Conference sponsored by:

Center for Biosecurity of UPMC

Deutsche Bank

The Contingency Planning Exchange

Avian Influenza: Current Status and Potential Impact
Robert Webster, Ph.D., Rose Marie Thomas Chair of the Virology Division, Department of Infectious Disease, St. Jude Children's Research Hospital; Director, WHO Collaborating Center on the Ecology of Influenza Viruses in Lower Animals and Birds

Speaker biography  |  Video

I can tell you that when H5N1 appeared in 2003 and Klaus Stöhr called a pandemic alert, within 15 days we had a new vaccine strain prepared and ready for use in the population. Has that vaccine been prepared in sufficient quantity? No.

The problems are not with the scientists but with the public. And, I'm afraid that, as a scientist, I've been talking to the choir too long, and it's a privilege to talk to you people, because you are the people that have to push to get these scientific achievements that are in place through the Congress, through the governments, so that they're put in place in time, so that [we're] not faced with a Katrina, which is a total disaster. We have the tools to build the levees higher. They are not doing it; they're piddling around here. But, let me go to my script now for a little bit. I just want to introduce influenza on the left.

I will give you a little background on influenza. We all think, or most people in this room think that influenza is a problem of humans. It really isn't. There are 16 families of influenza. They all live in the wild aquatic birds of the world, and they live in total harmony, no disease, no problems at all.

So far, of these 16 families, 3 have appeared in humans over the past century and caused problems. The threats we see at the moment are H5, H7, and H9. These are all possible pandemic threats that we have to deal with. Just to look back at the last century, [at] the last pandemics and how they appeared: The pandemic of 1918 was catastrophic, [killing] somewhere between 20 and 50 million people. That virus emerged from the aquatic birds of the world by direct transmission. It didn't reassort somewhere. It came, as Jeffrey Taubenberger tells us, from the wild birds of the world, by accumulating like mutations, and it became [such a] dreadful killer [that] many cities of the world couldn't bury the dead. In my own native New Zealand, whole villages just disappeared, and this was a catastrophic event.

The other we know much more about -- the Asian pandemic. It killed about a million people in the world. That virus reassorted probably in the pig. It got its coat proteins from a duck in Asia, three gene segments, and its transmissibility from the human strain, so it shuffled its genes. It had viral sex, if you like, in the pig, shuffled its genes, and it got transmissibility from the previous human strain, and it killed about a million people and continued to evolve.

And, then in 1968 a similar kind of thing occurred. So we've got two strategies, two major strategies for influenza viruses to acquire transmissibility, either by mutation, accumulations of point mutations, or what we call "viral sex" probably in the pig.

So let's turn to H5N1. We've heard that this virus has spread across Asia, and all the countries in Eastern Asia have been affected. Hundreds of millions of chickens and domestic poultry have been culled to try and stop its spread. The bottom line is that there have been more than 100 cases and more than 50% of those have died. Those are not good odds.

If we look at the various countries, the activity is still going on in Vietnam, a lot of activity in Indonesia. The great worry at the moment is Indonesia. The number of cases is uncertain, but probably increasing. Thailand, I want to look at for a moment; because, in Thailand, there are no new cases in 2005 in humans.

The Thais have been doing something correctly, which sends a message--there are things still to be done out there to stop this virus spreading, and the Thais are doing that, and so we could come back to that in the question time.

The genesis, I want to walk through how these viruses appear. These viruses, we first met them in Southern China, in Guangdong in 1996, where a few geese started dying. A virus in the wild birds of the world spread into geese, mutated, and started killing a few geese. That virus got into the live poultry markets in Hong Kong, and the goose viruses mated with a quail virus and a duck virus, and reshuffled their gene segments to give us a virus that infected humans.

The Hong Kong authorities wisely culled all of the poultry, got rid of that virus. We've never seen it again, but the virus kept reappearing out of Southern China, out of the goose population, and that virus reassorted with multiple other viruses to give us the current lot of viruses. And, up till 2002, it didn't kill ducks, but after that, it learned that trait.

There have been three waves of this virus through Asia and we can ask, "How pathogenic is it, how bad a virus is this one?" The prototype of these viruses is called Vietnam H5N1. If we inoculate this virus into chickens this afternoon, they're all dead tomorrow morning. It's a real killer. It kills ducks in one to two days, high risk of death in humans, with diarrhea, respiratory signs, and neurological symptoms. Diarrhea and neurological symptoms are not standard flu.

If we put these viruses into ferrets, the animal that we classically use for working with influenza, [in which] influenza usually causes a mild infection, respiratory [signs], and a high fever. This [virus causes] respiratory signs, diarrhea, hind leg paralysis, and they die. This is the first one of these influenza viruses that kills the ferrets--spreads throughout the body to the brain, and they die with paralysis.

These are extraordinarily bad viruses. I've worked with influenza all my life, and these are the worst influenza viruses I've ever seen.

What about pigs? We mentioned earlier on that the pig probably plays an important role in getting these viruses across from the avian reservoir to humans, and I should point out, at this time, the only characteristic this virus doesn't have is its ability to transmit human-to-human. It transmits from the chicken population to humans and kills a high percentage.

What this virus hasn't learned to do yet is to transmit from you to me, me to you. If it learns that trait, then we're in terrible trouble, and we ask this question: Would these viruses replicate and transmit in the pig? Because that would an indicator of what's happening.

We put a human, a chicken, a duck, a goose virus into pigs in our isolated facilities. We put two pigs in a cage, and the virus infected every one of the pigs, but it didn't transmit. The virus hasn't got the characteristics of transmissibility, and there is a tendency, at the moment, to think what's been done since 1997. It hasn't learned to transmit yet. Well, we can forget about it--it's not going to do it.

Don't believe it. This virus is going to learn to do it. Historically we can go back to Helen of Troy. We've seen influenza all centuries, and we've had the privilege, if you like, of watching this one evolve very slowly from 1997-acquired new characteristics, and it's probably going to do it . . .

[sick chickens were fed to tigers and leopards in Thailand, they all died . . . [a] group in the Netherlands fed the infected chickens to domestic cats, they died. [They] not only died, they transmitted . . . cat-to-cat. Many people in this room have cats as pets. If this virus gets away, that's going to be another animal for transmitting.

The duck, we now recognize, is one of the big problems with this virus, because early on in 2002, the virus started killing ducks. The assumption was if the virus was in the community, the ducks would die. But the virus and duck have been together for millions of years, and the virus is evolving rapidly and many of the ducks, at the moment, are not dying. And so in the duck, the virus retains its high-pathogenic characteristics for chickens and presumably humans. It keeps drifting along and changing its characteristics, and the virus is currently quite stable in the environment.

A big question is whether the wild, migrating birds of the world, which mainly migrate north to south in the hemispheres, have been involved in transmitting. We're not sure if that was the case early on. We now know that these highly pathogenic viruses are in the wild birds of the world.

From when the deaths that occurred in Western China (on April 30) there were a few dead geese on Qinghai Lake. By May the 4th there were daily mortalities of over 100 geese and by June, five thousand geese had died, and this is in an area where there's no domestic poultry.

Since that time, the virus that occurred in May . . . has been spreading westward into Southern Russia, in the Novosibirsk region and now to Kazakhstan, and right up to the border of Europe, with migrating birds transmitting.

The Europeans in Holland and France have put their commercial birds inside. A lot of arguments, the Dutch have just taken them out again, but the worry is that this virus will spread westward and extend its range. By extending its range, it extends the number of times it multiplies, the number of times to make mistakes and to learn this trick of human-to-human transmission.

So what's the good news? What do we have, as scientists? What do we have to offer the world? In 1997, when we first found it, [the] drug amantadine was effective. However, with this drug, an ion channel blocker, you get resistance rapidly. The recent human strains are totally resistant, so that drug is not available to us.

However, the good news is that the neuraminidase inhibitor, also known as oseltamivir, is efficacious. This is the study in a mouse model to show that if we use 10 mg/kg per day, the drug is effective. So this is our ace in the hole. That's been developed in the last five years based on basic science and structural biology.

What about vaccines? There are no vaccine strains available, but scientists in the last three years can make any influenza virus that we think about by a process called "reverse genetics." We can make these viruses and make vaccine strains extremely rapidly.

The studies on these vaccine strains in ferrets show complete protection of homologous challenge, cross protection between one strain and the next, and with no virus shedding, no weight loss, no virus in the brain. And so we can manipulate this virus to make a perfect vaccine strain very rapidly.

The problems are with liability. These are the problems, not enough vaccine factories, certainly not in the United States, and so the scientists, I argue, have done their work. Time has probably got it right. There is a bird flu epidemic hatching in Asia.

So the question that people here are likely to ask is, "What is the economic impact?" We can look back at SARS. With 8,000 cases, about 70 to 74 people died, and the GNP dropped by 0.2 to 1.8%. With pandemic influenza, up to 35% of the global population, millions, probably billions would die in the first wave, and the effects would be catastrophic. The comments raised at the back, you're absolutely right, our culture as we know it today would be drastically affected. SARS hammered the Canadian economy and H5N1 would [do so] much, much more.

I'll just finish by showing you the Vietnam chicken. It's the Year of the Chicken, and my colleagues in Vietnam pointed out [that] during the last Year of the Chicken 12 years ago, millions of people died due to the war and starvation. They're concerned the same thing could happen this Year of the Chicken.

And so I'll just summarize what I've said. This H5N1 is lethal for wild waterfowl, so it's going to continue spreading in the world, [it's] lethal for humans, lethal for ferrets, lethal and transmissible in the cat families, and the infection and transmission in pigs in Indonesia -- it is a great worry. This virus is evidently in the pigs in Indonesia and is now causing death, and that is a big worry.

This summarizes what the United States is doing about the bird flu epidemic. I think that we have to accept that fact that we're sleeping on top of a time bomb. I repeat: the scientists have done their jobs. Now it's up to you people to push, to use that science to put our levees in place.

I'd like to conclude by acknowledging that the work was supported by NIH, that many people in the world working on flu, especially from Hong Kong, Indonesia, Vietnam and Thailand, contributed the viruses and work. I'll stop there.

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