HERE IS AN UPDATE FROM THE CENTERS FOR DISEASE CONTROL

HERE IS THE ASSOCIATED PRESS RELEASE

October 12, 1976: Nurse Jacqueline Spaky administers a swine-flu injection with an injector gun on the first day of the immunization program in New York City.

Tamiflu resistance prompts Canada to change drugs in pandemic stockpile.

Supplies of the drug zanamivir — sold as Relenza by GlaxoSmithKline — will be beefed up in the national emergency stockpile, says Dr. Arlene King, the senior official responsible for pandemic influenza planning at the Public Health Agency of Canada.

As well, some stocks of an older flu drug, amantadine, will be added to the mix as an inexpensive extra. Scientists are studying whether using Tamiflu in combination with amantadine or a sister drug, rimantadine, will lower the likelihood flu strains will develop resistance to the few drugs currently marketed to treat influenza.

"I think the general view is that from a scientific perspective, greater diversification [of stockpiles] would be desirable," says King, director general of the public health agency's centre for immunization and respiratory infectious diseases.

"And as I've said, we've made that decision at a federal level."

King says discussions are still underway with provincial and territorial partners about whether to diversify the holdings of another stockpile, known as the national antiviral stockpile, where the bulk of Canada's pandemic flu drugs are held. The cost of building up and maintaining this stockpile is shared by the federal, provincial and territorial governments.

The national antiviral stockpile contains 55.7 million doses, enough to treat nearly 5.6 million people. Tamiflu, which is sold by Hoffman-La Roche, makes up 90 per cent of the holdings. Relenza accounts for the remaining 10 per cent.

Over the past five years a number of countries have stockpiled antiviral drugs — mainly Tamiflu — as a hedge against a feared flu pandemic. Tamiflu seemed to be a safe bet. Resistance to the drug was rarely seen. And laboratory studies suggested viruses that acquired resistance would be weakened and less able to spread from person to person.

To widespread dismay that theory was proven to be wrong in the winter of 2008. A resistant strain of influenza A virus of the H1N1 variety emerged in Northern Europe. The strain took off, rapidly spreading around the world.

U.S. weighs stockpile change

It is now the dominant strain of H1N1 viruses circulating. Almost 100 per cent of all H1N1 viruses tested in North America this winter were resistant to Tamiflu.

While other flu viruses — including the worrisome H5N1 avian flu strain — have not followed suit, the demonstrated vulnerability of the drug has prompted a number of governments to rethink how heavily their pandemic response plans lean on Tamiflu.

The U.S. Department of Health and Human Services is considering altering the composition of its national pandemic stockpile, which is 80 per cent Tamiflu to 20 per cent Relenza, according to Dr. Robin Robinson, director of the department's biomedical advanced research and development authority, which oversees pandemic preparedness.

And earlier this year Britain bought more than 10 million additional doses of Relenza, which to date hasn't developed the resistance problem seen with Tamiflu.

In Canada, Tamiflu makes up the lion's share of both the national emergency stockpile, which is maintained by the federal government, and the national antiviral stockpile.

The two stockpiles combined, along with other stores of flu antivirals held by governments, are estimated to contain enough antivirals to treat about a quarter of the population during a pandemic, King says.

That is within the range of the holdings of a number of similar countries, though Britain has stockpiled enough of the drugs to treat half its population.

Expiring drugs

Canada's national emergency stockpile, which is meant to act as a backup to the larger stockpile, currently contains 14 million doses, enough to treat about 1.4 million people. Relenza makes up just under 30 per cent of those supplies. King says an additional two million doses of antivirals will be added this year.

"This upcoming year we'll be purchasing a little bit more zanamivir and a little bit more amantadine," she says.

As well as adding drugs, authorities are now facing decisions about what to do with expiring drugs. Some of the supplies in the stockpiles have reached their expiration date or will do so this year and next.

"The replacement strategies right now are being considered and acted on by each of the jurisdictions that have expiring stock," King says.

In the national emergency stockpile alone, enough drugs to treat roughly 275,000 people will have reached their expiration date by 2010-2011. King says the federal government is looking at a variety of strategies, including approving an extension of Tamiflu's shelf-life.

Tamiflu was originally sold with a five-year shelf-life, but Roche has data showing the drug is still active at seven years.

As well, the company has offered governments the opportunity to reprocess expiring supplies of Tamiflu.

In an interview last year, Roche's Dr. David Reddy said the company could extract the active ingredient, insure its quality and purity and reformulate it into capsules.

That process is the equivalent of "resetting the clock on the drug," said Reddy, the company's pandemic influenza task force leader. He would not say what the process costs, but said it provides significant savings over the cost of buying new supplies of the drug.

PUBLIC health experts warn that the world might be close to a repeat of the flupandemic of 1918, which killed millions. But could it instead be close to a reprise of the 1976 pandemic that never happened?

That is the year President Gerald R. Ford announced a crash program to "inoculate every man, woman and child in the United States" against swine flu. But the virus never became a killer, and vaccinations were halted two months after they began after reports that 500 people who received the shot developed a paralyzing nerve disease and more than 30 of them died.

Bettmann/Corbis

A vaccination in Watsonville, Calif., in 1976 as part of a crash program to fight swine flu.

If scientists were wrong in 1976, could they be wrong now? Some arguments being made about why a pandemic is looming echo those made three decades ago. But many experts say the situation now is different enough that a false alarm is less likely.

"We just know a lot more about the influenza virus than we did in 1976," said Ira M. Longini Jr., a professor at Emory University who is an expert on epidemics.

Still, a lot can be learned both from what did and did not happen back then.

The 1976 scare started in February when a handful of soldiers at Fort Dix in New Jersey got sick and one of them died. Scientists determined that the virus was one that infected pigs and was different from the human influenza viruses circulating then. On March 24, barely a month later, President Ford announced the vaccination plan.

One reason for the concern was that scientists thought the 1918 pandemic had been caused by a swine virus and that the Fort Dix outbreak marked its second coming. Furthermore, experts warned that pandemics tended to be cyclical and that another one was about due.

Today, thanks to genetic analysis - a technique not available in 1976 - scientists know the 1918 virus was a bird virus that mutated. So now there is concern that the H5N1 avian strain ravaging birds in Asia could in like fashion evolve into a form that can spread easily among people. The avian virus shows some mutations similar to those in the 1918 virus, said Jeffery K. Taubenberger of the Armed Forces Institute of Pathology. And experts are again warning that the world is overdue for a pandemic.

Edwin M. Kilbourne, a professor emeritus at New York Medical College who argued for the vaccination program in 1976, said there was actually less reason to be concerned about a pandemic today. That is because the swine flu virus at Fort Dix clearly passed easily from person to person, while the current avian flu has not.

Many experts disagree, however. In retrospect, they say, the 1976 decision to vaccinate was based on much less solid evidence than is available today.

"Part of the problem was convictions outpacing evidence," said Harvey V. Fineberg, president of the Institute of Medicine, part of the National Academies, and co-author of "The Epidemic That Never Was," a book about the 1976 experience. "I don't think that's happening today."

Even in 1976 there seemed to be more doubt than there is today about the issue. The World Health Organization and many European nations, for instance, did not see what the fuss was about. Today, they are busily preparing for a pandemic.

Doubts grew through the summer of 1976 when the virus was not detected outside Fort Dix. That first death turned out to be the only known one from the virus. Moreover, studies suggested that several hundred people at Fort Dix had been infected but most never got sick.

"That's very different from 120 cases with half the humans dying," said Dr. Fineberg, referring to the approximate toll so far from the Asian bird flu.

Perhaps the biggest mistake in 1976 was giving the vaccine to millions of people rather than just stockpiling it until clearer signs of an epidemic emerged. W. Paul Glezen, a professor at Baylor College of Medicine in Houston, said the prevailing belief was "we should use it because if it started spreading there wouldn't be time."

The vaccination program had problems. Production was delayed after one company produced the wrong vaccine. Another delay occurred when manufacturers demanded that Congress protect them from liability. Mass inoculations did not start until October, which might have been too late had a pandemic begun.

Still, by the time the program was halted in December, only 10 months after the virus was identified, about 150 million doses had been made and 45 million given.

There are lessons from 1976 that might be applied to today's preparations. A 2004 draft of a government plan for a pandemic listed some.

One is that "making clear what is not known is as important as stating what is known." Another is that a program should be re-evaluated periodically rather than left on autopilot.

And this time, federal officials said, the vaccine won't be used until there are signs a pandemic is under way.

Dr. Fineberg said another lesson is that Congress should provide liability protection for vaccine makers now, rather than waiting until the crisis occurs.

He said the wrong lesson to draw from 1976 would be "the superficially obvious one" - that because it didn't happen then it won't happen now and preparations are not necessary.

Still, repeated cries of wolf can make the public blasé.

"There's so much expectation for it to develop into a pandemic that if it does not in the next year or two it's quite possible you would see a backlash like the 1976 experience," said Dr. Taubenberger. "What I fear is that people would make the conclusion, falsely, that influenza is not such an important public health problem.

Do Not Take A
Swine Flu Vaccine!
From Patricia Doyle, PhD
4-25-9