DR. DOUGLAS CAUSEY: Thank you. Can you hear me? My name is Douglas Causey and I am new here to UAA. I just started in June. I've been working in the state since 1970. And coincidentally, or not so coincidentally, I've been working on avian influenza since that time which is why they asked me to be the moderator.

What we will do in the next period here is the three panelists to my right will give presentations on various aspects of avian influenza. Flu that effects humans. And some of the other aspects of that have been talked about, but I have to tell you have not been talked about very well. At the end of their three presentations, depending on time and what's been covered, I will give a short overview as well. And then as was mentioned, if you have any questions at all please fill out a card and at the conclusion of the talks we'll have the panelists respond to them. So first I'd like to ask Jay Butler to speak and then we'll proceed from there. Thank you.

DR. JAY BUTLER: Thank you. I'd like to thank you for the opportunity and for the honor to be able to speak with you today. They say in public speaking it's not a good idea to begin with an apology but let me start with one. You've been asked here and you have a nice lunch and then somebody turns down the lights and puts up some slides. And I apologize personally for that. I'm challenged. I have a hard time speaking without PowerPoint. Even if I'd been asked to give the invocation I probably would have started with may I have the first slide, please. And I'm going to signal Carrie for advancing the slides.

Just an overview and sort of thesis of what Dr. Mandsager and I would like to cover today. Max Bazerman has introduced a concept of predictable surprises. He's spoken at the Harvard Business School quite a bit on this concept and actually has a book with that same title. A predictable surprise are those things that happen that you should have seen them coming. They often lead to the downfall of individuals and businesses and government agencies.

The thesis today, which I hope if you remember nothing else you'll leave with this, is that pandemic influenza, we'll define that better over the course of the next 15 minutes, is a predictable surprise. I'm going to spend time on basically a little bit of the science about influenza and why influenza pandemics are predictable. Answer some questions such as what is influenza, what is a pandemic, what is avian flu, what is bird flu? Why should we care? Why should we stay awake after lunch for this?

What are some misconceptions about these problems? Then I'm going to turn the microphone over to Dr. Mandsager who will discuss influenza prevention and discuss some of the reasons why the predictable surprise of pandemic influenza can be not as much of a surprise if you're prepared.

So what is influenza? Influenza is primarily a respiratory tract infection caused by an influenza virus. People will sometimes use the term stomach flu. There's no such thing. Primarily influenza is a respiratory illness. I'm a doctor, we're lazy, flu is easier to say than virus, so we may say stomach flu but we really norwalk virus. Influenza though -- the course of our discussion today is talking specifically about influenza viruses and the illnesses they cause.

It's spread person to person by respiratory droplets. You have a great picture of respiratory droplets here. Basically these are the particles that come out of our mouth when we cough, when we sneeze, even when we talk. I'm sorry, Alice, you're sharing my respiratory droplets as we stand here. Basically these are the way primary infection is going to spread, probably not more than a meter or two, as I stand here talking. Little bit of evidence that maybe it can spread through the air, but that's probably not the primary mode of transmission for influenza. So in the back of the room you guys are safe.

The incubation period is about one to five days. Incubation period is a period between when you're exposed to the virus and when you become ill. The period of infectiousness is the day before or the day of illness onset, and lasts for about three to five days. A little longer in children. And these are important components of the disease as we consider how to predict it -- how to prevent it. The incubation period is fairly short and infectiousness can actually begin prior to onset of the illness. And that's going to be one of the factors which limits the ability to isolation and quarantine to prevent spread. It's a very different disease than SARS. Also about 20 percent of infections can occur without illness. Although it's not real clear in how important asymptomatically infected people are in transmission.

When we talk about influenza viruses for humans there's three major groups. Influenza A, which is going to be mostly what we're going to talk about today. This is the type of influenza that causes pandemics. Influenza B, you may hear about because sometimes influenza B is what causes winter influenza, the epidemics we see. Influenza B is included in the flu vaccine that you may have gotten this year. That I hope you've gotten this year, in addition to influenza A. Influenza C, I just put in here because here's a chance to be smarter than your doctor because most physicians don't know there's such a thing as influenza C. Probably not very important. I'm just saying this so you'll know it exists.

So what does influenza A look like? A lot of big words on the slide but you picture the virus as a orange. I don't know if you do this at your house, but we do it at mind. At Christmas time you put cloves in it. It ruins a good orange but it makes the house smell better. If you picture the virus as having two kinds of cloves sticking off. You have a good image of what the influenza virus looks like. And the type of cloves that stick out are two different molecules. One called hemoglument (ph), the other norminadase (ph). You can shorten those names as simply H and N. They each have a function that's important as to how the virus spreads and causes disease.

The reason I bring up the H and N is the sub typing of influenza virus is based on the molecular structure of H and N such that we get names like H3N2, which is the primary cause of human influenza in Alaska this winter. We also get names like H5N1, which you're probably aware of because that is the bird flu that's being transmitted into Asia now.

Influenza A is unstable. I like to say it's one of the psychotics of the viral world. Always changing, unpredictable, and indeed changes in very important ways. Sometimes minor changes that we call antigen drift. It's very small changes in the gene, they make very small changes in the surface of the virus but might make us susceptible to that new strain that comes out. This is why the flu vaccine changes every two to three years, why new types of influenza A are in there because the vaccine will not protect us year after year after year because the virus is always changing.

Every now and then the virus makes a major change. Antigen shift occurs when there is a new virus that emerges. And that can happen by a couple of ways. We've recently learned that the virus can make major a change in its genome, spread from one species to another. That's what our fear is with H5N1. More commonly an animal will be co-inspected to two types of influenza A. If you think of the genes of influenza as decks of cards. Those cards can get shuffled. A new virus emerges and then a pandemic can occur. So it'd be a new H or H&N combination. In the past 20 years there have been three pandemics of influenza. 1918 is the granddaddy of all pandemics. H1N1 pandemics occurred again, much smaller in 1937 and in 1968.

There are all together 16 H types. Nine N types. All known types of influenza A can infect and indeed have a reservoir in nature in aquatic birds. Occasionally though they will jump species. They will make the necessary change to infect other species. Pigs, horses, porpoises, whales, seals. Horses are susceptible to a certain strain. And domestic poultry are critically important, both in terms of the economic impact and now human health with regards to H5N1.

While the aquatic fowl are generally not ill with avian influenza, the other species generally do get sick.

So what is avian influenza? This is a term for influenza A viruses that are found mainly in birds. And they come in two major types. We've already heard one of these phrases today. Low pathogenic is a type of avian influenza that causes disease that may be mild or all together absent in birds. In domestic poultry it can be manifested as just a bad feather day, ruffled, egg production is down. But it's of concern. Not only because egg production can go down but these low pathogenic strains - low pathogenic just means it has a low likelihood of causing disease - can mutate to become high pathogenic strains. H5 and H7 types are the ones that are known to do that. And they can be really devastating in a commercial flock and will literally wipe out millions of birds of a large operation.

You may recall in 2004 there was an outbreak of highly pathogenic Avian influenza in the Fraser River Valley in British Columbia. That was not H5N1, but from a bird standpoint it had the same impact of killing birds in commercial operations. And that outbreak was controlled through quarantine of the birds. And I'm not going to go any further into avian influenza right now being that there are people with much greater expertise in this area on the panel that can correct anything that I've said wrong, I trust.

Back to the territory that's a little more familiar to me, avian -- rather human influenza. These are the influenza A sub types that spread widely among humans. Three of the sub types that are currently circulating in the world are up there. H2N2 caused disease in the past century. The pandemic of 1957. It's currently not existing anywhere in labs and yes, H2N2 was the one that was accidentally sent out from a laboratory in Cincinnati to 18 labs around the world back about two years ago. Fortunately those were destroyed. But those are the kind of things that make people like Dick and I wake up at night in a cold sweat. H5N1, Avian flu, was first isolated from terns in South Africa in 1961. These were low pathogen varieties. In 1961, just two years before The Birds came out, maybe that was Alfred Hitchcock's inspiration. It's been found to circulate globally in the world. You may have heard that H5N1 has been found in Canada. Well, it has been, but it's not the H5N1 that's causing bird flu in Asia. It's a low pathogenic strain. It's a different animal. And I realize the terminology can be confusing, particularly when it comes to the media.

In 1997 a highly pathogenic strain emerged among domestic poultry in Hong Kong. And that was in, as I said, 1997. One of the things that was unusual is that this virus had the ability to be transmitted from birds to humans and it caused fairly severe disease. And that's the syndrome that we've coined the term bird flu, for better or for worse. That particular virus was eradicated through isolation of infected flocks and destruction of infected flocks. However, a new highly pathogenic H5N1 virus then emerged in late 2003 in southeast Asia, Vietnam. It appears to be a different virus in that virus primarily the ones that had the Z clone, a rather unimaginative anme, has spread now fairly widely through Eurasia.

Transition of bird flu to humans appears to require direct contact with infected domestic poultry or their secretions. There are no known instances of transmission from migratory fowl, to hunters, for instance. Human to human transmission appears to be really rare to date. From 1997 there were studies of health care providers who took care of some of these patients with a severe H5N1 infection. There was evidence of mild infection. Antibody responses to the virus. But it does not appear to be a virus that is easily transmittable to persons.

There was one family cluster that occurred in Thailand in September of 2004 that's a little more concerning. So it does appear that in rare instances transmission, person to person can occur. But what has not happened is that person to person to person to person transmission, which is what really is the ground work for a pandemic.

What's happened in the past year, the virus has spread. The slides are already a little out of date because you see Turkey highlighted with color that represents countries which has had outbreaks in birds. And of course this is, right now, the hot spot for human H5N1. Human disease has been reported in six countries. Primarily in southeast Asia but the appearance in Turkey is concerning. The spread to the west is, I think a little surprising, considering the migratory paths. Perhaps Rick will address that a little more.

Next slide. I did want to just offer one -- wasn't sure if Rick was going to address this or not, but there is more than just migratory birds to keep in mind, that would be in illegal animal transport. Or even legal animal transport in some of the countries that have been involved. I just offer this as an anecdote that at Brussels airport in October 2004, this is a picture of someone's carry on luggage, which contained two crested hawk eagles at the airport arriving from Thailand. The birds were well on examination but according to EU rules, primarily for introduction of other poultry diseases they were killed, they were tested and both found to have inflammation of their digestive tracts. One had respiratory tract inflammation and Avian influenza, H5N1, the one we're worried about, was isolated in both birds.

So what? Who cares? This is why. This slide shows the recipe for an influenza pandemic. The first ingredient is a new influenza virus which the population has little or no immunity. We have that in the form of H5N1. Second, the virus has to be able to replicate in humans and cause disease. We know H5N1 can do that. There's been officially now 184 cases with 79 deaths in Eurasia since the re-emergence in December of 2003 through Monday. Now 148 is the official WHO count, and includes only four of the cases from Turkey. I know that there are now including those first four, twenty- one cases that have been confirmed in Turkey. So I think in the next week we will see that number go way up because of the transmissions in Turkey.

In Turkey where -- seems to be the hot spot right now, which is just ironic that Turkey is where all this occurred, all of the transmission appears to be from domestic poultry. Many cases are occurring in children who are involved in care of back yard flocks. The other thing that's disturbing about what's going on Turkey is how diffuse the event seems to be occurring. Several provinces are involved even at opposite ends of the country.

The third ingredient, the one that's most concerning for an influenza pandemic is efficient and sustained person to person transmission. I'm up here, I spread it to Alice and Alice gets sick tomorrow, she spreads it to her family. Her family goes to school, and to work and spreads it there. That's how pandemics spread. That has not happened yet with H5N1. So I think it's important when we talk about bird flu, keep in mind that that is not pandemic influenza, at least not yet.

Why do we care about pandemics? Well, this slide shows overall mortality rate per 100,000 per year. It's the way epidemiologists keep track of health and life expectancy during the 20th century. And you can see the impact of the 1918 pandemic on that slide. It's not subtle. Many of you are aware of some of the anecdotes of what happened in 1918 and in 1919 in Alaska as the H5N1 strain spread throughout Alaska. Particularly the impact it had in rural Alaska.

The Department of Health and Human Services has looked at the rates of disease and death, hospitalizations and what-not from the earlier pandemics, projected that to the United States. Two points that I would make is that there is, first of all, a lot of people sick and even a lot of people who have died if a pandemic were to occur today. Keep in mind these numbers do not include some of the tools that we have today such as modern health care, antibiotics, the possibility of vaccines. But those numbers are very large and the health care system will be strained to and beyond a breaking point.

The other point I would make is the variability there. The number of deaths that can occur, for instance. There's a ten-fold difference depending on whether or not the next pandemic is like '57 and '68 or more like 1918. A ten-fold difference in estimate look like we don't have a clue what we're talking about. And basically the problem is we don't have a clue what we're talking about. We can't predict the future of how the next pandemic strain will occur. If we look at these numbers relative to the population in Alaska, we're talking about 200,000 people sick, 100,000 coming into clinics probably over a period of about 18 months. When we start talking about hospitalizations, ICU admissions, requirements for mechanical ventilation and the number of deaths we get much more into the murky water where there's at least a ten-fold difference depending on what type of virus causes the next pandemic.

The impact on business could be significant as well. We anticipate high rates of absenteeism due to an employee illness, ill family members, limits on public transportation, school closures, just general fear. There's a lot of things that could change whether or not employees are willing to come into work. There's also possibilities that people will stop flying there could be restrictions on public gatherings. That could lead to reduced ability to provide goods and services. That could change customer demand both up and down depending on what type of services you provide.

In my section I wanted to address three common misperceptions about pandemic influenza. The first one, and this is one that you hear quite a bit, is that an influenza pandemic is overdue. That's really the gambler's fallacy. There's no biological clock ticking. Pandemics happen. They happen when they happen. If you've seen one, you've seen one. They're very hard to predict.

But one thing that's different in 2006 is we have much better technology to recognize the trends of bio-evolution. We've never before been able to know to the degree that we have today, what's going on with the flu viruses in the animal population, for instance. We also have modern communications that tells much more about what's going on with animal health and human health than in the past. So our ability to see beyond the horizon is much longer than it has ever been before. Another common misconception is that a pandemic is like a forest fire. If we jump on it early it can be knocked out.

I don't want to say that's totally impossible, but I think given the short incubation period, viral shedding early after infection, the ease of spread, this is unlikely. We need to change the paradigm of how we think of pandemic influenza to other national disasters. I was stuck in Boston for an extra day last week thanks to Augustine. We know that we have volcanos right in our back yard. Here's a picture not far from where we're standing right now, 1964. We don't talk about preventing volcanic eruptions or preventing earthquakes.

We talk about being prepared, being able to mitigate the losses due to these catastrophes. And that's how we need to think about pandemic influenza. Another common one is well, there's nothing we can do anyway, and the government's going to take care of this. Katrina certainly strained that misperception. Let me just say that preparedness is critical for mitigation. But a couple of things that are going to be challenges to our response. Vaccines will not be available at the beginning of the next pandemic most likely because we don't know what's strain is going to cause the next pandemic.

We're certainly spending a lot of time preparing for H5N1, because that's probably the most likely character right now. But H5N1 may very well go away over the next couple of years and not be an issue. Alternately H5N1 may turn out to be an entirely different health threat. It may be a virus that comes much more easily transmitted from birds to humans. It may become more like Psittacosis. If you're familiar with that, parrot fever it's sometimes called. A disease that people sometimes get from birds and may become much more common. We'll have to deal with that if that happens. But bottom line is we don't know for sure what the next strain that causes pandemic influenza will be. There's a lot of reasons to think that it could be H2N2 coming back again. But I'm getting out of my depth certainly going that far in trying to predict strains.

Another likelihood, particularly if a pandemic occurs any time in the next year, anti viral drugs would be in short supply. They just aren't that many in the world. Tamiflu comes from a natural -- comes from the star anise tree, for instance. And my understanding is that -- the manufacturers of Tamiflu buy about 90 percent of the world's harvest of that agent. There is now a way to synthesize that precursor to oseltamivir but it's more than just cranking up the production capabilities by making bigger factories Some of it is learning how to make drugs better.

But again, the other caveat here is there are things that we can all do and on that note I want to turn the podium over to Dr. Mandsager to tell us how we might be able to be less surprised by this predictable event.