Pandemic Flu

[Pete]

Originally Posted by mugwump

More research fom today's CDC presentations.

Hang in there mugwump;

I find this thread very informative and follow it right regular.

Pete

[mugwump]

Originally Posted by Pete

Hang in there mugwump;

I find this thread very informative and follow it right regular.

Pete

Will do. Just please tell me to shut up if this stuff is over the top.

I have the patience of a three-year-old. I have to just sit and wait for 5-7 minutes umpteen times per day as programs compile or I wait for a device to complete a run. I scan news sources and jot these notes during these times.

It's therapeutic.

[mugwump]

So here's one for you: what do you do when you live under a major flyway and your dog takes to goose poop like a metrosexual with a bottle of Hugo Boss?

GoosePoopEbo.jpg

Eats it, rolls in it, would string it on a necklace and wear it if he could, LOL. He will bear watching if the flu gets into the Canada geese.

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[mugwump]

March 22 interview with Dr. Michael Osterholm, associate director of the Department of Homeland Security, director of the U of Minn Center for Infectious Disease Research and Policy (CIDRAP), and Chair of the HHS's National Science Advisory Board on Biosecurity.

This guy is well-respected but he makes people very uncomfortable. Interesting read. Osterholm is the guy who got DHS to initiate supply-chain studies with U. of Chicago economists.

"...We also are approaching this from a very American-centric point of view, which in the end will be the death of us. What's going to happen is, even if we could produce vaccines for our country in a timely manner, this global just-in-time economy we live in today is going to see the rest of the world shut down. Eighty percent of all the drugs we use in this country—all the childhood vaccines, everything—come from offshore. Your cardio drugs, your cancer drugs, your diabetes drugs, 80 percent of the raw ingredients come from offshore. I could go through a whole laundry list of other critical and essential products and services that come from offshore. If the rest of the world experiences a pandemic, we're still screwed. That's what people don't understand."

Sobering. This guy pulls no punches.

http://citypages.com/databank/27/1320/article14219.asp


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[mugwump]

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[CoLawman]

...

It is getting late............but I have somehow lost my place. WTF!!! Did you post this on the wrong thead? Great information and wanted to add my experience with a perilymph fistula caused by a dive accident or weightlifting.......but not sure how that ties into what I came here to read........going to take my spins and fistula to bed.

[mugwump]

This is what I was trying to post last p.m. and screwed up:

There's a lot of talk in the popular media about two new studies, presented at the CDC conference on 22March2006, which document binding sites in the body for seasonal flu vs. human infection with avian flu. Seasonal flu binds with receptors high in the respiratory system while avian flu must penetrate deep into the lungs before infection takes place. This is very important information and it jibes nicely with other data that's been released recently. For instance, it explains why there have been very few people with antibodies to the avian flu and no symptoms (why no mild infections). Most seasonal flu infections start as bronchitis. If the bronchioles can't be attacked then a much higher viral load, inhaled deeper into the lungs, is needed to cause the disease (and antibody formation). This virus is nasty all on its own, but if it starts as pneumonia deep in the lungs then the chances of survival are much less. Not a formula for mild infections.

This is maybe really good news if the worst does happen. I haven't seen discussion of this yet, but this research may explain a mechanism for a dramatic decrease in the death rate -- from the current 55% down to something approaching the 1918 levels of 2.5% -- if this vrius ever "learns" to spread efficiently in humans. My thinking: to pass efficiently it must attack higher in the lungs - the bronchioles. If the flu starts from the git-go as a (milder) bronchitis instead of a (life threatening) pneumonia then you have a greater chance of fighting it off. This doesn't address the cytokine storm but that's another kettle of fish.

We know that transmission from birds to humans and from human to human is quite difficult. This study seems to explain why that transmission is so inefficient. What I don't understand is why this is being touted as "proof it may never cross to humans." Don't we already know transmission is inefficient? Yes. Don't we already know that mutation is required to make viral binding more efficient in humans? Yes. The paper cited at the top of the thread documents changes to the exact sites that this new research addresses. Does this downgrade the threat level? I emailed a researcher and this is what I got (and f-me, it's mostly gibberish to me too). I include this to show how hard it is to get an anser out of a scientist.

I'll let you know if I get an answer in English on whether this research lowers the threat level.



I've already put this out in public so pass on at will. As the two recent papers about binding of H5N1 to human respiratory-tract-cells show, recombination of H5N1 might not be required and a series of single-nucleotide-changes could do the trick.

I measured the “clustering” of mutations of the genes (this might indicate recombination):
PB2:223:496, 7497:15,353:620,,120:599, 979: 7, 637:1131
PB1 75:428, 483:17,266:590,, 81:492, 385: 5, 620: 996
PA 192:383, 820:17,340:651,, 77:484, 448: 5,1119:1387
HA 385:526, 859:47,489:660,,156:499, 360:15,1072:1224
NP 310:413, 584:15,260:663,,163:298, 281: 4, 876:1253
NA 169:527,10414:24,244:673,,176:369, 2341: 2, 830:1242
M 357:473, 2104: 5,224:755,,106,127,15054: 1, 735:1793
NS 204:510,42870:16, 39:764,, 27:343,34789: 3, 602:1966

the exact meaning of the numbers is hard to explain, but the 2nd value after “:” is always from a randomized run. The 2nd part after “,,” considers only 3rd position mutations (in codon), these often don’t change the properties of the virus.



Everyone all together: "WTF?"

Finally, nice journal article on the differences between the three pandemics in the last century -- with a picture. I like pictures.

http://content.nejm.org/cgi/content/full/353/21/2209

.panflu_mechanism.jpeg

[mugwump]

Well, FWIW I got an answer on the new resarch vis-a-vis threat levels. This receptor research apparently hasn't changed any minds -- those who think the threat is overblown still think that way and those who think H5N1 may go pandemic haven't changed their minds either. I was referred to look up info on the young girl and her uncle who died in Turkey. The implication is that this was a h2h case and genetic analysis showed the point mutations had already occurred which are being touted as unlikely in the popular press in light of this new research ("nearly impossible", "like winning the lottery twice", etc.).

Don't get me wrong, this research is considered very significant -- it just doesn't answer the 'big' questions.

This is in the Michael Osterholm interview I cited @ 20:31 yesterday:

"Then, when you look at the Turkey virus—that thing mutated. This is the case of the young girl in Turkey who died from her infection, and so did her uncle. We definitely have clusters where it’s not just bird contact [spreading the virus]. The uncle’s only exposure to this virus was riding in the ambulance with her from hospital one to hospital two. He became ill three days later and died. Her virus has now been fully sequenced, and there were three mutations that occurred in that virus, between the bird version and hers. One was the substitution of a glutamic acid with lysine at the 223-hemagglutinin position. That is what changes it from a bird-receptor virus to a human-receptor virus. The second thing was two other substitutions that served to make it look more and more like a human virus."

New question: if it mutated, why didn't it spead?

..

[Seth]

Layman's question, Mugwump:

If the bronchioles receptors theory proves valid, how critical is that information to both vaccine and possible weaponization efforts?


-Seth

[mugwump]

Originally Posted by Seth

Layman's question, Mugwump:

If the bronchioles receptors theory proves valid, how critical is that information to both vaccine and possible weaponization efforts?


-Seth

Smart questions, layman. I should say "I'll give you a very technical answer: I don't know" but I'll plow through anyway. I wasn't going to talk about the following because it's, well, worrisome and I don't know how useful this is at this stage. But, you asked so...the weaponization, or stupidization potential is at the end after some exposition/explanation.

First. The data in these papers are good, and the receptor results are accepted as indisputable at this stage. So it's not an "if valid" scenario. I can say this without sounding petty because I don't do research, but this isn't rocket science. There has been so little work done on flu that there is low hanging fruit, research-wise, all over the place. These papers are actually more important for mapping the distribution of alpha 2,6 receptors ("mammal" receptors found in the upper respiratory system) and alpha 2,3 receptors ("bird" receptors found deep in the human lung and in bird guts) than they are in answering questions about the virus -- regardless of how the press is spinning it. Note they used isolates from 2004 - a snapshot from the past. What the papers do is describe "what was", probably not "what is" and definitely not "what will." Since the samples in this study were obtained, the virus has split into two distinct genetic branches and had multiple mutations in each branch. It's good work and more like it is needed but the crystal ball is still as murky as before, at the end of the day.

What the newspapers don't tell you is that "they" (see below) already know the gene sequence needed to code the receptor mutation that will cause the H5N1 pandemic. They've even actually created the virus - pray they don't let it loose. They are now arguing about how the proteins produced by these "key mutations" get folded into the proper shape for the proper lock-and-key fit. This field is moving very quickly.

As far as vaccine efforts go, no, it doesn't help. That two-branches split I mention has really made things more complicated. What will help is the virus not mutating for at least another 12-18 months so we can get vaccine manufacturing infrastructure in place. Note that Congress, world governments, WHO, industry, and academia all have to pull together on a crash basis even then. The odds of that happening are left to the reader to calculate. The receptor research might assist in developing new tools to help identify any h2h virus that breaks out. But realistically, any such breakout will probably be identified epidemiologically -- by the 16 then 32 then 64 then 128 etc. cluster that is first identified.

Check out Minor Mutations in Avian Flu Virus Increase Chances of Human Infection. It discusses in a more understandable way the original study that I cite in the first message of this thread. Note that they've actually inserted the "bad" genes into the Viet04 H5N1 virus and created a virus with the affinity for the alpha 2,6 receptors (the "Oh, crap!" ones). I repeat - .

http://www.scripps.edu/newsandviews/...320/avian.html

"The study showed that relatively small mutations can result in switching the binding site preference of the avian virus from receptors in the intestinal tract of birds to the respiratory tract of humans.These mutations, the study noted, were already "known in [some human influenza] viruses to increase binding for these receptors."

The bird gut receptors they refer to are the alpha 2,3 ones, and the human resp. tract ones are the alpha 2,6 mentioned in the "bronchiole" study. You will note that this study directly contradicts the statements of the Japanese researchers and the press who imply many difficult mutations are needed ("odds akin to winning the lottery twice"). Such is science and human nature.

“Our recombinant approach to the structural analysis of the Viet04 virus showed that when we inserted HA mutations that had already been shown to shift receptor preference in H3 HAs to the human respiratory tract, the mutations increased receptor preference of the Viet04 HA towards specific human glycans that could serve as receptors on lung epithelial cells,” Wilson said. “The effect of these mutations on the Viet04 HA increases the likelihood of binding to and infection of susceptible epithelial cells.”

These guys are at Scripps, that DOD-research-center-in-Maryland-that-we-won't-name, and the CDC -- so hopefully their containment is up to snuff.

If they can engineer a flu virus into a pandemic form, someone else can do it. I don't figure it's easy, but then I've got a gene sequencer on a bench in the next room that they say can sequence a whole human genome in a month. I still have to cypher out how the dang thing works, though.

It would be pretty stupid to do if you didn't have a vaccine, but there you go.

[mugwump]

I am out of the country for a week, not cowering under my bed covered in tinfoil.

Later.

[Seth]

Thank-you for reply, Mugwump.

I appreciate your prespective and time, on this topic.

Have a safe journey.

-Seth

[Stargazer]

Originally Posted by mugwump

If they can engineer a flu virus into a pandemic form, someone else can do it. I don't figure it's easy, but then I've got a gene sequencer on a bench in the next room that they say can sequence a whole human genome in a month. I still have to cypher out how the dang thing works, though.

Mugwump, which system do you have?

[Maisy]

Mugwump, this is a great thread, thanks for starting it.

Out of curiosity, I did a quick search to see how seriously Australia is taking the issue. The answer is pretty damn seriously.

According to figures released last year, Australia now has one of the largest per-capita on-shore stockpile of anti-viral drugs in the world The current stockpile will cover 20% of the population should a pandemic break out.

Interestingly, to get that much on-shore, we pretty much cornered virtually the entire tamiflu world market for about 12 mths. This is in addition to both current hospital supplies and to off-shore expected supplies. The govt also stockpiled huge amounts of syringes and surgical masks, and got over 300 extra ventilator machines in. All this in addition to working on developing a proper vaccine, and on getting enough anti-virals to bring the stockpile up to the WHO recommended 25% pop. coverage.

The biggest expenditure though is in what we are spending to help SE Asian countries develop their agricultural surveillance and lab testing capabilities, as that's currently where the greatest threat seems to come from.

http://www.health.gov.au/internet/mi...abb251005a.htm

[mugwump]

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