http://www.freerepublic.com/focus/news/1483862/posts?page=1
Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals
The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date.
To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans.
Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997.
One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain.
Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice.
The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses.
However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.
http://seattlepi.nwsource.com/national/apscience_story.asp?category=1500&slug=Bird%20Flu
U.S. buys $100 million of bird flu vaccine
By LAURAN NEERGAARD
AP MEDICAL WRITER
WASHINGTON -- Mass production of a new vaccine that promises to protect against bird flu is poised to begin, as the government on Thursday agreed to stockpile $100 million worth of inoculations.
The new contract with French vaccine maker Sanofi-Pasteur marks a major scale-up in U.S. preparation for the possibility that the worrisome virus could spark an influenza pandemic.
While the vaccine is still experimental, preliminary results from the National Institutes of Health's first testing in people suggest the inoculations spur an immune response that would be strong enough to protect against known strains of the avian influenza, sparking the new investment.
But just how many doses the $100 million will buy isn't yet clear.
That's because there is contrasting research on just how much antigen much be in each dose to provide protection, explained Sanofi spokesman Len Lavenda. The range is huge - from 15 micrograms of antigen per dose to 90 - and the protective amount likely will wind up somewhere in between, he said.
Previously, the government has said it has stockpiled 2 million doses of bird flu vaccine.
Sanofi stored that vaccine in bulk, and the 2 million estimate assumed a single 15-microgram dose per person, Lavenda said. In contrast, the preliminary NIH research suggested it may take two 90-microgram shots to provide protection.
Simple math suggests that means the $100 million purchase could provide enough doses to protect anywhere from 1.7 million people - "we're quite sure it's going to be a lot more than that," Lavenda said - to a maximum of 20 million people.
A study now under way in France pairs the vaccine with an immune booster, called an adjuvant, that may help stretch doses. Sanofi expects results later in the year.
Regardless of the ultimate number, clearing the way for mass production now is a big step. Sanofi's factory in Swiftwater, Penn., can produce bird flu vaccine in September and October - months not occupied making vaccine for regular winter flu - and separate bulk lots into agreed-upon doses later.
The government's ultimate goal is to stockpile 20 million vaccine doses, a first wave of protection if the H5N1 bird flu strain eventually sparks a pandemic.
It's a quest gaining urgency. The virus has now killed or led to the slaughter of millions of birds, mostly in Asia but in parts of Europe, too. Although it has killed only about 60 people, mostly poultry workers, that's because so far it doesn't spread easily from person to person. If that changes - and flu viruses mutate regularly - it could trigger a deadly worldwide outbreak, because H5N1 is so different from the flu strains that circulate each winter that people have no residual immunity.
The nation also plans to stockpile 20 million doses of anti-flu medication, and the government announced Thursday it was purchasing enough of the drug Relenza, from maker GlaxoSmithKline, to treat 84,300 people.
Already in stock is enough of a competing drug, Tamiflu, to treat 4.3 million. Tamiflu is a pill, while Relenza must be inhaled, a drawback. The government still is planning additional Tamiflu purchases.
"These counter-measures provide us with tools that we have never had prior to previous influenza pandemics," said Health and Human Services Secretary Mike Leavitt.
http://www.freerepublic.com/focus/f-news/1485526/posts
http://seattlepi.nwsource.com/national/apscience_story.asp?category=1500&slug=Indonesia%20Bird%20Flu
THE ASSOCIATED PRESS
JAKARTA, Indonesia -- Indonesia on Friday confirmed its fourth human death from the bird flu virus, and warned that more cases in the sprawling country were inevitable.
Tests from a Hong Kong laboratory showed that a 37-year-old woman who died last week had contracted the H5N1 bird flu virus, said Nyoman Kandon, the health ministry's director general for illness control and environmental health.
He said Indonesia would continue to report cases because the virus was rife in poultry farms across the country. "It will be like in Vietnam and Thailand," he told The Associated Press.
The virus has swept through poultry populations in large swathes of Asia since 2003, resulting in the deaths of tens of millions of birds - and 63 people, most of them in Vietnam and Thailand.
Most of the human deaths have been linked to contact with sick birds. But the World Health Organization has warned that the virus could mutate into a form which is more easily transmitted from human to human, possibly triggering a pandemic that could kill millions worldwide.
Relenza (zanamivir)
FDA has approved Relenza (zanamivir), an anti-viral drug, for persons aged 7 years and older for the treatment of uncomplicated influenza virus. This product is approved to treat type A and B influenza, the two types most responsible for flu epidemics. Clinical studies showed that for the drug to be effective, patients needed to start treatment within two days of the onset of symptoms. The drug seemed to be less effective in patients whose symptoms weren't severe or didn't include a fever.
Relenza is a powder that is inhaled twice a day for five days from a breath-activated plastic device called a Diskhaler. Patients should get instruction from a health-care practitioner in the proper use of the Diskhaler, including a demonstration when possible. Relenza has not been shown to be effective, and may carry risk, in patients with severe asthma or a lung condition called chronic obstructive pulmonary disease. Some patients with mild or moderate asthma experienced bronchospasm (marked by shortness of breath) after using Relenza.
Some patients have had bronchospasm (wheezing) or serious breathing problems when they used Relenza. Many but not all of these patients had previous asthma or chronic obstructive pulmonary disease. Relenza has not been shown to shorten the duration of influenza in people with these diseases. Because of the risk of side effects and because it has not been shown to help them, Relenza is not generally recommended for people with chronic respiratory disease. Anyone who develops bronchospasm worsening respiratory symptoms such as wheezing and shortness of breath should stop taking the drug and call their health-care provider. Patients with underlying respiratory disease should have a fast-acting inhaled bronchodilator available when taking Relenza.
Relenza is not approved for use in prevention of influenza (prophylaxis) and is not a substitute for influenza vaccine.
Transcript of the Antiviral Advisory Committee Date: 2/24/99; Topic: Relenza (zanamivir); NDA 21-036. Optional format: PDF. Also available: Minutes PDF.
Combined Memorandum. (Issued, 7/15/99, Posted, 8/27/99) This memo addresses several concerns raised by the Antiviral Drug Advisory Committee held on February 24, 1999.
Division Director Memorandum. (Issued, 7/26/99, Posted, 8/27/99) This memo states the Director's rationale for recommending approval of Relenza for treatment of uncomplicated influenza, plus comments on other noteworthy aspects of the application.
http://www.fda.gov/cder/news/relenza/default.htm
http://abcnews.go.com/Primetime/Investigation/story?id=1130392&page=1
Sept. 15, 2005 — It could kill a billion people worldwide, make ghost towns out of parts of major cities, and there is not enough medicine to fight it. It is called the avian flu.
This week, at the United Nations Summit in New York, both the head of the U.N. World Health Organization and President Bush warned of the virus's deadly potential.
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"We must also remain on the offensive against new threats to public health, such as the Avian influenza," Bush said in his speech to world leaders. "If left unchallenged, the virus could become the first pandemic of the 21st century."
According to Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University's Mailman School of Public Health, Bush's call to remain on the offensive has come too late.
"If we had a significant worldwide epidemic of this particular avian flu, the H5N1 virus, and it hit the United States and the world, because it would be everywhere at once, I think we would see outcomes that would be virtually impossible to imagine," he warns.
Already, officials in London are quietly looking for extra morgue space to house the victims of the H5N1 virus, a never-before-seen strain of flu. Scientists say this virus could pose a far greater threat than smallpox, AIDS or anthrax.
"Right now in human beings, it kills 55 percent of the people it infects," says Laurie Garrett, a senior fellow on global health policy at the Council on Foreign Relations. "That makes it the most lethal flu we know of that has ever been on planet Earth affecting human beings."
No Natural Immunity
The Council on Foreign Relations devoted its most recent issue of the prestigious journal, Foreign Affairs, to what it called the coming global epidemic, a pandemic.
"Each year different flus come, but your immune system says, 'Ah, I've seen that guy before. No problem. Crank out some antibodies, and I might not feel great for a couple of days, but I'll recover,'" Garrett says. "Now what's scaring us is that this constellation of H number 5 and N number 1, to our knowledge, has never in history been in our species. So absolutely nobody watching this has any natural immunity to this form of flu."
Like most flu viruses, this form started in wild birds — such as geese, ducks and swans — in Asia.
"They die of a pneumonia, just like people," says William Karesh, the lead veterinarian for the Wildlife Conservation Society. "When you open them up, you do a post-mortem exam. Their lungs are just full of fluid and full of blood."
Karesh has been tracking this flu strain for the last several years as it has gained strength, spreading from wild birds to chickens to humans.
"We start at a market somewhere in Guangdong Province in China," explains Karesh. "And it's packed with cages, and you'll have chickens, and you'll have ducks. You might have some other animals — cats, dogs, turtles, snakes — and they're all stacked in cages, and they're all spreading their germs to each other."
In response, Asian governments have killed millions of chickens in futile attempts to stop the flu's spread to humans.
"The tipping point, the place where it becomes something of an immediate concern, is where that virus changes, we call it mutates, to something that is able to go from human to human," says Redlener, director of the National Center for Disaster Preparedness.....