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Gold9472
10-01-2005, 10:05 PM
'We Are in Real Trouble'
A health expert warns of the increasingly real possibility of an avian flu pandemic and what we can do prepare

http://www.msnbc.msn.com/id/9547047/site/newsweek/

By Jennifer Barrett
Updated: 7:28 p.m. ET Sept. 30, 2005

Sept. 30, 2005 - Since its discovery in the late 1990s, the avian flu virus, or H5N1, has infected at least 100 people, more than half of whom have died. But public health officials around the world are warning that the casualty numbers could be much higher if the virus becomes more easily transmittable between humans. On Thursday, Dr. David Nabarro, an executive at the World Health Organization and newly appointed United Nations coordinator for avian and human influenza, stoked fears even more when he warned that a flu pandemic could strike at any time, killing five million to 150 million people. On Friday, the World Health Organization backed away from the high end of those estimates, but concurred that millions could die in a pandemic. Laurie Garrett, a senior fellow for global health at the Council on Foreign Relations and author of “The Coming Plague: Newly Emerging Diseases in a World Out of Balance” (published in 1995 by Penguin) spoke with NEWSWEEK’s Jennifer Barrett about the possibilities of a pandemic, and what we can do to prepare. Excerpts:

NEWSWEEK: The avian flu first emerged more than eight years ago. At what point did health experts begin to worry that it could turn into a deadly pandemic?
Laurie Garrett: The turning point in concern came in 2003 when the virus emerged in slightly different form. It had mutated a bit and become extremely virulent in both chickens and human beings. At that point, there began to be massive killings of chickens... We’ve come to a recognition starting at that point that we are in real trouble.

The avian flu has infected about 100 people and killed more than half of them. Do we know how these people are being infected?
Some are infected by human to human transmission; but by very, very close contact—not like regular flu. It’s still a hard virus for a human being to catch. I don’t think anyone is really sure of how these cases have occurred. There were cases in Jakarta [in Indonesia] where the only common exposure was at a zoo. But it’s hard to come in close contact with animals at a zoo.

How likely is it that the flu will jump from birds to humans?
I don’t think there’s any dispute that some cases were human-to-human within clusters. We have seen so many family clusters. Yes, it’s possible all the family members were exposed to the same darn chicken. But it’s also possible that one family member caught it and transmitted it to the rest of the family… What hasn’t happened yet, and if it had we wouldn’t be having this conversation, is the crucial mutational change that would make it highly contagious as per a typical flu contagion level.

What needs to happen for that to occur?
We don’t know exactly what nature of genetic change is necessary to make this type of human-to-human transmission possible. This particular type [of flu] has never been in our species—to our knowledge anyway. So there are two implications. That absolutely no one reading this article is immune. And, two, that we don’t know how it tracks in human beings. It is not a normal flu. For this flu to get into a form that would rapidly spread from one human to another or from a human to a towel or a cup or a doorknob or a subway pole to another human, we don’t know what would have to change. We also cannot answer another question that comes up. Will it still be killing 55 percent of all people if it changes? We don’t know if it has to forsake most of the virulence if it changes. We hope so, but we don’t know if that is the case…It could happen through a recombination event or a mutational drift event.

What does that mean?
Genetic drift means an individual nucleotide swaps for another and maybe a couple more swap and slowly but surely the virus takes on new characteristics. It’s clear that process has been underway since the avian flu first surfaced in 1996. Recombination is a far more dramatic event and potentially far more catastrophic. The virus is very sloppy; it stores as genetic material in the chromosome but not neatly packaged and with integrity. When it reproduces itself, the chromosomes fall apart and genetic material goes into the cytoplasm of the cell it infected and randomly absorbs genetic material from the environment.

So it could pick up other viruses?
We know that H5N1 has already recombined a couple of times. It recombined with the bird virus in 1997 and that’s what emerged in Hong Kong. The fear is that a human being or a pig or some other high form of mammal would be simultaneously infected with a highly contagious garden variety flu and they would swap genes and the resulting [virus] would have high virility characteristics and high transmission characteristics.

So it’d be very contagious and very potent?
Yes, one reason we’re worried is that we are entering flu season so there’ll be regular flu floating around and more people infected with one. If anyone gets infected with the other, that would be worrisome.

Not everyone is so worried. Marc Siegel, an internist and associate professor of medicine at New York University School of Medicine, claims there’s no direct evidence that it is about to mutate into a form that would transmit from human to human.
I don’t know what Dr. Siegel is talking about. By the time we have direct evidence, we have a pandemic. If we are waiting for absolute proof that H5N1 has turned into a typical human to human transmission flu, then we are dealing with a pandemic.

Is there any reason to believe it won’t morph into something more contagious?
Evolution has its lack of predictability and is often directed by selection pressure. If it favors the emergence of extremely wimpy viruses and if it moves in that direction, it could die out in poultry. But we’ve seen just the opposite in the last year; it went into migratory birds, and is killing some of them, and spanning a territory that is extraordinary—from Indonesia to eastern Europe to the far western frontiers of China to Vietnam. But nothing would please me more than for us to be on the phone five years from now and for your first question to be: `You really scared the be Jesus out of us in 2005 and now that it is 2010 don’t you feel like idiot?’ And I’d say, ‘Not an idiot. No one could be happier.’

I understand there’s no vaccine yet. Why is it so hard to create a vaccine when we’ve been studying the virus for so long?
There is a vaccine announced by the National Institutes of Health that targets a particular strain of H5N1 in a particular strain in chickens... But it seems only to provide protective immunity for humans at the highest possible dose. It would mean two rounds of vaccinations. You’d have a real high drop-out rate… The other problem is that the vaccine must be thought of as a prototype because the human-to-human transmitter will have changed itself [so the vaccine might not protect you from it].

But there is a treatment made by Roche Pharmaceutical in Switzerland: Tamiflu. Is that the only one?
It’s not really a treatment. It doesn’t cure you, but it slows the ability of the virus to overwhelm your body and make lots of copies of itself and that buys you time to develop appropriate immunity and kill it off. Even then, you need to take it in the first 36 hours. You need to know how to tell the difference between a cold and the flu. You have to be able to pay for the prescription, while you are deathly ill, and dose yourself in less than 36 hours.

I understand that the U.S. has ordered about 6 million doses. But the U.S. government has estimated it needs at least 20 million doses.
At the current rate of production, by the end of 2006, there would be enough Tamiflu for 1.5 percent of the world’s population. If the company revved up production to the maximum, it would hit two percent. So it would take 10 years at maximum production to make enough for one out of five people.

Why not set up more plants?
Even an Indian generic manufacturer said it would take at least two years to get to the point of doing it. It’s a very difficult synthesis, I’ve been told. It’s more involved and very difficult and it requires unique production facilities.

How long do these treatments last?
If I understand it, Tamiflu in raw powdered form lasts 10 years. In capsule form, it has a shelf life of five years, assuming you are keeping it in cool dry place.

It’s not as if those at the highest levels of government are unaware of the threat. So why haven’t we done more to prepare?
My response to that depends on my mood in a given moment. There are times when asking that question will get steam pouring out of my ears and I’ll be a raving lunatic. And at times I become more cynical… When [former President Bill] Clinton ordered a multi-agency study on emerging threats, pandemic flu was number one. It is not new that the scientific community has been warning about it. What is new is that we are well past a warning. We have got [figurative] ambulances rolling through the streets with sirens wailing saying: Get out of the way, there’s trouble coming!

What can we do now?
There are various stages of government preparedness plans underway in Washington now. You’ll see some released to the press in the coming months. They will be controversial and there will be arguments and there will be changes well into the middle of 2006. But the real bottom line for Americans is that … there won’t be Tamiflu or hospital beds for everybody, or vaccines. We will be in a situation where, to a tremendous degree, every community will have to take care of itself. It’s an eye opener for all of us.

© 2005 Newsweek, Inc.