Bird Flu: Science and Policy

[Biowatch]

Monitor Children on Flu Drug, F.D.A. Urges

[Apparently Tamiflu use is much higher in Japan than elsewhere, so adverse events would show up there sooner.]
http://www.nytimes.com/2006/11/14/health/policy/14tamiflu.html?_r=1&oref=slogin

By THE ASSOCIATED PRESS
Published: November 14, 2006

WASHINGTON, Nov. 13 (AP) — Doctors and parents should watch for signs of bizarre behavior in children treated with the flu drug Tamiflu, federal health officials suggested on Monday in citing an increasing number of such cases from overseas.

Food and Drug Administration officials do not know whether 103 cases recently reported, including three deaths from falls, are linked to the drug or to the flu virus, or to a combination. Most of the cases involved children.

Still, F.D.A. staff members suggested updating the Tamiflu label to recommend that all patients, especially children, be closely monitored while using the drug. They also acknowledged that stopping treatment with Tamiflu could harm influenza patients if the virus were the cause of delirium, hallucinations and other abnormal behavior like aggression and suicidal thoughts.

The pediatric advisory committee of the drug agency is to discuss the recommendation on Thursday. The agency is not required to follow the advice of its outside panels but usually does. A spokeswoman for the agency did not immediately return a call for comment.

A year ago, the same panel rejected linking Tamiflu to reports of 12 deaths in Japanese children since 2000 and voted against changing the drug label to suggest such a concern. At that time, however, the committee recommended that the drug agency continue to monitor the drug’s safety and return a year later with an update.

The panel decision after reviewing the update is likely to be closely watched because Tamiflu could have an important role in an outbreak of avian flu. The drug does not prevent flu but can reduce the length and severity of its symptoms.

Most of the 103 recent cases of bizarre behavior are from Japan, where the number of Tamiflu prescriptions is about 10 times that in the United States, with more than twice the population. The cases occurred from Aug. 29, 2005, to July 6, 2006.

The Japanese Tamiflu label now warns that disturbances in consciousness, abnormal behavior, delirium, hallucinations, delusions and convulsions may occur. It also recommends patients be carefully monitored and the drug be stopped if any abnormality is observed.

Even though severe flu cases of the flu can set off those conditions, the number and nature of the cases — along with comments from doctors who believed that the abnormal behavior was associated with the drug — have kept the drug agency from ruling out Tamiflu as the cause, according to agency documents.

The agency staff called the proposed changes prudent, because American use of Tamiflu could jump to Japan’s levels. The current American label mentions only “seizure and confusion” seen in some patients.

Tamiflu is made by the Swiss pharmaceutical company Roche Holding. A spokesman for Roche did not immediately return messages for comment. Previously, Roche has cited studies from the United States and Canada that show the death rate of influenza patients who took Tamiflu to be far below those who did not.
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FDA Urges Caution on Flu Drug
By PATRICIA KOWSMANN
November 14, 2006; Page B2

WASHINGTON -- Food and Drug Administration staff recommended that the label for Roche Holding AG's flu drug Tamiflu be updated to include a precaution related to possible psychiatric problems in patients who take it.

The move follows a 10-month review that found 103 cases of "neuropsychiatric adverse events," including the death of a 14-year-old boy who fell after climbing on a balcony railing.

Of the cases, 67% were in children and 95% occurred outside the U.S., mostly in Japan, Tamiflu's biggest consumer. Two other related deaths by people who took Tamiflu were reported, including an adult who left a suicide note.

The officials still don't know if the new cases, reported from August 2005 to July, are linked to the drug, to the flu virus, or a combination of the two.

In Japan, Tamiflu's label already carries information on such events.

"Roche continuously reviews post-marketing safety information, and as a result, has agreed with the FDA that the Tamiflu label be revised to include reports of neuropsychiatric events such as self-injury and delirium in patients with influenza," a Roche statement said.

Write to Patricia Kowsmann at [e-mail]
URL for this article:
http://online.wsj.com/article/SB116344215315321759.html

[DewDiligence]

Skin Patches Instead of Shots

http://biz.yahoo.com/ap/061106/healthbeat_patch_vaccines.html?.v=1

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By Lauran Neergaard

Skin Patches Instead of Shots? Testing Under Way for Vaccines

GAITHERSBURG, Md. Nov 6 (AP) -- Dreaded vaccinations one day could be as simple as sticking on a Band-Aid -- ouchless and do-it-yourself.

Early tests of skin-patch vaccines are beginning in hundreds of volunteers, one version designed to protect against the flu and another to prevent travelers' diarrhea.

The idea isn't just pain-free vaccination. The National Institutes of Health is helping fund patch research in hopes of strengthening today's imperfect flu shots, and gaining extra help if bird flu or some other super-flu ever triggers a pandemic.

Indeed, patch developer Iomai Corp. proposes that the mailman, not a doctor, deliver flu vaccine during a pandemic. Once a vaccine is brewed, simply ship patches to people's homes with instructions to slap one on.

Doctors might not like the go-it-alone method. But the technology's main promise may be in developing countries. Unlike syringe-based vaccines, patches wouldn't need refrigeration -- nor pose the infection risk of reused needles, a continuing problem.

Only time will tell if the patches really work. Iomai is in initial stages of human testing, and years of additional work are required for proof. But previous research does suggest the skin could provide an improved route to rev up the immune system, perhaps allowing doctors to use lower vaccine doses.

"It may be that the expectations for vaccine patch technology are now slowly bearing fruit," says Dr. William Schaffner of Vanderbilt University, a vaccine expert who has long monitored the field.

"It is what I would call an alluring technology."

If it works against one disease, a patch likely could be tweaked to deliver numerous kinds of vaccines. Iomai also has Defense Department funding to help develop an anthrax vaccine patch.

"The approach is novel and may be the way many vaccines are given in the future," says Dr. Herbert DuPont of the University of Texas Health Sciences Center in Houston. A specialist in diarrheal diseases, he is helping Iomai test the travelers' diarrhea patch in U.S. tourists headed for Mexico.

Most of today's vaccines are shots into muscle. But doctors have long known that getting vaccine just inside the skin is deep enough. History's first crude inoculations, against smallpox, merely involved scratching pus from a related but milder virus into the skin. And recent research using small needles to push flu vaccine just inside the skin found lower doses could be as protective as full-strength muscle shots.

The question is how to do skin vaccination without actually breaking the skin. Patches frequently deliver medications, such as nicotine or birth control. But [those] drugs are very small molecules that can fairly easily penetrate skin to reach the bloodstream. Vaccines typically contain much larger proteins.

Iomai's method, discovered by one of its founders at the Walter Reed Army Institute of Research: Just get past a thin outer layer of dead skin to the epidermis, the first living skin layer. There, specialized cells called Langerhans cells can recognize a pathogen and speed to the lymph nodes to alert the immune system.

In Iomai's laboratory in Gaithersburg, Md., outside Washington, CEO Stanley Erck demonstrates: He brushes his skin with a gadget bearing a bit of sandpaper, like the kind used for filing fingernails. The round patch then is stuck to the scuffed spot for several hours.

"We're not inventing anything new, just exposing pathogens the way humans have seen them all their life," Erck says.

Now come the tests:

--Furthest along are patches designed to protect against an E. coli strain called ETEC, a leading cause of travelers' diarrhea. DuPont's study aims for up to 300 participants to spend at least two weeks in Mexico or Guatemala, visiting pre-specified clinic sites there if they do get diarrhea to see if the patch failed or if the culprit was some other germ. In an initial challenge study at Johns Hopkins University last year, patch recipients who drank the bacteria suffered significantly less diarrhea than their unvaccinated counterparts, Erck said.

--Last month, Iomai began first-stage testing of flu vaccine patches in 270 volunteers, to track the patches' safety and whether recipients develop as many flu-fighting antibodies as those given standard flu shots.

--Another goal is immune-stimulating patches to boost a vaccine's effects. The elderly are less protected by today's flu shots than young people. And studies of bird-flu vaccine show that a huge dose will be required regardless of age, unless immune-boosters can help stretch supplies.

Iomai's travelers' diarrhea patch also seems to give the immune system a general boost. In a small study last year, giving elderly volunteers that patch plus a standard flu shot spurred a greater immune response than the shot alone. The company now is preparing a larger study, and competing for a government contract to add immune-boosting patches to a federal stockpile of flu pandemic supplies.

"There definitely is promise to that idea," says Dr. David S. Cho of the NIH's flu product development office, who monitors the patch project -- although he cautions that Iomai must prove if the immune booster works with a variety of flu strains.
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[DewDiligence]

Scientists Say Latest Strain of
Bird Flu Resistant to Vaccines

http://msnbc.msn.com/id/15486614/

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The Associated Press
Oct 30, 2006

WASHINGTON - Scientists have discovered a new strain of bird flu that appears to sidestep current vaccines.

bIt’s infecting people as well as poultry in Asia, and some researchers fear its evolution may have been steered by the vaccination programs designed to protect poultry from earlier types of the H5N1 flu.

The discovery by Yi Guan of the University of Hong Kong and colleagues is reported in Tuesday’s issue of Proceedings of the National Academy of Sciences.

The new variant has become the primary version of the bird flu in several provinces of China and has spread to Hong Kong, Laos, Malaysia and Thailand, the researchers report. It is being called H5N1 Fujian-like, to distinguish it from earlier Hong Kong and Vietnam variants.

“We don’t know what is driving this,” report co-author Dr. Robert G. Webster of St. Jude’s Children’s Research Hospital in Memphis, Tenn., said in a telephone interview.

New vaccines will have to be developed, Webster said.

Many scientists are going to think the vaccination program encouraged the virus to evolve resistance, he added, but high-quality vaccines can reduce the level of illness and prevent emergence of variants.

'Virus is continuing to drift'

While the new virus has infected people, there is no evidence that it can pass easily from person to person, Webster said. However, he added, “this virus is continuing to drift.”

Dr. Michael L. Perdue, of the World Health Organization’s Global Influenza Program in Zurich, Switzerland, said the new variant doesn’t indicate any increased risk for people “other than the fact it seems to be pretty widespread.”

The virus is continuing to change, he added.

Perdue, who was not part of Webster’s research team, said WHO is working with the Chinese Ministry of Health to develop a vaccine for the new form of the virus.
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[DewDiligence]

If We Must Ration Flu Vaccine, Who Calls the Shots?

http://online.wsj.com/article/SB116008629662084219.html

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By SHARON BEGLEY
October 6, 2006

You have 100 doses of a vaccine against a deadly strain of influenza that is sweeping the country, with no prospect of obtaining more. Standing in line are 100 schoolchildren and 100 elderly people.

The elderly are more likely to die if they catch the flu. But they also have fewer years left to live and don't get out enough to easily spread or catch the disease. The kids are more likely to act like little Typhoid Marys, sneezing virus over anyone they encounter, and have almost their whole life ahead of them. But they're also less likely to die if they get sick.

Whom do you vaccinate?

This dilemma is haunting experts concerned that avian influenza might start spreading from person to person instead of (as far as we know) mainly from birds to people. But it also applies to regular old flu, which always has the potential to reach pandemic proportions. In response, studies now are shedding light on the ethical issues and the most effective strategy for reducing illness and death if vaccine must be rationed. Sadly, they make a pretty good case that current U.S. policies leave a lot to be desired.

First, ethics. In May, scientists at the National Institutes of Health stirred things up with a paper calling into question the policy that aims to save the most lives by first vaccinating the old, the very young and the sick, putting last those who are two to 64 years of age.

The value of a life, they argued, depends on age. A 60-year-old has invested a lot (measured by education and experience) in his life, but has also reaped most of the returns. A child has minimal investment. A 20-year-old has great investment but has reaped almost none of the returns. Conclusion: To maximize investment in a life plus years of life left, 13- to 40-year-olds should have first claim on rationed vaccine, explains NIH's Ezekiel Emanuel.

Second, efficacy. Let's leave aside the fraught question of the value of a life. Evidence keeps accumulating that vaccinating the elderly might not even be the best strategy for minimizing deaths. The reason is that during some flu pandemics, the mortality rate among the elderly is hardly higher than during nonpandemic years. The flu certainly kills some old people, says Dr. Emanuel, but many would have died anyway. In addition, they may not benefit from flu vaccines as much as is assumed: A 2006 study found that the antibody response by people over 65 is less than half that in young adults.

Critics reply that the elderly are more likely to die if they get the flu, so ethics requires you protect them, the most vulnerable, first. Indeed, in the 1957 and 1968 pandemics, the very young and very old had the highest flu-mortality rates. But in the 1918 pandemic, 20- to 40-year-olds and children under five had the highest mortality rate. The elderly were more likely to either not become infected or to survive if they did, perhaps because only someone with a sturdy immune system lived to a ripe old age back then.

The common-sense notion that vaccinating the elderly is the best way to save the elderly also deserves scrutiny, according to a study this week in the journal PLoS Medicine. Infants and the elderly don't spread the flu as much as, say, a schoolchild or business traveler. Might you decrease both illness and death, including among the old, by vaccinating other age groups first?

As it happens, that is what doctors did in Tecumseh, Mich., in 1968. They vaccinated school-age kids, whose lower natural immunity and many contacts (not to mention a tendency to sneeze all over the place) makes them high transmitters of infectious disease. That tactic slowed the spread of disease and cut the death rate from flu to below that in a matching community.

Last year, scientists showed in a model that if you vaccinate about 60% of U.S. schoolchildren, flu deaths among the elderly would fall to 6,600 from the typical 34,000. "It's not necessarily true that the best way to protect someone is to vaccinate that person," says Ira Longini of the Fred Hutchinson Cancer Research Center, Seattle. "In the case of the elderly, flu vaccine doesn't protect them very well, so breaking the chain of transmission provides greater protection."

In the PLoS study, mathematician Lauren Ancel Meyers of the University of Texas, Austin, and colleagues analyzed patterns of flu transmission under different assumptions about how likely a carrier is to infect other people. Using data on household size, age distribution and other factors, they compared a strategy that targets infants and the elderly with one targeting those most likely to catch flu: school-age kids.

For moderately contagious strains, says Prof. Meyers, the optimal strategy is to vaccinate the kids. "This severs the transmission chain," she says, thereby indirectly protecting the old. For very contagious strains, it is better to vaccinate those most likely to die if they catch flu, such as the elderly. "Highly contagious strains can find their way around this buffer of immunized schoolkids," she explains.

The flu season began this month, and is expected to peak between Christmas and March. As usual, scientists took an educated guess about which strain would show up this year and made vaccines against New Caledonia, Wisconsin and Malaysia. Now, all they can do is hope that they guessed right -- and that there is enough vaccine to go around -- so that the need to ration shots remains theoretical.
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[DewDiligence]

More on the same story…

http://www.yorkshiretoday.co.uk/ViewArticle2.aspx?SectionID=55&ArticleID=1802160

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Breakthrough May Mean End to Flu Misery for Millions, Says Scientist

By Chris Benfield
04 October 2006

Science may have come up with a way to stop flu.

Warwick University professor Nigel Dimmock has spent 20 years looking for a general antidote to flu viruses and says he is now ready to make one on a large scale.

He is sure it would work against H5N1 – the new strain of bird flu which has been causing worldwide concern – and its variants.

And he is ready to start trials on humans, farm chickens and other animals governments and businesses might want to protect.

The university is launching a company in which it and Prof Dimmock have a stake, ViraBiotech, to raise money for trials and preparations for manufacture.

In theory, a human flu-preventer based on the Warwick discoveries could be ready in three years.

It would not wipe out flu viruses, but it could stop the epidemics which disrupt economies and cost lives when a virus mutates and spreads suddenly.

It could also prevent run-of-the-mill misery and cost arising from the 144 viruses already established in humans and animals such as pigs, poultry and horses.

Prof Dimmock's method promises to work against all viruses in the Influenza A category – the family which causes most trouble – and it might also work against some Influenza B.

It involves "protective viruses" – incomplete imitations of a full flu virus, which occur naturally along with the viruses they mimic.
Nobody knows what they are for, in evolutionary terms, but one theory is that, by competing for resources, they stop the damaging virus from killing its host too quickly.

Prof Dimmock, 66, is an expert on what happens when a protective virus gets into a host before the real thing.

On its own, it cannot reproduce, because there is a bit missing from one of its strands of RNA, the genetic material which carries the codes for building cells.

When a real virus arrives, they team up and both reproduce, but the dummy virus works faster, because it is smaller. It swamps the "nasty" version, so the body can develop antibodies before damage is done.

Prof Dimmock has seen the process in laboratory cultures, mice and ferrets. A dose is effective for six weeks and should cost no more than existing vaccines and anti-viral drugs.

He now has a protective virus from the Influenza A family which he can reproduce consistently and check for quality. But he stresses that genetic modification is not involved.

"It is a naturally occurring product," he said yesterday.

The system could lead to similar medicines against colds, hepatitis and other viral illnesses.

An independent expert, John Oxford, head of virology at three London hospitals, said the idea had "huge potential".
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[DewDiligence]

This sounds too good to be true…

http://www.innovations-report.de/html/berichte/agrar_forstwissenschaften/bericht-71409.html

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Protecting virus’ offers instant flu protection & converts flu infections into their own vaccines

04 Oct 2006

Research led by Professor Nigel Dimmock at the University of Warwick is developing an entirely new method of protecting against flu. This has been shown to protect animals against various strains of flu, and could offer protection against the full range of influenza A infections, including H5N1 and any new pandemic or epidemic strains infecting humans.

The ‘protecting virus’ provides instant protection, and completely prevents flu symptoms developing by slowing influenza infection rates to such an extent that the harmful infection becomes a vaccine against that very form of influenza. It can also counter an actual infection and offer protection if given up to 24 hours after first infection (and possibly longer).

Existing vaccination methods depend on stimulating the body’s immune system, so that white blood cells produce antibodies that attach to the surface of the virus and start the process of killing it. This works well for many diseases, such as smallpox, polio and measles, but is much less effective with influenza, as the coat of the flu virus is continually changing. Vaccination against one strain of flu, for instance H3N2, is totally ineffective against another, such as H5N1. This is especially problematic when a new pandemic strain emerges, as all existing vaccines are likely to be totally ineffective.

Professor Dimmock has spent more than two decades investigating an entirely new method, that uses a ‘protecting virus’. This has now been shown to provide instant protection against all flu symptoms and to slow the development of an influenza infection to such an extent that harmful infections are transformed into a vaccine against that form of influenza.

‘Protecting virus’ has a significant alteration to one of the virus’s genes. The genetic material of a flu virus consists of 8 individual segments of single stranded RNA. Professor Dimmock’s protecting influenza virus has a huge but specific deletion of around 80% of the RNA of one of these 8 strands.

This deletion makes the virus harmless and prevents it from reproducing by itself within a cell, so that it cannot spread like a normal influenza virus. However, if it is joined in the cell by another influenza virus, it retains its harmless nature but starts to reproduce – and at a much faster rate than the new influenza virus. This fast reproduction rate – spurred by the new flu infection – means that the new invading influenza is effectively crowded out by the ‘protecting virus’. This vastly slows the progress of the new infection, prevents flu symptoms, and gives the body time to develop an immune response to the harmful new invader. In effect the protecting virus converts the virulent virus into a harmless live vaccine.

Research indicates that the ‘protecting virus’ would have the same beneficial effect whatever strain of influenza is infecting you. This is because the coat of the virus is irrelevant to the protection process – the effect works on the virus genes inside the cell. It thus promises to be a highly effective tool when combating the spread of any new strain of virus, as well existing strains. One could give it as a preventive measure without the need to tailor it to a particular flu strain or mutation. This has obvious benefits when dealing with the sudden outbreak of a major epidemic, as one would not need to know the exact make up of the new strain before deploying the protecting virus making it much more useful than vaccines, which are effective only against particular existing strains of virus. In addition it protects instantly, whereas protection generated by conventional flu vaccination takes 2-3 weeks to become fully effective.

Experiments so far show that a single dose of protecting virus can be given 6 weeks before an infection with flu virus and be effective. This could also have a substantial advantage over anti-viral drugs that only give less than 24-hour protection. Another advantage is that influenza virus does not appear to become resistant to ‘protecting virus’, although drug-resistance is a serious problem with many microbes.

‘Protecting virus’ also protects when given up to 24 hours after infection (and possibly longer). It is thus able to counter an actual infection. It could therefore also be used as a treatment for family and other direct contacts of infected individuals.

‘Protecting virus’ is easy to administer as it targets the same cells as any other flu virus and uses the same method to enter the cell. Laboratory work to date has used a drop of saline containing the protecting virus, squirted up the nose. Aerosol administration, used already for some vaccines, would be another way and is more user-friendly than injections.

The protecting virus could also be a useful treatment for domestic animals. Ducks get a gut infection and chickens a combined gut and respiratory infection, so it may be possible to simply deliver the protecting virus to them in their drinking water. One dose should protect a chicken for weeks. Flu is a major problem in the horse racing industry and in domestic horses. It also has very recently become a problem in domestic dogs in the USA and domestic cats are susceptible to H5N1 virus.

The Warwick research team has now filed a patent on the protecting virus and they are exploring ways of taking ‘protecting virus’ through human clinical trials and testing on birds.

The University has established a company – ViraBiotech – to help advance those aims. This may involve venture capital support, and collaborations with pharmaceutical companies, to enable this novel technology to be rigorously tested in a wide range of animals and humans, and using a wide range of influenza strains.
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[DewDiligence]

BAX Touts Cell-Based Bird-Flu Vaccine

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20061004:MTFH17847_2...

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By Julie Steenhuysen

CHICAGO, Oct 4 (Reuters) - An experimental vaccine for bird flu using new cell-based manufacturing methods showed promise at combating several strains of the virus in an early clinical trial, Baxter International Inc. <BAX> said on Wednesday.

The health-care products maker said preliminary results from a 270-patient study suggest the vaccine was safe, well-tolerated and may provide wider protection against H5N1 -- the bird flu virus -- for a larger number of people.

Although early, Baxter's study suggests the vaccine could be stockpiled and used as a weapon against an emerging bird flu pandemic, said Hartmut Ehrlich, M.D., vice president of global R&D for Baxter's BioScience division.

Ehrlich said the early-stage study suggests the vaccine could offer cross-protection from similar strains of the H5N1 virus.

"We're seeing cross-neutralization, which of course we hope will be translated to cross-effectiveness in a pandemic situation," Ehrlich said in an interview.

H5N1 mainly affects birds, but experts fear it could mutate into a strain easily transmitted from person to person, capable of killing millions of people in a global pandemic.

Deerfield, Illinois-based Baxter said the results are the first data from any bird flu vaccine made using cell-based techniques, a new and better way for developing vaccines that holds the promise of producing much larger quantities of vaccine in much less time.

Vaccine makers currently rely on egg-based production methods, which require steady supplies of carefully grown eggs and months of cultivation. The new method grows the vaccines in labs, in batches of cells called cell cultures.

"Our system will allow us to begin vaccine production significantly earlier than the egg manufacturers," said Noel Barrett, Baxter's vice president of global research vaccines.

He said Baxter is the only vaccine maker using the highly virulent "wild type" strain of the virus, which is the authentic virus circulating in nature. Baxter is also using the whole virus.

Other companies must genetically manipulate the virus to make it less toxic to chicken eggs and must have its safety checked before vaccine production can start. Because of those extra steps, Barrett estimates the company could have a seven to 10-week advantage over the egg-based manufacturers in the event of a pandemic.

LATE-STAGE CLINICAL TRIAL EARLY 2007

Ehrlich said the Baxter-funded study of healthy adults in Austria and Singapore suggested the vaccine had similar side effects to those reported for seasonal flu vaccines.

The preliminary results suggest the vaccine is highly capable of producing an immune response and can create antibodies to H5N1 even at the lowest dose level.

Serum samples from study subjects showed the vaccine was able to neutralize the virus contained in the vaccine as well as other diverse strains of the H5N1 virus.

Baxter plans to begin a late-stage clinical trial of the vaccine early next year and said it will present final results by the end of 2007.

Joy Amundson, president of Baxter's Bioscience business, said in an interview the company is in active discussions with ministers of health concerning bird flu preparedness. "We've got a commercial scale facility that is able to produce product immediately," she said.

Baxter is under contract to supply bird flu vaccine to the U.S. and British governments.

Amundson said the company will deliver some 2 million doses to the British government in the fourth quarter and is in the process of delivering product to the U.S. government as well.

Europe's biggest drugmaker GlaxoSmithKline Plc <GSK> in July said its egg-based vaccine could be mass produced in 2007.

French drugmaker Sanofi-Aventis <SNY> and Swiss drugmaker Novartis AG <NVS> are also working on an H5N1 vaccine.
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[mskatiescarletohara]

Novavax Initiates Pre-Clinical Testing of Intranasal Influenza Vaccine
Tuesday September 19, 7:00 am ET
New Delivery Route May Provide Alternative to Administration by Injection

MALVERN, Penn., Sept. 19 /PRNewswire-FirstCall/ -- Novavax, Inc. (Nasdaq: NVAX - News) said today that it has begun pre-clinical testing of intranasal versions of its influenza vaccines in development, providing a potential alternative to administering these vaccines by injection.


"This is an important advancement for our existing technology because it will allow us to reach an even broader population," said Dr. Rick Bright, Novavax's Vice President of Vaccine Development. "There are many parts of the world that do not have accessibility to enough sterile needles to respond to an influenza crisis."

Historically influenza vaccines have been administered though intramuscular injection. However, the World Health Organization (WHO) has been proactively seeking alternative delivery methods. "The problem with needles is that conditions must be highly sterile in order to prevent contamination during the mass vaccination that would take place in the event of an emergency," Dr. Bright said.

Novavax is investigating the intranasal delivery route using both the company's seasonal and pandemic virus-like particle (VLP) vaccines in pre-clinical models. "Our early data indicate that we can trigger a protective immune response with the intranasal vaccine that is as robust as our intramuscular formulation," Dr. Bright said. "We are eager to further explore this route of delivery in additional pre-clinical work as well as human studies."

Using the company's proprietary VLP technology, Novavax scientists create a particle that is nearly identical to a virus but does not have the virus's genetic material required for replication or infection. When inoculated into the body, these particles have the ability to attach to cells and trigger a natural immune response that is capable of protecting against viral infection.

Novavax scientists are using the Clade 2 H5N1 influenza virus -- for both the intranasal and intramuscular versions of its pandemic influenza vaccine. The Clade 2 variant, identified in birds from China and Indonesia before spreading to Europe, the Middle East and Africa, is primarily responsible for human infections and mortality over the last year. The WHO recently changed its H5N1 avian influenza guidance to indicate that pandemic vaccine candidates should target viruses from the Clade 2 family rather than the earlier Clade 1 family.

"By creating our vaccines against the Clade 2 strain of pandemic influenza, we are targeting protection against the most current form of this deadly H5N1 virus," Dr. Bright said.

[DewDiligence]

Bird Flu Complacency

[This appeared as an op-ed piece in the San Diego Tribune.]

http://www.aethlonmedical.com/pdfs/BirdFluComplacency.pdf

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By James A. Joyce
September 13, 2006

Earlier this year, the media deployed the best and brightest from the science world to discuss the imminent threat of bird flu mutating into a form that would allow for human-to-human infection. ABC News produced a special report on world-renowned researcher Robert G. Webster, who stated:

“Society just can't accept the idea that 50 percent of the population could die, and I think we have to face that possibility.”

As time passed, however, the public became distracted by multiple wars in the Middle East, inflation, rising oil prices, tumbling financial markets, global warming and a host of other issues. Unfortunately, evolving evidence underscores the reality that bird flu, otherwise known as H5N1 Avian Influenza, is still a very real threat.

Influenza is already a big killer, as it is responsible for more than 35,000 deaths and over 200,000 hospitalizations in the United States each year. Avian flu occurs naturally in birds and has historically demonstrated the ability to infect humans. It already is unprecedented as an animal illness in its rapid expansion, and has cost 300 million farmers more than $15 billion during its recent spread in poultry around the globe.

World Health Organization officials claim the H5N1 strain of avian flu poses a greater challenge to the world than any other infectious disease, including AIDS. As of July 20, WHO officials confirm that of the 230 individuals known to have been infected, 132 died since the virus re-emerged in 2003.

Among humans, there is no natural immunity and no vaccine to treat the H5N1 strain of avian flu. WHO Assistant Director General Margaret Chan stated, “We have never seen such a high case-fatality rate where more than 50 percent of people affected by the infection die from the disease.” As a comparison, the fatality rate of the Spanish flu of 1918 (also a form of avian flu), which was only 2.5 percent, caused the deaths of over 40 million people during an 18-month period.

To provide perspective, it has taken 25 years for AIDS-related deaths to reach such levels.

Scientists, increasingly worried that the H5N1 strain of avian flu could mutate into a form that could be passed between humans, received bad news on June 23 when researchers documented that the virus had successfully mutated to be passed through human-to-human transmission in a family in Indonesia. Fortunately, these same researchers reported that the virus did not pass beyond the infected family members, who all died from the infection.

In the face of such dire news, researchers are unraveling the mystery of why the H5N1 strain of the avian flu virus is so lethal. It appears H5N1 hyper-activates the immune response, a frightening trait also inherent in the Spanish flu.

In the case of H5N1 infection, viral sepsis leading to major organ failure is often the cause of death. This is triggered when the immune system over-responds to infection by releasing a cascade of inflammatory cells and chemicals in what is known as a “cytokine storm.” As a result, the likelihood of death in individuals with robust immune systems equals or exceeds the immune compromised who are normally most susceptible to regular seasonal flu strains.

Unfortunately, antiviral drugs are unable to shut off a cytokine storm once it has been triggered. As a result, the antiviral drugs being stockpiled as part of a global strategy to treat avian flu have no therapeutic value once the cytokine storm has been triggered.

At present, only one antiviral, oseltamivir (Tamiflu), is known to offer some level of effectiveness against the H5N1 strain of avian flu. Tamiflu, however, is indicated only as a treatment for normal household varieties of influenza if administered within 48 hours of first symptoms. The treatment window for an ultra-virulent H5N1 strain is likely to narrow considerably. Reports indicate the potency of Tamiflu against the avian flu virus is reduced, even when taken within 24 hours of the first symptoms of the disease. In addition, the drug is directed toward symptoms and does not provide an anti-viral effect.

Prolonged incubation combined with a short antiviral treatment window also concerns researchers. Dr. Tim Uyeki, a medical epidemiologist with the influenza branch of the Centers for Disease Control and Prevention, stated to The Wall Street Journal:

“Patients aren't presenting (symptoms) early in the illness. If the cytokine storm has already been triggered, antiviral drugs aren't going to turn it off.”

A successful global strategy against H5N1 will, at a minimum, have to rely on therapeutics that can modulate the overproduction of cytokines.

The March 2 issue of The Lancet reported that researchers at the well-regarded Karolinska Institute in Stockholm are proposing the use of chemotherapy to kill off excess immune cells as a means to curb the cytokine storm leading to viral sepsis in H5N1 patients. While the concept may seem radical, researchers are likely to agree that any treatment able to damp down the immune system might be helpful.

Unfortunately, taming the immune system without destroying defenses against infection has yet to be demonstrated with drugs. Until effective therapeutics surface, we are all naked to the effects of H5N1 avian influenza. Let's hope the evolving evidence dissipates to justify bird flu complacency!

[Joyce is chief executive officer of Aethlon Medical, a San Diego research laboratory that will file with the Food and Drug Administration for approval of its technology to treat avian flu.]
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[DewDiligence]

Live H5N1 Vaccines Have the Inside Track

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20060912:MTFH49836_2...

>>
By Maggie Fox, Health and Science Correspondent

WASHINGTON, Sept 11 (Reuters) - Three experimental vaccines using live but weakened versions of the H5N1 bird flu virus appeared to protect animals from infection, and might offer a way to stockpile vaccines ahead of a pandemic, U.S. researchers said on Monday.

They said the approach was already being tested in people, and might provide the start of a repository of vaccines against various potential strains of pandemic influenza.

"We have been developing live, attenuated influenza virus vaccines because they have properties that make them attractive vaccines for the prevention of pandemic influenza in humans," the researchers wrote in the online journal Public Library of Science-Medicine.

Unlike some of the other experimental vaccines being developed, it takes only a single dose of a live, weakened vaccine to stimulate a good immune response, the researchers said.

Such vaccines induce what is known as cross-protection, meaning the vaccine protects against other, similar strains of the virus, the researchers said. This would be useful because the current flu mutates a little every year, forcing vaccine makers to reformulate annually.

"If an influenza pandemic were imminent or underway, we would need a vaccine that could stimulate immunity quickly, preferably with a single dose," said National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci.

Experts fear the H5N1 avian flu virus now killing birds globally could evolve into a form that easily infects people, sparking a pandemic that could kill millions.

Although H5N1 has infected just 244 people and killed 143, governments, companies and other organizations are racing to produce a vaccine.

Some of the vaccines use pieces of DNA from the viruses and others use a virus that is completely inactivated, or killed. Most seasonal flu vaccines use a virus that has been killed, an approach that offers little cross-protection.

Maryland-based MedImmune Inc. <MEDI> takes a different approach, engineering a live but weakened virus that is delivered as a nasal spray instead of injected by needle.

MedImmune researchers worked with teams at the National Institutes of Health and the U.S. Department of Agriculture to make a live H5N1 vaccine. The teams, led by Dr. Kanta Subbarao of NIAID, used three different strains of H5N1 dating back to when the dangerous form first emerged in Hong Kong in 1997.

Mice that got a single dose of vaccine, given in a nose spray, all survived normally lethal doses of H5N1, the researchers reported. Mice and ferrets given two doses of vaccine were protected and their bodies also suppressed the virus, the researchers found.

The team artificially constructed their viruses using weakened flu strains and added key proteins from H5N1 strains that infected people in 2004, 2003 and 1997. But they used the usual low-tech approach to produce the vaccine, growing it in chicken eggs -- the same way seasonal flu vaccine is produced.

MedImmune said in June it was already testing one of the vaccines in human volunteers, in what is known as a Phase I safety trial.

The researchers noted it is not possible to predict which strain of H5N1 or any other influenza virus might cause a pandemic. There are hundreds of different possible combinations of hemagglutinin (the "H" in a flu strain's name) and neuraminidase (the "N").

"If the vaccine candidates described in this paper elicit a broadly cross-reactive protective immune response in humans, they would support the approach of developing one or two pandemic vaccine candidates for each subtype (H4 through H16) ..." they wrote.
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[DewDiligence]

Akzo Nobel Signs Deal to Develop Avian Flu Vaccine

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20060830:MTFH81807_2...

>>
AMSTERDAM, Aug 30 (Reuters) - Dutch chemical group Akzo Nobel NV (AKZOY) said on Wednesday it had signed a research agreement with U.S.-based Centers for Disease Control and Prevention to develop a pandemic avian flu vaccine. "The agreement -- co-signed with Nobilon's international partner, Australian-based BioDiem Ltd -- involves the development of a live attenuated cold-adapted cell culture vaccine against the H5N1 strain of the avian influenza virus," Akzo Nobel said in a statement.
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[DewDiligence]

Biologists Don't See Deadly Bird Flu in Alaska

http://www.msnbc.msn.com/id/14574671/

>>
After testing 13,000 samples, they've only found less virulent virus

The Associated Press
Aug 29, 2006

BARROW, Alaska - Hundreds of miles above the Arctic Circle, biologists working in the frosty marshes of Alaska's North Slope are keeping a lookout for migratory birds that might bring a deadly avian flu strain to the United States.

Interior Secretary Dirk Kempthorne, visiting a bird nesting site outside Barrow, reported Tuesday that 13,000 bird samples have been tested. While some less virulent forms of the flu were found, there has been no sign of the deadly H5N1 strain, linked to the death of at least 141 people, mostly in Asia.

"I think it's going very well," Kempthorne told The Associated Press after he helped a volunteer biologist gather a test sample from a young Dunin shorebird at a site on Beauford Sea, near the northernmost point in the United States.

The fowl offspring's parents likely flew here from Japan or Korea, Audrey Taylor, the volunteer, told Kempthorne.

Deborah Rocque, the bird flu testing coordinator for the U.S. Fish and Wildlife Service in Alaska, said the program is concentrating on testing on the North Slope and the Yukon Delta. Both are areas where tens of thousands of migratory birds nest in the summer after arriving from Asia.

"Some go straight back to Asia and some go right down the Pacific Flyway," Rocque said.

Kempthorne, making his first visit to Alaska's North Slope, was to take a helicopter tour later Tuesday over Lake Teshekpuk, an environmentally sensitive region where the department is putting oil leases up for sale despite protests from conservationists.

He said he has no plans to postpone the lease sale, scheduled for late September and that he believes the restrictions on drilling will protect wildlife, including caribou and nesting birds.

"It is a national petroleum reserve. That's what the reserve is," Kempthorne said of the vast area west of the Prudhoe Bay oil fields. The area was set aside in 1923 for its energy resource, but there has been no production to date.

Amid the lagoons and wetlands that dot the miles of Alaska tundra, hundreds of thousands of wild birds - geese, swans, mallards and loons - have been nesting on the North Slope, preparing for their annual flight south in the coming weeks.

Biologists wonder whether some of the globe-trotting fowl might carry the deadly bird flu virus that was discovered nearly a decade ago in Asia and since has hopped continents, surfacing in Africa, Europe and the Middle East. More than 180 people have been infected, and at least 141 have died from the virus, and 200 million birds, mostly poultry, have been destroyed to contain the disease.

The Fish and Wildlife Service and the Agriculture Department have been testing bird samples since April, concentrating on Alaska where the first sign of the highly pathogenic form of the bird flu virus might surface.

Interior officials said Tuesday that of the 13,000 samples taken so far, 113 birds tested positive "to some form of influenza" that poses no threat to humans. But no evidence of the more potent H5N1 strain has been found. Biologists expected coming across low-level flu samples since there are 144 subtypes of bird flu, most of which are not harmful to humans.

The Alaska studies have targeted 26 species because their migratory patterns are most likely to meet the H5N1 strain before arriving in Alaska.

Wherever the disease has spread to humans, it has been through people's direct contact with the birds, mostly in Asia involving poultry. While no transfer of the bird flu among humans has been documented, scientists fear it eventually could mutate and spread from person to person, causing a flu pandemic.

The $29 million bird flu monitoring program hopes to test between 50,000 and 75,000 birds, said Dale Hall, head of the Fish and Wildlife Service. Earlier this month, the government announced that testing would be expanded to cover the entire nation.

Biologists test tissue samples or feces of both live birds, who are tagged and then released, and of dead birds brought in by hunters.

The test samples are sent to a laboratory in Madison, Wis., and those showing an h5 strain are sent to the Agriculture Department lab in Ames, Iowa, to determine if it might have the highly dangerous form. Nine samples containing the H5 strain have been sent to Ames, but none was found to have the H5N1 virus, Rocque said.
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[DewDiligence]

New Test Speeds Diagnosis of Lethal Avian Flu Strain

http://www.nytimes.com/2006/08/29/health/29flu.html

>>
August 29, 2006
By DONALD G. McNEIL Jr.

In an advance that speeds up diagnosis of the most dangerous avian flu, scientists have developed a detailed influenza test that takes less than 12 hours, federal health officials said yesterday.

The new technology, a microchip covered with bits of genetic material from many different flu strains, cuts the typical time needed for diagnosis of the A(H5N1) flu to less than a day from a week or more. In addition, rather than giving just a yes-or-no result, it usually reveals which flu a human or an animal has.

That means that public health officials investigating, for example, a flu outbreak in poultry or in humans in a remote Asian or African village will be able to decide quickly whether to kill thousands of birds or to treat hundreds of potentially exposed people with expensive antiviral drugs.

Right now, ascertaining whether a flu is of the lethal A(H5N1) strain requires that a sample be frozen and shipped to a highly secure laboratory, usually in a major city like Atlanta or Hong Kong, where the virus can be grown in eggs, isolated and genetically sequenced. That process takes four to five days plus shipping time and runs the risk of samples defrosting in transit and being ruined.

The new test, called FluChip, can be performed in any laboratory that can amplify bits of genetic material; many countries have such laboratories in their national capitals, if not in provincial hospitals. Samples need not be frozen, and because only bits of genetic material are multiplied rather than whole viruses, the work can be done in laboratories with lower biosecurity levels.

Nancy J. Cox, chief of the influenza branch of the Centers for Disease Control and Prevention in Atlanta, said the chip “really allows us to get a lot of information about a virus in a short time.”

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which announced the creation of the test, called it an “encouraging advance” that could be “invaluable to international flu surveillance efforts.”

Dr. William B. Karesh, chief field veterinarian for the Wildlife Conservation Society, who led a 2005 expedition to Mongolia to track the lethal avian flu virus as it first moved out of Asia in migrating wild birds, said the new test “sounds fabulous.”

“It could be an incredibly powerful tool,” Dr. Karesh said.

A more advanced version to be used in the field may be ready within two years, said Kathy L. Rowlen, a University of Colorado chemistry professor who led the team that developed the test.

At present, animal and human health experts trying to fight avian flu in remote areas are forced to make important decisions based largely on guesses because it is too risky to wait a week for a laboratory to confirm that a highly dangerous virus is loose.

A dipstick test done on the spot, which a veterinarian working in Indonesia said was as quick and as simple as a home pregnancy test, can tell only if a flu is type A.

Getting more information requires polymerase chain reaction amplification, which Dr. Rowlen described as “separating the genetic material of the virus itself from all the other things you find in a nasal swab, and then making a million copies of it, like using a photocopier.”

That requires a machine costing about $20,000, which can be found in most countries’ national laboratories and in some provincial hospitals, Dr. Karesh said. One he saw in Mongolia was “a kitchen-tabletop-type thing,” he said.

Currently, such machines and follow-up tests can tell in about four hours whether a flu is an H5 strain.

The FluChip, sometimes called a microarray, or gene chip, greatly enhances that technology. It is coated with 55 short stretches of RNA selected from 5,000 samples of human, bird, pig and horse flus provided by the C.D.C., and including H5N1 and routine human flus of the H3N2 and H1N1 strains. The broken-up DNA in the amplified sample is, in effect, poured across the chip, and fragments stick to the matching bits of RNA. By noting the matches, scientists can deduce which flu it is.

In recent tests, the technology correctly identified 72 percent of samples and partly identified an additional 13 percent, according to the disease centers.

Moreover, as the flu mutates, Dr. Cox said, stretches of RNA from newly emerging strains could be added.

Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, called the chip “good news, because it clearly moved ahead the diagnostic tools we have.” It also has the potential to speed up mass testing because dozens of samples can be tested on dozens of chips at once.

But if a flu pandemic were to erupt, Dr. Osterholm warned, the test could quickly be rendered useless because most of the chemicals needed for the preliminary DNA-amplification steps come from abroad, and the chaos that a pandemic would cause would interrupt supplies.

“You can have all the guns you want,” he said, “but if the bullets are offshore, you can’t shoot very much.”
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[DewDiligence]

See #msg-12722832 for more on the same story.

[Biowatch]

Avian Influenza: A Hole In One

Cavity in N1 enzyme of H5N1 flu virus could be exploited for new flu drugs

http://pubs.acs.org/cen/news/84/i34/8434notw6.html

[Biowatch]

Celera Genomics Receives NIH Grant to Develop and Commercialize Avian Flu Diagnostic Test
Monday August 21, 7:00 am ET

ROCKVILLE, Md.--(BUSINESS WIRE)--Aug. 21, 2006--Celera Genomics (NYSE:CRA - News), an Applera Corporation business, today announced that the National Institutes of Health (NIH) has awarded Celera approximately $900,000 to develop and commercialize an in vitro diagnostic (IVD) test for the highly pathogenic influenza A/H5 virus (Asian lineage, H5N1). The test Celera plans to develop will be based on the Primer and Probe Set and protocols used in the test from the U.S. Health and Human Services' Centers for Disease Control and Prevention (CDC) recently cleared by the U.S. Food and Drug Administration (FDA). The CDC assay is the only FDA-cleared assay for detection of the H5N1 virus, and its use is limited to the laboratories designated by the Laboratory Response Network. Celera's access to the H5N1 assay information will be through a license to be obtained by Celera from the CDC. The test is expected to be sold through Celera's alliance with Abbott.

"Early detection of avian influenza H5N1 in humans could allow for intervention with antiviral therapeutic drugs and institution of vaccination or quarantine strategies to prevent or delay spread of the infection," said Tom White, Ph.D., Chief Scientific Officer at Celera. "An accurate, standardized, and robust test would enable testing in more locations, and most importantly, enable investigators to make meaningful comparisons between laboratories quickly and reliably across the globe. The assay format that we're developing is expected to be suitable for widespread testing should a pandemic occur."

The grant will partially support a multi-phased, three year project. Performance testing and validation will be done in collaboration with the CDC, which has accumulated a large collection of influenza strains and clinical respiratory specimens as a World Health Organization (WHO) Collaborating Center for Surveillance, Epidemiology and Control of Influenza, as well as with other interested laboratories.

"We have a track record of developing and commercializing molecular diagnostic tests for human viral pathogens based on real-time PCR technology, which specifically and rapidly detects and quantifies low levels of pathogens," said Michael Zoccoli, Ph.D., Vice President of Development at Celera. "The information from the CDC's FDA-cleared test and their vast influenza strain and specimen collection, combined with Celera's diagnostic product development and manufacturing expertise, should drive rapid progress on a test that could be broadly used in the event of a pandemic."

The avian influenza test to be developed by Celera is expected to run on Abbott's new m2000(TM) instrument system for detecting and monitoring infectious diseases, using automated real-time PCR technology from Applied Biosystems. The m2000 is currently available in Europe with CE Mark certification and is pending 510(k) clearance with the FDA in the United States.



http://biz.yahoo.com/bw/060821/20060821005155.html?.v=1

[DewDiligence]

Scientists Hail Breakthrough in Bird-Flu Drug Quest

http://news.yahoo.com/s/nm/20060816/hl_nm/birdflu_dc_1

>>
By Jeremy Lovel
Aug 16, 2006

Scientists said on Wednesday they had made a breakthrough in the race to develop a drug for the H5N1 bird flu virus if it mutates into a form that can jump from human to human. But they warned that it could take five years or longer to convert their discovery of a potential weak point in the N1 part of the virus into an effective drug.

…a team of scientists lead by John Skehel of London's National Institute of Medical Research say they have found a cavity in the N1 or neuraminidase part of the H5N1 virus that could be exploited as a potential weak point.

"The hope is that any new information like this which shows something specific for the N1 neuraminidase will be able to be used to develop a drug against the H5N1 virus," he told Reuters.

The team presented their detailed findings in the science journal Nature, concluding: "Our analysis suggests that it might be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs."

Any new drug is still years away, Skehel said. "This is not just round the corner. It could easily be more than five years to develop a new drug," he said.

Some countries have begun stockpiling Tamiflu and Relenza, but because the H5N1 virus mutates regularly it is not known how effective they would be against an H5N1 human pandemic. "The Achilles heel of the neuraminidases has already been identified in the development of Tamiflu and Relenza. They are good drugs and they work," Skehel said.

"What this potentially will do is make the use of those drugs better by preventing the development of resistance."

The idea is that an array of drugs -- some specific to H5N1 and some like Tamiflu and Relenza to other N variants but effective against N1 -- would not stop the virus mutating but would stop it developing drug resistance, he said.

"It is a race. You have got to try to keep ahead of variation -- and in the case of H5N1 particularly the emergence of transmission from human to human," Skehel said.

"The hope would be that you would develop drugs which did not respond to the mutations that might come up and make neurominidases resistant to Tamiflu and Relenza," he added.
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[DewDiligence]

Avian-Flu Study Reveals Hurdles for a Pandemic:

#msg-12386725

[mskatiescarletohara]

Novavax Succeeds in Making Vaccine to Protect Against New Mutation of Avian Influenza

Monday July 31, 9:38 am ET
Novavax to begin pre-clinical testing immediately

MALVERN, Pa., July 31 /PRNewswire-FirstCall/ -- Novavax Inc. (Nasdaq: NVAX - News) -- Novavax Inc. said today its scientists have succeeded in making a vaccine candidate designed to protect against the H5N1 clade 2 influenza virus. Pre-clinical testing of the vaccine has already started.


"We believe this is the first vaccine to be made that targets the H5N1 clade 2 virus isolated from people in Indonesia who have been infected with this mutated version of avian influenza," said Novavax President and Chief Executive Officer Rahul Singhvi. "This is a very significant milestone for Novavax and our proprietary virus-like particle (VLP) vaccine technology. This demonstrates how rapidly we can respond by making a vaccine to protect against emerging pathogens worldwide, compared to older egg-based manufacturing methods."

The H5N1 avian influenza virus is rapidly evolving into antigenically distinct clades, or families. H5N1 clade 1 flu viruses were identified in Vietnam in 2003; by last winter, a second clade was identified in Indonesia. Department of Health and Human Services Secretary Michael O. Leavitt has said that the emergence of clade 2, which is the strain that is spreading throughout Asia and parts of Europe, "dictates that we begin developing a second pre-pandemic vaccine."

Leavitt and other global public health experts maintain that due to H5N1's rapidly mutating nature, multiple vaccines will be needed to protect against the many variations of the virus. The H5N1 vaccines currently in clinical trials by many manufacturers and being stockpiled around the world target only the clade 1 family of the virus.

"It is critical that we have vaccines that can protect against the multiple variations of the virus and, most importantly, against the strains of bird flu that are currently infecting and killing people," said Dr. Rick Bright, Novavax's Vice President of Vaccine Development. "Our vaccine technology allows us to create a vaccine directed at mutated viruses very rapidly so that we can protect people from the newest circulating strains of bird flu. We have also demonstrated in pre-clinical models that we are able to generate protective levels of antibodies against influenza using a single dose of VLP vaccine without the requirement of adding an adjuvant."

Novavax's new vaccine candidate uses the company's VLP technology, which allows scientists to create a particle that is nearly identical to the virus but does not have the virus's genetic material required for replication or infection. When inoculated into the body, these particles have the ability to attach to cells and trigger a natural immune response -- sometimes from a single dose -- that is capable of protecting against viral infection.

"We are eager to see if this vaccine is as effective in pre-clinical models as we expect it to be," Dr. Bright said. Novavax has already seen successful results from pre-clinical studies of its other pandemic and seasonal influenza vaccines.

Pre-clinical testing of the H5N1 clade 2 vaccine has already been initiated and is likely to take several months. "Once we collect and analyze results of our pre-clinical tests, we will then be in a position to take this timely vaccine into human clinical trials," Dr. Bright said.

[DewDiligence]

GSK Reports Significant Advance in H5N1 Pandemic Flu Vaccine Program

http://biz.yahoo.com/prnews/060726/phw012a.html?.v=5

>>
Wednesday July 26, 2:55 am ET

PHILADELPHIA, July 26 /PRNewswire-FirstCall/ -- GlaxoSmithKline plc (NYSE: GSK ) today announced headline data showing that its H5N1 pandemic flu vaccine achieved a high immune response at a low dose of antigen. The vaccine, which uses a proprietary adjuvant, enabled over 80% of subjects who received 3.8 micrograms of antigen to demonstrate a strong seroprotective immune response. This level of seroprotection meets or exceeds target criteria set by regulatory agencies for registration of influenza vaccines. Efficacy results at these levels of antigen dosage have also not been reported for any other H5N1 vaccine in development to date, including those using other adjuvants such as alum.

Commenting on the data, JP Garnier, GlaxoSmithKline's Chief Executive Officer, said: "These excellent clinical trial results represent a significant breakthrough in the development of our pandemic flu vaccine. This is the first time such a low dose of H5N1 antigen has been able to stimulate this level of strong immune response.

"There is still a lot more work to be done with this program, but this validation of our approach provides us with the confidence to continue developing the vaccine, including assessment of its ability to offer cross-protection to variants of the H5N1 strain. All being well, we expect to make regulatory filings for the vaccine in the coming months."

The results were based on an interim analysis of a clinical trial conducted in Belgium which involved 400 healthy adults aged 18-60 years of age. The vaccine tested was produced from inactivated H5N1 virus and contained a novel, proprietary adjuvant. An adjuvant is an ingredient which stimulates the immune system and increases response to the vaccine. Trial participants were vaccinated twice during the course of the trial and four different levels of antigen dose were tested, with 3.8 micrograms being the lowest dose assessed.

In this study, immune response was defined as the increase in the number of antibodies an individual produced in response to the vaccine. Levels of antibody protection were established through measurement of hemagglutination inhibition (HI), hemagglutination being the clumping together of red blood cells, which cannot occur when antibodies are present. HI is a standard efficacy measure used in the evaluation of influenza vaccines, and an individual with an HI titer of greater than 40 is considered to be protected, or to have "seroprotection." In this clinical trial, over 80% of subjects, who received 3.8 micrograms of antigen with adjuvant, demonstrated a seroprotective immune response. GSK's adjuvanted investigational pandemic vaccine has not received marketing approval from any regulatory agency.
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[DewDiligence]

EMEA backs first avian flu vaccines for birds

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20060721:MTFH07353_2...

>>
LONDON, July 21 (Reuters) - European regulators have given a green light to the first two avian influenza vaccines for use in birds, the European Medicines Agency said on Friday.

The decision means vaccines will be available to control avian flu in chickens and ducks in the high-risk autumn and winter 2006 period.

Both vaccines -- from Intervet, a unit of Akzo Nobel <AKZO.AS>, and Fort Dodge Animal Health, part of Wyeth < WYE > -- reduce mortality and virus excretion in vaccinated birds exposed to infection.

The agency's expert veterinary committee said they should only be used in disease control campaigns carried out by government-appointed authorities, adding that their use would be reviewed annually.

"Authorisation of these products provides assurance to national authorities of the quality of the vaccines should vaccination be used as a measure to control avian influenza in birds," the agency said in a statement.

The decision on whether or not to use the vaccines will be made by national governments in consultation with the European Commission.

The virus strains present in the vaccines are H5N2 and H5N3, respectively, which the agency said had been selected to protect birds against exposure to virulent H5N1 field strains.

Effective control of avian flu in birds is considered important not only for animal health but also to reduce the risk of a human pandemic flu strain sparked by the virus.

The H5N1 avian flu virus has spread among birds across Asia, Europe and Africa. So far, it is relatively hard for people to catch, but it has killed more than 130 around the world who have come into close contact with infected birds. Scientists, however, fear H5N1 will mutate into a strain that spreads easily between humans, sparking a pandemic in which millions of people could die.
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[DewDiligence]

Baxter Initiates Clinical Study With Cell-Based Candidate H5N1 Pandemic Vaccine

http://biz.yahoo.com/prnews/060705/cgw050.html?.v=57

>>
Wednesday July 5, 4:47 pm ET

DEERFIELD, Ill., July 5 /PRNewswire-FirstCall/ -- Baxter International Inc. (NYSE: BAX ) today announced that it has initiated a Phase I/II clinical trial to test the company's vero-cell based candidate H5N1 pandemic influenza vaccine. The study is being conducted with several hundred healthy adults in Austria and Singapore using the fully inactivated wild-type H5N1 strain A/Vietnam/1203/2004. Four different antigen concentrations ranging from 3.75mcg to 30mcg are being tested in formulations with and without alum as adjuvant.

"We look forward to receiving clinical results this fall on the safety and immunogenicity of the candidate vaccine for pandemic flu," said Noel Barrett, vice president of Global R&D for Baxter's vaccines business. "Our goal is to produce a safe and efficacious pandemic vaccine and demonstrate the advantages that vero-cell based production can offer for manufacturing influenza and other vaccines. The study will provide us with critical data concerning the vaccine dosage required to induce protective immune responses, and information about the ability of a vaccine, based on a single H5N1 strain, to induce protective immune response against a range of different H5N1 strains. Preclinical studies in animal models have shown very good cross-protection to date, and we are looking forward to confirming this with studies in humans."

Baxter is developing both seasonal (or inter-pandemic) and pandemic influenza vaccines based on the company's proprietary vero-cell technology, which has the potential to significantly reduce production time compared to traditional vaccine production methods that use embryonated hens' eggs. The company is already licensed to produce vaccines at its commercial scale cell- culture vaccine manufacturing facility in Bohumil, Czech Republic, which is GMP approved and fully validated to Biosafety Level Three (BSL-3).

Cell-based systems for production of vaccines offer a number of potential benefits over more traditional egg-based systems. Baxter's vero-cell technology is capable of producing high yields of influenza virus without the addition of any animal-derived serum. Through the company's research and development work, Baxter has been successful in growing wild-type virus at pilot and commercial scales using its unique vero-cell technology. This means the company is currently capable of manufacturing pandemic vaccine without having to wait for high-growth or attenuated virus reassortants normally used when vaccine is produced in eggs. The requirements for such reassortants may involve considerable delay in vaccine production in the event of a pandemic.

In addition, Baxter is working with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), in partnership with Fisher BioServices Inc., and with the U.S. Department of Health and Human Services in partnership with DVC LLC, a Computer Sciences Corporation Company, to develop vero-cell based H5N1 pandemic and seasonal influenza candidate vaccines. Both collaborations are the result of U.S. Government contract awards. Baxter and its partners will be providing the vero-cell based candidate vaccines to the agencies for further clinical testing in the United States, which is expected to begin later in 2006 and 2007. Baxter is currently in discussions with several other governments regarding its candidate pandemic vaccine, and has been awarded a contract to supply two million doses of cell-culture based candidate H5N1 vaccine to the U.K. government.
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[DewDiligence]

Avian Flu Tends to Kill Youths as in 1918 Wave

[The “cytokine storm” explanation gains ground.]

http://www.nytimes.com/2006/07/02/world/02flu.html

>>
July 2, 2006
By DONALD G. McNEIL Jr.

Avian flu tends to kill younger people, much as the 1918 Spanish flu epidemic did, the World Health Organization said Friday as it released an analysis of more than 200 cases.

Deaths from the disease surged in the winter for the last three years, the report said, so a rise in fatal cases can be expected late this year even if the virus does not mutate into a form more easily transmitted.

Moreover, the report warned, the risk of the virus becoming more transmissible remains high "because of the widespread distribution of the H5N1 virus in poultry and the continued exposure of humans."

The median age of victims with confirmed cases was 20 years, the report said. The highest death rate — 73 percent — was among patients ages 10 to 19, while the overall fatality rate was 56 percent. This pattern has been noted before, but the new analysis takes in more cases; the typical age is drifting downward.

A high death rate among young adults echoes the pattern found in the 1918-1919 epidemic, said Dr. Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. Scientists contend that year's H1N1 virus was also an avian flu that mutated until it spread easily among humans; although it was fatal to only about 2 percent of those who caught it, that was enough to kill between 40 million and 100 million people worldwide.

When the second wave of the Spanish flu struck Boston in the fall of 1918, Dr. Osterholm said, the flu death rate among people ages 18 to 30, which had been about 30 per 100,000 people in previous years, soared to 5,700 per 100,000. (The figure was for civilians in Boston, he said, so it was not confounded by the high numbers of deaths in troop ships or trenches in Europe.)

The annual flu, by contrast, tends to kill the very young and the very old, often from secondary bacterial pneumonia.

In the Asian and Middle Eastern countries where the disease is most pervasive, people of all ages are exposed to chickens, but 90 percent of the cases have been in people under 40, so something in young adults must make them more susceptible.

Unpublished W.H.O. data from blood sampling around recent outbreaks, Dr. Osterholm noted, shows that few people carry antibodies to the virus, so there is not a huge pool of survivors of mild avian flu.

Evidence suggests that many young people in 1918 and quite a few in this outbreak are killed by a "cytokine storm" — the body's own immune reaction, which floods the lungs with fluid. Young adults generally have strong immune systems.

The W.H.O. is tracking changes in the virus, trying to predict if it will mutate into a more infectious form and hoping to build vaccines against it in time to head off a pandemic.

Fatalities from the virus have almost tripled this year compared with last year. Indonesia, with 39 deaths, is close to surpassing Vietnam as the hardest-hit country with 42. Vietnam has not had a human death or poultry outbreak this year.

The typical avian flu victim is sick enough to be hospitalized four days after falling ill, and dies five days later, the report said. People over 50 have the lowest death rate, but it is still 18 percent, which is a huge impact compared with seasonal flu.

"The more we see what H5N1 is doing, the less we know about what's really happening with it," Dr. Osterholm said.
<<

[DewDiligence]

U.S. to Subsidize State Purchases of Tamiflu

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20060630:MTFH24808_2...

>>
NEW YORK, June 30 (Reuters) – The U.S. government said on Friday it will spend about $149 million under a two-year contract with Swiss drugmaker Roche Holding AG to provide federally subsidized Tamiflu tablets to all 50 states, so they can begin stockpiling the drug as a potential treatment for any pandemic influenza outbreak.

"Our ultimate goal is to stockpile sufficient quantities of antiviral drugs to treat 25 percent of the U.S. population," U.S. Secretary of Health and Human Services Mike Leavitt said in a release.

Under the contract, 59 jurisdictions will be able to buy Tamiflu at a federally negotiated price from Roche and receive a 25 percent federal subsidy for a prescribed number of treatment courses, the release said.
<<

[Biowatch]

Strange twist on bird flu publication

[Did someone hack their e-mail address?]

>>China Scientists
Back Publication
Of Bird-Flu Letter

By ROBERT TOMSHO
June 26, 2006

BOSTON -- The New England Journal of Medicine said a Chinese co-author of a letter about avian flu has said his research group didn't seek to withdraw the letter before it was published in the medical journal's current edition.

The letter by eight Chinese scientists described a study of a Chinese man originally thought to have died of severe acute respiratory syndrome in late 2003. The study found the man had died from bird flu instead. The Chinese government didn't acknowledge having its first case of bird flu until 2005.

On Wednesday the journal said the researchers had sent it emails asking that their letter not be published. Although the related edition had already been printed, journal editors tried to contact the researchers for an explanation.

Friday, the journal said it had been contacted by telephone by Wu-Chun Cao, one of the letter's co-authors. Karen Pedersen, a journal spokeswoman, said Dr. Cao told a journal editor he hadn't sent the emails and that his group stood by the letter. Dr. Cao, a researcher at the State Key Laboratory of Pathogens and Biosecurity in Beijing, also faxed the journal a signed affidavit attesting to that fact, Ms. Pedersen said.

Dr. Cao didn't respond to an email seeking comment.

Some international health officials suspect the death toll from bird flu in China could be higher than reported and the Chinese government has been sensitive to criticism that it isn't fully cooperating with the global fight against the disease.

Write to Robert Tomsho at [e-mail]
URL for this article:
http://online.wsj.com/article/SB115127200908490118.html
<<

[DewDiligence]

Research Raises Questions About China's Bird-Flu Approach

http://online.wsj.com/article/SB115100160949387761.html

>>
Letter Suggests First Case
Of Human Infection Came
Two Years Earlier Than Said

By NICHOLAS ZAMISKA
June 23, 2006

HONG KONG -- Research suggesting China had its first human case of virulent bird flu two years earlier than it has said raises questions about the spread of the disease and the accuracy -- and possibly openness -- of the Chinese government in dealing with it.

A letter published by eight Chinese scientists in Thursday's New England Journal of Medicine reports on a study of a 24-year-old Chinese man originally believed to have died of severe acute respiratory syndrome in late 2003. The study found that the man hadn't died of SARS, which had been spreading in the region earlier that year, but of a particularly deadly strain of bird flu.

Adding more mystery to the matter, one of the scientists, Cao Wuchun of the State Key Laboratory of Pathogens and Biosecurity in Beijing, sent a stream of emails to the journal just before publication seeking to withdraw the letter, according to Karen Pedersen, a spokeswoman for the publication.

"We returned [the emails] with a message from the editors telling them that it was too late to withdraw since the issue had already been printed," Ms. Pedersen says. "We asked them for an explanation, and we asked them if they would like to retract the letter. We have not yet received a response."

China has said it discovered its first human case of bird flu late last year. If the scientists who submitted the letter are right, it could change health authorities' understanding of the path that bird flu has taken since it re-emerged in late 2003, and of the number of human cases China has seen. International health officials have long suspected that the actual death toll from bird flu in China might be higher than stated.

Some have voiced suspicions that the government might be covering up cases, while others point to the immense challenge of tracking the disease in such a large country with limited resources. With bird flu resurfacing in the region just after SARS had petered out, confusion between the two wouldn't have been extraordinary.

The Chinese government is extremely sensitive to perceptions that it isn't fully cooperating with global health authorities in the fight against bird flu, which since its re-emergence has infected more than 200 people, killing more than half of them. Scientists fear that if the virus -- which passes occasionally from birds to people and, still more rarely, from person to person -- mutates to one that can be spread rapidly among humans, a pandemic could ensue, possibly taking millions or tens of millions of lives.

In working to ward off such an event, groups such as the World Health Organization have pressed Beijing to share data on the disease's incidence within China's borders. Many have praised the government for showing far greater cooperation than it did in the fight against SARS, when it concealed the outbreak of that disease, which caused a world-wide scare before it ebbed after taking about 800 lives.

The Chinese Ministry of Health said it was caught off guard by the scientists' letter. "We just found out this morning," an official with the ministry in Beijing said Thursday afternoon, adding that his office was first alerted to the case when reporters from Hong Kong began calling with questions, which then prompted officials at the ministry to begin an investigation.

The World Heath Organization sent a letter Thursday to the ministry requesting more information about the previously unreported case, according to Roy Wadia, a spokesman for the health agency in Beijing. He said the ministry has told the WHO that it is investigating the matter and will reply.

It isn't clear why Dr. Cao might have attempted to take back the letter at the eleventh hour. The letter made no mention of this being China's first human bird-flu case, focusing instead on a detailed discussion of the virus's genetic makeup.

Qin E'de, a researcher at the State Key Laboratory in Beijing and one of the eight authors of the letter, declined to comment when reached by telephone at his office. Zhu Qingyu and Dr. Cao, of the same laboratory, as well as Yu Jun at the Beijing Genomics Institute, weren't at the office Thursday, according to colleagues. The four other researchers who signed the letter also were unavailable for comment.

The journal sent an email to reporters on Wednesday, signed by editor-in-chief Jeffrey M. Drazen, informing them that it had received the request to withdraw the letter from publication. "We do not yet have an explanation from the authors," Dr. Drazen wrote.
<<

[DewDiligence]

Human-to-Human Infection by Bird Flu Virus Is Confirmed

http://www.nytimes.com/2006/06/24/health/24flu.html

>>
June 24, 2006
By ELISABETH ROSENTHAL

ROME, June 23 — An Indonesian who died after catching the A(H5N1) bird flu virus from his 10-year-old son represents the first confirmed case of human-to-human transmission of the disease, a World Health Organization investigation of an unusual family cluster has concluded, the agency said Friday.

The W.H.O. investigators also discovered that the virus had mutated slightly when the son had the disease, although not in any way that would allow the virus to pass more readily among people.

"Yes, it is slightly altered, but in a way that viruses commonly mutate," said Dick Thompson, a spokesman for the agency in Geneva. "But that didn't make it more transmissible or cause more severe disease."

The greater importance of the slightly modified virus is that it allowed researchers from the W.H.O. and the Centers for Disease Control and Prevention in the United States to document that the virus almost certainly was passed from person to person. In previous cases where human-to-human transmission was suspected, researchers could not test samples from the patients, or the virus in the patients was the same as that in poultry in the area.

The genetics work vindicates some Internet flu watchers who had disputed statements by a W.H.O. official and the Indonesian Health Ministry soon after the cluster was reported, saying it was possible the whole family had been infected by a barbecued pig, poultry or chicken manure.

The independent flu watchers, relying on local Indonesian news media, had argued that the pattern of dates on which different family members fell ill suggested that the virus had jumped from human to human to human.

Scientists have long said the A(H5N1) virus, which has killed or led to the culling of hundreds of millions of birds worldwide, does not spread easily to humans or among them. But they have worried that it might mutate to acquire that ability, setting off a devastating pandemic. More than 200 people have contracted bird flu worldwide, almost all of them after very close contact with infected birds.

International health officials have been in Indonesia for much of the past month, investigating a family outbreak that affected seven relatives in Kubu Sembilang, a remote village in the mountainous Karo district of Sumatra. Six of the seven died, and one is still hospitalized.

Although Indonesia has been struggling all year to control bird flu outbreaks among poultry, the family on Sumatra had no known direct contact with sick birds, although the first to die was a woman who sold vegetables in a market that also sold birds.

But scientists have long suspected that A(H5N1), though an avian virus, could also spread between people in rare cases, if there was prolonged close contact.

The family members in the cluster had a banquet in late April when the vegetable merchant was already ill and coughing heavily. Some spent the night in the same room with her, and some nursed sick relatives.

The first five family members to fall ill had identical strains of A(H5N1), one found in animals in Indonesia. But that virus had mutated slightly in the sixth victim, a child, and he apparently passed the mutated virus to his father, who cared for him in a hospital without proper protection, said Dr. Tim Uyeki, an American epidemiologist on the W.H.O. team.

Still, Mr. Thompson said there was no evidence that the mutated virus was better adapted to human infection. To the contrary, the agency has been following 54 relatives and neighbors for a month and none have caught it.

"So we know it is not more easily transmitted," he said.
<<

[DewDiligence]

Statin Drugs Might Provide Bird Flu Weapon

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20060621:MTFH22966_2...

>>
By Maggie Fox, Health and Science Correspondent

WASHINGTON, June 21 (Reuters) - The world's top-selling drugs, cholesterol-lowering statins, might provide a way to treat feared bird flu, according to a doctor and retired drug company executive who is trying to get the researchers to study the possibility.

Antivirals that affect the influenza virus are in short supply, and it will be years before vaccine makers can ramp up capacity enough to immunize the world's population against a pandemic flu.

But what if there was a cheap and widely available drug that helped treat the flu's worst symptoms and possibly save lives?

Evidence suggests that statin drugs, designed to lower cholesterol, might help turn a potentially deadly infection into a milder disease, according to Dr. David Fedson, who thinks world health authorities ought to take a harder look at the possibility.

"Generic statins are available in virtually every country," said Fedson, a retired U.S. physician living in France.

"You'll be able to take five days of statins in India for less than a dollar," Fedson, who was also director of medical affairs at Aventis Pasteur (now French drug company Sanofi Aventis < SNY >), said in a telephone interview.

"We have something that conceivably could save tens of thousands of lives. This research is so important that we cannot afford not to take it."

Fedson, an expert on vaccination, cites several recent studies that show that statins reduce inflammation. Designed to lower cholesterol, the drugs work on several biological processes and may reduce the risk of Alzheimer's disease, some cancers, and multiple sclerosis.

In January, researchers in Canada reported that statins act against sepsis, a dangerous blood infection and a 2005 study published in the journal Respiratory Research found the death rate was 64 percent lower in pneumonia patients who had been taking statins.

IMMUNE STORM

Fedson cites yet other studies that suggest strongly that people who are infected with avian influenza have an immune system overreaction known as a cytokine storm.

Their immune system signals chemicals rush to fight off the alien virus, causing an inflammation of the lungs and other organs that may be what kills them.

"It's an idea, just an idea and it needs to be substantiated with both cellular-based and animal-based studies," Fedson said. "We need to do it and we need to do it fast."

He is getting some attention.

Fedson presented his idea last week to the Congress of Infectious Diseases in Lisbon, Portugal, and is to speak to a bird flu conference next week at the Institut Pasteur in Paris. He also has a paper in next month's issue of the journal Clinical Infectious Diseases.

Statins -- which include Pfizer Inc.'s < PFE > $10 billion-a-year Lipitor, Bristol-Myers Squibb Co.'s < BMY > Pravachol and Merck and Co. Inc.'s < MRK > Zocor -- are the world's best-selling drugs, taken by millions to reduce the risk of heart attack.

Experts say a pandemic of some sort of influenza is inevitable. The H5N1 avian influenza sweeping countries in Asia and also affecting Europe and Africa is considered the most likely candidate. So far it has rarely infected people, but has killed 130 out of 228 infected and just a few mutations would turn it into a form that could be passed easily from one person to another.

If this happens in the next few years, the World Health Organization and other experts agree the world is very poorly prepared and that millions could die.

A WHO spokesman said the agency had no immediate comment on Fedson's work, and spokespeople for companies that make statins said they had not looked into the possibility of testing the drugs in influenza patients.
<<

[Biowatch]

Glaxo aims to file bird flu vaccine in October
Thu Jun 22, 2006 6:44 AM ET

GENEVA, June 22 (Reuters) - GlaxoSmithKline Plc <GSK.L> plans to seek European approval in October for a new vaccine to prevent bird flu in humans, the head of its vaccines business said on Thursday.

Europe's biggest drugmaker, which started clinical trials of two experimental vaccines in March, has previously said it expected a protective shot would be ready for manufacture by the end of the year.

"We will apply for regulatory approval of a vaccine in October 2006," Jean Stephenne told reporters at a briefing.

Glaxo hopes to have the clinical data necessary to assess the effectiveness of its vaccines by August and September, he added. It also intends to present the results of its clinical studies to a scientific conference in October.

Several drugmakers are working to develop vaccines against the H5N1 strain of bird flu, but Glaxo believes it may have an advantage because it is using special adjuvants -- additives put into vaccines that boost the immune system.

Scientists believe vaccines from Glaxo and rivals such as Sanofi-Aventis <SASY.PA> might protect people from "drifted" strains of H5N1 -- those that have evolved slightly and do not precisely match the strain of virus used in the vaccine.

That could make them a good option for governments building up stockpiles.

The H5N1 strain of avian influenza has spread rapidly out of eastern Asia in recent months. It almost exclusively infects birds but has killed 130 people since 2003, mostly in Asia.

Experts believe it poses the greatest threat yet of a pandemic, a global epidemic of flu that could kill millions, if it acquires the ability to pass easily from human to human.

No one knows how well human H5N1 vaccines will match a future pandemic strain, but they might prime a person's immune system, reducing sickness and death.

The normal seasonal flu vaccine provides no protection against H5N1.

[DewDiligence]

Akzo Nobel to test mass bird flu vaccine

http://yahoo.reuters.com/news/articlehybrid.aspx?storyID=urn:newsml:reuters.com:20060612:MTFH69556_2...

>>
By Harro ten Wolde

AMSTERDAM, June 12 (Reuters) - A bird flu vaccine prototype that can be sprayed to inoculate large avian populations is ready for testing next year, Dutch chemical group Akzo Nobel NV <AKZO.AS> <AKZOY.O> said on Monday.

The prototype, developed by Akzo's animal health unit Intervet, is effective against avian influenza and another ailment that afflicts birds, Newcastle Disease, the company said. It is designed to make it easier to inoculate large bird populations.

"The prototype combines the efficacy of the present vaccines with a mass application tool and could prove invaluable in helping to quickly protect large numbers of birds, which currently have to be injected individually," Toon Wilderbeek, Akzo's executive in charge of pharmaceuticals, said in a statement.

The H5N1 avian influenza, which has spread out of Asia into Africa and across Europe, has killed or forced the culling of tens of millions of birds. In January, the virus had killed 79 people, all of them in Asia. Now it has infected at least 224 people in 10 countries, and killed 127 of them, according to a recent report by the World Health Organization.

Although analysts welcomed the news, they noted a human vaccine for bird flu would be a more significant development.

"The vaccine will probably generate not more than 50 million euros ($63.11 million) in annual sales," analyst Mark van der Geest at Rabo Securities said of Akzo's plans to test the bird vaccine.
<<

[Biowatch]

Positive Results of DNA-Based Flu Vaccine in Humans

Study in the Journal VACCINE Reports Positive Results of DNA-Based Flu Vaccine in Humans
Wednesday May 31, 2:00 am ET

OXFORD, United Kingdom and FREDERICK, Md.--(BUSINESS WIRE)--May 31, 2006--PowderMed, Ltd. today announced the publication of positive results from a Phase I study evaluating its proprietary prophylactic DNA influenza vaccine in the latest issue (volume 24, issue 21) of the journal VACCINE. Based on these results, PowderMed will start phase II studies using both annual and bird flu strains later this year.

Authored by lead researcher Dr. Hansi Dean, the report in VACCINE documents the safety and immunogenicity of PowderMed's monovalent influenza DNA vaccine delivered with the company's Particle Medicated Epidermal Delivery (PMED) needle-free injection system. The trial examined three doses of a DNA plasmid encoding the H3 haemagglutinin (HA) gene for Panama flu (1, 2 and 4 micrograms) administered as a single dose to 36 healthy adult volunteers. Immune response was assessed according to criteria set by the Committee for Proprietary Medicinal Products (CPMP) for the approval of annual flu vaccines in the European Union. Key findings include:

* At the maximum dose tested (4 micrograms), all subjects achieved a seroprotective level of antibodies demonstrating that this DNA vaccine is a viable candidate for expanded clinical evaluation as a potentially powerful defense against influenza and pandemic flu.

* The maximum dose (4 micrograms) passed the CPMP criteria at 21 days and was well tolerated. All three doses passed the CPMP criteria at 56 days.

"Recent years have seen a number of new influenza vaccine approaches tested in animal model systems and in the clinic. However, this study is the first successful demonstration of immunogenicity of an influenza DNA vaccine in humans," said Dr. Hansi Dean, now with the International AIDS Vaccine Initiative. "The relative immunogenicity of PowderMed's DNA vaccine compared to intramuscular DNA vaccination is likely attributable to the efficiency of intracellular DNA delivery by PMED."

"The publication of this study in the prestigious journal VACCINE adds to the growing body of scientific evidence that PowderMed's DNA vaccine and the PMED platform show promise to address the major healthcare challenge posed by influenza, particularly in the event of an avian flu or other pandemic outbreak," said Dr. Clive Dix, CEO of PowderMed. "DNA vaccines have the potential to significantly limit the burden of disease. The advantage of a DNA-based approach is that the vaccines can be manufactured very rapidly and in large quantities, while yielding an efficacious immune response at low doses."

VACCINE is the pre-eminent journal for those interested in vaccines and vaccination. It serves as an interface between academics, those in research and development, and workers in the field. Relevant topics range from basic research through to applications, safety and legislation.

About PowderMed

PowderMed (http://www.powdermed.com/) is a private immunotherapeutic company based in Oxford, UK. The Company is focused on the clinical development and manufacture of therapeutic and prophylactic DNA-based vaccines for viral diseases and cancer. The company has 4 clinical and 3 pre-clinical stage projects. The lead clinical programme has shown positive Phase I results in the treatment and prevention of human influenza. This technology is uniquely and easily adaptable to treat avian flu and to address the pandemic threat. PowderMed also has a product for the treatment of genital herpes in Phase I trials, and two partnered Phase I programmes in Cancer (Ludwig Institute) and HIV/AIDS (Glaxo SmithKline). PowderMed vaccines are delivered using PMEDTM (Particle mediated epidermal delivery), a needle-free, virtually painless delivery system that requires minimal medical training, allows self-administration and requires no refrigeration for stockpiling. Specifically, PowderMed's technology delivers DNA to the epidermal layer of the skin where it is presented to the cells of the immune network, thereby creating immunity and thus facilitating both treatment and prevention of disease.

The Company has a highly experienced management team that has a combined 160 years of experience, with Rolf Stahel as the chair of the board. The Company has sufficient funds through to the end of 2006 having raised GBP 20 million in venture financing to date, with an additional GBP 5 million available from its existing investor syndicate that comprises Abingworth Management, Advent Venture Partners, Isis College Fund, Oxford Bioscience Partners and SV Life Sciences.

http://biz.yahoo.com/bw/060531/20060530005920.html?.v=1

[mskatiescarletohara]

World reknowned influenza expert Dr. Arnold Monto gave some comments to Reuters today regarding the recent cluster in Indonesia, along with a few other scientists.

http://today.reuters.com/investing/FinanceArticle.aspx?type=bondsNews&storyID=uri:2006-05-24T192...


By Maggie Fox, Health and Science Correspondent

WASHINGTON, May 24 (Reuters) - A suspicious-looking cluster of human bird flu cases in Indonesia illustrates just how difficult it will be to detect the beginning of a pandemic, should one occur, scientists said on Wednesday.

The World Health Organization issued assurances on Tusday that the virus had not changed into a clearly dangerous form, but experts said if it had changed, the information would have come much too late.

In fact, they said, the only way anyone will know that a dangerous form of the virus is circulating will be when people start to become sick and die in large numbers.

"We are not going to know it until a lot of people are infected," said Dr. Eric Toner, an expert in emergency medicine at the Center for Biosecurity at the University of Pittsburgh Medical Center.

And the canaries in the mine will be people trying to cope with the outbreak.

"If it being transmitted efficiently, we would see health care workers being sick," Toner said.

High technology genetic sequencing may give some answers after the fact, but the only way to actually detect a beginning epidemic will be after it has already started, using old-fashioned epidemiology -- the study of a disease's impact on a population.

"We have to, because the genetics of the virus is going to come too late," said Dr. Arnold Monto, an expert in infectious disease epidemiology at the University of Michigan. It takes days or weeks to completely sequence the eight genes of a flu virus.

WHO hopes that countries will be able to quickly identify and isolate human cases of bird flu while investigators check to see how dangerous the strain is.

But the case in Indonesia shows this does not often happen in the real world.

"We are going to be making some crucial decisions based on very incomplete information and speed is of the essence here," said Michael Osterholm, an infectious diseases expert at the University of Minnesota.

And nothing happened speedily in Indonesia. "The first cases were in late April," Osterholm said. WHO issued its first definitive statement on the situation on Tuesday -- nearly a month later.

Had efficient and sustained human transmission been underway, that would be time for many people to have been infected.

The H5N1 avian influenza virus is still almost exclusively a bird virus. It has killed or forced the culling of hundreds of million of birds as it has moved through Asia, across Europe and into many parts of Africa.

It only occasionally infects people -- 218 in 10 countries, killing 124 of them. But only a few genetic changes would allow the virus to easily infect people, and it would likely sweep around the world if this happened, killing millions.

Scientists fully expect the occasional human case of avian flu. But they become more concerned when they see a cluster, like the case of the seven family members in the northern part of Indonesia's Sumatra island.

So far everyone known to have been infected was either in close contact with an infected bird, or in very close contact with an infected person -- and in fact, with a blood relative, which suggests some people may be genetically susceptible to infection.

But in Indonesia it is not yet clear how the first victim in this cluster, a 37-year-old woman, became infected.

Scientists were reassured by the first genetic analysis of virus samples taken from some of the Indonesian patients, although no one is certain of all the genetic changes that would be needed to allow the virus to infect many people.

"We do know some of the things to look for -- we know some of the virulence elements," Monto said.

"But I think the proof in the pudding is watching what happens in the region."

[DewDiligence]

It’s notable that there have evidently not yet been cases of human transmission to non-blood relatives such as spouses: #msg-10992499.

[Rawnoc]

Human-to-human spread suspected in latest Indonesian bird-flu death
19:15:48 EDT May 22, 2006
http://www.cbc.ca/cp/world/060522/w052252.html

HELEN BRANSWELL
(CP) - The World Health Organization appears to be edging closer to suggesting that an Indonesian man who died from H5N1 avian flu Monday may have been infected by his 10-year-old son, not through exposure to sick poultry or some other environmental source.

WHO officials had earlier expressed the theory that a thorough investigation might reveal a potential source of contagion in the community, such as use of contaminated chicken feces as manure. But expert disease investigators seem to be ruling out that possibility, a spokesperson for the WHO said from Geneva.

"There's no supporting evidence to suggest that this is a continuing environmental source that we've uncovered yet in the investigation," said WHO spokesperson Dick Thompson.

"The investigation is still ongoing. We wouldn't discount the possibility that it is human-to-human transmission."

Limited spread of the virus among people is believed to have happened on several previous occasions. But in each of these suspected cases, transmission of the virus petered out. Sustained human-to-human spread of the virus would be needed to trigger a pandemic.

Meanwhile, an Indonesian official revealed that the man who died Monday refused treatment and fled from authorities after falling ill - behaviour that highlights the difficulties of disease containment in settings where an unfamiliar disease is extracting a high death toll.

"This is precisely what we see, time and time again," medical anthropologist Barry Hewlett, a veteran of a number of WHO missions to contain outbreaks of Ebola virus in Africa, said of the panicked reactions Indonesian media have reported.

Reports have suggested fear and distrust have been running high in the affected community, which has watched in horror as multiple members of an extended family fell gravely ill in recent weeks, with most dying.

Dr. Heinz Feldmann of the Public Health Agency of Canada's National Microbiology Laboratory said in his experience fighting outbreaks of diseases like Ebola and Marburg fever, panic and distrust of authorities and medical outsiders is exacerbated when the death toll starts to rise.

"There are these white doctors who come in. Everyone thinks they're getting help, and then they're realizing they're not getting help. And everyone who goes into isolation (in hospital) is basically dying or a lot of them are dying," said Feldmann, a leading expert on hemorraghic fevers who heads the Winnipeg lab's special pathogens division.

"Then the community turns against you."

In cases dating back to late April, three of the man's siblings, two nephews, and two of his children became infected with the H5N1 virus. Only one family member who fell ill, a brother, has recovered from the infection.

The man's older sister, believed to be the first case in this cluster, died without being tested and is not on the WHO's official case count. With this latest case, the number of confirmed H5N1 cases in this family rises to seven, with six deaths.

The man, 32, is said to have nursed his son while the boy was dying, putting him in the path of blasts of virus-laced droplets.

When he himself became ill, he evaded authorities, the director-general of communicable disease control for the Indonesian health ministry told a news conference Monday.

"He ran away after he received Tamiflu," said I. Nyoman Kandun. "He was found in the village later but refused treatment."

Both Hewlett and Feldmann said getting people in such settings to co-operate with public health officials is a significant challenge that requires lots of communication with the community, sensitivity and a willingness to try to figure out what is motivating the behaviour.

Hewlett, a professor at Washington State University in Vancouver, Wash., recalls seeing Ugandans fleeing ambulances during a major Ebola outbreak in that country in 2000.

It turned out that there were rampant rumours that the team wasn't fighting disease, but was kidnapping Ugandans for body parts. The urban myth was fuelled by the fact that family members weren't allowed to visit their loved ones during their illnesses or after their deaths because of the fear of further spread of disease.

"My point is simply that you need to work with local people if you're going to make these things successful. Otherwise there's going to be resistance and the outbreaks will get worse rather than get better," said Hewlett, adding the WHO often now includes medical anthropologists or psychologists on outbreak teams as "social mobilizers" who can bridge the divide between the people affected and medical experts.

Feldmann said he can see another possible source of conflict with the Indonesian villagers - the fact that H5N1 control requires the culling of affected poultry. Demanding people give up animals they need, and which they often don't believe are a source of infection, can create tension, he suggested.

© The Canadian Press, 2006

[DewDiligence]

Avian Flu Wanes in Asian Nations It First Hit Hard

[Perhaps this message board is on its last legs. Let’s hope so.]

http://www.nytimes.com/2006/05/14/world/asia/14flu.html

>>
May 14, 2006
By DONALD G. McNEIL Jr.

Even as it crops up in the far corners of Europe and Africa, the virulent bird flu that raised fears of a human pandemic has been largely snuffed out in the parts of Southeast Asia where it claimed its first and most numerous victims.

Health officials are pleased and excited. "In Thailand and Vietnam, we've had the most fabulous success stories," said Dr. David Nabarro, chief pandemic flu coordinator for the United Nations.

Vietnam, which has had almost half of the human cases of A(H5N1) flu in the world, has not seen a single case in humans or a single outbreak in poultry this year. Thailand, the second-hardest-hit nation until Indonesia recently passed it, has not had a human case in nearly a year or one in poultry in six months.

Encouraging signs have also come from China, though they are harder to interpret.

These are the second positive signals that officials have seen recently in their struggle to prevent avian flu from igniting a human pandemic. Confounding expectations, birds making the spring migration north from Africa have not carried the virus into Europe [#msg-11054768].

Dr. Nabarro and other officials warn that it would be highly premature to declare any sort of victory. The virus has moved rapidly across continents and is still rampaging in Myanmar, Indonesia and other countries nearby. It could still hitchhike back in the illegal trade in chicks, fighting cocks or tropical pets, or in migrating birds.

But this sudden success in the former epicenter of the epidemic is proof that aggressive measures like killing infected chickens, inoculating healthy ones, protecting domestic flocks and educating farmers can work, even in very poor countries.

Dr. Nabarro said he was "cautious in interpreting these shifts in patterns" because too little is known about how the disease spreads.

Other officials agreed.

"To say the disease is 'wiped out' there is probably too strong, too positive," said Dr. Wantanee Kalpravidh, chief of flu surveillance in Southeast Asia for the United Nations Food and Agricultural Organization, which fights animal diseases. The governments of Thailand and Vietnam "believe they got rid of it," she said, "but they also believe that it might be coming back at any time."

Very different tactics led to success in the two countries.

While Vietnam began vaccinating all its 220 million chickens last summer, Thailand did not because it has a large poultry export industry, and other nations would have banned its birds indefinitely. (Vaccines can mask the virus instead of killing it.)

Instead, Thailand culled wide areas around infected flocks, compensated farmers generously and deputized a volunteer in every village to report sick chickens.

It vaccinates fighting cocks, which can be worth thousands of dollars, and even issues them passports with their vaccination records so they can travel, Dr. Nabarro said.

Government inspectors sample birds everywhere; in February, Thailand reported that samples from 57,000 birds had come back negative.

According to Dr. Klaus Stöhr, a flu specialist at the World Health Organization, Thailand and Vietnam also delivered the antiviral drug Tamiflu to even the smallest regional hospitals and told doctors to treat all flu patients even before laboratory diagnoses could be made.

Dr. Nabarro particularly praised the leaders of the two countries for ordering high-level officials — deputy prime ministers — to fight the disease, and for making sure that enough cash to entice farmers to hand over their birds for culling flowed down official channels without being siphoned off.

Hints suggest that the disease is also being beaten back in China, the country where it is assumed to have begun. International officials tend to greet official public health reports from China skeptically, in part because it concealed the outbreak of the SARS virus there for months. It did not officially report any bird cases for years, even though many scientists contend the virus incubated there between its first appearance in humans in Hong Kong in 1997 and the current human outbreak, which began in Vietnam in 2003.

Some top Chinese officials have blamed the reluctance of local officials to report bad news to Beijing. Dr. Nabarro said he recently met a vice premier "who made it clear that they are absolutely determined to get the fullest possible cooperation from provincial authorities."

China's reported human cases have remained low: 8 last year and 10 this year.

Perhaps more important, its poultry cases — which lead to human cases and increase the risk of a mutant pandemic strain — seem to be dropping.

According to the World Health Organization, China said it had outbreaks in 16 provinces in 2004. In 2005, it reported outbreaks in only 12 provinces, but one in November was so large that 2.5 million birds were culled to contain it.

After that, the Agriculture Ministry announced that it would vaccinate every domestic bird in China, which raises and consumes 14 billion chickens, ducks and geese each year. The official news agency reported about the same time that a fake flu vaccine, possibly with live virus in it, might have spread the disease.

Dr. Stöhr, who is in charge of W.H.O. flu vaccine efforts, said he was told by Chinese agriculture officials that the country was now producing 46 billion doses of poultry vaccine a year, and was supplying vaccines to Vietnam.

China's most recent monthly reports describe much smaller outbreaks than were previously common: findings of a few dead wild birds and culls of 126,000 birds in one spot and 16,000 in another, for example.

"We are hopeful that China has turned the corner," Dr. Nabarro said.

In Cambodia and Laos, which separate Thailand and Vietnam, the situation is vague.

Laos has reported no human cases and last reported poultry outbreaks two years ago. Cambodia's reported human cases dropped to two this year, from four last year. No poultry outbreaks were reported, but surveillance is so spotty that some must have occurred and gone unnoticed, Dr. Kalpravidh said, because the country's six human victims were infected by poultry.

Cambodia was slow to compensate farmers for their birds because of problems with corruption in a previous cash-for-guns program.

Health specialists generally agree that there is little clear chance of infected birds landing in the United States.

Where the Southeast Asian governments have taken action, however, the risk of the virus returning is ever present, Dr. Nabarro said.

For example, he said, it probably exists in Vietnam in Muscovy ducks, which can harbor the virus but do not get sick, and it has turned up in isolated birds in open-air markets near the Chinese border. (Single birds do not constitute an outbreak.) Since Chinese farmers can get three times as much for a chicken in Vietnam as they can at home, the temptation to smuggle persists.

"Tomorrow, the whole thing could change again," Dr. Nabarro said. "We need to be on the alert at all times."
<<

[DewDiligence]

Adjuvanted Formulation of sanofi pasteur H5N1 Pandemic Influenza Vaccine Candidate Demonstrates Significant Immune Response

http://biz.yahoo.com/prnews/060510/nyw138.html?.v=50

>>
Wednesday May 10, 7:00 pm ET

LYON, France, May 10 /PRNewswire-FirstCall/ -- A study published online in The Lancet on May 11 demonstrated that multiple dosage formulations of a candidate H5N1 influenza vaccine developed by sanofi pasteur were well- tolerated and generated an immune response, with and without adjuvant. Of the formulations being tested, an alum-adjuvanted 30 microgram dosage generated the most substantive immune response (66.7% HI [haemaggluttination inhibition] seroconversion rate after two vaccinations) and was well-tolerated in the clinical study.

This is the first trial of an H5N1 pre-pandemic influenza vaccine candidate comparing vaccines with and without adjuvants. A study of a similar, unadjuvanted candidate H5N1 vaccine produced by sanofi pasteur in the U.S. that was published in the New England Journal of Medicine in March required two 90 microgram doses to generate a significant immune response in about 50 percent of trial participants. Because the French and U.S. studies were conducted independently, it is not possible to make direct comparisons of the results. The immune response of the adjuvanted 30 microgram formulation was consistent with requirements of the European Agency for the Evaluation of Medicinal Products (EMEA) for licensure of seasonal influenza vaccine. The French study was sponsored by sanofi pasteur using vaccine produced by the company in France.

The data will be submitted as part of the company's core vaccine dossier to the EMEA. The core dossier is being developed in strict accordance with EMEA guidelines. This process is expected to reduce the time necessary for approval of a pandemic vaccine in Europe once a strain is identified and a pandemic is declared.

In subsequent trials, sanofi pasteur will explore different dosages that may be helpful in answering questions about dose-sparing strategies, which are being widely discussed among the public health community. The lower the dosage of a pandemic vaccine, the more doses can be produced and the more people that can be vaccinated should a pandemic occur.

The vaccine for the study was produced at sanofi pasteur's Marcy L'Etoile facility in France. Follow-up studies, currently being planned, will be performed using vaccine produced at the company's Val de Reuil, France facility, where it will be produced on an industrial scale, which will mimic the manufacturing scale that will be used during a declared pandemic.

A similar study with a U.S-produced, adjuvanted H5N1 candidate sanofi pasteur vaccine is currently being conducted by the US National Institutes of Health's National Institute for Allergy and Infectious Diseases (NIAID).

Sanofi pasteur remains committed to global pandemic preparedness and, as part of the company's pandemic program, is also exploring alternative adjuvants that may further enable expansion of capacity.

The Study Design

The study published in The Lancet was multi-center, randomised, open-label and non-controlled with 300 healthy, 18 to 40 year-old participants. Each study volunteer received one of six inactivated split influenza A/Vietnam/1194/2004 (H5N1) influenza vaccine formulations. Enrolled subjects were randomly allocated to one of six groups that received 7.5, 15 or 30 microgram of HA (haemmagglutinin), with or without adjuvant. Each subject received two intramuscular injections of the assigned formulation into the deltoid (each subject received two injections of the same formulation). Vaccines were given 21 days apart. Randomization lists were stratified by center and was created using the block method with decreasing block sizes of 18, 12, and 6 so that a similar number of subjects were enrolled into each group at any given time.

The trial objectives were to describe the safety profile and the immune response 21 days after each vaccination. Subjects attended three trial visits (Day D0, D21 and D42) for vaccination (D0, D21 only), blood sampling and safety data collection. Subjects were kept under observation for 30 minutes after vaccination, and were given safety diaries, digital thermometers and rulers to assess and record adverse events (AEs). For the period D0-D7, diaries included a list of solicited injection site and systemic AEs, including those recommended for the evaluation of interpandemic vaccines by the CHMP.

All formulations induced an immune response, and responses were detectable in some subjects after only one dose. The adjuvanted 30 microgram formulation induced the greatest response. Adjuvant did not improve the response to the lower doses. Two vaccinations of non-adjuvanted 7.5 microgram, adjuvanted 15 microgram or non-adjuvanted 15 microgram seroconverted >40% of subjects (HI test only). HI and neutralizing results followed similar trends.

Sanofi Pasteur and Pandemic Preparedness

Sanofi pasteur, the vaccines business of the sanofi-aventis Group, is committed to global pandemic preparedness. As the world leader in research, development and manufacturing of influenza vaccine, sanofi pasteur is actively involved in other projects in the U.S. and Europe, with the goal of developing a vaccine to protect against a pandemic influenza virus.

Sanofi pasteur is investing in a major expansion of its influenza vaccine production capacity in the US, and also of its vaccine production capacity in France (Val de Reuil facility).

In the U.S., sanofi pasteur has a number of pandemic-related agreements with the U.S. government involving development of pandemic vaccine stockpiles, production of investigational doses and the development of cell culture technology, including:

-- In May 2004, sanofi pasteur contracted with the U.S. National Institutes for Allergy and Infectious Diseases (NIAID) to produce investigational doses. The doses were shipped to the NIAID in March 2005. The studies were completed in 2005 and the results were published in New England Journal of Medicine (March 30, 2006).

-- In September 2004, the company signed a contract with HHS to produce two million doses of bulk vaccine derived from the H5N1 viral strain.

The bulk doses were produced and are being stored and can be formulated and filled upon government request.

-- In November 2004, the HHS awarded a contract to sanofi pasteur to expand and safeguard the egg supply needed to produce influenza vaccine and to formulate each year investigational doses for a potential pandemic influenza vaccine.

-- In April 2005, the HHS awarded a contract to sanofi pasteur to accelerate the development of a cell-culture influenza vaccine in the U.S. and to design a U.S.-based cell-culture vaccine manufacturing facility.

-- In September 2005, the HHS awarded a contract to sanofi pasteur to produce a vaccine to help protect against the H5N1 influenza virus strain. The $150 million contract calls for sanofi pasteur to manufacture the vaccine in bulk concentrate form at its U.S. headquarters in Swiftwater, PA. The agreement provides for additional fees to be paid to sanofi pasteur for storage of the vaccine as well as for formulation and filling of the vaccine upon government request.

-- In February 2006, sanofi pasteur supplied NIAID with 15,000 investigational doses of H5N1 vaccine formulated with and without alum adjuvant for use in NIAID-sponsored clinical studies.

-- In Europe, sanofi pasteur initiated and runs a large range of projects:

-- In France, sanofi pasteur sponsored the first clinical trials of an H5N1 influenza vaccine candidate that compared vaccines with and without adjuvants (the study in the current online issue of The Lancet.)

-- In France, sanofi pasteur was awarded a contract by the French Ministry of Health to produce a 1.4 million dose stockpile of the H5N1 candidate studied in the above-mentioned trial. By this agreement, the company could also provide enough vaccine to protect up to 28 million people in France in the event of a pandemic being declared, once the actual virus strain responsible is identified.

-- Sanofi pasteur is the only vaccine manufacturer to participate in FLUPAN, a European Union (EU) funded collaboration. FLUPAN partners include the NIBSC, the University of Reading (UK), Instituto Superiore di Sanita (Italy), the Health Protection Agency (UK) and the University of Bergen (Norway). FLUPAN is intended to improve the level of pandemic preparedness in the EU. Sanofi pasteur is also producing another strain with pandemic potential (H7N1) to be used in a FLUPAN clinical study.

-- In February 2006, sanofi pasteur provided candidate H5N1 vaccine to the Italian Ministry of Health and entered into an agreement to provide an actual pandemic strain of vaccine, once a pandemic has been declared.

In Australia:

-- A contract has also been signed with the Australian government for the supply of vaccine in the event of a pandemic influenza outbreak.

Influenza Overview

Influenza is a highly contagious virus that is spread easily from person to person, primarily when an infected individual coughs or sneezes. An influenza pandemic is a global epidemic of an especially virulent virus, new for humans, with the potential for severe morbidity and mortality. According to the World Health Organization (WHO), the next pandemic is likely to result in 1 to 2.3 million hospitalizations and 280,000 to 650,000 deaths in industrialized nations alone. Its impact will most likely be even more devastating in developing countries. These reasons have lead many countries to organize national plans against influenza pandemic

About sanofi-aventis

The sanofi-aventis Group is the world's third-largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular disease, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The sanofi-aventis Group is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY - News).
<<
Sanofi pasteur, the vaccines business of the sanofi-aventis Group, sold more than a billion doses of vaccine in 2005, making it possible to protect more than 500 million people across the globe. The company offers the broadest range of vaccines, providing protection against 20 bacterial and viral diseases. For more information, please visit: http://www.sanofipasteur.com
<<

[DewDiligence]

Birds Return to Europe Without Virus

http://www.nytimes.com/2006/05/10/health/10cnd-flu.html

>>
May 10, 2006
By ELISABETH ROSENTHAL
International Herald Tribune

ROME, May 10 — The flocks of migratory birds that winged their way south to Africa last autumn and then back over Europe in recent weeks did not carry the H5N1 flu virus or spread it during their annual journey, scientists have concluded, defying health officials' dire predictions.

International health officials had feared that the disease was likely to spread to Africa during the winter migration and return to Europe with a vengeance during the reverse migration this spring. That has not happened — a significant finding for Europe, because it is far easier to monitor a virus that exists domestically on farms, but not in nature.

"It is quiet now in terms of cases, which is contrary to what many people had expected," said Ward Hagemeijer, an avian influenza specialist with Wetlands International, an environmental group based in the Netherlands that studies migratory birds.

In thousands of samples collected in Africa this winter, H5N1 was not detected in a single wild bird, officials and scientists said. In Europe, there have been only a handful of cases detected in wild birds since April 1, at the height of the northward migration.

The number of cases in Europe has decreased so dramatically compared to February, when dozens of new cases were found daily, that experts believe the northward spring migration played no role. There was one grebe in Denmark on April 28 — the last case — as well as a falcon in Germany and a few swans in France, according to the World Organization for Animal Health, based in Paris.

In response to the good news, agriculture officials in many European countries have this month lifted restrictions designed to protect valuable domestic poultry from infected wild birds.

In the first week in May, both the Netherlands and Switzerland rescinded mandates that poultry be kept indoors. Austria has loosened similar regulation and France is considering doing so, as farmers (and their poultry) chafe under the restrictions of indoor life as the weather warms.

The February cases in Europe were attributed to infected wild birds that traveled west to avoid severe cold in Russia and Central Asia but apparently never carried the virus on to Africa. The international scientists who had issued the prior warnings are perplexed, unsure if their preventive measures — like intensive surveillance and eliminating contact between poultry and wild birds — helped defuse a time bomb, or if nature simply granted the reprieve. And they warn that H5N1 could return to Europe in the future.

"Is it like Y2K, where also nothing happened?" asked Juan Lubroth, a senior veterinary official at the United Nations Food and Agriculture Organization in Rome, referring to the expected computer failures as the year 1999 turned to 2000. "Perhaps it is because it was not as bad as we feared, or perhaps it is because people took the right measures."

Still, he and others say, the lack of wild bird cases in Europe only underscores how little is understood about the virus.

"Maybe we will be lucky and this virus will just die out in the wild," Dr. Lubroth said. "But maybe it will come back strong next year. We just don't have the answers."

…Specialists from Wetlands International, who were deputized by the Food and Agriculture Organization, sampled 7,500 African wild birds last winter in their search for the disease. They found no H5N1, Mr. Hagemeijer said, so it is not surprising that H5N1 did not return to Europe with the spring migration.

While avian influenza has become a huge problem in domestic poultry on farms in a few African countries, like Egypt, Nigeria and Sudan, experts increasingly suspect that it was introduced there through imported infected poultry and poultry products.

Mr. Hagemeijer thinks that the virus's strength among wild birds may have weakened as the southward migration season progressed — a trait common in less dangerous avian influenza viruses, he said. That probably limited its spread to Africa, he said.

H5N1 is the most deadly of a large family of avian influenza viruses, most of which produce only minor illness in birds. Many avian influenza viruses are picked up by migratory birds in their nesting places in northern lakes during the summer and autumn breeding season. As the months pass, the viruses show a decreasing pattern of spread and contamination.

"So it tends to be mostly a north-to-south spread, and then it wanes," he said.

Still, this means that the cycle could well start again this summer, if the H5N1 virus — which can live for long periods in water — has persisted in those breeding areas. Many bird specialists believe that a small number of wetland lakes in Central Asia and Russia may harbor the H5N1 virus all the time, serving as the origin of European and Central Asian infections.

In fact, so much remains uncertain about the path of the virus that the European Union and some countries, like Germany, have decided to keep at least some precautions in place. Germany this week extended a law, due to expire May 15, that keeps poultry inside if they live near wetlands or in other areas that have had bird flu cases.

"There is still no systematic risk assessment — we've tested thousands of birds, but really tens of thousands need to be tested," Mr. Hagemeijer said.

Scientists still do not know which birds carry the virus silently and which die from it quickly, or also how it typically spreads from wild bird to wild bird, or between wild birds and poultry.

At the Beijing donor conference sponsored by the World Bank, $1.9 billion was pledged. "But none of it was for researching the role of wild birds," Mr. Hagemeijer said. "It was all for stockpiling Tamiflu" — the anti-viral drug for use against bird flu.

The disappearance of the virus from wild birds in Europe would be important, nonetheless, because it is easier to monitor a virus that exists only on farms.

Farm-based outbreaks of avian influenza are still occurring constantly in a number of countries, although not in Europe. The Ivory Coast had its first outbreak of bird flu, on a farm, last week.

But other countries, like Turkey, have made good progress in containing the disease among poultry, Dr. Lubroth said. He added that he hoped that quick measures to limit outbreaks had reduced its spread in Africa.

After the disease was found on farms in Nigeria in January, most experts expected it would spread rapidly among farms and into wild birds in the region. Apparently, it did not.

"Why didn't it sweep up the coast from Niger, to Benin and Senegal and back up through Europe? Why didn't it hit Africa's big lakes?" Dr. Lubroth asked.

"All we have are a few snapshots of the virus. What we need is a movie of its life cycle."
<<

[fructose]

Bird Flu TV Movie Tonight

Think this could trigger a little wave of panic?

http://jam.canoe.ca/Television/2006/04/28/1555933-ap.html

http://abcnews.go.com/Entertainment/wireStory?id=1902688&CMP=OTC-RSSFeeds0312

[DewDiligence]

IOMI
Skin Patch May Strengthen Flu Vaccine

http://yahoo.reuters.com/investing/FinanceArticle.aspx?type=economicNews&storyID=urn:newsml:reut...

>>
Tue May 9, 2006 5:22 PM ET
By Maggie Fox, Health and Science Correspondent

WASHINGTON, May 9 (Reuters) - A skin patch designed to boost the immune response may help stretch out scarce supplies of influenza vaccine at the start of a pandemic, researchers at a small U.S. company said on Tuesday.

The patch is coated with diarrhea-causing E. coli bacteria, a strain known as enterotoxigenic E. coli or ETEC, formulated to pass into the skin. These stimulate the immune system and, in theory, strengthen the immune response to the vaccine.

Tests on mice and guinea pigs showed using the patch allowed a much smaller dose of vaccine to be used than normal to stimulate an immune response, said Dr. Gregory Glenn, chief scientific officer at Iomai Corporation.

Animals given vaccines against either seasonal influenza, or the H5N1 avian influenza vaccine, required a much lower dose -- 100 to 10,000 times lower -- to get the same immune response if patches were stuck to their skin than without the patch, Glenn said.

"We hope that would translate in humans to 10- to 50-fold (lower)," Glenn said in a telephone interview. Glenn presented his findings to a meeting in Baltimore sponsored by the National Foundation for Infectious Diseases.

"We have data showing you can attach a patch at the time of injection," Glenn said. "Instead of putting on a Band-Aid, you put on the patch. We are activating the skin's immune system."

Glenn, whose company is discussing testing the patch as part of H5N1 vaccine trials at the National Institute of Allergy and Infectious Diseases, said the patches could be made now and distributed ahead of a pandemic.

"You can stockpile it well in advance. It not going to be dependent on the strain (of influenza)," he said. "You could have 600 million patches sitting there in the U.S."

The H5N1 avian flu virus, which has swept across Asia, Europe and into Africa in just months, still mainly affects birds. But experts say it poses a great risk of evolving into a form that can easily pass from person to person. If it caused a pandemic, vaccines would be the best defense but a closely matched vaccine cannot be made until an actual pandemic strain occurs, because influenza is such a mutation-prone virus.

There are not enough vaccine factories in the world today to make the amount of vaccine needed to protect the population so government and corporate experts are trying to stretch vaccine doses to allow more people to be vaccinated. Iomai's is a unique approach, said Dr. Bruce Weniger of the U.S. Centers for Disease Control and Prevention.

"It's a fascinating new technology," Weniger, a vaccine expert, said in a telephone interview from the conference. "It seems to be very simple to apply."

The company also makes the patch as a vaccine against traveler's diarrhea, which Glenn says has been shown in Phase 2 studies to be safe in people. The patch as an influenza adjuvant may not be tested in people for some time -- unless a pandemic develops, Glenn said.

He said the patch stimulates antigen-presenting cells in the skin called Langerhans cells, which travel to the nearby lymph nodes to produce a sustained immune response.

Iomai has applied for U.S. Health and Human Services Department contracts for the vaccine. Last week, HHS announced $1 billion in contracts to five companies develop new and better influenza vaccines, and to make them on U.S. territory.
<<

[Biowatch]

Tamiflu, Gilead, and Rumsfeld make it to snopes.com

http://www.snopes.com/politics/medical/tamiflu.asp

>>Rumsfeld is in a "damned if you do, damned if you don't" position because of his stock holdings, even though he apparently has no say in what Gilead does (he's no longer on its board) and has removed himself from being part of governmental decisions that affect it (he's recused himself)...

...If Rumsfeld holds onto his stock and its share price rises (which one would expect it to do if an avian flu pandemic becomes a reality, or if concerns about such a pandemic continue to grow), he will be seen to be profiting mightily from sales of a product the U.S. government has been buying in large quantities. If he sells his stock and so divests himself of further interest in Tamiflu sales, he will be accused of locking up profits from the rise in share price that has already occurred. (In 2001, shares of Gilead Sciences, Inc. traded in a range between $6.64 and $17.93. Between January and April 2006, its price range has been $53.00 to $65.62.) <<

[DewDiligence]

Genetics Might Be Why Some People Get Bird Flu

http://www.msnbc.msn.com/id/12628611/

>>
Many of over 200 human cases have occurred in families, disease experts say

May 4, 2006

SINGAPORE - People who have been infected with the H5N1 bird flu virus might be especially susceptible to avian viruses because they are genetically predisposed to them, leading disease experts suggested on Thursday.

Of the 205 reported cases of human infections since late 2003, there have been many family clusters involving blood relatives, such as father and children, mothers and daughters. Of the total infections, 113 people died in nine countries.

“There have been family clusters. So there has to be certainly a genetic aspect to it,” Robert Webster of the St Jude Children’s Research Hospital told a bird flu conference organized by the Lancet medical journal in Singapore.

Another leading expert Hiroshi Kida, who has spent more than three decades working on viruses, has long harboured the same theory.

“There has not been a single case of infection involving husband and wife,” Kida said told Reuters in an interview. Kida is with the department of diseases control at Hokkaido University in Japan.

Kida explained that people infected with H5N1 have a carbohydrate receptor on cells lining their throats. The receptor — called alpha 2,3 — is predominantly found in birds and avian influenza viruses like to bind to this class of receptors to replicate and cause disease.

Human influenza viruses, however, prefer to bind to another receptor called alpha 2,6, which is dominant in humans.

“I think people who are infected with avian strains are special. They must have alpha 2,3 receptors,” Kida said.

Although humans have some amount of alpha 2,3, Kida said alpha 2,6 was by far more “dominant” in most people.

Dangerous mutation

Kida is now trying to look for H5N1 survivors in Vietnam and Thailand to verify his theory, and if it proves to be true, it could mean that most people simply cannot catch H5N1 easily — unless the virus mutates.

“If it changes receptor specificity, then it must be dangerous,” Kida said.

Many experts see H5N1 as possibly triggering an influenza pandemic that is long overdue. But that could only happen if it mutates sufficiently to become easily passed among people —something that has not happened.

Most of its victims contracted the virus directly from sick birds. And there have not been any proven cases of human-to-human transmission.

Although very little is known about the virus, much work has been done to find out how it is transmitted and even why so few people have been infected and why it hasn’t yet become infectious among people.

A group of researchers recently postulated the reason why it has not been as infectious as feared is because the virus lodges itself deep in the lungs, and not in the upper respiratory tract where it could more easily dislodge itself, get out of the body and spread.

But while Kida does not dismiss this theory, he thinks it is not the only one.
<<

[DewDiligence]

Group Points to Liability Shield for Flu Remedy Firms

http://www.boston.com/globe/business

>>
By Diedtra Henderson
May 5, 2006

WASHINGTON -- A consumer advocacy group says the pharmaceutical industry ''blanketed" Congress in 2004 and 2005, employing at least 158 lobbyists and spending $91.2 million, including on flu vaccine or pandemic issues.

The group, Public Citizen, said about 84 of those lobbyists had federal ties, including seven former members of Congress, two senior health policy aides to Senate Majority Leader Bill Frist, and the son of Speaker of the House J. Dennis Hastert.

The group says it pored through e-mails and other documents exchanged between drug industry lobbyists, the White House and, Frist, a Republican from Tennessee. In December, Frist added a liability waiver to a must-pass defense bill to broadly shield most doctors and companies that make, deliver, or administer pandemic flu remedies.

Frist could not be reached for comment yesterday.

Three members of Congress instrumental in the law's passage -- Frist, Hastert, an Illinois Republican, and Republican Senator Richard Burr from North Carolina -- received a total of more than $1.2 million in campaign contributions from pharmaceutical and biotechnology companies since 1999, according to Public Citizen.

Senator Edward M. Kennedy, Democrat of Massachusetts, this week sought to counter Frist's action. Kennedy attached an amendment to another must-pass bill that would provide $289 million this year to compensate victims harmed by pandemic flu treatments.

The White House this week updated a $7.1 billion plan that outlines how the government would contend with a lethal flu outbreak by speeding vaccine production, stockpiling medicine, and tracking likely US entry points for the flu. Experts estimate that 200,000 to 2 million Americans would die and that travel would be disrupted should such a pandemic occur.

Congress already approved $3.8 billion to fund the plan. Bills facing votes in the Senate would add to that tally.

Last fall, as the number of people infected with avian flu rose in Asia, the Bush administration made pandemic planning a high-profile goal and invited drug manufacturers to the White House.

As early as mid-November, Dave Boyer, director of federal government relations for BIO, which lobbies on behalf of biotechnology companies, said he was concerned the proposed measure would leave drug companies vulnerable to lawsuits. People killed or seriously injured could sue if they proved a drug maker's actions amounted to ''willful misconduct."

The Washington, D.C.-based organization's 1,100 members include America's top 10 drug manufacturers, who control more than half of the nation's drug market. Between 1998 and 2005, BIO more than tripled its lobbying budget from $1.7 million to $5.8 million, Public Citizen reported.

As early as Dec. 1, Republican leaders in the House and Senate vowed to attach the liability shield to a Defense Department appropriations bill, according to Public Citizen. Alarmed Democrats received assurances that such a tactic would not occur.

On Dec. 18, Republicans and Democrats met to ensure that the House and Senate versions of the defense bill matched. The 422-page bill they reviewed did not include a liability waiver for drug companies. Four hours later, Frist asked Hastert to authorize adding another 40 pages that included the liability waiver in a move that Kennedy derided as ''an absolute travesty."

Jim C. Greenwood, BIO president, said chief executives from the nation's major vaccine manufacturers told him a strong liability waiver was essential. The companies willingly offered to stop production of profit-making drugs to devote their manufacturing capacity to help the nation fend off a pandemic. But not if it meant ''being driven out of business and eaten alive by lawsuits," Greenwood said. Because of the threat of a pandemic, he said, the waiver had to be granted quickly.

But Public Citizen alleges the waiver ''far exceeded the scope of the Bush administration's proposal, which would have applied the shield only to drugs and vaccines created specifically to combat the avian flu."
<<

[Biowatch]

>>We should be prepared to "camp!"<<

The Mormons have been thinking about this for a long time.

http://www.providentliving.org/channel/0,11677,1706-1,00.html

[Biowatch]

Draft Report Outlines Plans for Pandemic

May 3, 2006

By LAWRENCE K. ALTMAN
The federal government will stockpile 75 million doses of antiviral drugs and 20 million doses of vaccine to combat any outbreak of pandemic flu, according to a summary of a draft response plan expected to be unveiled today by the White House.

A flu pandemic would severely disrupt the economy, and private businesses and government agencies should assume that up to 40 percent of employees would be absent for up to two weeks at the height of each wave of infections, the undated 17-page draft summary says.

Local police departments and state National Guard units would have primary responsibility for keeping order, but the military would be available to assist.

The secretary of health and human services will lead the government's response, with the Department of Homeland Security in a supporting role, the summary said.

An administration official, who was granted anonymity to speak because the plan had not been formally announced, said it would lay out measures that businesses and agencies should take to minimize spread of a virus.

The measures include allowing telecommuting, cutting back on the number of meetings, introducing liberal leave policies and staggering employee shifts.

The goals include helping make sure that "people aren't coming and going from a workplace at the same time" and generally to "encourage people to stay at home" if they have any sense they are infected, the official said.

"The main purpose of this implementation plan is to say, 'Department X, you need to be doing the following,' " he said.

The plan says, however, that setting up operational logistics will be up to the various departments.

The first part of the plan was released in November. Under it, the federal government shouldered responsibility for developing a vaccine and stockpiling antivirals, and state and local governments were told to plan for the medical response and quarantine.

Many of them soon complained that they had no money and no control over privately owned local hospitals.

The nation's borders would almost certainly not be closed, the draft summary says, because the virus would enter the country anyway, enforcement would be difficult, and such an action would "present foreign affairs complications and have significant negative social and economic consequences."

The federal government will establish policies for screening travelers for flu symptoms and make recommendations about quarantines. It could also restrict unnecessary domestic travel.

In addition to increasing the stockpile of human vaccines and antivirals, the government will increase the stockpile of poultry vaccines to 110 million doses.

It will create separate stockpiles of masks, suits, disinfectants and antiviral medication for poultry workers. (American policy now is to avoid vaccination and to kill any infected chickens that may be found, but countries like China and Vietnam began vaccinating when the virus began spreading faster than flocks could be tested and culled.)

Under the government's plan for the worst-case possibility, a pandemic flu could cause up to two million deaths in the United States.

Jim Rutenberg contributed reporting for this article.


Copyright 2006 The New York Times Company

[DewDiligence]

There Are 31 Avian & Pandemic Prototype Vaccines

[c/o LJM on SI]

http://www.ifpma.org

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02 May 2006

The IFPMA's research-based vaccine manufacturing members are conducting a growing number of clinical trials of “prototoype” influenza vaccines, designed to counter to the threats of avian and pandemic influenza. “Industry is increasing its commitment to help minimize the global health impact of emerging influenza threats” said Dr. Harvey E. Bale, Director General of the IFPMA. “This is documented in the IFPMA summary ‘R&D for Avian / Pandemic Influenza Vaccines by IFPMA Influenza Vaccine Supply International Task Force (IVS ITF) members' published today.” This unique information resource lists all the prototype avian / pandemic influenza vaccines under development by these IFPMA member companies. As such, it covers the vast majority of R&D projects being undertaken in this field.

A total of 31 avian/pandemic prototype vaccine clinical trials are now listed by IFPMA, compared to 28 in January 2006. These vaccine trials involve 15 manufacturers, located in Australia, Austria, Canada, France, Germany, Italy, Japan, the Netherlands, Switzerland, UK and USA. sanofi pasteur alone has no less than eight different vaccine trials either recently completed or underway. A total of eleven Phase II clinical trials of prototype vaccines are either on-going or planned for 2006. Three prototype vaccines, one from Chiron / Novartis and two from GSK, have already been submitted as “Mock Up” dossiers for approval by the EU regulatory authority (EMEA).

The majority of projects target specific strains of influenza virus (H2N2, H5N1, wild type H5N1, H5N3, H7N1, H7N7, H9N2), but Merck focuses on development of a universal influenza vaccine, using an M-2 peptide conjugate protein. Among the influenza strain-targeted projects, 26 use an inactivated virus (10 whole virus, 10 split virus, 6 surface antigen), and 4 use a live attenuated virus.

Almost all prototype vaccines use a traditional injection delivery system, although MedImmune uses a nasal spray. Sixteen projects use Aluminum salt as an adjuvant. Berna/Crucell uses a virosome carrier/adjuvant system; CSL, Aluminum phosphate; Chiron/Novartis, MF59 and GSK, a novel adjuvant system. Twenty-five projects use the traditional egg culture technology currently used to manufacture seasonal influenza vaccines, while 6 use cell culture systems.

About the IFPMA Influenza Vaccine Supply International Task Force

The IFPMA Influenza Vaccine Supply Interventional Task Force (IVS ITF), established in February 2002, brings together research-based influenza vaccine manufacturers from around the world, which are conducting the R&D necessary to develop safe, effective, high-quality vaccines agains avian and pandemic influenza threats. The IVS ITF works within the constraints of anti-trust law to address the advocacy, communication, policymaking, regulatory, scientific and technical issues related to interpandemic and pandemic influenza vaccines. IVS ITF members are committed to make their unique expertise in R&D, logistics, manufacturing, safety and regulatory issues available to help governmental and intergovernmental bodies in pandemic planning and decisionmaking.

For more information, see:
ifpma.org/pdf/pandemic_backgrounder_23Jan06.pdf.

About the IFPMA

The International Federation of Pharmaceutical Manufacturers & Associations is the global nonprofit NGO directly representing twenty-six research-based pharmaceutical, biotech and vaccine companies and sixty national industry associations in developed and developing countries. The industry's R&D pipeline contains hundreds of new medicines and vaccines being developed to address global disease threats, including cancer, heart disease, HIV/AIDS and malaria. The IFPMA Clinical Trials Portal and the IFPMA Health Partnerships Survey help make the industry's activities more transparent. The IFPMA strengthens patient safety by improving risk assessment of medicines and combating their counterfeiting. It also provides the secretariat for the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
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[Biowatch]

Fear the phone, not the doorknob, US germ expert says

By Maggie Fox, Health and Science CorrespondentTue May 2, 8:37 AM ET

Worried about colds, flu and other germs? Go ahead and touch those doorknobs and elevator buttons, but watch out for the telephone, fresh laundry and sinks, a top expert advises.

And while you should always wash your hands before making a meal, many people do not realize that they should do so afterwards also, says Charles Gerba, a microbiologist and clean water expert at the University of Arizona.

"Most of the common infections -- colds, flu, diarrhea -- you get environmentally transmitted either in the air or on surfaces you touch. I think people under-rate surfaces," Gerba said in a telephone interview.

And when they are cautious, they are usually cautious about the wrong things. Germs do not stick where people believe they will.

"Doorknobs are usually on the low side," said Gerba, who has conducted dozens of surveys of bacteria and viruses in workplaces and homes. "I guess they are not moist. Never fear a doorknob."

A recent informal survey of a Reuters office helped him illustrate how microbes take advantage of misconceptions to propagate themselves.

Two computer keyboards, for example, carried far more bacteria than an elevator button, the handles and button on the communal microwave oven or the office water fountain, an analysis by Gerba's lab found.

Keyboards and telephones -- especially when they are shared -- are among the most germ-laden places in a home or office, Gerba said.

LUNCH COUNTER FOR GERMS

"Keyboards are a lunch counter for germs," Gerba said. "We turn them over in a lot of studies and we are amazed at what comes out of a keyboard."

In fact, the average desk harbors 400 times more bacteria than the average toilet seat, says Gerba, whose latest survey focuses on the germiest professions.

"Nobody cleans the desktop, usually, until they stick to it," he says.

Perhaps not surprisingly, teachers have the highest exposure to bacteria and viruses, Gerba has found. Accountants, bankers and doctors also tend to have microbe-laden offices, while lawyers came out surprisingly clean in the germ-count stakes.

Offices are, however, becoming cleaner, Gerba says.

His lab does a simple overall bacteria count for its most general surveys. The person swabs each surface and sends it to Gerba's lab, which then cultures the bacteria in a lab dish.

The growth of whatever bacteria are present can be used to estimate an overall load of germs, including harmless E. coli bacteria -- which are found in the gut and are an indicator of what scientists delicately call "fecal contamination."

Some other bacteria usually present are Klebsiella pneumonia, Streptococcus, Salmonella and Staphyloccus aureus, some of which cause disease and some of which do not. And where there are bacteria, there can be viruses, which can hang onto a clean and dry surface for days and to a wet surface for weeks.

Such knowledge may be particularly useful as experts warn that a pandemic of H5N1 avian influenza may be looming. While the virus currently infects birds almost exclusively, experts say it shows the greatest potential of any virus in decades to cause a human pandemic.

If it begins to spread, basic hygiene would be essential to avoid infection. But viruses are of course invisible to the human eye and Gerba notes that people tend not to know where the most infectious places are.

For example, the bathroom.

"Toilets get a bad rap. So does the door on the way out," Gerba said.

Bathroom sinks, however, are another matter. "Sinks are usually high (in bacterial counts) to begin with," Gerba said. "They have got everything a bacteria likes. It's wet, it's moist. In a home we usually find more E. coli in a sink than a toilet."

Men's rooms, too. "Usually the dirtiest handles in public restrooms are urinal flush handles," he said.

DIARRHEA, NOT GONORRHEA

But urban legends about getting sexually transmitted diseases in a public restroom are untrue, Gerba said. "It's really diarrhea, not gonorrhea, you have to worry about," he said. Commonly found restroom germs include noroviruses, shigella, hepatitis A and Salmonella.

Food preparation is another good way to get germy, especially when handling raw meat, Gerba said.

And few people know just how dirty laundry is -- clean laundry.

"Most people don't realize that they actually should wash their hands after they make dinner and also after they do the laundry," Gerba said.

Americans have moved to short-cycle, cold-water washes to save energy and wear and tear on clothing, but this leaves viruses and bacteria largely intact.

"Water at 140 degrees F (60 degrees C) will sanitize laundry," Gerba said. But only 5 percent of Americans use hot water for laundry.

And viruses such as hepatitis A, rotavirus and bacteria such as Salmonella -- all of which cause stomach upsets and diarrhea -- can easily survive the average 28-minute drying cycle.

These are all carried fecally. "There is about a 10th of a gram of feces in the average pair of underwear," Gerba says. "You don't want to be doing your handkerchiefs with your underwear."

Gerba's studies are often funded by companies that make disinfectants, but Gerba says antimicrobial wipes and alcohol-based gel hand sanitizers do work.

"It has been shown that you can reduce a lot of absenteeism by using hand sanitizers," he says.

"We don't want to make people overly paranoid here," Gerba added. "You can reduce your risk of getting colds and flu by a few simple actions. You are always gambling with germs. You just want to keep the odds in your favor."

http://news.yahoo.com/s/nm/20060502/ts_nm/germs_dc;_ylt=AvJg6JwDtm4A.6EBeXt.0RoDW7oF;_ylu=X3oDMTBhZD...

[DewDiligence]

Roche donates Tamiflu stockpile to WHO

http://yahoo.reuters.com/stocks/QuoteCompanyNewsArticle.aspx?storyID=urn:newsml:reuters.com:20060419...

>>
Wed Apr 19, 2006 4:08 PM ET
By Tom Armitage

KAISERAUGST, Switzerland, April 19 (Reuters) - Drug maker Roche <ROG.VX> handed over 3 million courses of bird flu treatment Tamiflu to the World Health Organization on Wednesday to be deployed in the event of a pandemic.

The donation of the treatment is part of Roche's efforts to help the world health body prepare developing countries for a potential global human epidemic of the virulent H5N1 strain of influenza.

Chief Executive Franz Humer said Roche was on track to produce 400 million courses of Tamiflu this year to meet demand from governments who are building stockpiles of the drug.

The donation -- and a decision to grant production sublicenses in China and India -- follows criticism that only rich nations had the resources to prepare for a flu pandemic which could occur if the current bird flu strain mutates.

"During discussions it emerged very clearly that many governments in Asia Pacific, where the first outbreak could happen, were not prepared," Humer told reporters at a news conference to mark the handover near Basel.

The 3 million course stockpile will be stored by Roche, partly at Kaiseraugst and partly in the United States, and would be sent to an international airport close to the outbreak if a human pandemic develops.

Roche has promised the WHO a further 2 million courses of the drug to be sent to build strategic stockpiles in regions where outbreaks are thought to be most likely.

The moves are part of the WHO's efforts to create a global preparedness plan, and the 3 million courses are seen as an initial defense that could quell an outbreak.

"The timing will be everything and containment has a chance to work if antivirals reach the area rapidly and no more than 21 days after the first case," WHO Director-General Lee Jong-wook told the news conference. "We can't afford to fail."

The H5N1 avian flu virus has spread quickly in recent weeks, and is now reported in 42 countries across Asia, Europe and parts of Africa. It has killed 110 people and infected 196, although it does not pass easily from human to human. If it acquires this ability it could easily cause a pandemic although if caught early enough in theory such outbreaks could be contained with the use of drugs such as Tamiflu.

Tamiflu, known generically as oseltamivir, has been used successfully in some patients who have been given the drug soon enough after they become ill.

Etc.
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[DewDiligence]

Katie et al:

>do you or anyone else have an issue with posting BP developments regarding the bird-flu vaccine, I'm not talking about Flu plays, I'm referring to folks like Sanofi, GSK, GILD, BCRX, etc who have adequate funding and government support....<

At your service! Here’s the most recent report from Citigroup:
http://www.smithbarney.com/pdf/global_port_strat.pdf

>there is a news tracker on the WSJ online website....can you post a link to it and I wonder if it can be accessible through your link, since I know you subscribe to it.<

The WSJ bird-flu tracker is at
http://online.wsj.com/article/SB112896461663164579.html
but it requires an online subscription to the WSJ. I check this periodically and post when there is something there of interest. Regards, Dew

[mskatiescarletohara]

We should be prepared to "camp!" Dew, there is a news tracker on the WSJ online website....can you post a link to it and I wonder if it can be accessible through your link, since I know you subscribe to it. May as well go to a medical supply store to stock up on latex gloves and masks.

Also, do you or anyone else have an issue with posting BP developments regarding the bird-flu vaccine, I'm not talking about Flu plays, I'm referring to folks like Sanofi, GSK, GILD, BCRX, etc who have adequate funding and government support....

katie....

[DewDiligence]

“Any community that fails to prepare—with the expectation that the federal government can come to the rescue—will be tragically wrong.”

http://www.washingtonpost.com/wp-dyn/content/article/2006/04/15/AR2006041500901.html

>>
U.S. Plan For Flu Pandemic Revealed

Multi-Agency Proposal Awaits Bush's Approval

By Ceci Connolly
Washington Post Staff Writer
Sunday, April 16, 2006

President Bush is expected to approve soon a national pandemic influenza response plan that identifies more than 300 specific tasks for federal agencies, including determining which frontline workers should be the first vaccinated and expanding Internet capacity to handle what would probably be a flood of people working from their home computers.

The Treasury Department is poised to sign agreements with other nations to produce currency if U.S. mints cannot operate [!] The Pentagon, anticipating difficulties acquiring supplies from the Far East, is considering stockpiling millions of latex gloves. And the Department of Veterans Affairs has developed a drive-through medical exam to quickly assess patients who suspect they have been infected.

The document is the first attempt to spell out in some detail how the government would detect and respond to an outbreak, and continue functioning through what could be an 18-month crisis, which in a worst-case scenario could kill 1.9 million Americans. Bush was briefed on a draft of the implementation plan on March 17. He is expected to approve the plan within the week, but it continues to evolve, said several administration officials who have been working on it.

Still reeling from the ineffectual response to Hurricane Katrina, the White House is eager to show it could manage the medical, security and economic fallout of a major outbreak. In response to questions posed to several federal agencies, White House officials offered a briefing on the near-final version of its 240-page plan. When it is issued, officials intend to announce several vaccine manufacturing contracts to jump-start an industry that has declined in the past few decades.

The background briefing and on-the-record interviews with experts in and out of government reveal that some agencies are far along in preparing for a deadly outbreak. Others have yet to resolve basic questions, such as who is designated an essential employee and how the agency would cope if that person were out of commission.

"Most of the federal government right now is as ill-prepared as any part of society," said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. Osterholm said the administration has made progress but is nowhere near prepared for what he compared to a worldwide "12- to 18-month blizzard."

Many critical decisions remain to be made. Administration scientists are debating how much vaccine would be needed to immunize against a new strain of avian influenza, and they are weighing data that may alter their strategy on who should have priority for antiviral drugs such as Tamiflu and Relenza.

The new analysis, published in Proceedings of the National Academy of Sciences, suggests that instead of giving medicine to first responders and health-care workers, as currently planned, it might be wiser to give the drugs to every person with symptoms and others in the same household, one senior administration official said.

The approach offers "some real hope for communities to put a dent in the amount of illness and death, if we go with that strategy," a White House official said.

Each year, about 36,000 Americans die from seasonal influenza. A worldwide outbreak, or pandemic, occurs when a potent new, highly contagious strain of the virus emerges. It is a far greater threat than annual flu because everyone is susceptible, and it would take as much as six months to develop a vaccine. The 1918 pandemic flu, the worst of the 20th century, is estimated to have killed more than 50 million people worldwide.

Alarm has risen because of the emergence of the most dangerous strain to appear in decades -- the H5N1 avian flu. It has primarily struck birds, but about 200 people worldwide have contracted the disease, and half have died. Experts project that the next pandemic -- depending on severity and countermeasures -- could kill 210,000 to 1.9 million Americans.

To keep the 1.8 million federal workers healthy and productive through a pandemic, the Bush administration would tap into its secure stash of medications, cancel large gatherings, encourage schools to close and shift air traffic controllers to the busier hubs -- probably where flu had not yet struck. Retired federal employees would be summoned back to work, and National Guard troops could be dispatched to cities facing possible "insurrection," said Jeffrey W. Runge, chief medical officer at the Department of Homeland Security.

The administration hopes to help contain the first cases overseas by rushing in medical teams and supplies. "If there is a small outbreak in a country, it may behoove us to introduce travel restrictions," Runge said, "to help stamp out that spark."

However, even an effective containment effort would merely postpone the inevitable, said Ellen P. Embrey, deputy assistant secretary for force health preparedness and readiness at the Pentagon. "Unfortunately, we believe the forest fire will burn before we are able to contain it overseas, and it will arrive on our shores in multiple locations," she said.

As Katrina illustrated, a central issue would be "who is ultimately in charge and how the agencies will be coordinated," said former assistant surgeon general Susan Blumenthal. The Department of Health and Human Services would take the lead on medical aspects, but Homeland Security would have overall authority, she noted. "How are those authorities going to come together?"

Essentially, the president would be in charge, the White House official replied. Bush is expected to adopt post-Katrina recommendations that a new interagency task force coordinate the federal response and a high-level Disaster Response Group resolve disputes among agencies or states. Neither entity has been created.

Analysts at the Government Accountability Office found that earlier efforts by the administration to plan for disasters were overly broad or simply sat on a shelf.

"Our biggest concern is whether an agency has a clear idea of what it absolutely has to do, no matter what," said Linda Koontz, director of information management issues at the GAO. "Some had three and some had 400 essential functions. We raised questions about whether 400 were really essential."

In several cases, agencies never trained for or rehearsed emergency plans, she said, causing concern that when disaster strikes, "people will be sitting there with a 500-page book in front of them."

The federal government -- as well as private businesses -- should expect as much as 40 percent of its workforce to be out during a pandemic, said Bruce Gellin, director of the National Vaccine Program Office at HHS. Some will be sick or dead; others could be depressed, or caring for a loved one or staying at home to prevent spread of the virus. "The problem is, you never know which 40 percent will be out," he said.

The Agriculture Department, with 4 million square feet of office space in metropolitan Washington alone, would likely stagger shifts, close cafeterias and cancel face-to-face meetings, said Peter Thomas, the acting assistant secretary for administration.

The department has bought masks, gloves and hand sanitizers, and has hired extra nurses and compiled a list of retired employees who could be temporarily rehired, he said. A 24-hour employee hotline would provide medical advice and work updates. And as it did during Katrina, Agriculture has contingency plans for meeting the payrolls of several federal departments totaling 600,000 people.

Similarly, the Commerce Department has identified its eight priority functions, including the ability to assign emergency communication frequencies, and how those could be run with 60 percent of its normal staff.

Operating the largest health-care organization in the nation, the VA has directed its 153 hospitals to stock up on other medications, equipment, food and water, said chief public health officer Lawrence Deyton. "But it's a few days' worth, not enough to last months," he added.

Anticipating that some nurses may be home caring for family members -- and to reduce the number of patients descending on its hospitals -- the VA intends to put nurses on its toll-free hotline to help veterans decide whether they need professional medical care. At many VA hospitals, nurses and doctors would stand in the parking lots armed with thermometers and laptop computers to do drive-through exams. Modeled after its successful drive-through vaccination program last fall, the parking-lot triage is intended to keep the flow of patients moving rapidly, Deyton said.

Much of the federal government's plan relies on quick distribution of medications and vaccine. The Strategic National Stockpile has 5.1 million courses of Tamiflu on hand. The goal is to secure 21 million doses of Tamiflu and 4 million doses of Relenza by the end of this year, and a total of 51 million by late 2008.

In addition, the administration will pay one-quarter of the cost of antivirals bought by states. The Pentagon, VA, USDA and Transportation Department have their own stockpiles -- and most intend to buy more as it becomes available.

Blumenthal, the former assistant surgeon general, questioned why two years after Congress approved a $5.6 billion BioShield program to develop new drugs and vaccines, so little progress has been made.

Homeland Security's Runge has a different concern: "One of the scariest thoughts is, if this country has successfully developed a vaccine within six months of an outbreak or our supply of antivirals is greater, there may be a rush into the United States for those things."

And even if those fears do not materialize, officials have warned that the federal preparations go only so far. Much is left to the states, communities and even individuals.

"Any community that fails to prepare -- with the expectation that the federal government can come to the rescue -- will be tragically wrong," HHS Secretary Mike Leavitt said in a speech April 10. The administration is posting information on the Internet at http://www.pandemicflu.gov .
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