Bird flu in Egypt

"But if I were a wagering man . . . "
You'd say...the first or second interpretation?

K from MI: I'd say the first.

Thank you for this analysis - it helps to calm down after being driven to the edge by reports in local Egyptian media.

It seems like B-H cases and the outbreak appears to be ending. Of course if you ask Niman and group, you might get a completely different answer.

But they're still throwing the infected killed birds onto the riverbanks, at least in some areas. www.el-wasat.com/details.php?id=21564
AnnieRN

Revere: I would agree with your first interpretation, if the H5N1 strain found in the dead and suspected cases turns out to be the same as the one in the past year or two in Egypt. If it turns out to be similar to the one in Indonesia, your second interpretation would be appropriate. The key is to sequence their current isolates ASAP to help confirm which one is the culprit.

revere,

I will "wager" on the first as well. We will find out in a few days if there are more suspect cases using ventilators and the like.

There was a story of one intoxicated fellow telling every one he had bird flu. That may well have been an indication of the intensity of the media campaign to look out for bird flu symptoms. I suspect there are lots of worried well, or normal cold/flu season cases. This reminds me of Thailand 2006.

It does not appear that the flu cases in Egypt are less and 4 people have died in several weeks with an CFR of 100% The problem in Egypt is far from over. Medclinician

If one measures opportunity in terms of template (geography - susceptible species) and total amount of active circulating virus both in terms of individual and/ or community infections in all animal species...

...then the endpoint becomes pure mathematics...

...and given that the virus has proved it can efficiently infect humans (as in kills them in short order)..

...and that it can evolve into (multiple) sub-types that also efficiently kill...

...and that it can evolve to transmit from human to human to human (repeatedly in distinct geographic niches)...

...do we want to really assume that H5N1 cannot make the final evolutionary step to efficient human to human to community to world transmission.

One other thing to keep in mind...

...For the last 100 years the world has been dominated by H1N1 and its descendents...

...with that in mind and considering geographical distribution and previously unseen (ever in human history)...intra and inter-species susceptibilities...

...then maybe it is time for the scientific community to unanimously acknowledge and we are seeing at the very least, a pathogenic paradigm shift.

The world will never be the same again.

If H5N1 achieves geographically widespread panzootic potential in poultry and pig populations...the cascading effects on humanity will be great.

If H5N1 evolves directly to achieve pandemic potential, it is now becoming clear that we will have a human catastrophe...

...and if H5N1 recombines or reassorts with other influenza subtypes to achieve pandemic potential then the effects on humanity will be great.

H5N1 arrived, was controlled in Hong Kong...was not controlled in China...and as a result is now completely out of all human control...

...it is here to stay and it will influence and most likely dominate animal and human health for the next century...

...and since logic says that that humanity is due for a pandemic...I wouldn't place a bet against this 'monster' of a virus.

I must say that it feels like Groundhog day. Everytime a few cases are confirmed in a relatively short period of time, the doomers come crawling out of the woodwork suggesting that things are finally different this time. Ever notice how the situation never changes though?

Some (ie Henry Niman) try to hype each and every one of these "events" for their own personal gain. They try to make you believe this is really bad and "cause for concern" by always citing "suspected" cases and assigning them to "clusters". This intentionally blurs the lines between suspect and confirmed cases and makes a spike in suspected cases even more worrysome...even though a spike in suspected cases is rather meaningless.

The final effort to extract maximum hype from these "events" by the doomer crowd is to attack the testing process itself. Their message is simply: "there surely can't be this many suspected cases without a high number of confirmed cases....poor test results must be the explanation." The inference is to make one believe that there are a much higher number of actual cases floating around, again blurring the lines between fantasy and reality. Clever, but after seeing this play out time and time again, it is also very predictable.

The bottom line is that this virus remains avian. It isn't spreading around Egypt by "H2H" or more "efficient B2H" no matter how hard some try to make us believe otherwise. Furthermore, once this "event" passes, we'll hear no more about it from the doomers. No retractions, no acknowlegment that they were wrong, instead they'll simply wait for another "event" to begin the cycle again.

Stan: My problem is that if it changes it won't look much different at the outset. Best to keep an open mind.

revere,
I vote for "a change in the epidemiological characteristics of the virus." , because it's the most important senario to rule out, or counter first, especially since there are already Tamiflu resistant strains of H5N1 floating around Egypt.

And since zanamivir was always a superior antiviral to oseltamivir, (except that a systemic delivery method was never developed i.e a pill), I would fast track the developement of intravenous Relenza and LANI (Long Acting Neuraminidase Inhibitor).

miso: Unfortunately this is not a "majority rules" thing. Your vote or my vote doesn't matter. We'll need to see if there in fact is an epidemiological change. I expect it will be evident soon enough. If this is the start of a pandemic, zanamivir will be mainly irrelevant, IMO.

Fine with me. I'm not bothered by false positives. I hope they are all false positives.

Me too!
I had an MD client I was booking on radio talk shows a couple of years ago when the first bird flu scare came up. He was kept very busy with the interviews and some of the speculative scenarios that were going around were down right scary!
Dave Briggs :~)

Since Dr. Niman gets accused of hyping the danger for personal gain, I would like to know if anyone can state to me what personal gain he has obtained by so doing.

Further I find that his concerns (stated actually rather mildly) are usually followed by events that make his concerns valid - continual spread of virulent H5N1 which has gone B2H and H2H in a small number of cases. Since the virus has come that far how is it doomist to project that it might make another step and become easily transmitted H2H. If it does it will sweep the world quickly and devastatingly so I cannot for the life of me see how his concerns are unwarranted.

BTW Stan-I would add a bit of credence to your "doomsayer" stuff with the exception of one thing. The preparations that are now going into this are absolutely massive. 500 million to Indonesia, the UK before Xmas announcing that they were moving to Pan Flu Level 3.1 equivalent US preps for their population to include off antigen flu vaccines, masks, eye gear and a plethora of other preparations.

Then there is the indisputable.... The WHO that would minimize a train wreck with 400 on board and all killed in front of their office in Geneva as a transportation accident, has called the ball. It is human to human now. This tips the scale of balance towards pandemic, not away from it. So better to be really damned safe with this one than massively sorry. Sorry in this case would at the high CFR's even if they halved would be fully 1/3rd of the planets people. Oh, they wont die of H5... Nope gotta have that RT-PCR for the confirmation and there arent that many test facilities on the planet. So they will die officially of pnemonia if it comes.

But why belabor the point? Its here. Lets get on and deal with it so Revere and I dont have to go to our chidrens and grand-childrens funerals. He can help raise a lefty kid and I'll help him and the only way so far to do that is prepare. Give me something else to throw at it and I will, else preparations are the only way and to try to throw water on that means if it comes, you killed someone indirectly. If you are right, they get to throw a big food party or give it to their local food bank as it approaches expiry date. Believe it or not in the US you can deduct it as a medical expense if you will take pictures of it and get expiration dates from cans or boxes and then write numbers on them. Then when you donate it if Stan is right you take another picture as it goes in and then you can write it off

I wouldnt want to be even half right about this Stan... zero, de nada. I get this one right its going to be bragging rights only. But so far you are getting it wrong because the proof is in the ground now.

Tom DVM. Questions.

http://www.rense.com/general76/pig.htm

Then there was the blue tongue thing.....

Are both of those animal flu or not? I know Newcastles is but does blue tongue occur in pigs when they get the flu too? The high fever disease killed millions of pigs. .... I cant believe it was strep....

MRK, one thing about you is that your montra is unfazed by facts. This thing is no closer to human panflu than it was in 1997. There is no greater affinity toward humans. As the virus continues to spread geographically, the number of human cases remains virtually static from year to year. This in countries where good hygiene isn't even their vocabulary. These are facts MRK.

As far as governments spending $$$, what does that mean? I'll tell you what it means....nothing! Don't believe me, take a look at the 100's of billions that are spent each and every year by our beloved government on nothing. Come on, you can do better than that can't you?

K,

Since you asked, I'll make it short. We have all heard of the consultant who borrows your watch to tell you the time.

Well, some would borrow your watch (show me the sequences) and patent the Time Machine with it. Whether the Time Machine or crystal ball or taro cards work or not, won't matter. If you throw enough up the wall, something's going to stick. Spring bride is now grandmother.

and the grand children live on Elm Street.

And certainly Stan you can no more say I am wrong than I can you. History is going to allow the other one bragging rights. If you are wrong and you are under about 45 you will be lunch. I might get sick but the averages are on my side. Under 45, well I will say that you will be missed here.

So sit back take the ride and with all of the experts suggesting that this is more than a splash in the pan, we have Stan. One more clustering somewhere else will pretty much make sure the point is moot. I hear concern, its dangerous, its everything but what you are asserting Stan but .....

I remain open and if the cases and CFR's were dropping I would be in your camp Stan, but they are not.

Facts are not separating between the two very well. Realities are that its growing in numbers, deaths and geographical reach. These are pandemic criteria and there are those birds where there is a full blown pandemic underway right now. As Tom asserts... we are only an animal whose buttons havent been pushed yet.

.
Revere wrote:
We'll need to see if there in fact is an epidemiological change. I expect it will be evident soon enough. If this is the start of a pandemic, zanamivir will be mainly irrelevant, IMO.

My reply / question: Do you feel that just zanamivir (Relenza) will become irrelevant as opposed to Tamiflu also??? Because the virus will become resistant to them that quickly? ? ?
.

zanamivir has to be inhaled which prevents its use on a more widespead basis. Tamiflu is a pill and is absorbed orally so has systemic effect, but resistance is more likely. But there are zanamivir resistant strains, too, and the antiviral modeling shows that resistance will eventually spread throughout the population even if it is rare. In the first wave you come out ahead with an antiviral (see my antiviral modeling posts), so the ease of administration of Tamiflu gives it the edge. OTOH, neither will stop a pandemic and if it happened now we don't have enough or the ability to distribute so both are likely to be of only marginal effect IMO.

I'm disappointed MRK that you didn't elaborate on your earlier premise that the issue gains credibility by whether the government allocate funds for it or not. If you are right, I guess it would argue against the existence of any political waste wouldn't it?

If you are right, they get to throw a big food party or give it to their local food bank as it approaches expiry date.

Or you can, if disciplined and organized, run a first-in, first-out queue of stored foods. Regularly drawing down older supplies each week and replacing them incrementally has a lot to recommend it.

Holding supplies as a big batch until close to their expiry date, and then having something untoward happen before they are replaced in toto, implies a possibility that the more perishable among those goods may not be there to be fully relied upon during a period of extended disruption.

I keep looking at handheld bar code scanners and musing about building a preparedness-pantry management tool, linking the handheld to a small database. One would obviously have to be ready to revert to paper in some circumstances.

And while you can scan in goods, you would still need some way to rapidly ID tag each individual can, to be able to individually reference its storage and best-by dates. So that you would be able to say, ah, it's March, I need to rotate out the following units for consumption or donation.

--

Hi Randolph.

There is an incredibile amount of environmental instability in all pathogens at the moment...and we do not have a scientific explanation for it...and that bugs me...because I have always found that no matter how difficult and confusing a problem is...in the end the answer is always simple and straightforward...as are the solution (s)...but if you can't find the etiology, it's pretty hard to get around the problem. /:0)

When you read a textbook, all diseases fit into nice little packages and are easily distinguishable...then you get out in the 'field' and everything looks the same.

There are multiple diseases evolving at different rates in Asia at the moment...so I personally wouldn't take any report as the truth...for the reasons I mentioned.

However, I would offer that if authorities like the World Health Organization really wanted answers to the problems...they could round up the required expertise in a week and have most of the answers in a month.

Tom: What do you mean exactly by environmental instability? And what's the evidence that whatever it is is different now?

Hi Revere.

What I meant was that there is genetic instability... mutability...mutations - changes in bacteria, viruses and parasites, animal and plant, to infect new species, increase virulence or transmissibility or new geographic areas.

Since this is occuring consistently around the world, the effect would have to be environmental in origin...

...something is influencing pathogens...and it would be nice to know what it is because the same pressure is pushing H5N1...and it sure doesn't need the help.

This one fact alone makes it highly unlikely that after ten years (a very long time in terms of emerging exotic pathogens), H5N1 is going to put itself out of business or go away without achieving pandemic potential...directly or indirectly...in my opinion and based on a lifetime of tracking animal diseases that tend to hide or lurk in nature and then pop up on a regularly irregular time frame...sometimes months...sometimes years...sometimes centuries.

In my opinion, it is not a question of 'if' but 'when'...

...and since my prediction, based on my experience, was Dec 2006 to May 2007...I guess it will take it's own sweet time...and will happen when it happens...

...hopefully not for a long, long time.

Nature often lulls us to sleep... before we get hit over the head...maybe we are just not quite at that point yet.

/:0)

Tom: Just pathogens? And how do you know this?

revere, with no disrespect intended, I must use Tom DVM's post above regarding "genetic instability" as exhibit A with regards to my posts about the lunacy of the doomer crowd. How can anyone make such outlandish statements without one shred of proof, and expect to be taken seriously. I understand why you ask for an open mind but come on.....this falls right into the same category with some of the proclamations/statements made by niman and others.

The uptick in cases in Egypt is, like all such, something to keep an eye on. I am in complete agreement that, at the outset, both interpretation A and B will be indistinguishable.

However, without being trying to be insensitive, my credo is and has been (rightly or wrongly): in a country with testing facilities, increased suspect cases will be followed by positive tests.

And, regardless of facilities, increased suspect cases will be followed by *bodies*. There is a very short lapse in time, relatively, before suspect cases become bodies in most positive cases.

We will know the situation is possibly dire when many of the suspect cases begin to die, regardless of the state of the pending status of their test results.

Imho.

Stan,

These were written as sermons (no disrespect to the religious or any religion) and therefore no proof or evidence was ever needed or intended. They were written repetitively until it sinked in, believed, conviction reinforced, worshipped.

Just like fortune telling.

Stan: There's no value in starting a Niman flame war here. If you want to comment on Tom's post, feel free, but Henry isn't involved.

Revere.

I'm not sure about your question but I am not sure what else is being affected...in terms of nature there are probably multiple effects.

Stan. I am sorry you consider my hypotheses "outlandish" but that is okay with me.

I honestly could never have concieved or a pathogen as bad as H5N1.

Anyway, it is common knowledge...even the head of the World Health Organization commented on the unprecedented emergence of exotic pathogens in one of her speeches this fall I think.

...and by the way Stan...this type of discussion goes on all the time...maybe all too often, behind the scenes and behind the facade of human's dominance over nature.

No one is or can control H5N1.

bannor: Egypt has testing facilities so we'll see soon. Until then, it's all speculation.

Sorry, I should have said 'and behind the facade of human's dominance over nature and disease.

Revere,
That was what I was, perhaps badly, trying to say. Either it's not dire, or it is. We will know soon enough, one way or the other, and it is moot to speculate too wildly, at this juncture, which it is.

In this case, Egypt, we have testing facilities, in other cases, like Pakistan or Indonesia, where results are not to be obtained quite so quickly sometimes, we may have to turn to the CFR. My bad: without quotes, it was not clear that my post was not commentary to yours, but in general to much of the widespread reaction to the current number of "suspect" cases.

bannor: No problem. Just clarifying.

Not trying to start a niman flame war revere, just trying to be brutally honest. :0)

Okay, back to square one for a minute. Here is the official very nervous US line is that it has breached a milestone. Confirmed human to human transmission. The Paki government even in the middle of a near civil war and an insurgency is passing out information to the public. I find it to be pretty sincere stuff.

If you just take it by pandemic criteria that THEY established we are in pandemic level 4.

We are in the top level of Pan level 4 which is the alert phase.

1. No or very limited human to human transmission. Geographically contained -Pan3.

2. Evidence of increased human to human transmission. Geographically contained-Pan 4

3. Evidence of significant human to human transmission. Not geographically contained.-Pan 5

4. Efficient and sustained human transmission. Not geographically contained-Pan 6.

Everything below pan 3 is shit anyway and conjecture and WADR Stan where have you been for the last four years. Three years ago we got lucky in Turkey. Cases were turning up, no RT-PCR's, no surveillance and people that were EU based turned up with suspected cases and we never heard about them again. But hey dont take just that. 2005 across the river.... You can find it under Ebola flu. Nice pictures. I actually have some video watching a woman die of this stuff. Did it merge up with something ? Dont know but I can say that I saw a piece of this womans lung come up and out onto her face. Grayish tissue wth a lot of blood. She died seconds later.

Then there are the birds. You HAVE to acknowledge that it is now endemic just as H1N1 in pigs is here in the US. We likely get our seasonal bout from them and we carry it too. It just mutates in and out and whacks us as our immunities drop periodically. But birds? MILLIONS of birds have been culled, killed or just dropped out of the sky. And what is the culprit? BF...H5N1.

Then lets move on down here to the fact that the numbers of cases are increasing rather than decreasing, they are also still killing at above 60%. I think that Indonesia just quit reporting it. You arent dying of BF, you have viral pneumonia. LOTS of cases... You know they do have obituaries there. Lots of pneumonia being reported. Kind of like Vietnam when they quit reporting it. The tropical diseases hospitals were seeing 1500 people a week. Cant call it bird flu because you have to do a RT-PCR to get a confirmation. So you have PNEUMONIA.

But we cant call it bird bug without the test. When it comes it will be pneumonia and not bird bug because you cant differentiate. So we will have the 20 million deaths from it because that will be about the limit that we will test for. Then thats it. No more testing and 20 million die. More like by my guess 2 billion from primary cause H5N1 and another 500 million to 750 from starvation of various types. Then we get hit with a mutated wave a year or two later and bang its H5N1 with a twist. Maybe fewer deaths, maybe not. Could we end up with only 600 million to a billion stretched out across the planet? Yup!

We know that Europe lost 1/3rd to the Black Plague. We DONT know how many in China and Asia. But its reasonable to assume by population hits in Europe that at least that many died in the East. So that would have been easily a billion. But no proof so we have to discount it... because we are scientists? Yeah you do, but its like that guy who goes and kills the blob, he will try everything until he gets the monster. The blob ate half the town. But no one is sure where they are. They could have drowned, been picked up by aliens or intercepted by Dale Ernhardt. But they are gone.

The bottom line though is whether you accept the signs. The WHO has at least moved us to Pan 3. I see nothing moving us towards Pan 2. Just the opposite. So what do you think is going to happen? Three schools of thought. We get hit, we get hit hard, we get hit not at all.

No matter where you go Stan, there you are.

Tom DVM says: What I meant was that there is genetic instability... mutability...mutations - changes in bacteria, viruses and parasites, animal and plant, to infect new species, increase virulence or transmissibility or new geographic areas.

Since this is occurring consistently around the world, the effect would have to be environmental in origin...

----------------------------------------------------------

Virus has peptides and nucleotides. Virus has to conquer the host's immunity defense (basically is peptide related in invertebrates, vertebrates have more complicated.) Secondary, the intruded virus nucleotides should be able to hijack the host's protein and nucleotides generation systems.

For the last 10 years, I have been involved with invertebrates' infections model by virus, especially the commercial shrimp virus. This infection model is based on water borne transmission. My speculations on Tom's genetic instability are:

1. Genetic instability, in my interpretation is not genetic material by nature itself, but is the quantity in virus reservoir. One million years in evolution, the virus species changes is not a major shift, not mention a decade or 100 years. Whereas, the viral loads in different environments and different times vary diversely.

2. The virus of 1918 Spanish flu existed before, in that time and now. The question is why it happened in 1918? My speculation is because of War time, the human body to become virus reservoir was prominent in that situation. It has threshold of viral load to have outbreak.

3. B2H, B2B viruses are relating to avian species. The poultry's bird thru generations, the immunity has become more naive. Wild birds are the vectors for millions years, why the last several hundred years to have bird flu outbreaks. It is the virus reservoir in poultry's birds. In other words, the immunity of chicken has evolved to become naive.

4. The prevention of H2H, the leverage shall place on human us. To prevent our immunity deteriorates to a point of threshold or/and to prevent the H2H reservoir such as dead bodies by wars or natural disasters and untreated for a long time.

So far, I have voiced the H5N1 prevention needs the collaboration of WHO and FAO. The reason is according to my brief speculation stated above.

As for H2H case, again are relating hygiene and proper sanitation of human living environments. This monster does exist for millions years, but only human being invites it to attack us. Nature is safe and fits to the pattern good as whole and billions years.

Addedum: The prion theroy speculates that protein can relicate istself, in the origin of life, the protein and nucletide have different modes of replication. And I further speculate that peptides are more primitive than nucletides, because survival is more critical than reproduction. So, our body has inherent design in fighting with pathogens. Now I would like to coin it " Evolution Safeguarded Immunity". It is my hypothesis, open to discuss.

You are correct anon, just like a religion. The type that requires you not to question, only to drink the Kool-Aid.

As I said in an earlier post, once this current "event" blows over and doomers abandon the "panflu in Egypt" montra, you'll hear nothing more about it. Not a single acknowledgement of this being yet another false alarm.

For those unfamiliar with LANI.

"Biota Holdings Limited announced that its long acting neuraminidase inhibitor (LANI), CS8958, an anti-influenza treatment, has demonstrated effectiveness against the avian flu virus H5N1, completed Phase I studies in Japan and received ethics approval to commence comparable studies in the UK.
CS8958 is a long acting neuraminidase inhibitor and offers higher potency, lower dose and the potential for once only treatment and once weekly prophylactic protection from influenza. These properties are known consumer advantages over existing inhaled and oral therapies."

http://www.bionity.com/news/e/64153/

"In summary, we have identified dimeric NA inhibitors that show remarkably high levels of and prolonged anti-influenza virus activities. We believe that, relative to zanamivir, the superior in vivo prophylactic activities of dimers such as compound 9 can be attributed to a combination of the improved antiviral potency and higher level of compound retention in the lung. These compounds provide a clear example of how suitable multivalent derivatives of a known therapeutic compound can introduce an extra mode of binding and, hence, give dramatically improved activity in vivo. These results raise the prospect for a new type of anti-influenza drug that could be used at very low doses administered once weekly, such that a single dose could be suitable for the treatment of influenza or such that treatment just once a week could be suitable for the prevention of infection."

http://aac.asm.org/cgi/content/full/48/12/4542

Stan-Since dead people and people in the hospital dont flip your skirt, what would you call pandemic?

I am very interested. Would it take a mob that was starving to death coming in and kicking the shit out of you and then taking your meager supplies. How about a family member coming down with it. I just cant fathom someone who puts their ear on the rail and hears the train but then calls it something else.

I dont discount what you are saying though. You COULD be right, but I bet not.

revere,
since your opinion carries so much weight allow me to rebut some of your comments on zanamivir. You'll note I prefer to let the literature do my arguing.

"there are zanamivir resistant strains"

"One strength of the neuraminidase inhibitors oseltamivir and zanamivir (Relenza) over the older adamantanes is that they are less prone to selecting for resistant influenza viruses. Indeed, no virus resistant to zanamivir, which is currently available only in an inhaled form, has yet been isolated from immunocompetent patients after treatment. The recent emergence of oseltamivir-resistant variants is therefore a matter of immediate concern.

Why is resistance developing to oseltamivir? Several years ago,structural analysis predicted that aspects of the chemical structure of oseltamivir (not present in zanamivir) could facilitate the development of resistance mutations that would permit neuraminidase to function, allowing drug-resistant virus to survive and propagate. This prediction is now being validated by clinical data."

http://content.nejm.org/cgi/content/full/353/25/2633

"Mechanism of Resistance to Oseltamivir (Tamiflu).

The neuraminidase active site on the virus surface changes shape to create a pocket for oseltamivir, whereas it accommodates zanamivir (Relenza) without such a change (Panel A). Any of several mutations may prevent the binding of oseltamivir by preventing the formation of this pocket (Panel B); the oseltamivir-resistant virus can nonetheless bind to the host-cell sialic acid receptor and to zanamivir. The pocket for oseltamivir, illustrated by key amino acids in Panel C, is created by the rotation of E276 and bonding of the amino acid to R224 � events that are prevented by the mutations R292K, N294S, and H274Y and therefore result in resistance to oseltamivir. An E119V mutation may permit the binding of a water molecule in the space created by the smaller valine, also interfering with oseltamivir binding. None of these mutations prevent the binding of zanamivir or of the natural sialic acid substrate."

http://content.nejm.org/cgi/content/full/353/25/2633

"Viruses resistant to zanamivir have been generated in vitro, but no resistant virus has yet been isolated from a zanamivir-treated immunocompetent patient. In contrast most resistant viruses isolated from oseltamivir-treated patients correspond to those selected in vitro.

Mutations conferring zanamivir resistance significantly affected enzyme activity, virus replication or NA thermal stability.

These data suggest that zanamivir-resistant H3N2 viruses may not readily arise in vivo due to their poor viability. "

http://jac.oxfordjournals.org/cgi/content/full/58/4/723

"Two different strains of highly pathogenic avian influenza A (H5N1) have been circulating since 2003. Clade 1 has been found in Vietnam, Thailand, Cambodia, Lao People's Democratic Republic, and Malaysia. Clade 2 subsequently emerged and spread from People's Republic of China to Indonesia, Europe, and Africa in 2004-2005.....

....We tested the neuraminidase drug sensitivity of clade 1 and clade 2 influenza A (H5N1). All viruses demonstrated similar sensitivity to zanamivir, but compared with the 2004 clade 1 viruses, the Cambodian 2005 viruses were 6-fold less sensitive and the Indonesian clade 2 viruses were up to 30-fold less sensitive to oseltamivir....

....No altered sensitivity to zanamivir occurred, which further supports the hypothesis of minimalist drug design and of maintaining the inhibitor as close as possible to the natural substrate to minimize the emergence of resistance."

http://www.cdc.gov/eid/content/13/9/1354.htm

"zanamivir has to be inhaled which prevents its use on a more widespead basis."

""Safety and Efficacy of Intravenous Zanamivir in Preventing Experimental Human Influenza A Virus Infection"

ABSTRACT

Zanamivir is a potent inhibitor of influenza A and B virus neuraminidases and is active topically in experimental and natural human influenza. We conducted this double-blinded, placebo-controlled study to evaluate the safety and efficacy of intravenously administered zanamivir. Susceptible volunteers were randomized to receive either saline or zanamivir (600 mg) intravenously twice daily for 5 days beginning 4 h prior to intranasal inoculation with ~105 50% tissue culture infectious doses (TCID50) of influenza A/Texas/36/91 (H1N1) virus. Reductions in the frequency of viral shedding (0% versus 100% in placebo, P less than 0.005) and seroconversion (14% versus 100% in placebo, P less than 0.005) and decreases in viral titer areas under the curve (0 versus 11.6 [median] log10 TCID50 � day/ml in placebo, P less than 0.005) were observed in the zanamivir group, as were reductions in fever (14% versus 88% in placebo, P less than 0.05), upper respiratory tract illness (0% versus 100% in placebo, P less than 0.005), total symptom scores (1 versus 44 [median] in placebo, P less than 0.005), and nasal-discharge weight (3.9 g versus 17.5 g [median] in placebo, P less than 0.005). Zanamivir was detectable in nasal lavage samples collected on days 2 and 4 (unadjusted median concentrations, 10.5 and 12.0 ng/ml of nasal wash, respectively). This study demonstrates that intravenously administered zanamivir is distributed to the respiratory mucosa and is protective against infection and illness following experimental human influenza A virus inoculation. "

http://aac.asm.org/cgi/content/full/43/7/1616

" Glaxo has stopped development of injectable forms of Relenza, which health officials had said might help treat severely ill avian-flu patients, Stout said.

``We asked people if they were going to buy any and they said `No, we want it to be there just in case,'' he said. The company faced ``huge, expensive clinical programs without any buyer.''

``It's just on hold,'' he said. Orders for the available, inhaled drug have slowed, he said. "

http://www.bloomberg.com/apps/news?pid=20601109&sid=amEj8Gs9hVNg&refer=…

""GlaxoSmithKline, which makes Relenza, has shelved plans to test an intravenous form of the drug in the United States, but is in discussions with a WHO-organized treatment network in Southeast Asia to test the new formulation there."

http://www.cbc.ca/cp/health/070318/x031806A.html

"If this is the start of a pandemic, zanamivir will be mainly irrelevant, IMO."

Unfortunately I have to agree with you, so little has been stockpiled, and trials of an injectable versions had languished for a decade. Uniformed opinion, politics, and commercial considerations have done us no favours.

Referring to Tom DVM's post from 9:51, this is what Chan said in September last year:

"Population growth, urbanization, intensive farming practices, the misuse of antibiotics, environmental degradation, and incursion into previously uninhabited areas have exerted enormous pressure on pathogens.

As a result, new diseases are emerging at an historically unprecedented rate. Old diseases are resurging, or spreading to new areas.

Resistance to mainstay antimicrobials is occurring at a rate that outpaces the development of replacement drugs.

Simultaneously, emerging and epidemic-prone diseases have become a much larger menace under the unique conditions of the 21st century.

The international spread of disease, and the disruption it causes, have been greatly amplified in our highly mobile, interdependent, and interconnected world."

Further to my speculations stated above, I would like to have the following implications for comments:

1. B2H prevention is on the poultry farming. If the farmed chickens have Evolution Safeguarding Immunity, then they will be not naive to become virus reservoir.

2. H2H prevention is on overall human health and hygiene, it is related to personal life style as well as the collective impacts such as the untreated human bodies by war or natural disasters, moreover, the hunger and malnutrition prolonged in specific areas will make human beings as virus reservoir.

MRK,
I AM right and this "event" in Egypt, which is already winding down, will pass like every other "event" before it without any over reaction from the WHO. Next week you'll be back to bitching about how the world as we know it will never be the same if Obama, Clinton, etc win and if you could put down your Kool-Aid and break out of the dark circle of doom, you'd be able to read the script as clearly as rest of us can.

~Cheers

Revere, Patch and dear friends:

I would be grateful to having your critical comments on my previous posts on Bird Flu in Egypt; my speculation places the surveillance on a larger picture of how virus infects and the area for new focus of system thinking on the prevention measures. For instances; poultry protocol appraisal to prevent chickens as virus reservoir, eliminate hunger and malnutrition to prevent human as virus reservoir.

Quoted the second post
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Further to my speculations stated above, I would like to have the following implications for comments:

1. B2H prevention is on the poultry farming. If the farmed chickens have Evolution Safeguarding Immunity, then they will be not naive to become virus reservoir.

2. H2H prevention is on overall human health and hygiene, it is related to personal life style as well as the collective impacts such as the untreated human bodies by war or natural disasters, moreover, the hunger and malnutrition prolonged in specific areas will make human beings as virus reservoir.

Posted by: paiwan | January 3, 2008 10:23 AM

Very interesting exchanges. I tend to the view expressed by Revere, bannor, and others: The initial display will be what we have already seen; several times, in fact. But, when it truly comes, there will be no possible way that we will mistake its arrival. "IT" will trumpet its arrival, in a massive, stentorian display of its power (how could it not?).

We're not there, yet. But, it's not showing any signs of retiring from the field, either.

We're not out of the woods, here; by any stretch of the imagination. H5N1 is out there...as it constantly reminds us...and it means us no good.

Stan what are you going to do if you are wrong?

I mean really. Have you made any preparations? Have you done anything at all?

Let's face it, domestic poultry can no longer be regarded as an easy and safe source of meat in countries like Egypt where bird flu is known to exist. Families living with their chickens is an open invitation to H5N1 to test it's luck in a new host.

The sooner steps are taken to limit poultry production to large farms where the health of the birds can be monitored, and contact with humans is limited, the better.

I'm not saying it's going to be easy.

miso and Dylan:

If poultry being proven as the source to infect human beings by H5N1 virus, then we need to appraise poultry production system now, it is the area that WHO and FAO have to work together.

As to H2H virus, can you imagine that a new world of compassionately collective efforts in dealing with hunger, malnutrition, wars, and etc, suddenly the problem is distant to us and sliding away?

Nature will not be mischievous to human community, as Einstein's words, God will not play dice.

What do you think?

MRK,
What preps any of us have or have not is immaterial to the discussion of whether Egypt is *it* or not. Personally? I believe that Egypt is *not* "it". But, could it be? Sure.

On the day, should it come, that "it" happens, the Event will start as every other false alarm - but, as Dylan said - there will be NO MISTAKING the "real" thing.

So is Egypt the "real" thing? Maybe. Talk to me a in week.

But the question of "preps" does not alter the validity of my position.

Paiwan, I think your message is hidden because your English is difficult to make out AND because your suggestions are unfamiliar to this crowd. To me, I can easily visualize a nano-sized flock of poultry crammed together on agar in a petri dish (with the lid off). Not a problem. I have a pretty good idea of what will happen to those organisms. I agree, animal husbandry has an important role in directing the virulence, aggressiveness or dissipation of a virus. The problem is, MONEY and CULTURE. Not to mention POLITICS! No one wants to go back to raising poultry in small flocks by many people. I suggest we may be forced into this if we resist.

Paiwan, I forgot to say that I agree that animal husbandry practices have created animals with weak immune systems. The only way to change that is let Nature teach us a lesson we won't forget...or force animal husbandry practices that don't create pandemic viruses. No one wants to be the one to force new practices is my guess.

phytosleth:

Thank you for our comments.
Because I have managed fish/shrimp farm for last 30 years, basically I am a farm person, though I have conducted commercial research in marine virus area.

Now I only can offer speculation for H5N1 in poultry, I think that the way of present production method has led to deteriorated status of chicken immunity. Again, this needs more quantitative data which I thought that FAO should place priority in rectifying this problem, or researsh.

Perhaps, the new direction of looking at animal husbandry is as important as at human public health level.

Funny thing is, I think everyone would *love* for Stan to be right. Anyone would prefer to say, "Sorry, false alarm" instead of volunteering for burial/cremation duty and crying "Bring out your dead."

phytosleth says: The only way to change that is let Nature teach us a lesson we won't forget...or force animal husbandry practices that don't create pandemic viruses. No one wants to be the one to force new practices is my guess.

-----------------------------------------------------

Agree with your analysis:
1. To let Nature teach us a lesson, we have to take reactive solutions
2. To force animal husbandry practices that don't take pandemic viruses, we have to take proactive stance.

The problem now is our ignorance of the true situations:

For instance, have the efforts that we have put in dealing with pandemics offered us true safety or pseudo-safety?

Vaccination is to treat the symptom, not to prevent the cause of pandemic. The investment in this area in comparing to improving the poultry protocol is much higher, but less effective. But it seems that the existing efforts have been only directed at this direction, is it a mindset or ignorance, time will tell.

Can we be proactive a bit this time?

Phytosleth, nobody wants to go back to raising small flocks of chickens in their backyards--except the people who do it every day, who consider these animals pets, or food sources, or the way that they earn the money to send their children to school.For many, many poor people around the world,backard poultry, goats, or whatever are their tickets to having a real home, an education for their children, and adequate food for their families. This is a huge issue for these people, and it's the reason that certain service agencies and micro-loans exist--just to help impoverished people to get out of poverty, one backyard at a time. I'm not denying that the backyard flocks are the problem in relation to H5N1--just addressing the reality of what WHO and other agencies have to deal with. If you wipe out their small flocks, you're wiping out their ability to feed their families. AnnieRN

Hi Revere,

My contacts at Flu Trackers and beyong are tonight at unprecedented level of stress concerning the Mosa�c of Regions and numbers of clusters presently in Egypt.

Upper and Lower Egypt are affected. Some GP state that some worrying happen and clinic got overwhelmed at some governate.

Still the cases held for observation today rose officially above 30.

Still wainting for some Comfort informations.

I think this hsould be posted, just hope you've got extinguishers before there are excess, extreme or extravandas.

Snowy

Dipl.-Ing. Wilfried Soddemann - Free science journalist - soddemann-aachen@t-online.de - http://www.dugi-ev.de/information.html - Epidemiological Analysis: http://www.dugi-ev.de/TW_INFEKTIONEN_H5N1_20071019.pdf

Posted by: Dipl.-Ing. Wilfried Soddemann | January 5, 2008 9:09 AM

------------------------------------------------

I read WHO report rcmd by the post above, and it seems that the BF infection by contaminated water is very high. And the low temperature will let virus survives very long time.

I am not sure that the cases in Egypt were mostly by water borne or air borne H5N1 virus? Is it possible that wild birds directly infect human by water borne, for instance, by drinking or swimming in the lake which has dropping from wild birds.

How poultry's chickens got infected? Air or water route?

Paiwan,

We have about 5 boots on the ground, no signs of Airborne but signs of genetical predisposition of unknown avians common sources.

I see 5 problems over Aegyptos at this time;

1- OUtbreaks in synchrone (what are the variable of cold and hot weather these days in Egypt?) Gsgs is working on it

2- It is obvious (Upper as Lower Egypt have outbreaks) and many governates and cities in those have outbreaks, more spread to territories.

3- Lets not forget that we are amidst an agressive awareness campaingn fo Egyptians via Egypt media

4- All this coincide with the very wide distribution of a new vaccine for poultry.

5- It is the nornal influenza season in conjugasion with the news is bringin more people at the hospitals thus increading the admissions. (lets not forget that we might experience the same upsurge in our Hospitals once the same sort of campaign of Awareness drives the MSM.)

Let.s hope that our govs, once they push the awareness campaign will not do it in the normal influenza period, thus not shovvling more on our HCW and sirge capacity.

Snowy