Estimating the impact of the next influenza pandemic: enhancing preparedne

[pandemic_1918]

http://www.who.int/csr/disease/influenza/preparedness2004_12_08/en/

Estimating the impact of the next influenza pandemic: enhancing preparedness

Geneva, 8 December 2004

Influenza pandemics are recurring and unpredictable calamities. WHO and influenza experts worldwide are concerned that the recent appearance and widespread distribution of an avian influenza virus, Influenza A/H5N1, has the potential to ignite the next pandemic.

Give the current threat, WHO has urged all countries to develop or update their influenza pandemic preparedness plans (see information on web pages below) for responding to the widespread socioeconomic disruptions that would result from having large numbers of people unwell or dying.

- Pandemic preparedness
Central to preparedness planning is an estimate of how deadly the next pandemic is likely to be. Experts' answers to this fundamental question have ranged from 2 million to over 50 million. All these answers are scientifically grounded. The reasons for the wide range of estimates are manyfold.

[pandemic_1918]

1. Case Fatality Rate

The latest official warning from WHO focuses on lack of preparedness and offers some explanation for the wide range of projected fatalities (from 2-50 million).

However, although no country is prepared from the upper limit of fatalities, that number is clearly not a worst case scenario.

The full report indicates that 20-50% of the world's population could be affected, which would be 1.2 - 3 billion people and the case fatality rate for H5N1 in 2004 is above 70%, which could produce a death toll 10-40X the upper limit cited in the latest report.

http://www.recombinomics.com/H5N1_case_fatality_rate.html

The latest report cites POSSIBLE reasons for lowing the fatality rate from the current 70% to a rate below 0.1%, but such a dramatic reduction seems to rely much more on wishful thinking than current hard data.

The initial cases from the 2004 H5N1 virus were reported almost exactly 1 year ago. Initially it was a mystery illness hospitalizing children in Hanoi and then became influenza A (but the H5 serotype was not given). The children were dying at a major infectious disease hospital in Hanoi and the current case fatality rate of 70% has been quite steady in both Thailand and Vietnam and both during the initial outbreaks at the beginning of this year as well as more current cases over the summer. The median age of the fatal cases has been 13.

Until a group emerges with a significantly lower case fatality rate, it seems unwise to arbitrarily lower the upper limit and call the lowering a scientific analysis.

[pandemic_1918]

2. 1933 Flu Sequences in Pigs on Farm

The report also does not mention the latest from Korea. Sequences deposited at GenBank last week show 2004 pigs with sequences from a human virus from 1933. These genes were in 6 isolates in various combinations. If the genes were not accidentally added by the lab doing the sequencing (and there is no evidence that this is the case), then this is a major problem

http://www.recombinomics.com/1933_2004_H1N1_farm.html

because the 1933 is quite virulent and neurotropic, should be easily passed human to human, and most born after 1933 would have limited immunity.

[Ian David]

3. Vaccine Manufacturers and the homosexual agenda

I think it would be great if we could convince the fundies to boycott the flu vaccine.

Does anyone care to do some research on:

1) The domestic partnership benefits and gay-inclusiveness of those companies

2) Who they contribute money to

3) The company boards their officers sit on and, which companies they invest in, and how "pro-family" those companies are.

[pandemic_1918]

4. Vaccine Suppliers

With Chiron on the sidelines, all of the US vaccine comes from French (Aventis-Pasteur) and German (Glaxo Smith Kline) companies.

[Kellanved]

19. aventis is German /French

The former Hoechst AG.

:hi:

[pandemic_1918]

24. Glaxo Smith Kline

Glaxo Smith Kline is starting flu clinical trials at 4 centers in the US

[pandemic_1918]

25. Nastionalizing Resources in Emergencies

Yes it is looking more and more like Chiron will not be ready for 2005-2006 so the US will rely on French, German, and Canadian manufacturers for their flu vaccines (and of course in case of emergency, those resources can be nationalized by the French, Germans, and Canadians.

[spotbird]

26. Any flu manfacturer produce the "abortion pill" overseas? nt

[Patiod]

5. Happy 100 posts, pandemic

I used to work for a company that tracks and predicts the spread of flu, and this is the sort of topic we actually used to debate in the lunchroom. Probably because of that, it's become sort of a dark obsession of mine, and I follow outbreaks and mutations the way other people follow sports scores.

I remember going on a hike once outside Philadelphia, and coming upon an abandoned and overgrown Jewish cemetary - probably a private family cemetary. We notices a cluster of gravestones - children, young adults and old people - with October 1918 dates, and realized they were probably all flu victims.

Given your handle, what's your involvement in the topic?

[pandemic_1918]

6. The Story Is In the Sequence

I have been following the H5N1 pandemic at the molecular level, looking at the sequences and it tells a story that most don't want to hear. The virus has been recombining and getting deadlier and deadlier and not the case fatality rate is 70-80% (if you go into the hospital with avian flu, odds are 3-1 against you coming out alive).

As you noted, its pretty easy to see where the bodies are buried from 1918, but there is a solid chance that the H5N1 pandemic could be much worse.

http://www.recombinomics.com/1918_case_fatality_rate.html

It is an efficient killer, there is no vaccine, and anti-virals look pretty iffy.

http://www.recombinomics.com/H5N1_anti_virals.html

If the virus acquires efficient human to human transmission, chaos will ensue.

[livinbella]

7. How will the virus be transfered from bird to man?

I mean physically. Do we get it by eating the bird. or what?

[Patiod]

9. Pandemic can probably answer that better than I can

I believe that exposure to fecal matter is the key way these things spread, vs. eating the infected animal A lot of these viruses originate in overcrowded regions of China, where humans, animals and birds all live in close proximity to one another.

What starts as a flu among birds can then jump species, and infect humans.

"For an influenza strain originating in a non-human species to become the cause of a human pandemic, the virus must undergo “genetic reassortment.” Genetic reassortment is the process where a virus incorporates most of the genes of a human virus while at the same time, altering or maintaining its own hemagglutinin and/or neuraminidase (surface proteins). The resulting ‘new’ virus is capable of being transmitted from one human to another while donning a surface protein to which humans have no immunity. This reassortment of genetic structure is an example of an antigenic shift.

Although antigenic shift occurs rarely, it has long been thought that one condition favorable to the process is humans living in close proximity to domestic poultry and pigs. Because pigs are susceptible to infection by both avian specific and mammalian viruses, including human strains, they serve as a critical “mixing vessel” for the s scrambling of genetic material from both human and avian viruses. Evidence is also mounting that, for some of the 15 avian influenza viruses, humans themselves can serve as those “mixing vessels,” driving the need for effective culling of infected flocks and bioremediation measures where humans are in close contact with a high number of infected poultry." - from "Avian Influenza - A Worldwide Cause for Concern" by Cynthia A. Botteron, Ph.D. & John Aquilino

Other viruses, such as encephalitis, can be transfered from birds (or horses, pigs, etc) via mosquito

[pandemic_1918]

14. Human to Human Transmission

As things develop in Asia, the chances of human to human continue to increase. Some birds have virus (H9N2) that can recognize human receptors. H9N2 is the prevalent serotype in Asia. Lately there have been reports of H9N2 and H5N1 infecting the same host and swapping genetic information. Dual infections is how the virus evolves rapidly

http://www.recombinomics.com/viral_evolution.html

and recent reports indicate H5N1 can grow in ducks and not make them sick. The ducks can get infected with H9N2 also, leading to a new H5N1 virus that can transmit human to human. This could be a major disaster and would not involve people or pigs, just birds. that is one reason why scientists are concerned.

There is another developing story in Korea. Viruses have been isolated from pigs which appear to have human genes from the first human virus ever isolated, in 1933

http://www.recombinomics.com/1933_2004_H1N1.html

the pigs were on a farm

http://www.recombinomics.com/1933_2004_H1N1_farm.html

and if the sequencing data is real, major problems will probably develop because the H1N1 versions should be able to easily transmit from human to human, and since the virus is from 1993, most born after 1933 would have limited immunity.

[pandemic_1918]

13. Avian Flu Transmission

You can get avian flu by eating uncooked birds (or something uncooked contaminated by the bird). Feeding infected chickens to tigers and leopards at a couple of zoos in Thailand was pretty disastrous, especially the more recent cases

http://www.recombinomics.com/more_tiger_deaths.html

However, most cases in southeast Asia involved some contact with live birds or disposing of dead ones. The latest news is that the H5N1 virus can grow to high titers in asymptomatic ducks, which may have led to additional cases not linked to dead birds (many keep ducks as pets).

The number of human to human transmissions has been limited

http://www.recombinomics.com/human_human_probable.html

but it would take much to achieve efficient human to human transmission, and then you could get avian flu as easily as human flu, which is pretty easy

http://www.recombinomics.com/H5N1_recombination.html

[muriel_volestrangler]

8. According to this, vaccine trials start in the new year

Clinical trials of human H5N1 flu vaccine to start soon

Nov 17, 2004 (CIDRAP News) – Clinical trials of a vaccine designed to keep the H5N1 avian influenza virus from sparking a human flu pandemic will begin early in 2005, the head of the National Institute of Allergy and Infectious Diseases (NIAID) said this week.

Under contracts with the NIAID, Aventis Pasteur and Chiron Corp. are each producing 8,000 to 10,000 doses of an H5N1 vaccine based on virus isolated from a human patient who contracted avian flu in Asia this year.

In a wide-ranging Nov 15 press briefing on flu research, NIAID Director Anthony Fauci, MD, said, "Production of pilot lots has begun, we expect them to be finished by the end of December, and we expect clinical trials to begin soon thereafter." He later mentioned January as the month when the trials will probably begin. A recording of the briefing is available on the NIAID Web site.

The vaccine will be tested for safety and immunogenicity, or the ability to trigger production of antibodies, Fauci said. Participants will not be exposed to the H5N1 virus, which has caused 44 human cases with 32 deaths in Asia this year.

http://www.cidrap.umn.edu/cidrap/content/hot/flu/news/nov1704niaid.html

[livinbella]

10. Will the vaccine work as the virus mutates?

This looks like one killer virus.
I wonder if it is transmitted from human to human
via the air we breathe.

[pandemic_1918]

17. Flu Transmission

If avian flu develops efficient human to human transmission, it will be as easy to catch as human flu.

The virus changes rapidly, but follows some very strict rules

http://www.recombinomics.com/vaccine_development.html

[pandemic_1918]

12. Pandemic Vaccines

I think Aventis is making a vaccine against H5N1 while Chiron is targeting H9N2.

[spotbird]

27. Are you familiar with Sambucol?

It it effective at all?

[pandemic_1918]

28. Tamiflu

Tamiflu works against H5N1 in lab cultures. It is pretty iffy in the field

http://www.recombinomics.com/H5N1_anti_virals.html

[spotbird]

30. But does Sambucol work against any flu?

Has it been tested at all? I'm wondering since the claims are grand.

[haele]

57. Most of what I've found is marketing hoo-ha...

...which I'm very skeptical of. Like I'll trust the claims of someone who wants to sell me something without further investigation...

However, it is possible that elderberry extracts (c.f. sambucus niger) can help a healthy body fight off a type A and/or type B influenza virus, as well as doing very well against the common rhinovirusii. It can't "cure" the flu, but from all information I've found on the net (as well as the "famous" Isreali study the product is based off of) and in my books, it should be of some help, along with other treatments such as rest, liquids, etc.
Heck, my greatX2 grandmother the midwife recommended an elderberry cordial mixture regularly during the cool months (as she called them) to keep from catching fevers. From what I can see, she used it as a highly effective preventitive; by accounts, she claimed most of her patients and family survived the 1918 pandemic by not catching influenza in the first place.
:shrug:
However, if you do catch it, a virulent influenza virus can develop into more serious problems, - even popular alternative health gurus such as Dr. Weil recommend that influenza should be seen by a doctor as well as using preventitive measures before you get sick.

Here's a recent study I came across - while I feel it's still rather tentative on it's conclusions concerning those with compromised immune systems, the actual reactions in 12 healthy subjects is worth noting -
http://www.ag.uiuc.edu/ffh/abstracts/Sambucol_and_inflammation.html

Remember also - most people who think they have the flu actually have a rhinovirus; a severe sinus or chest cold. YMMV, but Sambucol seems to do very well against the cold. But then, Pine Needle tea and natural honey does very well, also - and has been used in the Americas for centuries against cold and flu.

Haele

[pandemic_1918]

71. Pandemic Vaccines - No H5N1 US Product

I believe that the posted article on flu vaccines is in error. The NIAID press release was a little ambiguous

http://www2.niaid.nih.gov/Newsroom/Releases/h9n2.htm

I believe that Chiron is making an H9N2 vaccine and Aventis is making H5N1 (leaving the US without a H5N1 pandemic vaccine made by a US company). The Canadian company, ID Biomedical, has also just announced plans to begin making a pandemic vaccine against H5N1.

If a true pandemic hits, it is likely that the H5N1 vaccines would be in very short supply, even after scale up, and such vaccines would be nationalized, leaving the US without a vaccine.

[starroute]

15. My grandmother died in the 1918 epidemic

It carried off a lot of people like her who were young and healthy.

But I've also understood that a lot of the spread of the 1918 epidemic was due to the conditions of the war, transmission among soldiers at military bases, and so forth. Is that true, and would it make a significant difference now?

[pandemic_1918]

18. Transmission Today

The flu infected a large number of troops, and traveling around on trains or cramped ships probably helped spread the flu. However, many of those who became ill died quite suddenly from viral pneumonia, which isn't handled much better today. Moreover, today people in general are much more mobile, so spreading the virus by plane or auto would be pretty effective.

You can just use human flu as a model. New versions appear yearly, but it doesn't take long to get around. Last year the H3N2 was changing from Panama from 1999 to Fujian from 2002 about 80% were Fujian. So far this year in the US all H3N2 that have been characterized are Fujian and already a new version, Wellington, has begun to replace Fujian, at least in the Southern hemisphere, so new flu virus waste little time in getting around.

http://flu.lanl.gov/vaccine/

Vaccines would help, but they are not ready yet and H5N1 in Vietnam and Thailand has already become resistant to Amantadine and Ramantadine. All that is left is Tamiflu and it didn't seem to help much with the H5N1 infected tigers

http://www.recombinomics.com/H5N1_anti_virals.html

Antibiotics would help with secondary bacterial pneumonia, but given that H5N1 has a case fatality rate of 70%, a current pandemic could actually be worse than 1918

http://www.recombinomics.com/H5N1_case_fatality_rate.html

[axordil]

20. I know that cemetary...

...and it was very sobering to stumble across.

My dad lost his sister in 1918. Only a tiny fraction of the population has any idea of what it was like...and could be like again.

[donheld]

67. Welcome to DU axordil

:hi:

[pandemic_1918]

22. 1933 Flu in Pigs on Korean Farms Looks Real

Further investigations into the 1933 human flu in pigs on Korean farms is looking increasingly real and increasingly serious

http://www.recombinomics.com/WSN33_Korean_farms.html

[Just Me]

11. We're way past due for an outbreak and the avian thingy,...

,...is pretty frightening!!! I've read that if it becomes a transmittable virus among humans,...we'll lose more people than all the wars combined over the last couple hundred years.

[pandemic_1918]

16. Details on 1918 Flu Pandemic

Details on the 1918 pandemic are at

http://books.nap.edu/books/0309095042/html/44.html#pagetop

It is not a pretty picture and remarkably, it could be even worse today. Many have not been paying attention.

[spotbird]

31. I've read of people boarding the subway in NYC and

dying before they reach their destination.

[pandemic_1918]

48. Playing Bridge - Dropping Dead

I have also seen reports of people actually dropping dead at the bridge table in 1918.

There are similar reports in animals today such as chickens being fine in the morning and the entire flock dead by noon with blood oozing from all orifices. There are many parallels between H5N1 in 2004 and the 1918 pandemic.

In took many forms and was mistaken as Dengue Fever and Cholera in 1918. The human to human transmission of H5N1 in Thailand was initially diagnosed as Dengue Fever

http://www.recombinomics.com/human_human_probable.html

and dead ducks in Vietnam were said to have cholera (there has been no confirmation on isolated organisms)

http://www.recombinomics.com/Viet_ducks.html

Dead H5N1 infected pigeons falling from the sky in Thailand was not a good sign

http://www.recombinomics.com/H5N1_pigeons.html

and there are plenty of alarm bells ringing

http://www.recombinomics.com/alarm_bells.html

[SmokingJacket]

21. I have a flu right now.

STAY AWAY!

[pandemic_1918]

23. Get A Flu Shot

Getting a flu shot isn't a bad idea because the background genes are from 1934, so if you haven't been vaccinated lately, you should think about getting a human flu shot.

[Heartland]

29. I got my Flu shot in Mecico

And bought one to take to may mom in Arizona who spend six hours in a line with 1100 people--There were only 600 shots. She's eighty one.

[donheld]

68. Welcome to DU Heartland

:hi:

[idealista]

32. what can one do, except hope they have good genes?

Let's say this thing does happen - first of all, does it happen in winter, like the seasonal flu? Or is it so virulent that it does not need the winter's help to reach critical mass and spread effectively?

Ok, will it hit most urban areas about the same time? I imagine in 1918 due to slower travel, it might have made a lazy/deadly tour of the world, but now???

Once it emerges, is that when scientists can begin coming up with an effective vaccine? Which then takes what - 5 months? 8 months to produce in quantity? And will we get it in the US if the makers are in Europe and Canada and politicians there will want their citizens taken care of first?

On a personal level, what about the stategy of trying to isolate yourself long enough that eventually you will be able to get the vaccine?

I know human flu is transmitted very easily, but its never been a life and death matter for me to find out just how easily, and by what means to protect myself.

Will animals here in our environment, birds, dogs, cats - also be carriers?

Can we shut ourselves up in our house, given enough food and if there are people still making sure water and electricity work, for instance, leave the mail untouched out in a box, and have a chance of avoiding exposure?

If someone 50 feet away sneezes, how long do the individual viruses survive, floating thru the air? AIDs, for instance, doesn't survive for any time at all outside the body, i believe. Some viruses stay alive on a doorknob for days, weeks? But not forever...where does flu fit in?

[pandemic_1918]

33. H5N1 Survival

H5N1 is constantly changing and a recent WHO announcement highlights some of the ominous changes on infectivity and survival of the latest version of H5N1

http://www.who.int/csr/disease/avian_influenza/labstudy_2004_10_29/en/

Viruses do better in the cold and lately H5N1 has been found at high levels in asymptomatic ducks. They have high levels of virus, shed virus for longer than in the past, and the virus survives long.

The virus changes during dual infections (same host infected with 2 versions of the virus)

http://www.recombinomics.com/viral_evolution.html

and high titers in healthy ducks is a very bad situation.

[donheld]

69. Welcome to DU idealista

:hi:

[idealista]

70. Thanks for the welcome, its the first one I've gotten! n/t

[Horse with no Name]

34. Sub Q flu vaccine

I am currently working with a company (Democrats) who have received a grant from the NIH for next seasons flu vaccines. They are testing the efficacy of flu vaccine given subcutaneously as opposed to intramuscular.
The benefit is that you can use less vaccine with subq--thus creating more vaccine simply by giving less of the standard dosage
This company has invented an autoinjector that would make it possible for people to give their flu vaccines to themselves after obtaining it prepackaged from a drugstore--eliminating a physician's visit and possibly being exposed to illness at the Dr. office.
It is mandatory to be vaccinated with an imminent pandemic and there was simply no excuse for American's not to be able to have that done other than poor planning by our administration.

[robcon]

35. This is overwrought and panicky, IMO

There is no avian flu epidemic, much less pandemic. With the quickness of spread today, if the flu virus existed now, it would spread widely, and quickly.

I think this is panic-mongering, like a lot of the reaction to SARS and West Nile virus.

[pandemic_1918]

36. H5N1 Pandemic

The H5N1 pandemic right now is in birds with over 100 million dead. The number of humans killed by the virus is small so far (44 reported cases), but the case fatality rate is 70-80%

These rates are considerably higher than the 1918 pandemic

http://www.recombinomics.com/1918_case_fatality_rate.html

which killed between 20-100 million in a population 1/4 size of today's population. Projections of 100 million to 1 billion have been made based on the current case fatality rate and the infectivity of such a virus that acquires efficient human to human transmission

http://www.recombinomics.com/H5N1_recombination.html

[pandemic_1918]

37. Life Expectancy Chart - US 1900-1998

Here is a life expectancy chart for the US between 1900 and 1998. See if you can tell when the flu pandemic happened

http://demog.berkeley.edu/%7Eandrew/1918/f2.pdf

If not, here's the age standardized death rate for the US for the same years

http://demog.berkeley.edu/%7Eandrew/1918/f3.pdf

Is there anything on either chart that kind of jumps out?

[NNN0LHI]

38. I think we should have a rule at DU

When the original poster accounts for over half the posts to a thread they have started, it should be locked immediately.

Don

[Digit]

39. Moving on.....

[livinbella]

44. I've learned a lot from this thread

Interesting stuff. pandemic_1918 presents a scenario that seems
totally plausible. And he presents plenty of real life current data to back up his assertions.
What the hell, a little doomsday talk is kinda fun.

[robcon]

40. Again, I think you are being panicky, pandemic 1918.

There is absolutely no reason to believe that this avian flu is going to be a pandemic. This virus is, like most viruses, destined to have a small - or even zero impact on humans.

There is no such thing as being "overdue" for a pandemic - that's pure bullshit, made to scare people. That concept has no scientific basis. There is no increased probability of suffering a pandemic based on past flu experiences. A virus does not 'know' how long it's been since there was a major human flu. That's an unscientific, and frankly, intentionally phony alarm you are giving, IMO.

I call bullshit, pandemic 1918.

[senegal1]

41. I don't see the panic -- I see well reasoned posts by

Pandemic 1918 based upon work which he/she has been doing. When someone posts over half of the posts in a thread with links, supporting data, and analysis and is working the field in which he/she is posting, we should call that a seminar! Frankly, I believe WHO did call an emergency meeting in November on the topic which Pandemic 1918 is discussing. I think the point here is that this situation is becoming increasingly possible. Which goes to two points brought up before -- one by someone sounding worried -- what can the average citizen do??? Go live in the woods or what? and the second post which Robcon makes which is that is does seem that statistically there seems little support for the idea that a pandemic is "overdue" . While medical science notes the fact that pandemics occur on a cyclical scale -- statistically it would seem currently unsupported that a pandemic could be overdue or occur on a specific time scale. Finally, I remember reading and still have a book written by a social scientist about his childhood in Sacramento CA. IN the book called "Barrio Boy" it ends with a flu epidemic where all his close relatives die basically while he and they and seemingly the whole world is laying on the floor in their house unable to do anything. Because there is no one to come, no place to go for help, and everyone is in the same state. He doesn't make a big deal of it in the book but the quiet way he talks about it is chilling -- at least to me.

[pandemic_1918]

42. What The Virus Knows

>>There is no such thing as being "overdue" for a pandemic - that's pure bullshit, made to scare people. That concept has no scientific basis. There is no increased probability of suffering a pandemic based on past flu experiences. A virus does not 'know' how long it's been since there was a major human flu. That's an unscientific, and frankly, intentionally phony alarm you are giving, IMO.<,

Clearly that is your opinion because there is sound scientific fact for pandemics occurring at specific intervals. The virus changes to avoid the population's immunological memory and therefore the density and genetic complexity of the virus is dependent on which hosts are worthwhile targets and which are not.

When there are lot of targets, the virus population increases and that leads to more dual infections, which accelerates the genetic changes in the virus leading to a greater likelihood than a pandemic strain will emerge.

The signals are loud and clear, which is why WHO is so alarmed. H5N1 is the main focus because it produces a 70% case fatality rate, which is an all time high, as is the number of H5N1 cases (6/18 died in 1997, 1/2 in 2003, and 32/44 in 2004).

At the same time H5N1 infections in birds in Asia set an all time record in 2004 with outbreaks throughout China, Cambodia, Laos, Indonesia, Vietnam and Thailand. The human cases were in Vietnam and Thailand. The H5N1 from those two countries now can infect ducks asymptomatically, providing a provocative target for H5N1 and secondary infections by H9N2. H5N1/H9N2 reassorted virus were involved in 1997 Hong Kong cases. Last year there were H9N2/H5N1 reassorted isolates in Hong Kong.

The more recent isolates have a broader host range, able to infect and kill mice, cats, and ferrets much more efficiently (as well as humans).

The handwriting is on the wall and readily read by anyone paying attention.

[Sufi Marmot]

59. Be careful not to anthropomorphize the virus...

The virus changes to avoid the population's immunological memory and therefore the density and genetic complexity of the virus is dependent on which hosts are worthwhile targets and which are not. I realize you probably didn't mean to, but you're implying that the virus is mutating in response to its environment (Lamarkism), rather than randomly, with successful random mutants able to make the species-barrier jump, or becoming much more virulent.

-SM

Edited to fix link

[pandemic_1918]

60. Elegant Evolution

>>rather than randomly, with successful random mutants able to make the species-barrier jump, or becoming much more virulent.<<

The virus' changes are far from random. Neighbors get together, exchange information, and out pops a pandemic.

Lamarck did not invoke genetic information. The virus does and it does so very intelligently.

Its call elegant evolution

http://www.recombinomics.com/paradigm_shift.html

[Sufi Marmot]

61. The recombination and assortment of viral genes is still random...

...viruses do not recombine with the specific intent (viruses don't have intent) to escape their hosts - the fact that they can jump species is simply a consequence of this recombination. Elegant, perhaps...intelligent, no.

-SM

[pandemic_1918]

62. Elegant Selection

There is selection for the best recombinant, but the evolution is elegant because they recycle previously successful polymorphisms.

The number of new mutations is very small. Viruses are the ultimate recyclers, and their method is quite efficient and elegant.

[Sufi Marmot]

63. Isn't that how evolution works in general...?

There is selection for the best recombinant, but the evolution is elegant because they recycle previously successful polymorphisms.. If I understand this correctly, viruses that keep useful mutations/polymorphisms that are either obtained by random mutation or by recombination with another virus strain are more successful at either jumping to new host species, or becoming more virulent, or both. Anything that gives the virus a propgation advantage will be selected for; viruses whose recombination events that remove useful polymorphisms will be selected against and won't propagate as efficiently. The previously successful polymorphisms aren't recycled, their just maintained because they continue to confer a propagation advantageto the new virus in the context of its additional changes. Isn't this just a case of genetic recombination effecting population genetics? What am I missing here?

-SM

[pandemic_1918]

64. Recycling Via Recombination

The virus recycles previously generated polymorphisms, but does so via recombination (not simple replication). The recombination creates new genes, but the new genes are recycled and recombined polymorphisms.

The virus changes every year and it does so by rearranging old polymorphisms (not randomly creating new ones).

It is elegant because it takes polymorphisms that have worked in the past, and puts together new combinations (using polymorphisms of neighbors). When the virus steps out of its neighborhood, or it's neighborhood changes, the changes in the virus also accelerate because the recombination uses more diverse and numerous polymorphisms.

[Sufi Marmot]

65. Again, you should perhaps be mindful of anthropomorphoic language...

It is elegant because it takes polymorphisms that have worked in the past, and puts together new combinations (using polymorphisms of neighbors).
Sorry to quibble but I think it's more accurate to talk of new combinations simply occuring, and being selected for because of their relative utility, rather than the virus "putting together" new combinations. I'm assuming here that the viral recombination is simply occuring via the host cells' intrinsic recombination machinery - is that correct? And new polymorphisms are initially generated by replicative error and initially selected by propagative utility, right?

When the virus steps out of its neighborhood, or it's neighborhood changes, the changes in the virus also accelerate because the recombination uses more diverse and numerous polymorphisms. I assume that what you mean here is that the number of different viral strains is increasing because there are simply more starting variants to recombine with each other, not because the recombination rate is itself increasing. That is, viral strains ABCD and abcd can produce a lot more different variations through interviral recombination than strains ABCD and ABCd.

Am I incorrect in simply seeing this as the viral equivalent of the homolgous recombination that occurs in eukaryotic cells? :shrug:

-SM

[pandemic_1918]

66. Influenza A Genomes and Homologous Recombination

The influenza A genome is single stranded and negative sense. The recombinations happen during dual infections and involve homologous recombination.

The homologous recombination between closely related sequences offers modest change. Recombination between more distantly related genomes offers more radical change (this can be seen best in the swine isolates from Korea that have genes half human and half avian).

Less frequently the virus can use non homologous recombination, which doesn't require dual infection.

However, the virus takes advantage of dual infections to evolve and this evolution is more dramatic when the dual infections involve more diverse haplotypes.

The virus only has 8 genes which are on 8 separate transcripts, so it can reassort, which also can facilitate recombination. But it is the recombination that drives viral evolution and it is used by all viruses, not just influenza, to evolve rapidly.

Contrary to dogma that states that influenza drifts are due to replication errors by a polymerase lacking a proofreading function and shifts are due to reassortment, the real rapid drifting and shifting is done by homologous recombination.

[idealista]

43. conceptual understanding of real-life factors is not panic

Perhaps some people are so alarmed at the implications of what is being discussed here that they instinctively attack Pandemic_1918 and try to close off the discussion....?

From the individual's point of view, we face many potential dangers in life, and it is only sensible to apply a kind of triage, asking: 1) how likely is it to happen to me? and 2) how bad would the consequences be? Also, 3)can I take effective action on my behalf? If not, there is no point even being aware of a danger, it only creates pointless stress.

I live in Los Angeles. Our earthquake risk has alot in common with this pandemic phenomena - it will inevitably happen, it will kill people, and no one knows exactly when. BUT WE DO TALK ABOUT IT AND WE DO PREPARE.

In fact, the best way to avoid "panic" is to be prepared, understand what you can do to best deal with any danger, and take the necessary steps beforehand. All of this means not sticking your head in the sand but rather being willing to think about the appalling and "unthinkable".

I'm an architect and I understand that the reason a 7.0 earthquake kills 50 people in California and a million people in Mexico City (approx. numbers - don't flame me) is that here we have analysed building performance, legislated appropriate codes, and enforced them, i.e. we have "planned ahead".

Likewise, I am very glad the WHO called an emergency meeting and that vaccine experimentation and all the other work of the scientists is being done. And I am glad Pandemic_1918 is providing this information to us. Don't read it if you don't like it.

[senegal1]

45. So Pandemic 1918 -- what can one do short of getting the flu shot

which has some relative response to 1934 flu genetics? Assume something does happen and the virus is able to pass from human to human. Living in the woods? Not go to work? Avoid crowds? Any special to help?

[toddaa]

46. WASH YOUR HANDS!!!

Basic hygenics. And avoid the antibacterial soap. Bacteria are evolving just as fast as virii and become just as deadly.

[pandemic_1918]

47. Clinical Trials

Actually Aventis and Chiron are starting clinical trials on pandemic vaccines, but the number of people who will be enrolled will be a small percentage of those who would like a vaccine.

At this stage individuals can remain aware of the situation and push more more efforts. The amount of money spent on pandemic flu is pretty small compared to other areas such as bioterrorism, etc and unfortunately, we are not that much better prepared today than in 1918. The only vaccine available will be in small clinical trials beginning in 2005. The antivirals require a prescription and only Tamiflu is somewhat effective against H5N1 in culture, but iffy in the field

http://www.recombinomics.com/H5N1_anti_virals.html

At this time you can wash you hands and think about getting a good surgical mask and goggles (the world will look much like Asia did during the SARS outbreak).

When the virus begins to spread, avoid crowds, hospitals, and unnecessary contact with a lot of people. The social and economic impact of a pandemic are much greater than most realize.

The planning still needs lots of work in most countries and none really have adequate surge capacity if a real pandemic hits. Under non-pandemic conditions the case fatality rate is around 70%

http://www.recombinomics.com/H5N1_SARS_case_fatality_rate.html

which is considerably higher than SARS or the 1918 pandemic. Hospitals would be quickly overwhelmed so infection with the current H5N1 in a pandemic environment could actually increase the case fatality rate because medical treatment will be compromised by the number of patients, first responders, and health care workers affected.

[pandemic_1918]

49. Breaking Pandemic News

You can also stay up to date on the news. Breaking news with comment is at

http://www.recombinomics.com/whats_new.html

In fact the news on the 1933 human H1N1 in 2004 Korean pigs appears well ahead of the news

http://www.recombinomics.com/WSN_33_Korean_farms.html

The human flu genes in Korean pigs should be headlines in the next week or two.

[senegal1]

50. Thanks for the reply. I have an idea about economic and

social consequences having lived in many 3rd world countries. Any natural or readily avaliable substances which have some efficacy? Sounds like there is not much we average joes can do in the face of a pandmeic.

[pandemic_1918]

51. Tamiflu

Tamiflu is the only antiviral available against H5N1.

http://www.recombinomics.com/H5N1_anti_virals.html

It works in tissue culture, but not as well against H5N1 as other human flu viruses. It is available by prescription for those who have just caught the flu as well as high risk people, like family members of flu cases.

However, there is a new flu threat emerging in Korea. That 1933 human flu virus is probably more susceptible to Tamiflu because its H1N1 (its probably much more infectious to humans) and you should be hearing much more about the H1N1 virus soon

http://www.recombinomics.com/WSN_33_recombination_reassortment.html

Since this virus is from 1933, a normal flu shot (the one being rationed in the US) because the H1N1 and H3N2 viruses used have contemporary H and N genes on a background of a 1934 human virus and that virus is closely related to the 1933 internal genes in the pigs in Korea.

However, only 1.5 million doses of Tamiflu is made in a year, so it is in short supply (and would probably be nationalized by Switzerland if a true pandemic hit - the same might hold for human flu made by French, German and Canadian companies - only Chiron is US and they have ad their license suspended - and the suspension was just extended).

[livinbella]

52. Does it kill by internal hemorrhaging?

Strange, I came across an article about N5H1
in the "National Geographic News" today.
Looks like the pandemic of 1918 may also have been
an "Avian Flu" of some kind.

[pandemic_1918]

55. H5N1 and 1918 Pandemic Strain

Yes, there are many parallels between H5N1 and the 1918 Pandemic. For H5N1 a flock of chickens can be fine in the morning and all dead by noon with blood oozing from all orifices.

1918 caused lots of internal bleeding and some actually dropped dead while playing bridge. Attacks can be sudden and fatal.

[livinbella]

56. Suddenly, we see this seeping into the news

Let's hope all strains morph into something gentler.

[pandemic_1918]

58. H5N1 Heading for Australia

Hope won't stop the H5N1 virus. It is heading south in Indonesia and closing in on Australia

http://www.recombinomics.com/H5N1_Indonesia.html

[pandemic_1918]

72. H5N1 in Wild Birds in Thailand

The morning is likely to be more bad news. Today Thailand reported H5N1 in more wild bird species

http://www.recombinomics.com/H5N1_Wild_Birds_Thailand.html

This will lead to more dual infections, more recombination, and more problems.

[Tinoire]

53. IOW Rumsefd and Schultz will be making millions off their Gilead stock?

So between Gilead's Tamiflu and Cidofovir, they'll be raking in a small fortune when Gilead's stock climbs even higher than it's been climbing for the last few years thanks to all its other products for infectious diseases?

Interesting...



====

Rumsfeld's Co. Gilead Sciences has nearly quadrupled its profits since Rummy entered the Bush Administration. How? By selling false hope to AIDS patients in poor countries, selling bogus smallpox treatments to the US government, and taking millions from Bill Gates to test HIV drugs on poor people in Cambodia, Africa, and India. And that is probably just the tip of the dirty iceberg.

This article also includes info on DynPort and BioPort. DynPort has scooped up huge anti-bioterror contracts from Bush - even though they have been proven incompetent, even though they are part of Dyncorps, which, in Bosnia, was exposed as running a white slave trade ring. Sound too awful to be true. I wish!!

http://baltimore.indymedia.org/newswire/display/5766/index.php
================


Want to guess how many shares of GILD Rummy still holds?

===

GILEAD SCIENCES, INC.: Rumsfeld's Old Company Reaps Benefits of Friends in High Places

From 1997 to 2001, Donald Rumsfeld was chairman of Gilead Sciences Inc., a biopharmaceutical firm in Foster City, Calif. He has also served as a director for Amylin Pharmaceuticals, Inc. and has millions of dollars worth of stock in both Amylin and Gilead, including some 68,200 vested shares in Gilead worth from $1 million to $5 million. Gilead certainly appears to have benefited from having a good friend in a very high place. Since 2001, Gilead sciences revenues have nearly quadrupled (they more than tripled in 2002 alone). How did they do it?


Although we may never find out what and how many strings were pulled, a few strings are dangling out in the open. For one thing, Gilead has scooped up a great big fat chunk of pork through Project Bioshield (see section on smallpox vaccine below). For example,
Bill Gates, who owes the Bush administration big time for getting him out of this anti-trust case with barely a slap on the wrist (relative to what should have been the penalty) has given over $6 million to Gilead Sciences to fund trials of an experimental use of the antiviral HIV drug Viread. These trials are being conducted on poor people in Cambodia, India, and several African nations.

(snip)
In any case, rhere is no doubt that Gilead Sciences has ties to the US government, to the Pentagon in particular. Rumsfeld was replaced at Gilead by Cordell W. Hull, who is now also chairman of the company's Audit Committee. Hull also serves as a director of Bechtel Group, Inc., Bechtel Enterprises and the Fremont Group.

http://dc.indymedia.org/newswire/display/86537/index.php

===================

Schultz also sits at the direction of Gilead Science, the giant of the pharmacy whose Donald Rusmfeld was the chairman until his return to the government. This firm has just obtained important public markets within the framework of the prevention of the chemical and biological attacks. Indeed, Rumsfeld succeeded in convincing its public opinion that the mode of Saddam Hussein would still hold some weapons of massive destruction that it to him had sold itself during the Iran-Iraq war and that Baghdad would plan to use them against the people states-unien. During last years, Gilead Science drew most of its benefit from antiviral which it produces to treat the AIDS. The high price of these treatments not allowing their diffusion in the Third World, several States tried to manufacture some except licence. They were condemned by OMC. In 1998, the antiviral identical ones
were manufactured except licence by a usin E pirate with Al-Shifa (Sudan). At the request of Rumsfeld and Schultz, Bill Clinton showed the Al-Shifa center to be a cover for the manufacture of weapons of massive destruction by Al Qaïda and made it bombard. Various international investigations showed later on that these charges were without bases.

http://usgohome.free.fr/actualite/guerre_english.htm

=======
CHIMERIX ANNOUNCES LICENSING DEAL WITH GILEAD SCIENCES

- Chimerix Obtains Rights to Cidofovir for Development of an Oral Drug to Treat Smallpox Infections -

San Diego, CA - September 12, 2003 - Chimerix Inc., an emerging biotechnology company developing orally available, targeted medicines from bioactive molecules, today announced that it has licensed rights from Gilead Sciences, Inc. (Nasdaq: GILD) to develop oral derivatives of Gilead's proprietary antiviral compound cidofovir, intended for the prevention or treatment of smallpox infections. Chimerix's initial focus will be to continue the development of its oral smallpox drug, CMX001, which is a chemically modified derivative of cidofovir, derived by incorporating Chimerix proprietary chemistry to enhance intracellular uptake and oral delivery.

The license permits Chimerix to sell CMX001 to governments anywhere in the world. The license also includes the rights to develop and sell oral derivatives of cidofovir for treatment of infections caused by related viruses such as vaccinia virus (the virus used for smallpox vaccinations) and monkeypox virus (a smallpox-related virus found in animals, which can be passed on to humans). Chimerix will pay Gilead royalties based on a percentage of net sales to governments. Specific terms of the agreement were not disclosed.

Cidofovir is an antiviral medication currently approved for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Marketed under the brand name Vistide®, Gilead's drug was cleared for marketing by the U.S. Food and Drug Administration in 1996 and by European regulators in 1997. Cidofovir is administered by intravenous infusion. Using proprietary technology, Chimerix is able to modify cidofovir (the parent compound), to yield a potent, orally available drug that has the potential to treat smallpox infections, or complications of smallpox vaccination. Chimerix was recently awarded a $36.1M grant from U.S. National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), under the Bioterrorism Act of 2002, to support development for its drug, CMX001, as a treatment for smallpox. The Bioterrorism Act of 2002 authorizes government spending for the National Pharmaceutical Stockpile.

(snip)
http://www.chimerix-inc.com/news_091203.htm

====

Riordan ceded his position as company president to Martin in 1996, and eventually left the board of directors, which had a stunning lineup of his recruits, including Donald Rumsfeld, who later left Gilead to become President Bush's secretary of Defense. Through Rumsfeld and his connections in the Republican elite, the Gilead board also landed former Secretary of State George Schultz. Also serving on the board are Nobel Prize winner and Stanford Professor Paul Berg and Intel co-founder and chairman emeritus Gordon Moore.

(snip)

Gilead's products and pipeline

Marketed products: ----- Therapeutic area: ----- 2002 revenues:

Viread --------------------- HIV/AIDS -------------- $226 million

AmBisome --------------- Fungal infection ------ $202 million

Hepsera ---------------- Chronic hepatitis B ---- $6 million

Tamiflu ------------------- Influenza A & B -------- $4 million

Vistide ---------------- CMV retinitis/AIDS ------ $4 million

DaunoXome -------------- Kaposi's sarcoma -------- $3 million


Experimental drugs: ---- Therapeutic area: ---- Clinical trials phase:

Emtricitabine ------------- HIV/AIDS ------------- Submitted for approval

Chronic hepatitis B ------- Phase III

Amdoxovir -------------- HIV/AIDS ------------- Phase I/II

Tenofovir topical gel -- HIV/AIDS ------------- Phase I/II

Clevudine -------------- Chronic hepatitis B -- Phase I/II

GS 7340 ---------------- HIV/AIDS ------------- Phase I/II

http://www.aegis.com/news/sc/2003/SC030405.html

[livinbella]

54. That's crazy

Too bad Rummy is a heartless bastard

[livinbella]

73. I hope you post updates as they come in (as new threads)

I think a lot of us are interested,
and it is definitely nice having an expert in the area
available for Q and A. (I usually hate that word 'expert' but in this instance it seems to fit.)

[pandemic_1918]

74. Updates

I agree that this thread is getting a bit messy, but when I tried starting a new thread it was moved to Science, which is not read by many. The avian flu really is much more of a political story than a science story.

There are those that don't think it is real and those that want to wait until human to human transmission is rampant (and then of course it will be too late to do much).

It is flu season, so there will be developments almost daily. In the past few days there were reports of H5N1 in Hong Kong

http://www.recombinomics.com/H5_Hong_Kong.html

Indonesia

http://www.recombinomics.com/H5N1_Indonesia.html

and Thailand

http://www.recombinomics.com/H5N1_Wild_Birds_Thailand.html

and each has serious implications.

However, starting new threads and having them locked and or moved is definitely not the best use of my time.

Talk to DU administrators. They seem to be out of control in their efforts to control, and I really don't have time to play their games.

[Moderator]

75. To help you keep this thread live without excessive kicking

I am moving it to the Health forum. Unless there is some major developments in the story, that is probably a better forum than LBN for this discussion.

[Tansy_Gold]

76. In the FWIW column. . . . . .

There has been a recent spate of astroturf letters to the editor about the avian flu pandemic. My local rag was hit with one last week. I was unable to track down a source: google only provided links to other, identical, LTTEs.

[pandemic_1918]

77. More Developments - Have Fun

There are developments every day. Canada and England just announced preparedness plans today and there are many stories each day on new H5N1 outbreaks.

C U Later.