Bird flu vaccine may be too late for pandemic: expert

[SillyGoose]

By Phil Stewart

ROME (Reuters) - Drug companies may not be able to produce enough bird flu vaccine in time to combat a human pandemic, a top United Nations official said on Tuesday as governments scrambled to contain the deadly virus.

It could take six months to manufacture adequate vaccine stocks, and current stockpiles may be useless because the flu virus has mutated, said David Nabarro, U.N. coordinator for global readiness against an outbreak.

He said "very high priority" efforts were under way to raise manufacturing capacity so that a vaccine could be produced more quickly once a virus emerged that could cause a pandemic.

Experts say the virus is mutating steadily and there are fears that if it takes a form which spreads quickly among humans it could kill millions.

(more)
http://news.yahoo.com/s/nm/20051011/ts_nm/birdflu_vaccines_dc

[Earth_First]

1. So does this article insinuate that the virus is on track to mutate

in a manner which would prove deadly to humans on a pandemic level?

I am receiving mixed messages by this article.

[Timmy5835]

3. The answer is........

NO. But let's not let the facts get in the way of a good scare.

[SillyGoose]

5. I think he's trying to say that it is mutating but they are not sure

what the future form might be, hence the difficulty in developing a vaccine to combat it.

Experts say the virus is mutating steadily and there are fears that if it takes a form which spreads quickly among humans it could kill millions.

"We do not know what the genetic makeup of the eventual mutant virus will be, therefore we cannot be sure that existing vaccines that have been stored up will be effective," Nabarro said.

[mike_c]

14. IF the virus recombines with another type A flu...

...(and that's the most likely means of acquiring easy human transmissibility-- far more likely than mutation) then the antigens it presents to the immune system will almost certainly change. The recombination event will change them. Any vaccine made against the virus in its present form would not work against the recombined, human virulent strain. Vaccine makers MUST wait until that recombination occurs, then isolate and identify the new virus strain that results before they can begin producing a vaccine. Of course, then it's a race against time, because that human virulent strain will be the one that starts a pandemic unless it's contained.

There are additional problems, however. The virus will have to be genetically manipulated first, because it is grown in chicken embryos to produce viral particles for vaccine, but wild type H5N1 is highly lethal against chickens. Even at top capacity, current producers can only make enough vaccine to immunize about 5 percent of the world's population, even under the best of circumstances. None is produced in the U.S. And so on.

[SillyGoose]

18. Thanks for that explanation of recombination, Mike. I understand this

much better now. I have 2 questions you may be able to answer...

If the virus does recombine and they are able develop a vaccine, could it then recombine once again or mutate thereby rendering the vaccine ineffective? How long does the recombination or mutation process take?

[mike_c]

22. the short answer is yes....

Recombination is essentially instantaneous, but infrequent. The process doesn't "take" any longer than it takes for DNA to replicate. It just happens VERY VERY rarely. But there's a caveat, and it's a big one.

Every infected cell in the host carries millions of virii. If a host is infected with two flu viruses simultaneously, he or she carries billions of BOTH virii in their cells, which are all feeding self copying instructions to the host cells they've invaded. Billions of sets of genetic blue prints being executed at once. All it might take is one transpostion of only a very small part of the instructions from the "common" flu virid into an avian flu virid. That happens very quickly-- just not very often. But with billions of chances in every host co-infected with two flu strains, it is statistically inevitable. The only remaining question is how much of the original lethality the recombination leaves intact.

This is likely to happen again after a pandemic starts, in fact, it might prolong the length of a pandemic. But on the other hand, a highly virulent flu strain is potentially less likely to do this-- after all, the chances of successful recombination decline when hosts die quickly. Also, once a virus is serially recombining (and mutating) within a single host species, the general trend is toward reduced virulence. But yes, it would likely continue changing at more or less the same rate as in the original infrequent, but inevitable event.

[kestrel91316]

25. One consideration: the pandemic could go on for a year or two, so

even if it took a while to gear up production of a vaccine, once you got going you would just keep producing for the duration. So there would be a lag time with no vaccine, but then it would finally become available and we would have a shot at averting total catastrophe. The trick would be to slow the spread to a crawl to buy time.

[mike_c]

30. yes-- another problem is that once committed to a specific seed...

...virus, vaccine production facilities cannot easily change over to a new virus.

[SaveElmer]

19. Isn't is equally as likely...

That this mutation would make the virus less deadly to humans? After all, as I understand it, the virus is so virulent to humans now is because it is based on the genetics of birds, not humans. In order to mutate to a version that can survive in humans (meaning easily pass from one human to another), it would seem to have to become less virulent to its host to be able to replicate itself!

[mike_c]

23. not really....

From an evolutionary perspective there are two favored solutions. First, as you suggest, to become less lethal to the host, thus prolonging the relationship. This is risky, however, because it increases the duration of contact between the virus and the host immune system. Still, it is the general trend for all parasites-- including many viruses-- that have a long evolutionary relationship with their hosts.

The other strategy is to simply become more virulent, infecting host cells more quickly so that more can be turned to virus production before the host crashes. A virus jumping the species barrier might find this route favored by natural selection, because the new host might have very inefficient defensive responses initially, and prolonging the relationship simply increases the host's chances of mounting an immune response. A fast and deadly virus might be more successful than a slower and less lethal one.

It's a balance, with the most successful pathogens walking the line between host mortality and maximal self replication efficiency.

[SaveElmer]

28. But doesn't that still work against the virus...

It does no good to become more virulent in a single host, if that host dies before there is a chance for it to spread. That mutation will succed in areas of dense population, as in some areas of asia, or more specifically among birds. The 1918 flu was deadly for this very reason. It incubated in the trenches of WWI. Which is likely why it adapted to kill young men.

Doesn't the law of natural selection imply that in areas of lower population, that a virulent strain will die out in favor of one which can stay with its host. Has this not been the pattern of virtually every strain of flu?

[Mojorabbit]

32. Do you have the stats

on how many women were killed by it? I have not seen this anywhere.

[SaveElmer]

37. Nor do I...

But I do know it hit disproportionately among young men, largely because of the living conditions soldiers in WWI were subject to. In fact the flu was one of the leading causes of death among the soldiers. And when they came home they spread it here.

[mike_c]

33. reduced virulence is only selected for when the virus and host...

...share a lengthy evolutionary history. Usually. The alternate strategy is to make the host a more efficient replication machine in a shorter time. And it's not really an either/or matter-- selection favors both strategies because they both increase the replication success of the virus. This is especially true when there are plenty of other hosts available. Flu fits all these characteristics. The worst strains are often those newly introduced to humans, with high virulence and easy transmissibility. Avian flu is lacks only the easy transmissibility, but obtaining it is damn nearly a statistical certainty. We just don't know how long that will take, or what other changes might occur to the virus along the way.

on edit-- the swine flu "epidemic" is a good example of why it doesn't pay to jump to a new host and be too non-virulent. Hosts have defensive systems.

[SaveElmer]

36. Doesn't that make my point...

I'm not saying there aren't highly lethal varieties of influenza that have become easily transmissable, but don't they need to breed in a densely packed population to spread? Birds would seem to be ideal for this. In densely packed chicken farms for example. Or, like I said, the 1918 virus became particulrarly virulent because it spread mainly in the trenches of WWI, infecting young men with well established immune systems.

We don't have that situation here. In Thailand for example, there have been no cases of chicken farmers contracting Bird Flu, despite the fact they live cheek by jowl with them 24 hours a day. The cases that have arisen are mainly from city dwellers coming into close contact with avian blood or feces (often handlers of roosters in cock fights). This strain of flu is engineered for birds. It does not work well in humans. And the mutation that may or may not occur to make it easily transmissable among humans in less densely populated areas would almost have to become less virulent to spread.

[mike_c]

38. all correct except for that last sentence....

Remember, flu is flashy in human populations-- it rarely evolves toward reduced virulence. Instead, once into humans individual strains engage in an arms race with the immune system, which they usually lose in the long run, but it's always the new variant-- not the one that has been around for a while-- that causes pandemics. Older varieties rapidly run into the brick wall of host immunity. That's a zero-sum game for influenza-- it's a respiratory virus-- even moderate virulence stimulates a full frontal immune system response from the host. That's also one reason flu virus antigen mutation rates are high-- that's the arms race part-- because that continually reintroduces the host to a "new" virus. There is never any time for selection to favor reduced virulence, especially when the only really favored reduction would be the one that slipped in under the host immune response.

Anyway, thanks for the interesting discussion, but morning comes early in the worker's paradise, and I've got to sign off for the night. :hi:

[kestrel91316]

27. One would hope so, but you cannot necessarily count on it. Rabies,

for instance, spreads very well in virtually all warm-blooded species, and is quite lethal: virtually 100%.

[SaveElmer]

35. Still adapted to remain with host...

It has adapted to not immedietely kill its host because it relies on saliva to blood contact to spread. Any more virulence and that would not be possible. And rabies is not a pandemic threat to these species. It has mutated to adapt to its particular environment. Sort of like the AIDS virus...requires personal contact.

There is also a vaccine for rabies, so like the flu, the immune system can be trained to ward off the disease.

[kestrel91316]

24. Suggestion to get around the "lethal to chicken egg it's grown in"

problem for flu vaccine: genetic engineering. Put the genetic material that codes for the target antigens into canarypox (harmless to humans) for a tidy little canarypox-vectored vaccine. For good measure, give it by needle-free injection system so the vaccine is in the dermis, rather than subcutis. This requires only 1/4 the vaccine volume (stretch those supplies) and places it where the immune reaction is much better.

This is how Merial made their Purevax Feline Leukemia vaccine, and it is a major safety and effectiveness breakthrough. Revolutionary. Also, Merial has developed an equine West Nile Virus vaccine with this same canarypox vector. Works great, I hear.

Not sure how they grow it, probably in some cell culture, maybe even in eggs, but they manage to grow the canarypox, which carried the antigen-producing genes into the vaccinate where they are expressed and the immune system mounts a vigorous response, and then the canarypox vector dies out because it is physically impossible for it to propagate at all in human/cat/equine cells.

If we are very lucky, Merial is already working on it. But we have to be sure the RW knows that Merial is a FRENCH company so they are sure to avoid their products, lol. And no, I don't work for them or own their stock.

[mike_c]

26. yep-- that's the idea-- modify the virus so that it's lethality...

...in chickens is lessened without changing its antigenic presentation in humans. That requires a development phase in which modified virii are screened before the one to use as a vaccine seed is identified and isolated.

on edit-- I just read your whole comment-- I missed the canary pox bit the first time through. IF that could be done with flu, it would be pretty cool, although the approval process for using one viral infection as a delivery vector for a vaccine antigen would likely be a hard sell. Any physicians out there in DU land want to comment on this? Are there any instances where this sort of therapy is approved in humans?

[kestrel91316]

31. I heard that they are working on a human vaccine of some sort

(I forget against WHAT - HIV perhaps????). It is VERY cool technology. Canarypox is totally harmless in humans, and all mammals IIRC. So it is 100% impossible for the vaccine to cause the disease being vaccinated for, or any other disease. The FDA has already approved the FeLV vaccine, a year ago; I think the WNV equine vacc is also approved, and they have had Feline Rabies with this same technology for a few years, but minus the needle-free injection system.

[HeeBGBz]

40. One thing I'm pretty sure of

I will be in the 95% that doesn't get the vaccine.

That 5% would just about cover the powers-that-be and/or the wealthy.

[John Q. Citizen]

8. Read this article by DUer sparosnare for an understanding of the

issues


http://www.democraticunderground.com/discuss/duboard.php?az=show_topic&forum=104&topic_id=4971678

[madrchsod]

2. 60 people in third world countries

and just how many billion people are there on this planet? 5-6 billion?

[xultar]

4. The white house wishes I'm sure.

[chat_noir]

6. Roche stalls on bird flu drug

Roche, the maker of the main drug that would be used against a possible bird flu epidemic, is under pressure to allow production of generic versions of the medicine.

But the company and some outside experts say the production of Tamiflu is so complex and time-consuming that even generic makers could not quickly expand global supplies.

Those putting pressure on the Swiss company include the head of the United Nations and health officials in some nations. They are asking whether the health of hundreds of millions of people in a possible pandemic should depend on the efficiency and productivity of a single corporation.

snip

The director-general of Taiwan's Centre for Disease Control, Kou Hsu-sung, was even more critical, saying that Taiwanese scientists knew how to make Tamiflu and were trying to balance respect for Roche's intellectual property with Taiwan's national security.

"We are disappointed that WHO refused to press Roche to make it a generic in a situation like this," Dr Kou said. He said that Roche was overstating the difficulty of Tamiflu production and that Taiwanese government scientists had devised a way to begin mass production quickly.

http://afr.com/articles/2005/10/11/1128796520148.html

[nodehopper]

7. but they keep reporting that the bird flu is showing resistance to tamiflu

[muriel_volestrangler]

9. Who keep reporting?

The most recent thing I can find on the subject is this:

It appears a misunderstanding, not a mutation, is behind recent reports suggesting the H5N1 avian flu strain is developing resistance to the drug Tamiflu.

The professor of pharmacology from Hong Kong University quoted as warning of an emerging resistant strain of the virus says he was citing old data, not new evidence, when he gave an interview last week.

He was trying to urge GlaxoSmithKline to reintroduce an injectable form of their rival flu drug, Relenza. The resulting report suggested Tamiflu was becoming less useful - a claim that was widely repeated.

"My point is to emphasize on the introduction of injectable drugs. But they use a headline 'Resistant H5N1 appears in Vietnam,' " Dr. William Chui, who is also chief of the pharmacy service of Hong Kong's Queen Mary Hospital, said in an interview.

http://www.canada.com/health/story.html?id=81201e24-9e91-4287-833b-9da02ff083ac

[nodehopper]

41. ok good to know!

[Lori Price CLG]

10. Right, but not too late for the pharma-terrorists to make a *killing*...

...by spreading the disease via the deadly vaccines, loaded with mercury.

Lori Price
http://www.legitgov.org/flu_oddities.html

[TruthIsReal]

12. Rumsfeld and Tamiflu

My wife used to work at Merck during the 90s and she just told me something interesting.

Tamiflu (oseltamivir) was researched and developed in the 90s by a company called Gilead Sciences. Donald Rumsfeld was the chairman of this company at the time, up until he left to take his position in the Bush cabinet. Roche did not develop Tamiflu, they only market and distribute it.

Does anyone here know anything more about this?

[NCPatriot]

13. Spot on! The plot thickens against Gilead

"Until being sworn in as the 21st Secretary of Defense, Mr. Rumsfeld served as Chairman of the Board of Gilead Sciences, Inc., a pharmaceutical company."

http://www.defenselink.mil/bios/rumsfeld.html

Also an interesting read here...

http://www.forbes.com/associatedpress/feeds/ap/2005/09/23/ap2242184.html

[kestrel91316]

29. Is this the same Gilead as in Margaret Atwood's "The Handmaid's Tale"??

As in "Republic of Gilead", the Christofascist paradise?

[area51]

15. Welcome.

Welcome to DU, TruthIsReal.

[Sgent]

16. That's a fairly

standard practice in the drug industry. In most cases, Roche has also supplied capital for the creating company to develop the drug.

The patent could be held by either company, but it doesn't really change anything.

[Megahurtz]

11. Is this something that

came out of Plum Island again?:eyes::tinfoilhat:

[SaveElmer]

17. The reporting on this has been very irresponsible...

Every day we are treated to new headline grabbing stories on this, all finding more alarming ways to say the same thing...nothing has truly changed over the last several weeks to warrant this.

And the reporting itself is heavily skewed to the alarming side, noting with great fanfare the worst case scenarios. Unmentioned is the fact that some scientists believe the strain everyone is so worried about may be unable to make the mutation necessary to move easily from human to human. This is based on the fact the virus has been in the wild at least 8 years and has yet to show these signs.

Also unmentioned is the likelihood that if the virus did mutate it would also become less deadly. It is an evolutionary fact that the more successful viruses are those that do not kill off their hosts in large numbers. As it spreads it becomes less deadly. It is currently so virulent because it is genetically mutated to infect birds.

It is also virtually unmentioned that it is very possible the mortality rate is significantly lower that the 50% being touted, as it is very possible there have been many more who were infected but did not become ill enough to go into the hospital.

We hear comparisons with the 1918 Pandemic, yet hear little about the conditions that contributed to that pandemic's deadliness. WWI was still ongoing. American was shipping sick soldiers to and from Europe. Communications were slow making modern methods of quarantine and isolation impossible. Handwashing was not a widely used form of hygiene as it related to disease. It is likely that many if not most of those who died, died of a bacterial infection secondary to the virus. There were no antibiotics in 1918. There were no vaccines or drugs to combat the disease. Most of Europe was devastated by the war. Malnutrition and disease were rampant before the spread of the flu.

We hear there is no vaccine. In fact a vaccine has been developed against this strain. Granted if it does mutate it will not provide 100% protection, but it will mitigate symptoms. ANd the efforts to ramp up production will speed up development of a vaccine matching any strain that does develop

We hear about the birds in Romania and Turkey, yet it is barely mentioned that the Avian strain H5N1 has yet to be confirmed in either case, and the fact that they are having trouble isolating the strain argues against it being this particular one.

In the article mentioned in the OP, it should be mentioned that the man who is quoted saying 6 months is not enough time for a vaccine, and that a pandemic is inevitable soon, is the same man whom WHO had to reign in when he made alarmist statements a couple of weeks ago. I have no doubt his intentions are good, and he believes the seriousness of the cause. But this attitude can also hinder objectivity.

I'm not saying we should not be vigilant, that is always wise. And I would argue the reactions of the Romanian and Turkish officials is cause for confidence. Their actions are precisely the kind of diligence which will help prevent any pandemic from occurring. But I believe the heavily alarmist press has done a poor job presenting all the facts in this story!!!

[SillyGoose]

20. Thanks for clarifying this. The media is throwing all sorts of information

at us and its hard to digest it all, especially if you're not well informed about viruses and recombination and mutation etc. I had not paid too much attention to this until today when we were bombarded with it all over the news and, I admit, they got my attention with the sensationalist coverage.

I have read a few threads saying that this pandemic may not occur this year, that it could take years to occur. I hope our leaders are paying close attention to this and developing sensible and meaningful strategies for handling a pandemic, not just looking for excuses to suspend posse comitatus.

[Bassic]

39. Well it has nothing to do with oil, so don't count on

our leaders being ready for antyhing.

[oblivious]

21. Thanks for that excellent analysis.

[progressivebydesign]

43. What you've written is actually what I had understood about it.

The medical information I've read that is currently circulating says that it's serious, but may not be catastrophic. There's a helluva lotta difference between medical care and delivery ssytems now, than in 1918. And.. the avian has not jumped to human to human transmission. It may never...

[Carolab]

34. Cindy on the "flu pandemic"

http://www.truthout.org/docs_2005/101005B.shtml

{snip}

In order to rally people, governments need enemies. They want us to be afraid, to hate, so we will rally behind them. And if they do not have a real enemy, they will invent one in order to mobilize us.
- Thich Nhat Hahn

While looking up sayings by my new friend, I came upon the above. This has been one of my feelings and themes for months. I know during the terrible war that Thay fought against the enemy was "Communism." Now, in this evil war that we are struggling against, the enemy is "Terrorism." I just saw a poll that said only 13 percent of Americans fear a terrorist attack. The war machine and the people who serve it in our government are getting a little afraid themselves of not being able to keep the industrial military complex rolling in the bloody dough, so George and friends have come up with a new enemy whose atrocities also can't be contained to borders and that doesn't wear a national uniform: The Bird Flu. What kind of person who doesn't bow before the warmongers and war profiteers calls the military as his first plan of action when a health threat is supposedly brewing? Instead of calling out the National Guard (who by the way are still fighting, killing, and dying in Iraq), do you think his first call should have been to the CDC? Or to his Surgeon General, and not his military Generals? These people do not walk on this earth anywhere near reality or peace. Our new enemy of the state will be Birds who may be ill and we shall be very afraid every time we sneeze and pray that our government saves us from more imaginary threats. While we are praying, the war profiteers are laughing at us on our knees as they are counting their stacks of wicked and immorally-gotten gains.

{snip}

[progressivebydesign]

42. Well.. lets all just give up now. Okay?

I mean.. what's the fucking point anymore?