do have data for the age distribution of people infected, not just fatalities, in this link.

What Monotreme raised is certainly the best example of lateral thinking.

So here’s what we have so far:

WHat does that tell us? Could we hypothesize that:

OK…so don’t laugh at this thought! The DIET of the very young and the very old could be similar because neither of them might have all of their teeth! This inability to chew (and eat) many foods could affect their body PH levels. It is a known fact that viruses replicate in a slightly acidic PH body environment, (high protein, meat especially, high starch, high sugar). A slightly alkaline body PH is viral unfriendly. Has anyone ever checked the PH levels of the very young and the very old to see if there is a PH connection?

The above comment(anonymous) was made by me. I didn’t realize I had to reinstate my name.

anon, Good try, and I’m not laughing. However, the median age for H5N1 death is 14 years.

PanicStricken,

“I didn’t realize I had to reinstate my name.”

That’s just so we can keep track of who’s just returned after the wiki got back up again.

Just kidding…

anon_22 every thought that you’ve had since has now been expressed by someone else Please say who you refer to! It makes me feel less silly if you’ve thought it too! I’m small and scared, I need reassurance!

Actually, I hope we are useful in advancing silly hypothesis that can be quitely tested by those on the ground. You know, like jokers for the king (buffoon).

anon_22, lateral thinking indeed - as applied to changing our own perceptions, which is what LT is about: (1) changing our own perception about the situation and (2) changing our own perception about what we can do.

I haven’t had time to carefully read this thread since yesterday, only skim. But regarding the age issue, has anyone considered a prior exposure may be protecting the middle age group?

“a prior exposure may be protecting the middle age group?”

The seroprevalence rate is practically zero at the moment, so there is no evidence for that.

Thank you anon_22, but couldn’t there theoretically be an exposure to a strain that hasn’t been specifically tested for that has enough chemical similarities to invoke protection? Just a thought.

LGCMA, some suggestions were made by a few scientists such as Palese, but there was never any credible data to support that.

anon_22, ok, but how would one find this “credible data” on an unknown strain? Just asking, and trying to reiterate that because of the mysteries of these viruses, we really can’t rule out anything.

maybe the new planned Dutch cat-study in Indonesia will reveal something..

LGCMA , the serology looking for flu virus is decent enough, although sensitivity and specificity is rarely published… it tells you exposure to H5N1 or not. The test was good enough to detect poultry worker exposure in hong kong in 2003.

Dem, I am suggesting that a strain other than H5N1 could be causing enough of an immune response to protect certain individuals. To give an analogy, consider that the exposure to one serotype of dengue fever can protect (at least temporarily) against the other three serotypes. Perhaps, in the same way, there is a yet to be identified flu strain that can invoke the immune response to protect against H5N1.

Referring to gs question at 00:04 (you slept when?)about young birds- Juvenile waterfowl have the biggest infection rate by far. However that’s in regards to all avian influenzas, not H5N1 which is too rare to find for comparison, but presumably will flare up at the same time. During nesting time in July and August, the viri population in water resevoirs boom exponentially.

From the USGS site: “The lack of documentation of substantial recurring mortality from diseases among colonial-nesting waterfowl and among waterfowl nesting in sites protected from predation indicates that diseases, by themselves, are not widespread major mortality factors affecting adult waterfowl or their eggs during the breeding season. The importance of diseases in the survivorship of prefledged waterfowl is unknown.”

A little surprising that it is unknown, but whether disease is a factor, some ducks species (larger geese and swans have higher survival rates) have a 90% mortality of hatchlings up to 2 weeks old. From 2–6 weeks, there is a 50% mortality, and up to one year old, still a 75% mortality.

I feel like a passenger on an enormous, surreal ocean liner, a truly titanic ‘Titanic’ with the Owners/Company and also the Captain/Officers analogous to our familiar universe of corporations, governments, the Establishment.

We passengers all have heard of ship losses, one especially disastrous in ‘1918′ and are aware of the ice-berg phenomena and some few of the passengers have been observing the weather, small occasional bergs and fog, etc and expressing concerns. The Captain assures us everything is under control and the crew will handle any small emergency that might arise.

Some have even gone so far as to examine the lifeboats and vests and to wonder if we aren’t possibly steaming at unwise speeds…. They are regarded as amusingly eccentric by the great majority of the other passengers.

None of this affects the round of dances, games, romances, gossip and the daily operations of the catering and the many engineering departments, to suggest but two… ‘Business as usual, chaps. Get about it now.’

I am sure the metaphor needs no further elaboration.

Does anyone else feed a deep foreboding, a soul-chilling sense of dread, the terrifying certainty that this gigantic pleasure cruiser is speeding blindly toward some dim, ill-defined but terminal disaster…?

thanks, NJ. Do you have the URL ? So, young birds die more odten in general and not as a result of H5N1 ?

I am guilty of the above flight, and would now delete it if I had access to the edit function. It clearly disrupts the flow of information and analytic thought. Sorry.

Hmmm…14…to…50? 14(onset of puberty)…to…50(onset of menopause)? Could this virus be needing a certain hormone to replicate? Makes me wonder because the generation with the raging hormones seems to be the hardest hit!

Hey Nikolai, that’s ok… I rather enjoyed your poetic analogy of the situation. And for the record, I am the opposite. While I think it’s smart to somewhat prepare, and I enjoy speculating about what might happen, I find it rather senseless to get caught up in the fear.

wow !!!glad to see this site back!!!thank you mel,dem and pogge,for all the hard and sometimes thankless work you have done.glad to see all the regulars with brains have remained at the roost!things are movin fast and this site has been missed.tomdvm is on a roll,great summation!

anon_22 at 04:39

b) h2h is quite difficult unless you are either related by blood (suggesting host susceptibility) or have very close extensive contact.

I agree with your summation and the two possible explanations. I lean towards the extensive contact idea, but of course, they aren’t mutually exclusive. I wonder if anyone has thought to genotype family members and look for markers associated with infection. Experimental studies could be conducted to more closely examine the exact means of transmission.

gs - site url for the USGS bird mortality report- http://tinyurl.com/hopgx

The information about age/death rates from influenza in wild birds is not there. It makes you wonder “What are they doing!?” Just to highlight some of their reasons-

“Hence, few dead, young waterfowl are found. Mortality is usually evidenced by disappearance of individuals.” (-They are good at counting live heads, and when the birds are missing, they are presumed dead.)

“Only a few investigators have attempted to partition causes of mortality or to quantify mortality rates based on birds found dead during the breeding season.” (-This is not a big career field.)

they could just have determined the age of the dead swans on Ruegen. But FLI is so secretative and doesn’t answer emails :-(

LGCMA,

I understand what you are saying about unknown strains, and therefore do we really know what to look for, etc. I guess the answer is that this speculation about prior immunity due to exposure to another H5 subtype has been explored numerous times since 1997, and there is as yet no data to support that. It doesn’t mean that that’s not possible. But as Dem would say, no data is no data.

(Dem, I think I am going to make a banner out of this NO DATA MEANS NO DATA) and trail it across my desktop:-)

Monotreme, “I wonder if anyone has thought to genotype family members and look for markers associated with infection.”

Do we know what markers to look for? By we I mean the current state of knowledge in virology, not us, at least not myself.

Do we have enough specificity with regards to markers to interpret results if studies are done? How would one go about doing that? Do you have any reference about this even if if it in general?

Hey All, it is good to see the group mind at work. I live with a pair of teen males and I know there are some distinguishing characteristics about this group: 1) They are eating constantly (more opportunity for hand to mouth transmission of germs?) 2) They are HIGHLY social 3) Thier skin is active (sweat, acne, etc) 4) Their hormones are even more active 5) Their mind-set pooh-poohs parental/society safety concerns (it’s not a big deal to drink out of the milk carton . . .) 6) They don’t take the TIME for maintenance (not just bed making, but also proper hand washing — much less a thought as to whether a door knob or telephone is clean) I know you are looking for physiological reasons why young people are more vulnerable, but it may all begin with behavior patterns

Can I also add the physical contact. My son and his friends are constantly wrestling, that kind of thing. They are in constant casual contact with each other, (except when the video games are on). My son knows all about the bird flu, (plus his own health problems) and I have told him about washing hands, all that- he says he will be more careful when it gets here. Having teenagers makes you look back fondly when they were in the “terrible two stage”.

Here’s a recent Cambodia test study, can anyone correct my memory about 600 people being similiarly tested in Vietnam?

http://tinyurl.com/ftl98

“In one of the largest studies of its kind, scientists in Cambodia took blood samples from 351 people in a small village where one of the country’s six bird flu deaths traced to the H5N1 virus was confirmed.

They found no antibodies for H5N1 in any of the specimens, indicating nobody became infected, having either recovered after falling only mildly ill or displayed no symptoms whatsoever.

The results mirror similar studies conducted in Vietnam, Thailand and Indonesia – where the virus has shown up in birds and the people it has infected, but left few other clues. The authors said they expected to find bird flu antibodies in at least 2% of the people they sampled, and were baffled why only one 28-year-old farmer became infected and died in the March 2005 outbreak.

Dead birds were reported in the village in Cambodia’s southern Kampot province and the H5N1 virus was detected in poultry there. Many villagers surveyed said they had very close, daily contact with the birds – collecting dead or sick poultry, feeding them, cleaning up faeces, plucking and eating them.”

Tom DVM at 22:26 why 15–25 Age range? Looking at Anon 22 referenced age chart and prior posts (that beat me to it). I too now think that perhaps there is an interaction problem going on here like bloodline X hormones X ??? lead to increased susceptibility.

Someone with a biological background could tell us more about how hormones interact with a virus. There does seem to be some interactive function going on here.

Anything more than a two way interaction is difficult for most people to understand (including me). I wonder if there is some sort of function with “protection” at one end and “infection” at the other mixed with lethality. No wonder this thing is difficult to understand, it is anything but linear.

Thank you NJ Preppie for that link - I knew I had read that somewhere as well but couldn’t be certain. As far as age goes, I think it is too early to tell for certain who will be at the most risk should it go H2H. So far there are only a few “suspected” H2H cases anyway. And even of all the 200+ “confirmed” illnesses and 100+ deaths (all of whom are presumed to be from “very close contact” with infected birds), that is still a relatively small sample size to extrapolate population generalizations by age group. I used to need bigger sample sizes working in research to claim “cookie a” tasted better than “cookie b”, let alnoe make any conclusions about worldwide illness projections. In addition, the fact that children/teens in most of those countries are left to tend animals, putting them at greater risk of infection, means that the data we do have is not representative of what might occur H2H. I don’t think we can definitively conclude anything yet.

In addition, in the cases where there has been any detail it seems that H5N1 victims at first get something like the regular flu but after a few days don’t get better and then start to decline. My recollection from Barry’s book is that the young adults who “stormed” went extremely quickly - literally some were fine in the am and were dead the next day. If 1918 victims could avoid that then their next concern was 2ndary infections and that was more random by age. Am I remembering correctly?

lauraB, well we do often work at the .05 level for an indication of interesting variables. One hundred deaths and 200 infections should be enough to give somebody ideas. Seems to me that those who have ideas are not talking.

If I could get a handle on the significant variables before this hits maybe I can in some way address these variables when we hunker down. If its bloodlines I can use that, if its hormones, I may or not be able to use that, If there is a mechanism of transmission, I can sure use that. If there is some sort of interaction going on I can use that. I have intentionally used first person in this post because that is what matters until we can get to the larger populations of which you speak. So for me this is a discussion on two levels, personal and social.

This has been stated before. As a toddler you breathe deeply naturally, as you get older you breath more shallowly. Actually older people are likely to be closely involved with toddlers. Look at us here in the states. I know completly strange toddlers make a beeline for me, across parking lots, anyplace any time because of my silvery hair. I’m a generic fairy grandmother. The kids always think they know me, and put their trust in me, climb up on me, and so on. Watch the rise and fall of a toddlers round belly. I would think older people would have become infected more frequently because of this trusting behavior by toddlers.

Woodson’s guide explains three phases of death risks from the 1918 pandemic flu-

Type 1. The 2–3 day massive respiratory failure, cytokine storm.

Type 2. Up to 7 to 10 days, after fighting the virus and losing from the accumulation of dehydration, damage and organ stress.

Type 3. After 2 weeks to 4 weeks or more, secondary bacterial pneumonia, stroke, heart attack.

In 1918, the younger people had the worst death rates, but the other age groups still got infected. I think we are wondering why there are not more infected, older than 30 yrs, people from H5N1.

Hi JoeW, LauraB and Lily et al. All of the points have been well thought out and correct and I thought I would give my impression based on them.

I would assume that since only a relatively narrow age range is being affected, then this indicates a partial adaption to humans. Whether it can fully adapt, no one knows.

If the age distribution is different from other diseases and other influenza’s then there must be an unknown physiological predisposition.

If we assume we have complete information from the WHO (may be a stretch), then we know that it does not break down by sex..more males infected then females or visa versa.

I don’t believe it is directly due to hormones or you would see a difference between sex because hormone expression is different in both groups.

There are a number of potential variables that have been named…and we must assume that our knowledge of the respiratory tract and immunology is limited because it is.

There is however one variable that hypothetically could explain it all (that’s not at the same time saying it is correct).

So here’s my knuckleball. It’s all due to metabolism (ie relative body temperatures).

When I was exactly twenty-five years old something happened to me…I gained twenty pounds…I didn’t even know that I was gaining it and after I realized, it took me six years to sort of lose it again.

I believe the reason it happened was because my body metabolism slowed and my thermostat got turned down for some unknown reason. The end point in metabolism must be a lower body temperature. This may very well be hormone mediated.

Now, I had some inside information because it is a known fact that younger animals have higher normal temperatures and since humans are animals, you would assume the same.

It has been well described that H5N1 likes higher lung temperatures (I think?). Since the internal lung temperatures would be higher in the young, there would be an increased probability of infection. The younger you get, the more relatively active you are and the end result is higher internal lung temperatures.

This is also an creative adaptive step by H5N1 because it would selectively infect children with other infections like…human influenza’s, increasing its opportunity to recombine etc…this is one smart virus.

The way we prove the hypothesis is for the WHO to allow us to talk to every adult that was infected. Did they have a predicating factor to their infection such as extreme exertion (running etc.) or did they have other infections that raised their body temperatures.

…or did they have other infections that raised their body temperatures…or are these adults actually outliers in body temperature. In other words, is their normal body temperature closer to the increased normal temperatures of children than the rest of the adult population.

Interesting thought Tom. I totally agree that as you age your motabolism slows down (I have the waistline to prove it) and that may play a role in how we fight an illness. We all know the aged are at higher risk from flu, etc. One would assume their immune systems have been exposed to most things at that point but children’s immune systems are undeveloped which is why they seem to always be sick (mine are anyway). But, I’m not sure I buy into the body temp part. A “normal” body temp for any human is 98.6 no matter what the age. A 101 temp is a fever in a toddler and an adult. I don’t know about the internal temp though - maybe the more rapid breathing and heart rate of children does impact this? Plus, as I rapidly approach menopause, where do hot flashes fit in? lol!

I also totally agree this is one smart virus…scary smart.

The cambodian data was discussed on this thread

Isn’t it true that people with higher metabolisms are thin. It would be nice to see some photos of infected people before they got infected. Probably not possible but it would help

If I look at the amount of clothes that people wear on a chilly day, I can see what TomDVM is talking about. Teenagers will often be wearing a tee shirt when I am wearing a coat. I have a teenage son and pre teenages son. They always have about two layers less covering (when they are sleeping, sitting or outside) than I do. I know people older than me who always have one or two layers of covering more than me. The simplest rational explanation is often the correct one.

Another study from vietnam on risk factors for human H5N1 at ICEID 2006; the abstract is on page 69 of this document

“In multivariable analysis, direct handling of sick or dead poultry in the 7 days prior to illness onset (p<0.05), having ill or dead poultry in the household (p=0.05), and lack of indoor running water (p<0.04) were independently associated with H5N1.”

For the statistics guys:

Of 97 confirmed WHO cases that were NOT reported dead only 57 had ages published in the WHO disease Outbreak News. Of these 57 individuals who apparently recovered, 35 (about 61%) were less than 20 years old. The remainder, 22 (39%) were 21+ years old.

Clearly young people represent the bulk of infected individuals and are dying more frequently, but they are also recovering at a higher rate. More detailed analysis of the numbers are called for.

I thought that older people had poorer circulation which is why they need more clothing and warmer houses. I remember stifling in my in-laws home. I think they kept their place heated to 80 degrees, but my mother had Altzheimers for such a long time, that nothing was normal in the household. I know I would run out in the snow with zori sandles, no coat till lately. Now my feet get cold in the night without an extra covering. Just informed my cross the street neighbors about prepping, since they asked what I had been doing. I’m the street vagabond. A few sentences only but talk of quarentine measures possible in the future, (next year, who knows) and the sense in having a stash of water and food. As far as being thin, Asians do have different eating habits. I remember a Chinese girl telling me a. they eat with chopsticks, so don’t eat as fast. b. They don’t consume milk products and cheese. So the thinness in Asians may not be metabolism but cultural dietary habits.My female cross the street neighbor is about 100 lbs, but she smokes, and probably has a stringent diet.

Oh,when I had acute bronchitus last month my internist took my temp and it was 97. Have only half my thyroid, so that could factor in, even though I take meds to compensate.The matter is certainly complex.What is normal for me is not normal for someone else.When I look at our own people and the rampant obesity here I beleive that we may well have greater problems than our thinner Asian counterparts.

Looking through the publication cited by anon_22 at 17:08 I found this article on Pg 67 “Clustering of Human H5N1 cases in Indonesia.” (2005). Sedyaningsih et al. Eleven pts admitted with H5N1, 8 of 11 assigned to one of four clusters with two or more cases in a household, relatives, etc.

Four deaths in three of the clusters. Mild respiratory disease especially among children. Each cluster had at least one adult and one child. CFR 75% in adults, 25% in children (age range 4–9). Only one of the index cases had direct poultry contact.

So children in this study were mildly affected. Adults tended to be the ones who died.

The next article says that 400+ families in Cambodia at risk had no symptoms during a predefined risk period.

This is one difficult to understand bug.

the 75% CFR is 3/4 deaths were adults in four identified clusters so don’t put too much into the percentage figure.

http://www.zaman.com/?bl=birdflu&alt=birdflu&hn=28434 Family Matters.

Using Robertson et al’s data discussed in another thread. Children are defined as those under 16 years of age. In 23 clusters reported over the last three years there are 44 children, 22 died, 6 recovered, and in 16 cases the outcome is unknown. The CFR in children is 79% (22/28). In adults there are 33 cases, 22 died, 7 recovered and in 3 cases the outcome is unknown. The CFR in adults is 81% (22/27 cases).

In 23 clusters reported 18 (78%) had children in the cluster.

The CFR is high in children and adults. Children are often infected when a cluster is identified.

The known CFR is 80% in the Robertson study but it should be noted that in 19 cases the outcome is unknown and it is probable that many of these people recovered and were not “news worthy.”

oops miscalculation in adults 22/29 died for a death rate of 76%, overall known death rate is 77% 44/57. If a mistake can be made with a calculator I can do it.

Hi JoeW. You run my computer…I’ll run your calculator.

That’s a deal. I have to get one with big keys, arms are getting too short. The keyboard on the computer is detachable. Nice that someone thought about us older folk.

Joe W. I know your working towards an overall point with your analysis…I’m a little to dense to get it. Was there something in these statistics re: clusters.

I think Monotreme hit the nail on the head in his first post…a mind bender…I would never have thought of it that way. It makes complete sense given the clusters we are seeing know. B-H more difficult than H-H once its there.

Is there anyway to count the cases within apparent clusters in numbers vs. the number of independent cases to compare?

Sorry I should have said is there anyway…cases to compare recently, ie in the past 3–6 months.

The first and last cases listed by Robertson et al are 2/2003 China and March-April in Egypt. This group lists a total of 57 cases and W.H.O shows 204 as of today. Apparrently clusters account for at least 28% 57/204 of the cases.

I am not necessarily going anywhere with these data. I am trying to get a handle on what is going on. Lots of comments re “most” are children, “many” children die etc. Thought I would try for a reasonable estimate of the frequencies as a base to asses comments by others and thought that others would like to see what I found. Perhaps some trained individual (such as yourself) can add more to the story. In addition to all my comments, I also lurk well when those who know more are talking. Grunt work is sometimes needed and helps others think through a problem.

I, for one, find some very interesting discussion and concepts here on the Forum and I learn a lot.

Guess that makes me a communist. From each to each sorta thing.

anon_22 – at 10:52

‘’Do we know what markers to look for? By we I mean the current state of knowledge in virology, not us, at least not myself.

Do we have enough specificity with regards to markers to interpret results if studies are done? How would one go about doing that? Do you have any reference about this even if if it in general?’‘

I recommend the following reference:

Infectogenomics: insights from the host genome into infectious diseases

Obvious potential candidates for alleles involved in susceptibility would include the MHC, cytokines, etc. The reference above also suggests an approach for identifying candidate susceptibility genes - use expression arrays to zero in on genes with altered expression during H5N1 infection.

JoeW That makes sense…28 % of clusters since the start but what if you broke the clusters down by year so that we could compare the cluster percentages from the last three and six months and per year back from there.

Tom DVM, I’m still trying to think through the implications of more efficient H2H than B2H. Frankly, I’m not sure what it tells us, but I don’t think it’s anything good. Either there are rare strains of H5N1 pre-adapted to humans that happen to hit a human every once in a while or else the thing evolves very quickly once it happens to get into a human. B2H was never the central problem. There’s really no evidence that B2H is getting any easier. But, increasing numbers of clusters and/or increasing cluster size are obvious indicators of evolution of more efficient H2H. As always, we need the 3 month old data from Turkey and the newer data from Azerbaijan. The very old data from Viet Nam, especially the northern cases would be helpful in determining if the clusters really are changing.

S—t, screwed it up again. Robertson’s clusters account for 76 people of WHO’s 204 so people in cluster’s account for at least 37% of the cases. Last time I did not include the “outcome unknown” in the overall calculation.

Monotreme. I think you are absolutely and exactly right. It was right in front of us all along and I didn’t notice. I think if we analyse the data, it will indicate that there is more cases within the clusters now than index cases…that’s proof enough for me.

What does it mean? To me, it means that you have clearly identified that H5N1 is a lot closer to the top of the evolutionary hill then I would have concieved of yesterday…but I hope we are wrong in the end.

There are too many variables and probabilities to control much longer…add them all up together and I think it’s pretty clear where this thing is headed.

JoeW. That’s how I felt last night about the spelling. Like you said, don’t worry about it…it takes time to work data in this way, especially since the WHO just happened to forget to give us complete data to work with.

In 2003 there were 7 people in clusters.

2004, there were 13 people in clusters.

2005 there were 34 people in clusters.

Through April of 2006 there were 26 people in clusters.

If we prorate 2006 we expect 130 people in clusters this year (with no geometric expansion)

Things are definitely getting worse. I can project 50–60 clusters in Africa and India if we assume at least 2 people per cluster these numbers are comparable. My projection is based on 1 cluster per 32 million pop and is conservative. It does not include the different strain in China.

Tom DVM, what about adaptation in other species? Humans wouldn’t be particularly special to this virus, would they? It would seem that once the virus jumped the barrier into cats, for example, that you would have the same situation where the virus would show a preference for cats where it had already jumped to cats. And what about pigs? Why haven’t we seen more pig infections? Are any of your vet counterparts scrutinizing H5N1 in these other animals, to your knowledge? Again, if this virus was looking to spread outside of birds, I would think there would be separate strains specializing in other species as well.

Quick comment on (way up in the thread) the fecal oral route, receptors and pH. As I noted in a post at Effect Measure, there is variability in the sensitivity of various strains and subtypes to low pH. According to Rob Webster, the crop of birds has a pH of .9 and H5N1 is an intestinal virus with them. Regarding gs’s claim that the receptors are in the lung (where in the lung we aren’t sure; there is very little evidence on the distributions of α2,3 and α2,6 in the lungs, only 2 papers using very different techniques show them in the alveoli, while Matrosovich 2004 using a third technique shows α2,3 in ciliated cells, i.e., upper tract), yes they are there. But we don’t know where they are in the alimentary tract. There is no data on this at present.

Regarding clusters, in my view the key thing to watch for is not the number of clusters but their size, particularly tertiary cases. Also note that it is reported 1/3 of vietnamese cases have no history of contact with poultry (according to EFSA monograph cited in my post at Effect Measure on risks of eating contaminated food).

Revere. Thanks for commenting. I have had one question tweaking me that I haven’t brought up as yet. Is there any chance that receptor types are different in very young vs. adult humans. It seems to me that there are other examples in physiology where similar changes occur in maturation.

De jure. I’m sure veterinarians are concerned and busy doing as much testing as possible. I agree with you threat assessment. H5N1 is attempting to adapt to an amazing number of animals at the same time.

Joe W. Way to go. It’s making more sense to me now. Is there a way to compare total of index cases in the same time period with total cluster cases?

Update # 1 In 2003 there were 7 people in 3 clusters or 2.3 per cluster. 2004, there were 13 people in 4 clusters or 3.25 per cluster. 2005 there were 34 people in 13 clusters or 2.6 per cluster. Through April of 2006 there were 26 people in 7 clusters or 3.7 per cluster.

Prorating 2006 we expect 130 people in 28 clusters or 4.6 per cluster this year

My guess is that those are expected numbers. Following Revere’s thinking if there are more than 3.7 per new cluster maybe its time to get really worried.

JoeW. Sorry, I wasn’t clear enough. If you took the index case out of all the clusters and then added all the other cases where there were no clusters…and then compared to them to the clusters minus the index case…you would have total number of index cases vs. total number of cases within clusters.

If I am making your head hurt then disregard this message.

That could be done (after the spinning stopped). However I don’t have the overall stats for those years. Let me see if I can find the stats I can probably do the gazintas (you know 5 gazinta 10).

JoeW Take a long break. I’m sorry I overloaded your circuits (computer joke from a computer illiterate).

I’m pretty sure that the end result will be that there have been more cases withing clusters after the index case is removed in 2006, then the total of index cases…not good.

Monotreme was right in his first post in this thread.

I agree that cluster size is the most important variable. However, the thing about the clusters is that they are not all the same size. Sometimes means can be misleading. The distribution may be more relevant. All we need is for a pandemic is one breakout strain. I keep coming back to Turkey, because I think the cluster sizes there may have been larger than other countries. If so, why? Environmental conditions? Close call with a rapidly evolving strain? Or is there a strain of H5N1 circulating among birds ready to create Turkey-size clusters over and over again? None of the options is attractive.

The sequence for this key strain is still being suppressed.

Monotreme. I agree that the size of clusters matters as an the measure of transmisible efficiency but for an overall trend-line, I would use the total index cases vs. total cluster number. This number would be an indicator of larger clusters to come. When it hits the bulls eye…if it hits the bulls eye, we won’t even have a chance to count the number.

I agree wholeheartedly with Monotreme’s initial supposition and the 22:47 post on the distribution being pertinent. I also believe that the “How” of transmission (epidemiology questions) is very important to differentiate each cluster. The ‘extensive contact’ or ‘dosage’ dependent discussion is foremost in my mind at the moment.

• Proximity = Opportunity
• Multiple Opportunities = Higher Likelihood of Symptom Onset

TomDVM-

I continue to agree with your analysis. Temperature may be important.

I do still hold that some growth factor is mediative to the age splits, as well as behavioural considerations. This / these growth factors may be now ranked as hormones or some other class of communicator / protein.

NSI. You are right. Any hormone regulating growth would increase metabolism and secondarily, increase internal body temperature. The distribution in 1918 was the young and pregnant women. I would expect a high level of metabolism pregnant women as well. If H1N1 and H5N1 had at one time a predisposition to higher internal lung temperatures, it would be explained. This would also explain the higher mortality rates in the second wave. The virus may have been slightly less transmissible and more virulent with the slight temperature restriction being the indicator…all hypothetical of course.

There is a problem with 2003, WHO lists 3cases (none in china) and the cluster data indicates 7 people in clusters. I don’t know what the problem is so will ignore 2003

2004 – 4 clusters, 9 infected by index. 9/46* = 20% in clusters. 2005 – 13 clusters, 21 infected by index. 21/95 = 21% in clusters. 2006 – 7 clusters, 19 infected by index 19/60 = 32% in clusters. - - -

• WHO Total for the year

Apparently the 10% increase is due to cases in Turkey and Azerbajan.

JoeW, the problem with 2003 is that the WHO doesn’t report this cluster, in China, in their cummulative numbers, even though they confirm that at least 2 members of this family were infected with H5N1. The reason? I think they don’t want to admit that this started in China. Too bad, Vietnam.

The large clusters from Turkey and Azebaijan are what worry me the most.

NSI. Here’s the thing. H1N1 was happily going down the path of adaption in the spring of 1919. It came to a fork in the road and turned left instead of right. It was actually mutating its way out of existence with increased mortality and decreased transmissibility…that’s when it was killing the young and the pregnant women. I believe that higher internal body temperature predisposition was the indicator of this. Then it reached another fork in the road and turned the right way and is still with us today. If it had turned the wrong way twice, it probably would have disappeared after the second wave…hypothesis of course.

Learned two things here: I now have good reason to keep women and children in the basement and I am staying out of the hot tub for the forseeable future :-)

BTW the new strain in Turkey and Azerbajan is indeed a potential H2H bomb.

Is anyone considering simple mediators like amino acid balances?

For example, L-Arginine when ingested out of ratio to L-Lysine (L-Arg Agonist) has a tendency to increase viral load due to replicative assistance in specimens with latent viral infection. Could our ‘growth factor’ under review work alongside or cause a more efficient usage of L-Arginine amplifying its effects in pregnant and young specimens.

I read somewhere that the US military fired something like 3,000,000 rounds of amunition for every Viet Cong they killed. It is just a way of doing things.

H5N1 seems to have a similar mode of operation. Now that it is in Africa, and spreading, it seems as if it is just going to just buy every pair of shoes in town until it finds a few pairs that fits.

We are, again, very freely giving the moniker of intelligence to these viral strains?

Let’s keep in mind for the general reader that we are observing a mathematical and biological puzzle (PF51 incursion) that is most likely guided by very simple rules:

• Propagate when given the right conditions
• Acquire new genetic material when available adjacently

The more proximity these viral strains have to hosts that also have exposure to ordinary influenza, then the more opportunity they have for genetic acquisition via recombination. If there are 1,000 hosts, the odds are much higher than if we have 990 hosts due to the number of individual organisms (H5N1 virus particles) found in each host specimen.

Each individual virus has the ability to acquire new information and then multiply rapidly.

Because H5N1 is known to multiply up to 50,000 times as rapidly as ordinary influenza (at 4 days post-infection), we can see the potential mathematically for concern. We alson know that H5 in an ecosystem / specimen tends to overtake by sheer numbers / count any other influenza strain in the specimen, becoming dominant in short order.

TomDVM-

I still believe that we must search for a mitotic growth factor, something at the cellular level that pings the mitochondrion.

or

Maybe a straighter, less compacted mitochondrion (as in the young, less-oxidised cell) is a draw for H5 biochemically?

What about an intermediate host for the virus when a cluster is involved? The common blow-fly can carry H5N1 and has an incubation period of about 12 hrs to 1 day from egg to larva and then 3 to 9 days to adult fly. If this vector is present in the household, it may be making it’s presence felt during sleep, at meals, at death, at defecation, etc. Just some lateral thinking. Great to hear from all of you again - I have missed this input for my tired old brain. Grin.

Dude-

A multi-phasic vector is always possible and in many places is likely.

My guess would be that within the ‘likely’ constructs (undeveloped nations, et al), that a blow-fly would only be a secondary concern after H2H.

The shortest FlightPath between any two points is Occam’s Razor.

Dude-

Did you uncover the H5 sequence that was isolated from the blowfly?

Note that the HA Cleavage site on the Kyoto Blow Fly is RERRKKR, certainly dangerous, but not quite Qinghai’s polybasic that has the additional Glycine and Arginine residuals of GERRRKKR.

I’m not sure if a Qinghai H5N1 varient has yet been published from a blowfly? The absence of publication, however, tells us little. Undoubtedly, any number of unrecognized, multi-phasic vectors are possible.

What makes birds fly south for the winter? Hormonal changes linked with increased slanting rays of the sun? It is interesting to note that ‘flu season’ is directly related to the position of the sun in the sky. I think the sun is an important key to this puzzle, one that is largely being ignored. If wild birds carry this virus, could it be possible that the birds are able to control it somewhat by staying in the direct rays of the sun by flying south when the sun starts to slant its rays? I suspect that sunlight (perhaps vitamin D) raises the body PH. (I dropped a D1000 tablet into reverse osmosis water and it raised the PH of the water from 5.5 to 6.5). Now if vitamin D raises the body PH to a more alkaline level, that might explain why flu season stops some time in April and resumes again in the fall.(Viruses replicate in a slightly acid environment). Does growth hormone lower the body PH?

I also think that birds must have very highly developed large lungs in order to fly. Is H5N1 a virus that inhabits the lungs of birds? Then maybe it jumps to humans with the CLOSEST match of lungs (perhaps similar body temperature might play a part, as well as PH, and also some type of growth hormone). I would think the ‘home’ a virus is seeking will be something that is similar to the one it vacated. More research has to be done on wild bird lungs and comparing it to the human lungs this virus is succeeding in invading.

I just want to say something about the under 40 age group contracting this disease. The under 40 age group have a lot more bowel movements and this virus resides in the bowels (?). Diarrhea is a symptom of having bird flu (?). I was just thinking of something that people under 40 have that is different from older adults.

the blowfly has the same cleavage site as the chicken from Kyoto, so you can’t blame the fly for it


H5N1 cleavage site:
RERRRKKR,353 , guangdong
RE----TR,61 , low path.
GERRRKKR,41 , Qinghai
R----ETR,40 , low path.
RERRRKR-,33 , Fujian
RETR----,29 , low path.
REIRRKKR,20
REKRRKKR,15
RKRK—TR,10
RERKRKKR,9
RERR-KKR,8 , Japan,Korea
RESRRKKR,0 , Indonesia,humans
>><<

What’s a cluster?

I mean, I don’t really know what I mean, but maybe …

A cluster is an aggregation of cases who are close to each other in time and space.

H5N1 mutates all the time so there’s a cloud of variations (think a cloud of insects with close but not identical x, y and z coordinates here) in each individual patient.

So each patient has a cloud and his time-and-space neighbour cases (all part of the cluster) have their clouds and all the clouds in the cluster are, if we overlay them, almost identical, because they share very similar x, y and z.

This doesn’t take me anywhere, sorry.

There may be different types of cluster - a not all clusters are created equal sort of thing. What we observe is an aggregation of cases, but this aggregation might have come to be because of a number of reasons:

• h2h appearing
  • changes in virus
  • host variables
  • both
  • any other reasons?
• increased b2h
  • changes in virus
  • increased exposure (keeping birds at home ‘cos it’s cold outside)
  • both
  • any other reasons?
• intermediate hosts
• any other reasons?

:-?

The mass culling of birds seems to have generated some clusters in Egypt for example I remember at least one person and maybe more persons that where involved in culling. Increased contact, mass panic in the bird pen, no safwty precautions, risky methods of slaughter, recycling of the carcases.

Here is an older article but emphasizes where the virus was isolated:

http://tinyurl.com/qgtxb

SUMMARY

In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed by seizures, coma, and death. The cerebrospinal fluid contained 1 white cell per cubic millimeter, normal glucose levels, and increased levels of protein (0.81 g per liter). The diagnosis of avian influenza A (H5N1) was established by isolation of the virus from cerebrospinal fluid, fecal, throat, and serum specimens. The patient’s nine-year-old sister had died from a similar syndrome two weeks earlier. In both siblings, the clinical diagnosis was acute encephalitis. Neither patient had respiratory symptoms at presentation. These cases suggest that the spectrum of influenza H5N1 is wider than previously thought.

I want to throw a thought into the ring. Please bear with my simplistic approach, since I am not versed in the biology of the influenza virus beyond a basic understanding.

My thought relating to age related infection:

1 - Is there not a possible difference in the lining of the respiratory track of younger versus older individuals? ie - a greater opertunity for viral infection in the younger individual.

2 - We as individuals are simply virus factories as far as the influenza virus is concerned. Those individuals who are producing many new cells (the young and the pregnant) are simply more efficient factories. Could there not be a break point where the virus has to have a certain number of fast multipliers (rapidly reproducing cells) to overcome the bodies first line of defence. After that it is simply a race between the virus and the immune system, with the unfortunate result being that in the young individual the virus has found a highly efficient virus factory, and the immune system responds in what is ultimately a self destructive manner.

Simply put, the virus needs to get into a host, and then it needs to be able to reproduce itself faster than it can be eliminated by the hosts defences. Do the young provide what the virus needs better than the old? Maybe it is easier for the virus to get into the factory easier in young people, and once there it is able to crank out copies of itself more efficiently.

At http://tinyurl.com/r7pnx - that News Items Apr 24, MaMa posted an article at 8:56 about two researchers finding a certain sequence pattern within protein chains, that they propose lends towards enhanced ability to replicate. They have labeled the pattern “replikin”. The more instances of replikin occurrence in a pathogen’s protein(s), the higher incidence of replication. They claim to have found higher replikin occurrence in the epidemic / pandemic influenza strains during the past century.

The researchers explain the science, and write about the influenza pandemics at http://www.replikins.com/ (click on “The Science” in the left sidebar). Additional information about the particulars of this sequence pattern can be found at their patent applications: 20030180328, 20050202415, 20030194414, 20020151677, and a related one at 20060024669.

These applications reveal the pattern, and give numerous examples of relevant sequences. They state the pattern requirements (definition of a “replikin”):

“peptide comprising from 7 to about 50 amino acids comprising: (1) at least one lysine residue located six to ten residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues.”

This is interesting material, and while not intending to give any credence to its validity, this goes to show the importance of early and timely release of influenza sequences. There are other sometimes very creative researchers who look at out-of-mainstream methods of overcoming a problem, but in this instance without the sequences, they cannot perform their analysis.

The researchers (Drs. Samuel and Elenore Bogoch) are also working at creating and testing a vaccine against the replikin pattern.

I forgot to mention in my previous post at 10:42 regarding replikins, the amino acid symbol for lysine is K, and for histidine is H. I’ve not had time to look at some of the hemaglutinin and neuraminidase sequences (PB2 might also be interesting??), but maybe others who like doing this type of thing would be interested. I’d probably start out by looking for a preponderance of K in a sequence. Then look for a nearby H. And then, check for the percentage of K within that area (needs to be 6%, according to the researchers). That’s only 3 out of a 50-letter region.

The Bogoch people have developed a software to find the regions.

beehiver,

I looked at their website and there is:

It would appear that they say they discovered this new group of peptides, gave it a name, trademarked it, and is now pushing the ‘technology’ to measure it, all without EVER having been published in peer-reviewed journals.

Several other links that showed the same information all originated from a press release from this company.

Re; Age disparity of infected individuals - could it be that the older individuals are either smokers or drinkers, and that the nicotine coating their lungs protects them, or that alcohol in the stomach inhibits growth of the virus?

What would bring anyones temperature down below 98.6. Would it be possible to lower your body temperature and would it make any difference. Why are some birds so affected, besides waterfowl and raptors, and others supposedly immune. I heard that pigeons are immune on the radio, but have no data to check it out. While we accept 98.6 as normal I register lower but never check it. At home I’m the red and flushed feel sick and you’ve got a fever school. I think I’m going to do a morning check. Metabolism, hormones, I think some of the doctors here, like rural physician, could start thinking this through. It’s always obvious after the fact, something very obvious is being overlooked. Just as i’m sure we could make ourselves unpalatable to the virus with herbs and foods, natural immunities that our habits will or won’t give us. Stupid maybe, but I never hesitate because one can hit the nail on the head with a seemingly silly idea.

There is an interesting discussion of the possible role of vitamin D regarding influenza at this website: http://tinyurl.com/zr5n9

Of particular interest are links to abstracts from work published by epidemiologist R. Edward Hope Simpson, who investigated seasonality of influenza infections, and who theorized that these outbreaks were not primarily a result of h2h transmission.

Thank you. This is a good reference. Many of us intend to use Vit. D. Its always good to have a recap of a pertinent bit of information. Things get buried in the threads.

I think the statistics that JoeW has come up with, really help to see the forest for the trees. There are lulls and busy peaks during the year, but seeing the year totals together, gives you the bigger picture. Something is developing.

Okieman at 9:17- reading someone else’s ideas, sometimes puts thoughts into gear that would not otherwise appear. I see this happening on this thread. I’m sure that nothing new has probably not been considered by professionals in the sciences, but if you have the interest to throw something out there, I’ll join you.

Okieman said “Is there not a possible difference in the lining of the respiratory track of younger versus older individuals? ie - a greater opertunity for viral infection in the younger individual.”

Any expert please correct me, but higher metabolism in younger people, equates to higher calorie consumption, without neccessarily higher body temperature. The body is able to shed the additional heat through the usual ways, so your temp stays close to normal regardless of the weather and your activity. Calorie consumption does involve the cells. For growth, and reproduction, the cells are taking in more fuel, they are more active in the jobs they do. In order to gain entry into the cell, the virus is making a tastebud trick with it’s imposter HA. “I am good tasting, suck me in”. Could it be that there is quicker and easier access into the cells of higher metabolism young people; the cells need to take in more fuels??

Thank you for the sequence information on the Blow-Fly. I can see that there is no relationship with these sequences and the virus in infected individuals. But, the thrust of my point is not that the published sequence needs to match in the transfer of virus particles from let us say the index case to others in the household, but the habits of these flies could be a vector by themselves regardless of what they do or do not carry. For instance, the fly tends to lay their eggs in any available mucus membrane. So, at night they would climb in your nose, mouth, anus, eyes, etc. and eat, defecate, lay eggs, or whatever they wish to do. I am a computer consultant so forgive me if I get some of the details incorrect….they vomit to help them digest what they want to eat. My point is that even not infected by the virus at all, they could be a vector that increases close contact bird, human, clusters.

We should catch some of these insects in a household that has an ongoing cluster and do some tests. Find out what types/kinds of insects are around. Get uninfected insects and let theses insects have access to an infection source. Remove the insects and transfer them to a closed environment with a (poor) test animal. See if an infection is transmitted. I am sure this is/should being done…right? In the absence of being able to quantify movement, interaction, washing, care giving, of human subjects in detail, it would help to at least eliminate other, I think, obvious vectors. What you have left is increased H-H if it all turns out negative or another way to fight the spread of the virus in humans by use of fly paper or appropriate extermination if it turns out positive. Sorry, for the second post, but the one at 17:25 posted before I was done.

Do you prefer blowflies to mosquitos? Mosquitos cause the greatest human deaths of any creature. They transmit such viruses and diseases as:

Dengue Fever..Yellow Fever..Rift Valley Fever..West Nile virus.. Chikungunya virus..Barmak Forest virus..7 varieties of Encephalitis.. Hepatitis..Malaria….

 and the Indonesians believe it spreads H5N1, and fog for mosquitos where there are outbreaks.

JAMA has posted something regarding BF. Sounded interesting, but the meanies…..they restrict full text unless you are a subscriber. If anyone out there can access, would you mind reading this and letting us in on the anything new.

http://tinyurl.com/nhxph

I don’t think there is any evidence anywhere that the flu virus can be insect borne, at all.

Anon_22-at 23:45….the information is contained in this thread. The sequences have been posted. It is also contained in information on the fluwiki, but I no longer find the reference. Look at gs@16:05

The recent collection of papers in Science contains quite a few gems. Here is a synopsis of portions of Host Species Barriers to Influenza Virus Infections relevant to this discussion.

For H5N1, there are several mutations that show consistent species preference and may therefore be species barriers:

If multiple mutations are required before the virus can establish itself in a new species, where those mutations occur is also important.

2 considerations:

Progressive Adaptation: If a large no of mutations are required to overcome the species barrier, each mutation that happens in the recipient species would require successful transmission within that species (ie h2h) for the mutation to be retained. Since this is a new host species, with no efficient transmission yet, this process is harder, more gradual and haphazard for the virus.

Chance transmission of multiple advantageous mutations: Mutations happening in the donor species, however, require only that the virus be spread to the next host in the donor species (ie b2b) for the mutation to be retained, which is obviously a lot easier since it is already transmitting efficiently b2b. Therefore, if multiple mutations required for causing a human pandemic were to occur within the donor species (birds) and become stabilized before jumping the species barrier, like E627K in wild birds in Qinghai, there is a higher chance of a sudden appearance of a pandemic strain.

it has been speculated that these 2 Turkey mutations E627K(PB2),S227N(HA), maybe with a G228S(HA) could already be sufficient to cause a pandemic and that we’d just been lucky to contain it early.

Anon_22: ‘Intracellular Replication’ PB2 is a polymerase protein important for intracellular replication…’ What is a polymerase protein? Is it more present in the young generation that is more afflicted? Can it be controlled by diet? Is it more present in bodies on high protein diets, less present in vegetarian diets? Are some proteins that we eat, higher in this protein? Is it somehow affected by growth hormones. Can it be isolated and protected by drugs?

We used to raise chickens and turkeys, when my family was young and I seem to remember that some type of growth hormones were in the feed to make the chickens and turkeys grow bigger and faster so they would have more meat. In fact, the growth hormones were making the birds grow so fast, some chickens ended up being crippled because their legs were not strong enough to support the birds’ extra weight. Since chickens and turkeys are such big targets for H5N1, one might suspect growth hormones playing a role in rapid virus replication. In fact, why wouldn’t they help viruses ‘grow’ too? Perhaps viruses are hormone sensitive. If this were possible, then there may be a hormone that stops replication. I still say the sun plays an important role here.

PS : pb2 is just one of the 10 genes of the virus. Responsible for replication and virulence in host (among others)

PanicStricken,

“What is a polymerase protein? Is it more present in the young generation that is more afflicted? Can it be controlled by diet? Is it more present in bodies on high protein diets, less present in vegetarian diets? Are some proteins that we eat, higher in this protein? Is it somehow affected by growth hormones. Can it be isolated and protected by drugs?”

Polymerase is an enzyme essential for replication of genetic materials. It is a viral protein, not belonging to the host, so the factors that you mention should not matter. AND I don’t believe we know enough about such intracellular molecules to be able to link them to life-style considerations.

Many hypothesis have been put forward on this thread for the age distribution. My point of view is that since the age distribution so clearly crosses cultures, nations, living environment, climates, lifestyle, and is so strikingly similar to H1N1 in 1918, the explanation is much much more likely to be biological than behavioral or life-style related. We have some clue because of the unique cytokine storm phenomenon with these 2 viruses that it is likely to be related to immune reactions. Exactly what this relationship is and what we can do to exploit it for prevention or treatment is one of the most important questions to be answered.

(NS1, I edited to prevent confusion. Thanks.)

gs, “it has been speculated that these 2 Turkey mutations E627K(PB2),S227N(HA), maybe with a G228S(HA) could already be sufficient to cause a pandemic and that we’d just been lucky to contain it early.”

I don’t know whether that is true but you are quite right conceptually that containment can stop the emergence of a pandemic virus.

There are 3 interfaces we need to look at when we are considering host species barriers:

Social isolation works to reduce h2h to a point where the virus is no longer able to sustain a growing chain of infection (ie R0<1).

The same applies to b2h, any reduction in human/infected bird interaction will reduce the ability of the virus to cross species. Hence, culling, biosecurity, hand-hygiene (notice ‘no indoor tap’ was an important factor for b2h in vietnam in my post at 17:08), etc all work to a certain degree.

if we only consider the Qinghai-strain, then there could be a 1:20 probability for the S227N mutation - we don’t know how often it occurred already. Now we had >=3 outbreaks in humans (Turkey,Azerbaijan, Egypt, maybe China - Boxun estimates 300 deaths at Qinghai) which were contained, although there were clusters. Suppose such an outbreak in an army camp or nurses’ home or student’s home or children’s camp or school

Perhaps it should be illegal for charities to supply poor countries with chickens until they can figure out how to stop H5N1 from spreading and mutating. I see H5N1 cropping up in wild birds and even domestic birds in more advanced countries (eg. Europe) but no human cases that I know of accompanied with the outbreaks. The poor countries with poor sanitation and little or no education on bird flu tranmission, should not be raising chickens for food until they learn proper sanitary procedures. They are putting the entire world at risk. I say cull the chickens and make replacement illegal until we get this problem figured out. There must be some other safer way to feed those people.

A provocative idea if there was one. Let’s get better ideas out of this.

But, I think, not in this thread. We might create a thread with “creative ideas on how to incite and help poor countries to do things better” or something like that. Please help yourselves!

PanicStricken,

“Perhaps it should be illegal for charities to supply poor countries with chickens until they can figure out how to stop H5N1 from spreading and mutating. I see H5N1 cropping up in wild birds and even domestic birds in more advanced countries (eg. Europe) but no human cases that I know of accompanied with the outbreaks. The poor countries with poor sanitation and little or no education on bird flu tranmission, should not be raising chickens for food until they learn proper sanitary procedures. They are putting the entire world at risk. I say cull the chickens and make replacement illegal until we get this problem figured out. There must be some other safer way to feed those people.”

I think you run a very fine line between trying to be helpful and being arrogant. The small household farmers who have been the major casualty of these outbreaks may be poor, but most are certainly NOT recipients of ‘charity’ as you described it, at least not in the form of supplies of poultry. They are families trying to survive on marginal incomes, who cherish their kids like we do, who suffer from the underdevelopment of their countries and often the corruption in the system, but nevertheless they deserve as much dignity as you and I sitting in our comfortable homes and never having to dirty our hands with chicken-shit.

Human cases have not appeared in Europe (yet) because of the nature of the farming practice, and yes because people are affluent, have better access to sanitation and education etc. But in a world where 99.999% of people have no control over social and economic conditions that make their lives the way they are (including us in the developed world who should by the same token not take credit for our superior quality of life)what gives us the right to say what they should or should not do? And remember that BSE and foot-and-mouth happened in Europe with their farming practices and their incompetence.

Sure ignorance, poor governance, unsanitary practices are putting the world at risk. But if those of us in the West continue to talk down to others (as in ‘There must be some other safer way to feed those people), without compassion and understanding, and the willingness to put ourselves in their shoes, then we shouldn’t complain when America and American values are received with such hatred all over the world.

Just about the only thing that I can agree with in your post is the necessity for culling. Everything else needs to be achieved via negotiations, understanding, technological and financial assistance, etc.

We live in an interconnected world. We may not like it, but our children’s future depends as much on what we do TO others as what we do WITH others.

One big boat on one very small sea.

anon_22,

Thanks for standardising on the abbreviations.

How did you accomplish the edit? We all frequently need to correct these typos and formatting errors?

Anon_22: I am sorry if I came across as arrogant but I beg to differ on your opionion “The small household farmers who have been the major causulty of these outbreaks may be poor, but most certainly not recipients of ‘charity’, at least not in the form of supplies of poultry”…You are obviously not aware of a new form of charity that is happening. My own children gave us a unique Christmas ‘gift’ this year. Instead of giving us a ‘gift’ they took the money of our ‘gift’ and donated it to a family in Indonesia by purchasing chickens and goats as a charity donation. This sort of charity is happening all over the world in such countries where there are poor and hungry people. People are not only choosing the country to donate in, but selecting the animals that are to be donated. I was merely suggesting that chickens be taken off the list of animal donations in countries where H5N1 is such a problem until the people learn how to handle them properly. What is the point of giving them a bunch of chickens and then turning around and killing them all the next?

And you might have spent your life in a comfortable home never having to dirty your hands with chicken shit, but I have not lived my life like that. We raised our family in a log home which my husband built and we raised chickens and pigs and kept huge gardens to feed our 4 children. Life was NOT easy for us.

At this critical time in our world, the practice of donating live chickens to feed the poor and hungry is like adding fuel to a fire that is already out of control…there are other ways to help the poor and the hungry without jepordizing the health of the whole world.

PanicStricken, I have read many of your posts and understand your intention. I agree with you.

Hi everyone. I thought I would just make a comment about chickens and industrial vs. backyard farming.

First, annon 22 is right on the BSE and foot and mouth outbreaks. I think it is a little early for Europe to start boasting that the virus has not entered factory farms. History has shown that some of the worst outbreaks occur in developed rather than developing countries, mostly because we over-estimate our superiority. Wars are usually lost by under-estimating the opposition and there has been no more skillfull opponent than H5N1 in the last 100 years, the potential risk is real.

I have been pondering how this disease emerged and the wild bird vs. domestic animal debate. I believe that the last three diseases to emerge were 100% manmade: HIV, SARS and H5N1. All of these diseases are zoonoses which means they are animal diseases that jumped the species barrier.

In response to Panic Stricken. Evolution produced a bird that was meant to fly and only periodically, twice a year would group for migration. Part of this evolution was huge lungs that are efficient for flying but are inherently extremely sensitive to infections. Man then took these birds, domesticated them and put them in groups of hundreds of thousands, in close quarters. There has not been enough time for a concurrent evolution of the lungs away from disease susceptibility. These herds are a breeding ground and melting pot for viruses.

The original source of the virus would have been in wild birds but the virus would have been a naturally occurring low risk variety of which there are many. It was within the factory farms of Asia (and more specifically China) that variability was instilled through mutation. This ‘weaponised’ virus then re-infected the wild bird population.

After a great deal of thought, I believe the main vector of spread through Asia, 1997–2005, was completely as a result of factory farms and movements of birds and waste…and cover-ups. The spread from May 2005 to the rest of the world was primarily as a result of migrating water fowl. I don’t think small farmers with backyard flocks deserve any of the blame.

Regarding the debate on hormones. I agree completely that growth and hormones are intricatly related but it is not the hormones directly but the expression of the hormones or a side-effect of this growth which is high internal metabolism resulting in slight increases in internal body temperature that favour the virus. That is the reason for the increased risk to pregnant women as their metabolism would be increased as well. Although it is known that body temperatures of the young are higher than adults, we may not notice the difference but the virus does.

Many diseases have been cured by understanding the expression of a pathogen without knowing the exact biochemical pathways that drive it.

Sorry, in conclusion, for what its worth which is nothing, the above data indicates to me that the virus is 80% adapted to humans rather than 5%. The same lull that we are experiencing now has occurred each year with H5N1 and with other seasonal influenza. It is related to weather changes as the virus appears to prefer months when it is colder in the Northern Hemisphere.

We should take no comfort in this lull and we should not let our gaurd down for one moment because the real danger is in the many Asian countries that are silent on the issue.

Tom DVM: Excellent summation.

I am not sure if this has been brought up before. Body temperature tends to drop with caloric restriction. With that fact as a given, could a “sweet spot” of caloric intake be arrived at that would achieve this goal of lessened body temperature without harming the overall health and vigor that would be needed for emergencies that might arise during a pandemic? Also, a side-benefit of this possible strategy would be to be extend the duration of your food stores.

Maybe one could lose weight during the waves and then start putting it back on during the interwave periods.

Any good studies on the overall benefits of periodic, light, fasting regimens, (other than losing unwanted pounds)?

Aren’t fewer “free radicals” produced when fewer calories are consumed? The same gene that is expressed with resveratrol is also turned on during extended caloric restriction. And resveratrol has some studies backing its use for influenza.

Also, belly fat has been proven to cause the release of excess cortisol into your body, increasing inflammatory conditions. Could those generalized inflammatory conditions be setting you up for more likely contracting the flu?

Medical Maven. Interesting points as always. It’s pretty hard to fight nature, the body has back up systems for the back up systems for the back up systems. Disease only results when the body runs out of back up systems.

The point I would make is that I don’t believe those with high metabolism could change it enough to lower the small change in internal lung temperature…the body would just kick in a back up system to compensate. In the young and pregnant women, you are going to get increased metabolism rates no matter what you do, in my opinion.

I believe our tendency to gain weight in middle age is as a result of natural selection with inherent advanatages.

Thin adults who can eat anything they want without gaining weight are outliers in distribution. This predisposition would make them specifically more susceptible to H5N1, again in my opinion.

There had to be an advantage to our spare-tires, It is just that Mother Natures subtle ways are not always apparent at first glance.

Panic, apologies for the rant. Because my background transcends several cultures and continents, I am keenly aware of how careless remarks (these days instantly accessible from anywhere in the world) especially by those (rightly or wrongly) perceived as richer or more powerful, can cause such aggravation while the protagonist remains blithely unaware of the insults they have inflicted on others.

One of the biggest sources of conflict in the world today IMO is the fact that we have globalization of information (eg you can watch CNN in Islamabad) but very little personal dialogue between cultures. People can get instant snapshots of how others live (affluently, badly, immorally, ignorantly etc) with no clear understanding of the challenges and nuances of that society. It becomes easy, almost automatic, then to project all of one’s own aspirations and disappointments on those whom they perceive as having taken unfair advantage of others.

It is interesting that often both sides of a conflict have equally honest righteous people feeling genuinely aggrieved to a remarkable degree. This instant but extremely limited access to other cultures makes it easier than ever before to turn people into caricatures, so that for example an American or Cambodian is no longer a father, a nurse, a farmer, but perceived as representative of all of America or Cambodia or that part of Asia and everything that is wrong with it, to be spoken of with the kind of vehemence that in times gone by would only be possible if there was some real personal grievance.

A pandemic is such a worldwide catastrophe that I’m afraid all these stresses will get many times worse, as shown in the Disaster Survival thread. Pandemic preparedness is therefore not complete without a vigorous attempt to understand the culture and living conditions of the rest of the world. The time to start doing that is NOW, not when death and trauma have eroded our reason and compassion.

Here here - - well said anon-22

I didn’t know we could edit our comments. Cool! Now how do we do that?

Scaredy,

“ didn’t know we could edit our comments. Cool! Now how do we do that?”

I got a password from Dem and have been editing stuff on and off, so no, it’s not a regular feature.

Sorry :-)

One may wish to resist removing another individual’s comments when editting our own.

From Cache Cow on the News Thread - http://tinyurl.com/zepg9 regarding recent statements from Dr. Nabarro. Does it seem that he’s turning up the heat somewhat?

NS1, sorry, I sorted out the E627K and then thought for reasons of clarity maybe we should remove both your question and my response. Didn’t mean anything else but had been operating on 3 hours sleep daily and massive jet-lag. Maybe I should have put those in brackets? so apologies again

mmmelody47, thanks for linking the Nabarro piece cos it has immediate relevance to what we are talking about here. He is turning up the heat not in the sense of arguing about whether there is going to be a pandemic, but more drawing attention to the plight of poor farmers and the enormous resources needed, both veterinary and (human) public health. Nabarro is one good guy IMHO. :-)

re anon_22 @ 16:30 -

Yeah, I’m sorry too :-(

anon_22 – at 16:54 - thank you for your reply. I will guess that your peers on this site and Nabarro himself would say same about you….IMHO.

anon-

Hang in there!

It sounds like you have a great deal of TOP (Time on Planes) like many of us, so we do understand the weariness and the scarcity of the gentile graces that follow such weariness. Did you do any good on your trips?

Keep up the good work here when you can. We are each willing to supply energies as needed if you can delegate your ideas, even simple proofreading and editting of texts for clarity and content if you’d like to form a review circle prior to publication on the wiki?

Have you found any new sequence entries or protein analysis data in the past month? The well seems dry at the moment?

NS1, thanks. “Did you do any good on your trips?” Contributed to airline solvency.

hehehe

I’m not very good at sequence analysis, usually leave that to folks like Monotreme gs and yourself :-) As you saw with the E627K, those letters and numbers cause my eyes to glaze over. The worst is all that cleavage stuff like these:

PQRERRRKKR*GLF – Clade 1 and 2 n PQRERRKKR* GLF – Clade 1 and 2 n PQRERRRKR* GLF – Clade 2 n PQRESRRKKR*GLF – Clade 2 (Indonesia/5/05) n PQGERRRKKR*GLF – Clade 2 n PQIERRRKKR*

Frankly, when I look at them, they turn into ZZZZZZZZZ

:-)

In general, the more letters (amino acids) in the cleavage area that are basic means higher potential tissue tropism and more trouble.

When the cleavage area amino acids all become Z then we no longer have to worry because we are restfully slumbering.

anon-

Where did you go this time? Did you lecture or participate in delivery?

Recent info on anti-viral effectiveness. May require no-charge registration for Medscape.

[[http://www.medscape.com/viewarticle/530017?src=mp|Drug-Resistant Influenza Seen in Immunocompromised Patients ]]

<snip>

Clinicians warn that drug-resistant influenza virus “emerges with increased frequency” in immunocompromised patients, limiting the benefit of currently available antiviral agents.

<snip>

In a related commentary, Dr. Jonathan A. McCullers from St. Jude Children’s Research Hospital in Memphis, Tennessee, voices concern that “transmission of this quasi species pool would allow perpetuation of undetected resistance.”

With so many immuno-compromised individuals in the world today, we may be looking at a substantial failure of typical treatments.

Think Africa and AIDS. Webster and others certainly are.

Or the US. We have our fair share of potential hosts.

About 1.2% of the US population is identified as HIV positive. One of every hundred people you meet is likely to be a carrier and as such, under treatment for HIV and H5N1, is likely drive resistance to our known pharmaceutical treatments.

HIV is not the only thing that will compromise the immune system. Cancer patients undergoing treatment, transplant patients, people who take steroid medication prescribed for various illnesses, and others also would be compromised.

NS1, the Tamiflu-resistance is for influenza B. When I look at the NA-sequences for influenza A and influenza B, they are so different that you have to wonder how a drug can be useful for both. And also that it should be possible to design a better drug when you concentrate on H5N1 and discard influenza B or HxNy with y>1. (But I admit, I don’t know how Tamiflu works ATM)

gs-

Resistance genes are known to be transferable between serotypes.

Some stuff on tamiflu resistance from the WHO containment thread

but this E119V is very rare, you hardly find a sequence with 119V in the database.

gs,

“but this E119V is very rare, you hardly find a sequence with 119V in the database.”

that’s good, then.

Rare can become common before you know it, given the right circumstances. Since oseltamivir and zanamivir appear to have slightly different modes of action (based upon reports of oseltamivir-resistant yet zanamivir-sensitive strains), would this mutation give rise to a strain that is more likey to be arrested by zanamivir? Granted that time and drug-delivery are critical issues, if E119V is detected in some areas, would it not be better to attempt to stockpile and deploy available Relenza supplies to these areas where this drug might have more effect? gs also raises a good point in that, with luck, not all strains will be resistant to all modes of intervention and that simultaneous use of an M2 inhibitor might prove useful in such circumstances. In any case, this would seem to be a purely academic exercise, as on the WHO containment thread, the idea of containment via government action appears to be crashing into a flaming and inglorious end.

zanamivir is not easily available. There is not so much around. Also, it has to be inhaled and only the lungs are protected while H5N1 goes also into other organs. But I know, that e.g. Germany has also stockpiled some Relenza. Now I’ll read the WHO-containment thread…

Some additional unreported info for consideration Reviewing the 28 clusters reported by Robertson at http://tinyurl.com/nyrxf I found

In one case the mother, father and children were infected.

In seven cases one parent (3 Moms, 4 Dads) and one or more children were infected.

In 19 cases two or more siblings were infected.

The remaining cases were in some way related by blood

The situation is indeed murky and there are alternative explanations such as caretakers. However, note that in these families in four of seven cases the father and children but not the mother were infected. This seems to support genetic differences. If it were simply caretakers then the mothers should be disproportionately represented. There are 45+ people in these clusters and that is not a sufficient sample. None-the-less, they are all related (within a cluster) and there does seem to be some sort of differential susceptibility.

Everyone keeps telling me “no” but the observations stand. It is not known how many of these were indeed family units with a mother, father and children. At the least it could be expected that everyone in the family should have been infected in some / several of these cases f it were simply a matter of environmental factors.

In only one of 28 reported clusters was everyone infected. There must be some sort of a lead here as that simply does not make sense. At the least it is “difficult” to become infected even within a family.

JoeW, just so you know, Robertson took the H5N1 cluster cases, verbatim, from a FluWiki page I created. You can find it here. I don’t mind other people using any material I collect here at FluWiki. I support GNU. But the implication of the press release is that he had a team of researchers working on this. Not true. He just came to FluWiki and did a copy and paste.

As regards how people get infected from other people. I think it requires very intimate contact. As I said above, my guess is fecal-oral. I suspect it is the primary caregivers who usually infected because they have not been told that bodily secretions of H5N1 patients are infectious.

all the chicken,mice,ferrets,tigers and cats get it, they needn’t be related. And it’s always in the lungs. When it infects in the intestine, why/how should it go into the lungs ? Intratracheal infection in cats is documented. OK, it could go fecal-oral and then into the lungs by breathing through the mouth. Hmm, is coughing,sneezing a symptom of bird flu ?

Thanks Monotreme, After looking at the link you gave I can see where your research was ripped off. That is impolite to say the least. I did not know about your work and assumed (wrongly as usual) that few others were interested in up todate information re clusters. I will not make that mistake again. Please accept my sincere apology.

A bit of a duplicate (from the news page) but it will persist with this thread. Here is an update from “Science” with links to several articles on what we do and do not know http://tinyurl.com/l4lx4

JoeW, You have absolutely nothing to apologize for. No way for you to know where Robertson got his cluster info. Again, I don’t mind anyone copying anything I do on FluWiki and using it for their own purposes. The more people who see it the better, IMO. I just didn’t like the fact that Robertson was pretending to have a research team behind him. Lack of truthfulness hurts our community.

As you can guess, I’m very interested in cluster data. The data I would most like is from Turkey, but most of that is still hidden by the WHO and/or the Turkish government.

Monotreme Why don’t they supply all the information anonymously?

Tom DVM: anonymously - what are you suggesting? Anonymous as in we don’t know the names of the patients or as in we don’t know the name of the reporter? I would guess it’s the first but wouldn’t mind the second if it were reliable.

Tom DVM. There’s no reason they couldn’t supply the information without revealing the patients’ names. As to why they don’t, your guess is as a good as mine. Really only 2 possibilities:

• A Gross incompetence
• B The cluster size would make it painfully obvious that we are at least at phase 4, which would have dire financial implications for a number of countries, especially China.

Of course, the 2 are not mutually exclusive.

Hi Guys. Sorry, I didn’t explain myself well enough. I meant the WHO could disclose all information on the clusters or anything else, without revealing the countries. Then there is no way to step on any toes.

Something sure has to change. Turkey was advertised by the WHO as being critical and they were the ones who announced the information would be released a long time ago. Now nothing, no strains even though we know they acted differently, no clinical information even though we know they were unique also.

My question would be…If they haven’t released it, have they seen it? Does the WHO have lists of this data?

Tom DVM, it would be pretty hard to release any useful data without revealing the country of origin. If they suddenly announce some large clusters, most involving teenagers, we’ll know it’s Turkey.

The WHO has to know by now what happened in Turkey. And it has to be very, very bad news. If the clusters were no different than other countries, then why not release it? We all know there were cases in Turkey, too late to keep that secret. The only motivation to not releasing the information is because the Turkish government and/or the WHO are afraid of the reaction if we found out about the large clusters, officially.

…and lack of seroprevalence data indicating aymptomatic infections which they were all counting on a few months ago to lower that “artificially high mortality rate”

You got it, Tom DVM. Big clusters, high mortality rate - even with truckloads of Tamiflu.

But don’t worry, no reason to raise the alert level, we’re still at phase 3. Go back to watching sitcoms and buying bobble heads from China. Don’t mind us (the WHO), we always buy body bags in bulk (in units of 100 million).

Monotreme. One day we will wake up, turn on the radio or tv and the headline will be… WHO announces stage six and there are now a thousand identified cases in 20 countries around the world, including several in Europe and North America…and we’ll all go…where the hell did that come from…everything was under control yesterday.

That’s exactly what happened with SARS in Canada. They announced the horses were out of the barn about two weeks after the horses had arrived unannounced at Toronto hospitals. They can re-invent all the history they want…its about to repeat itself for the same reason.

Yes, Tom, I think you’re right. Condemned to repeat history against our will.

Maybe my Lt. Governor knows what we know (or seem to know). I just buttonholed him after he gave a speech. I walked up to him, introduced myself, and saw fear in his eyes when I mentioned pandemic flu. He said “It will happen”, twice. He went on for a minute about National Guard exercises as part of their preparation. I only had time to stress the current CFR, and the fact that there is little reason for the CFR to decrease if easier transmissability occurs. I then emphasized the difference between the 1918 CFR and the current H5N1 CFR. I wanted to get across to him in that way that whatever they have planned they better redouble their efforts. I hope I did some good.

Medial Maven, they know it could be bad. They just don’t know what to say to the people. And it may be much worse than their worst nightmares.

We would all like to think that they have well-thought out plans that will be flawlessly executed when TSHTF. Katrina taught us that’s not true. It’s our job to make the plans and to educate TPTB. Sounds like you’re making a good start.

monotreme, it could also be because Turkey just doesn’t want _any_ discussion about it because of tourism. They have some agreement with WHO, the details of which we don’t know. If there were bad info about the clusters in Turkey, we should also hear something similar from Iraq,Azerbaidjan, Africa,Russia. It’s almost the same virus there.

Tom DVM – at 22:58 and Monotreme-

everything was under control yesterday.

You said that right!

Even we are likely to be caught unaware only because we’re perpetually being misled by the worms and other spinmeisters.

Their information management and flow reduction is becoming preposterous even to the rank amateur.

Hi everyone. How many countries, within the long established pathway of H5N1, have not reported anything concerning human or avian infection?

Excellent inquiry Tom DVM, but is it not true that this would be purely speculation? Or should we start with The Philipines?

http://www.recombinomics.com/News/02160505/Meningo_Meningitis_H5N1.html

Secondary infections might be a key to finding the H5N1 link. What we do not know will harm us.

gs: I also think there is some kind of agreement between the WHO and Turkey about releasing the cluster and sequence info. Where I differ from you is that I think something especially bad happened in Turkey - very large clusters and new strains. We don’t know whether the same strains are infecting other countries because the Turkish sequences are being witheld by the WHO. That being said, it would not surprise if the large Azeri clusters were due to the same strain that caused the large Turkish clusters. As for Iraq and Iran, who knows what’s going in either of those countries? Iraq is on the verge of complete collapse and Iran is hardly a paragon of openess.

Tom DVM, there are a large number of “miracle countries” that somehow managed to avoid either avian or human infections despite being surrounded by countries with infections. Burma was a major candidate, but they have finally admitted to having it. North Korea is another top candidate. So is Bangladesh. And perhaps Australia, yes Australia. Right in the flight path of migratory birds, and one quick boat ride from Indonesia. Here’s a map, just to remind people of the proximity -

Map of Australia

Anyone here live in Darwin?

Monotreme: Even if Turkey was unique in its sequences, am I not correct in surmising that if it happened once, it will happen again? Remember the study some time back about containment strategies and how a successful containment of Panflu would buy only a little time because the virus would just turn the same trick or a slightly different one elsewhere. In other words, if it is capable of doing it once, it will certainly do it again.

Medical Maven. They… might …catch all the human cases: probably won’t catch the all the cases in pigs, dogs, rodents, etc. etc. etc. and Oh Yeah…birds.

There are several streams of infectiveness. The few we see and the many that are invisible.

Your hypthesis makes perfect sense to me.

Monotreme There are migratory birds that come to Australia but they are all very small waders that come down from Siberia. There is a testing program in place and so far no positives have turned up which isn’t surprising as these species are known to <i>not</i> be susceptible to bird flu(at least no positive test results have been found). The maps of bird migration paths are somewhat misleading in this regard.

The most likely bird route into Australia will be from New Guinea by locally nomadic ducks and geese spp. across the Torres Strait but so far none of the Indonesian cases have been reported from Papua or the eastern islands. (Mind you at the moment that would be the last thing that Indonesia would reveal at the moment given the current tense diplomatic situation between Australia and Indonesia over the issue of human rights in that province.)

Monotreme. If we added them up, how many countries etc. should have reported outbreaks and have not. The number and area would be one more indicator of the opportunities for the virus to adapt invisibly.

kyangadac. Thanks for the information. I believe that Australian Regulators are amongst the toughest in the world; probably due to your relative geographical postition.

India and Afria have nearly 2 billion people if it infects at a similar rate to Turkey etc 1/32 Million. that is 50 - 60 opportunities in these places.

if the smuggled birds vs migratory birds leans toward smuggling it could explain country reporting gaps.

So could non-reporting of actual cases, of course, and when it comes to N Korea, Burma, etc, there’s just no way to know. Parts of Iraq and Afghanistan have no functional government.

The gaps in africa are worrisome, as well. But the absence of data certaibnly doesn’t prove the presence of cover-up, especially the longer we go on with no news.

DemFromCT. I wasn’t talking about a cover-up. You must have knowledge to cover something up. I was talking about farmers knowing birds are dying without being given any instruction about what to do. Infections in these countries would take their course naturally, without any control measures. Who knows what the end result will be? If they don’t know anything about bird flu then I must also assume they wouldn’t know anything about a fast growing cluster of human infections.

Medical Maven, I agree, what happened in Turkey will happen again (and perhaps did in Azerbaijan). Without sequence data, we are blind to where that strain is currently. There is sequence data from Iraq, but large clusters were not reported there. My guess is that we will see large clusters in Central Asia and/or Europe in the fall, next flu season. But possibly sooner.

kyangadac, I have heard before that only a relatively small number of birds migrate to Australia. Still, so close to Indonesia… Also, I think the smuggling angle is a real possiblity, given the proximity. There have already been cases of smuggled birds with H5N1 in Europe (Belgium and the UK). Hard to believe that no-one smuggles birds from Indonesia into Australia. Of course, I don’t know how many chicken farms there are in Darwin and surrounding areas. It may be that Australia has been lucky so far, but I wouldn’t count on that luck to hold out much longer.

Tom DVM: I haven’t added up all the countries that should have reported cases, but in terms of population density, the two largest countries have already admitted to having cases, China and India. I’d be willing to bet countries like Macedonia have it too, but in the bigger picture, I don’t know if that matters.

Africa is a concern for many reasons. For one thing, the background rate of death is very high, especially in children. It will take alot of death to get noticed. Also, the public health infrastructure is almost non-existent in many African countries, especially in the countryside. So, I doubt there is much surveillance going on. The same goes for vertinary reporting in those countries, I think. I am in agreement with your post at 16:38. We won’t know what’s going on in Africa until rich people start dying or there is a massive outbreak in the countryside.

Monotreme. Actually I was looking at this almost like a probability equation indicating the opportunity for unregulated mutation and spread. If we first identified all countries that, given our experience, should have outbreaks and take their land mass in porportion to those countries with outbreaks, some interesting comparisons on mutation and pandemic risk could result.

Info today from a woman whose son is an inspector at NYC port: he recently found an illegal shipment of birds ie ducks, geese from China in lower and back portion of a boat- all were seized, but no inspectors etc issued/wore protective gear! I begged her to have him insist on getting PPE’s, including footgear, from his boss and to be a PIA until everyone was equipped.

Monotreme the most likely route into australia will be probably through Magpie Geese which aren’t migratory but are nomadic and regularly cross between northern australia and new guinea, the australian quarantine service is actively testing magpie geese in the northern territory but given the numbers and the distances involved - the chances of early detection aren’t high. One needs to remember that there are less than 1 million people north of the Tropic of Capricorn( i.e. the northern 1/3) for a very good reason - the harshness of the environment. There aren’t a huge number of chicken farms in Northern Australia.

Smuggling chickens deliberately into oz is a non starter. But chickens on board indonesian fishing boats have already been mentioned as a possible threat in the local press. The number of incursions into australian waters is currently estimated to be about 3000 a year and is the focus of a lot of community and political angst. Fishing boats that are caught are generally burnt. However, I suspect that the ‘chickens on fishing boats’ theory is a bit of xenophobic fantasy and is highly unlikely in fact.

Oz quarantine maintain sentinel flocks of chickens across northern australia to detect outbreaks of mosquito borne diseases such as Ross River Virus and Murray Valley encephalitis.

Once bird flu gets into magpie geese populations the spread of bird flu throughout australia will be virtually gauranteed. Swans, ducks, geese, pelicans and cormorants are nomadic across Australia, following the rainfall and ephemeral lakes. These birds congregate on the coast when it’s dry in the interior but arrive in vast numbers at the inland lakes(like Lake Eyre) when there is a lot of rain - it will be a mini Quinghai if the virus gets into one of these large gatherings.

Tom DVM, I take your point. But distinguishing between coverups and variabiles that influence the spread of H5N1 will be difficult.

kyangadac, thanks for your very informative analysis. It sounds like Australia is doing everything it can and that they have held off the monster, thus far. Please keep us informed if anything changes.

I think that the lack of information from some quarters is a form of ‘cover up’ but not in the sense that many people believe. Governments, the world over are most concerned about maintaining political stability. This keeps the global peace. Political stability occurs when there is economic and social stability, and when the interests of differing world powers are not in direct conflict (competition for resources).

In the Turkey/ Iran/ Iraq region there is much driving potential social instability and political instability. Adding economic pressures to these regions by announcing and reporting on bird flu problems and measures taken will simply further destabilise an already very unstable position. Hence, publically, we dont hear much from this area. Don’t expect anything to change soon IMO. Hopefully, those who need to know the data are being given access to it, and are finding ways to inform the rest of the scientific community.

Bumped for easy accessibility…and importance!

http://tinyurl.com/hj9l8

[snip]

Another scientist said it’s important to explore various methods through which the virus could spread, especially through the vast day-to-day movement of poultry worldwide. “Don’t rush to blame the migratory birds straight away,” said Kennedy Shortridge, emeritus professor of microbiology at the University of Hong Kong, who worked closely on the 1997 bird flu outbreak in Hong Kong that killed six people. “We’ve got to look at birds, we’ve got to look at flies, we’ve got to look at beetles, poultry manure, maggots,” he said. “When you see these poultry operations, there’s litter everywhere in many of them.” Hong Kong was able to stamp the virus out by slaughtering the entire poultry population, but Shortridge said he believes it was only one or two mutations away from exploding. He said it’s impossible to predict when or if this H5N1 virus, which is genetically different from the Hong Kong virus, could mutate into a pandemic strain. But he warned that other viruses should also not be overlooked. “I can’t say whether we’re as close as ‘97 or how distant we are because it’s really in the lap of the gods,” he said. (AP)

[snip]

I wonder if this scientist is planning to author any studies of additonal vectors for H-H and B-H transmission? Maybe one of our experts could contact him about this and report back to us. He seems to agree with my point@17:55.

Dude, I just listened to Shortridge today. He is on a crusade to clean up the poultry business, which is a worthy cause. He also believes that given time, say 20 years?, 50 years? we can get rid of influenza completely.

No, this was not a typo. He wants us to aim for eradicating influenza as a disease by doing extremely tight biosecurity and surveillance of birds, pigs, of everything.

He also firmly believes in the ‘Qinghai Express’. No, not Niman’s version where migratory birds from Qinghai spread the virus to Europe, but that it was all spread by railways, from Langzhou, the provincial town near Qinghai on trains to Turkey and Nigeria.

He didn’t explain the swans in the UK, though.

Just to clarify, Shortridge was talking about cleaning up the whole world.

In case you were wondering.

anon_22 - “He didn’t explain the swans in the UK, though.”

They just floated in from abroad, didn’t they?

He lost me from the… ‘aim for eradicating influenza as a disease by doing extremely tight biosecurity and survelliance of birds, pigs, or everything’.

Tom,

Yep, exactly what he is proposing. How, I have no idea.

Annon 22. With all due respect to Dr. Shortridge who I am sure is doing his best, that is the most ridiculous statement I have read in my past approx. three months on flu wiki.

There’s a new vaccine that sounds promising…

St. Jude test of bird flu vax proves successful [May 2 Memphis TN USA]—A commercially developed vaccine has successfully protected mice and ferrets against a highly lethal avian influenza virus, according to the investigator who led the study at St. Jude Children’s Research Hospital. The vaccine was developed by Vical Incorporated in San Diego, California.

This finding, coupled with results of previous studies that showed protection against multiple human influenza strains, suggests that such a vaccine would protect humans against multiple variants of the bird and human influenza viruses, according to Richard Webby, Ph.D., assistant member of Infectious Diseases at St. Jude. Such a vaccine could protect humans against an H5N1 “bird flu” virus that mutates so that it adapts to humans and can readily spread from person to person, Webby said.

Webby is scheduled to present the findings of this study at the U.S. Public Health Service Professional Conference in Denver, Colo., May 3 at 12:30 pm EDT.

The investigators used two versions of Vical’s multi-component, DNA-based vaccine in the studies. One vaccine was directed against three viral proteins: NP and M2, which are “conserved” proteins that generally do not mutate quickly and therefore, are slow to avoid immune responses triggered by the vaccine; and H5, a “variable” protein on the surface of the bird and human flu viruses that is critical to their ability to infect cells. This variable protein is known to mutate readily, thereby foiling previous immune responses it triggered—whether due to natural exposure or vaccination. The other version of the vaccine contained only the two conserved viral proteins.

In the St. Jude study, the full, three-component vaccine (H5, NP and M2) provided complete protection in mice against lethal challenges with a highly virulent (Vietnam/1203/2004) H5N1 avian influenza virus. Moreover, other studies showed that a smaller version of the vaccine containing only the NP and M2 components provided significant protection against several strains of human influenza virus as well as the H5N1 “bird flu” strain.

“Such cross-protection against bird and human influenza is considered by researchers to be the ‘Holy Grail’ of flu vaccines,” Webby said. “By stimulating immune responses against targets not likely to mutate, the vaccine could trigger an immune defense against a broad range of variants of the virus.

“Even if the bird flu virus mutates so it becomes adapted to humans, this kind of cross protection will allow the immune system to track and attack such an emerging new variant without missing a beat,” Webby said. “We wouldn’t have to wait to start developing a vaccine against it until after the original virus mutated.”

Webby’s team showed that all mice and ferrets that received the DNA vaccine survived the challenge with the virulent H5N1 strain, while those that received a “blank” vaccine control did not survive. The vaccine also prevented weight loss in all animals challenged with the virulent virus, suggesting that the vaccine might also protect humans against serious flu-related sickness.

The studies included 16 mice or six ferrets in each vaccine or control group. The DNA vaccines targeted NP and M2--with and without the H5 avian influenza virus surface protein. All test DNA vaccines were formulated with the company’s VaxfectinTM adjuvant. An adjuvant is an additive administered with a vaccine that has little effect by itself, but improves the response of the immune system to the vaccine.

The St. Jude study was supported by the National Institutes of Health.

I wonder if it will work the same on people…

Some support for the positionthat genetics are involved

“There have been family clusters. So there has to be certainly a genetic aspect to it,” Robert Webster of the St Jude Children’s Research Hospital told a bird flu conference organized by the Lancet medical journal in Singapore.

Another leading expert Hiroshi Kida, who has spent more than three decades working on viruses, has long harbored the same theory.

“There has not been a single case of infection involving husband and wife,” Kida said told Reuters in an interview. Kida is with the department of diseases control at Hokkaido University in Japan.

Kida explained that people infected with H5N1 have a carbohydrate receptor on cells lining their throats. The receptor — called alpha 2,3 — is predominantly found in birds and avian influenza viruses like to bind to this class of receptors to replicate and cause disease.

Human influenza viruses, however, prefer to bind to another receptor called alpha 2,6, which is dominant in humans.

“I think people who are infected with avian strains are special. They must have alpha 2,3 receptors,” Kida said.

http://tinyurl.com/mw956

the clusters could also be explained by families living in close contact rather than genetics. This is also supported by the onset dates. Older people get it more rarely, that could explain why husband and wife rarely both have it. We also had uncles infected, has the genetic aspect been examined by all samples we have ? That seems to mean that only few people are suspect to this genetic “defect” - maybe 10% or such ? Also maybe that this defect is predominant in some geographical regions

we should already know these things by now. I wonder, how much money is invested in H5N1-research and i.e. how the virus spreads ? We know so little here. Could it be, that the threat is considered much lower than what they are trying to make us believe ? I mean, a lot more research would be going on if it were such severe a threat. Look at the WHO-budjet, the withholding of data, the nonexistent local pandemic plans, the lacking public awareness and lacking reports in the media.

Closed due to length. Conversation is continued here.