Pandemic Flu

[mugwump]

With all of the talk about bird and human receptors I thought a picture would be worth 1,000 words. The hemagglutinin that bind to the alpha 2,6 receptor (mammal, upper respiratory tract) are on the left and right -- the middle one binds to alpha 2,3 receptors (bird gut, deep in the human lung). The speculation is that if a mutation occurs that eliminates the little isthmus in the middle of the H5 variant (like happened in the 1918 version) then H2H transmission would be possible.

HaReceptors.jpg

This is from a great article by Taubenberger et al, the guys who resurrected the 1918 virus.

http://www.mcdb.ucla.edu/Research/Go...gKillerFlu.pdf

[mugwump]

Two articles about the same pandemic simulation. Note that Switzerland and France are the sites of the two companies with whom the US has contracted for bird flu vaccine (Sanofi Pasteur and Berna Biotech Ltd -- just as with sneakers, bath towels and pharmaceutical feedstock, we don't have any manufacturing capability on-shore anymore).

Koombayah Europe (or spin A)

BRUSSELS (Reuters) - A European exercise to simulate an influenza pandemic showed the countries involved were reasonably prepared but exposed flaws in the system used to report national health crises, officials said on Thursday.

http://today.reuters.co.uk/news/news...-INFLUENZA.xml

Every-Man-For-Himself Europe (or spin B)

Plans by Switzerland to seal itself off in the event of a flu pandemic triggered "serious concern" by other countries during Common Ground, a recent simulation exercise, because of its strategic location as home to many drug and vaccine manufacturers...Similar concerns were raised about France, another important drug production centre, which also said it was considering border closures. However, French officials stressed they would exempt pharmaceutical workers and materials from travel bans.

http://news.ft.com/cms/s/62e60ba6-c0...6-0820abe49a01.

India

Worrying news from India -- another one of those things to watch. Note that there has been significant culling of birds lately in the West Punjab region and that H5N1 presents as both pneumonia and encephalitis in the very young. There are many reasons for infant mortality in India, but they are historically the biggest prevaricators when it comes to reportable diseases (they make the Chinese look good). :

Deaths of a dozen children since Tuesday, six of them within 12 hours yesterday, rocked Burdwan Medical College and Hospital last night.

[snip]

Murshed said of the 12 deaths, six occurred within a span of 12 hours yesterday. “The babies, suffering from meningitis, pneumonia and septicaemia, died because of cardiac failure and malnutrition.”

http://www.telegraphindia.com/106040...ry_6042980.asp

[The Reaper]

Maybe we could trade them trial lawyers for vaccine and pharmaceutical manufacturers?

TR

[mugwump]

2006.04.04

HONG KONG—Authorities in the central Chinese province of Henan are holding more than 400 university students in isolation after they contracted a mystery fever. Meanwhile, authorities in Shanghai have called for better preparedness as the highly pathogenic avian influenza spreads.

The students, from the Henan University of Science and Technology in the city of Luoyang, were being held at an undisclosed location other than the university hospital, a local employee said, confirming earlier official media reports.

“The students with high fever symptoms are quarantined...at a specific place,” an employee at the No. 1 University Hospital told RFA’s Cantonese service. “But we don’t know how many students are there now.”


http://www.rfa.org/english/news/2006.../asia_birdflu/

NOTE: There is NO confirmation that this is H5N1 and no word of deaths-- there is a WHO team on the way. There are conflicting reports on this -- the original reports said they were hospitalized and then released, then that they were quarantined "at a different place than the hospital", then this one which appears to be a combination of the two.

.

[mugwump]

For "...new technologies that radically accelerate the manufacturing of protein vaccines and protein-based therapeutics..."

Only 3 million doses -- hey, where's mine? I particularly like the award floor, though.


Category of Funding Activity: Science and Technology and other Research and Development

Expected Number of Awards: 999999999999999
Estimated Total Program Funding: $999,999,999,999,999
Award Ceiling: $999,999,999,999,999
Award Floor: $999,999,999,999,999
CFDA Number: 12.910 -- Research and Technology Development
Cost Sharing or Matching Requirement: No

Eligible Applicants
Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility"

Additional Information on Eligibility:


Agency Name
Defense Advanced Research Projects Agency
Description
Accelerated Manufacturing of Pharmaceuticals (AMP) BAA06-31, Proposals Due 1600 ET, June 21, 2006, POC: Michael Callahan, M.D., DTM&H, DARPA/DSO; Phone: (571) 218-4596. DESCRIPTION The Defense Sciences Office (DSO) of the Defense Advanced Research Projects Agency (DARPA) is seeking proposals for new technologies that radically accelerate the manufacturing of protein vaccines and protein-based therapeutics. This program is a key component of an overall DARPA focus to accelerate the insertion of critical therapeutics essential for the military. The vision of the Accelerated Manufacturing of Pharmaceuticals (AMP) program is to create an extremely rapid, flexible and cost-effective manufacturing system capable of producing three million doses of GMP-quality vaccines or monoclonal antibodies (mAB) within 12 weeks....

http://www.grants.gov/search/search....IEW&oppId=8774

[The Reaper]

mugwump:

You are doing a fine job here of keeping us updated. Thanks.

TR

[mugwump]

Originally Posted by The Reaper

mugwump:

You are doing a fine job here of keeping us updated. Thanks.

TR

You're welcome.

We apparently got a sneak peek at the Germann data (see the 3/20/06 13:09 post). This should be interesting when it comes out.

LOS ALAMOS, N.M., April 3 (UPI) -- Los Alamos, N.M., scientists say supercomputer models of a national bird flu emergency have generated "stark" results.

Researchers from the Los Alamos National Laboratory in New Mexico, the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle used the supercomputer to predict the possible course of an avian influenza pandemic, given today's environment of worldwide connectivity.

The large-scale, stochastic simulation examined the nationwide spread of a pandemic influenza virus strain, such as an evolved avian H5N1 virus, should it become transmissible human-to-human.

The simulation produced a city- and census-tract-level picture of the spread of infection through a synthetic population of 281 million people during 180 days. It also examined the impact of interventions, from antiviral therapy to school closures and travel restrictions.

The study's authors -- Timothy Germann, Kai Kadau and Catherine Macken of Los Alamos and Ira Longini of the Fred Hutchinson Cancer Research Center and the University of Washington -- presented the study online in the Proceedings of the National Academy of Science. The study will appear in print in the April 11 issue of the journal.

[mugwump]

This surprised me, and probably has broad application to all infectious disease.

According to a guy who knows these things (no cite yet, I've asked for one) the #1 correlate in those who contracted the flu in 1918 and then survived was immediate bed rest at the first sign of symptoms. Those who tried to tough it out and go to work had a significantly worse outcome.

Now this raises questions in my mind like maybe those who stayed home were better able to miss a day's wages (were richer) and had better nutrition, or better access to nursing support, etc. but it's interesting nonetheless.

[Gypsy]

Originally Posted by mugwump

This surprised me, and probably has broad application to all infectious disease.

According to a guy who knows these things (no cite yet, I've asked for one) the #1 correlate in those who contracted the flu in 1918 and then survived was immediate bed rest at the first sign of symptoms. Those who tried to tough it out and go to work had a significantly worse outcome.

Now this raises questions in my mind like maybe those who stayed home were better able to miss a day's wages (were richer) and had better nutrition, or better access to nursing support, etc. but it's interesting nonetheless.

Not to mention that they'd further infect others. I get VERY annoyed when people are obviously ill and continue to come to work and expose the rest of us to their ick.

My newest boss (ughhhh) seems to think it "looks better" to take sick days as vacation days, something about not being thought of as unreliable. I responded that if I'm sick it's no vacation...thanks but no thanks.

Great thread and info mugwump, thank you. I know where I'm headed when this would hit Chicago.

[mugwump]

A very interesting article in today's WSJ relates "statins could be part of a world-wide effort to reduce morbidity and mortality from avian flu," says Joe G.N. Garcia, chief of medicine at the University of Chicago and a leading lung-disease researcher.

Statins are anti-cholesterol drugs like Lipitor and Zocor, not the ones where you should seek immediate medical attention if your erection lasts longer than four hours.

Note that most humans who contract H5N1 present with ARDS at admission (bleeding from the nose, gums and rectum). Either they are in the late stages when they hit the hospital or ARDS is an early event with this type of flu.

In a demonstration of situational ethics, I have appended the full article for non-subscribers, minus one sentence. I consider this "fair use." Mods, if you disagree, please let me know.


WSJ article on statins

Even Without a Vaccine, Existing Drugs Show Promise In Treating Bird Flu

By THOMAS M. BURTON

April 4, 2006
No one knows whether an avian flu pandemic will ever strike, or if a viable vaccine will be found before it does. But many of the life-threatening symptoms of the flu resemble other conditions that are occurring in thousands of patients now, and the drugs to treat these conditions could be used to treat the bird flu, researchers say.

One of those conditions is acute respiratory distress syndrome, or ARDS, a lung condition involving inflammation and fluid buildup that often follows viral pneumonia and septic infections. Drugs to treat such conditions may be useful for treating bird flu, even if vaccines and antivirals aren't available.

.Because the avian flu virus acts much the same way as ARDS, researchers are now hard at work studying drugs currently used to treat ARDS that could have the potential to fight bird flu too. "We have a lot to offer people if the flu should strike." says Michael A. Matthay, a researcher at the University of California-San Francisco.

Some of the drugs are exotic and experimental, used so far only on mice. Other pills are household names, such as Merck & Co.'s cholesterol drug Zocor and the generically available asthma drug albuterol. Some are in-between, like Eli Lilly & Co.'s Xigris for septic infections, which is used in emergency settings at thousands of dollars a dose.

What these medicines have in common is the ability to fight the constellation of lethal symptoms of ARDS, which some researchers call "vascular leak" because the walls of blood vessels supplying the lungs grow inflamed and porous, causing fluid to seep into the lungs. About 75,000 Americans die annually from ARDS and related conditions, according to critical-care physicians. Researchers at leading institutions like the University of Chicago, the University of Michigan and UCSF are working on ways to treat vascular leak, partly by enhancing the walls of capillaries that supply the lungs.

"If vaccinations do not prevent it, therapy for bird flu is no different than for the inflammatory process of ARDS," says Augustine Choi, chief of pulmonary and critical-care medicine at the University of Pittsburgh Medical Center.

The avian flu virus has killed more than 100 humans since its detection in Hong Kong in 1997. Recent research suggests that because it mostly infects cells deep in the lung, it might be difficult for the virus to spread from person to person. However, some doctors say the deep-lung viral attack may make people cough more heavily and thus make the illness highly transmissible. The government hopes it can ward off a flu epidemic with its stockpile of antiviral drugs and with vaccines in development, but that's far from a certainty. The Asian strain of H5N1, which is known to mutate rapidly, has shown resistance in human cases to antivirals. A recent test of a vaccine in development by the U.S. government and France's Sanofi-Aventis SA had only tepid success.

Doctors are optimistic that statins, the class of cholesterol-lowering drugs that includes Zocor and Pfizer Inc.'s Lipitor, could play a role. That's because statins also fight the inflammation that causes leaky vessels. Although these drugs aren't currently prescribed for respiratory illnesses, "statins could be part of a world-wide effort to reduce morbidity and mortality from avian flu," says Joe G.N. Garcia, chief of medicine at the University of Chicago and a leading lung-disease researcher.

At the University of Chicago, pulmonologist and critical-care doctor Jeffrey R. Jacobson and colleagues have produced ARDS in mice, then hooked the mice up to miniature ventilators as humans with avian flu might be. The mice were then tested with treatments like Zocor, generically called simvastatin. The researchers found that simvastatin relieved vascular leakage and enhanced the artery-wall barrier keeping fluids in -- and that these findings "have broad clinical implications."

"We've clearly demonstrated that these drugs affect blood-vessel function," Dr. Jacobson says.

There's also evidence that statins can help in humans in respiratory distress. Doctors at Ben Gurion University in Israel found that, of patients admitted to the hospital with acute bacterial infections, use of statins made a big difference. The 2004 study of 361 patients found that 19% of the no-statin patients needed intensive care when their infections progressed to severe sepsis, versus 2.4% of those who had taken statin drugs.

While the study involved using statins as a cholesterol drug, researchers believe giving them early in treatment could produce similar beneficial effects for respiratory illnesses. Using Zocor "would be the lowest-hanging fruit" of possible drugs for bird flu because it's relatively inexpensive, and already widely available, Dr. Garcia says.

It also could get patients off ventilators faster. That's important because the ventilator itself can cause injury to the lungs. And if an epidemic were to strike, ventilators could become a scarce commodity.

Dr. Garcia and colleagues have found that experimental drugs that mimic a naturally occurring compound in the body, sphingosine 1-phosphate, produced "significant decreases" in vascular leakage in animal tests. Scientists also have found that Lilly's Xigris, already on the market, appears to build up capillary walls that hold in fluid. UCSF's Dr. Matthay and colleagues are investigating the use of the asthma drug albuterol in ARDS patients. It acts, he says, by "removing fluid from the air spaces of the lungs, and it may also work by decreasing inflammation of the lungs."

And if bird flu never strikes, much of this research will nevertheless be vital: The University of Chicago's Dr. Jacobson says that, at any given time, more than one-fourth of patients in the medical intensive-care unit are suffering from acute respiratory distress and related conditions.

WSJ article on statins

[mugwump]

More...

This statin thing may be the real deal. This study deals w/ bacterial infection, but the inflammatory response is similar in viral infections.

Lipitor ain't cheap, but at least it's widely available.

"...Severe sepsis developed in 19% of patients in the no-statin group and in only 2.4% of the statin group (P<0.001)..."

Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

AHA Statin Study

[mugwump]

Originally Posted by Gypsy

I know where I'm headed when this would hit Chicago.

LOL I've heard that before. I've gone mute on this subject except for here and with my brothers and professional contacts.

I told my wife when she said "Tell them to stop sending all this crap -- where is it going to go?" that if the flu really hit it would all be gone in five days. She has 7 bros. and sisters, all raving Democrats--the really Dean-wing loony sort--whose idea of planning is to have a sign that says "Help ME!" for waving on the roof. We all get along...usually. If things get dull at family gatherings my smart-ass daughter will walk into the room and whisper "Hillary". Like throwing a road flare into the California chaparrel in August.

I've always taken The Reaper's approach to this stuff: being prepared is just common sense, a duty really, and is not difficult. There are a hundred things that could throw a spanner into the works. I buy disability insurance and hope to never use it. Same with this stuff.

It's interesting, really. The old-school, pioneer spirit of being prepared for contingencies is perceived by many as "giving in to fear."

/Rant off

[mugwump]

"What I can say is the infection is now under control, and we can't give any further information,"

Ooookay. Edited to add: Maybe Chikungunya or something else? If they are not lying then it doesn't sound fluish. Given the current climate and China's history of bald-faced lying, "open and honest" would probably have been the better strategy.

Henan authorities refuse to reveal cause of university flu outbreak

Shanghai. April.3 INTERFAX-CHINA- Henan Department of Health has
refused to reveal the cause of a flu-like outbreak which has infected
400 students at a university in the province.

Students at Henan University of Science and Technology, in Luoyang
city, started to become ill on March 26 which resulted in many needing
hospital treatment - as many as 400, according to state media.

Henan Department of Health said laboratory tests showed the infection
is not type A or type B influenza.

Interfax asked vice director of the disease control and prevention
division of Henan Department of Health, Shan Xinguo, why so many
students contracted the disease at the same time, but he declined to
give any details.

He said, "What I can say is the infection is now under control, and we
can't give any further information,"

Shan Xinguo said the students had contracted upper respiratory tract
infections.

He said, "It's normal for students to have upper respiratory tract
infections, especially in spring. And at colleges, students are
concentrated, so it's easy for many students to become infected with
the disease at the same period of time."

Another official from Henan Department of Health, who declined to be
named, said the situation is now under control, and the fever was
starting to pass.

"The reason why so many students developed fever continuously still
remains unclear," she said, "We are still investigating the matter,
but we are sure the students are not victims of an epidemic influenza
infection."

She said the main symptoms of the sick students were fever and joint
pains, and that most recovered one or two days after medial treatment.

Shan Xinguo said the ill students had been quarantined and treated,
and that some TCM preparations have been sent to students to prevent
the disease. Over 2000 dormitories as well as 130 classrooms are now
being sanitized twice a day.

As of April 2, ten students were still in hospital for clinical observation

http://www.curevents.com/vb/showthread.php?t=44938

[AngelsSix]

Okay...wait a minute. Isn't this the same damn thing that happened in the late 80's when we found out that even thought the smallpox virus had been eradicated, the Russians were still (and so were we, for that matter) conducting biological tests and so forth to make a super virus? The idiots killed a bunch of people because they let Anthrax get out of one of their labs....who's to say that the same thing hasn't happened here? Who's to say this isn't genetically engineered with the express purpose of wiping people (or their food source) out??

Ideas??

[AngelsSix]

From the CDC site:

Infected birds shed influenza virus in their saliva, nasal secretions, and feces. Susceptible birds become infected when they have contact with contaminated secretions or excretions or with surfaces that are contaminated with secretions or excretions from infected birds. Domesticated birds may become infected with avian influenza virus through direct contact with infected waterfowl or other infected poultry, or through contact with surfaces (such as dirt or cages) or materials (such as water or feed) that have been contaminated with the virus.

Mug: So while the bird's poop may be infectious (interesting that a virus can survive outside of the body so long) the possibility that the dog gets it??? Good question....what we need to know here is how the virus works to attack the immune system....I guess.