BATTLING BIRD FLU: Are we facing a Pandemic?

Owen Egan

A representative of the World Health Organization recently warned that we may be on the brink of a global pandemic of avian flu. As Chief of McGill's Division of Infectious Diseases, Associate Director of the Centre for Tropical Diseases and an investigator in the Centre for the Study of Host Resistance, Brian Ward, MDCM'80, is an expert on viruses and vaccines. We asked him to comment on the likelihood of a worldwide outbreak of disease and how prepared we are to meet it.

Do you agree with the World Health Organization official who said that the world is "in the gravest possible danger of a pandemic" of avian flu?

Many of the people in the WHO have been using words like that for several years, so he wasn't the first, nor will he be the last. Of all the biological threats we are currently confronting as a species, a pandemic of influenza is the most credible, and certainly among the most serious. Some people would say he is using hyperbole, but he is very likely to be right. The influenza pandemic of 1918 killed somewhere between 19 and 50 million people, most of them in the first six to eight months - not a whole lot of time to react.

Are we any better prepared now to deal with such an outbreak?

Our entire worldwide capacity to produce influenza vaccine right now is around 250 million doses per year. In other words, roughly 4% of the world's population could be protected in the first year. And that assumes that we could make a vaccine, that we could distribute it effectively, and that the mortality didn't occur in the first six months. If most of the deaths occur in the first six to nine months, we might do far less well.

The fear is that the avian flu virus may become highly contagious among humans. How likely is that?

This is a question of chance and statistics. There is a flu epidemic every year, and there have been flu pandemics every 25-35 years. Since the last pandemic was in 1976 (the "swine flu"), you don't have to be a math genius to know that we are pushing 30 years. We are due for another pandemic, and maybe due for a really bad one. Avian influenza, if it maintained its current level of mortality, would be devastating. A third to two-thirds of the people who have acquired this disease have died from it, and these have not been elderly or debilitated individuals. Most of them have been healthy and young. So, if a pandemic were to occur and we had nothing to protect ourselves, that would be among the gravest possible threats.

How might it become contagious for our species?

All influenza viruses can mutate and the H5N1 strain of viruses have been actively mutating in bird populations since 1978. The big fear is that the virus will mutate progressively towards being better able to transmit itself from human to human. This kind of change would be called "genetic drift," incremental changes drifting by chance in the direction of human transmissibility.

This is not the only way a pandemic virus could emerge from avian flu in birds. It could also come via another animal susceptible to influenza A infection, such as a human, a pig, or even a cat. (Type A influenza viruses are usually responsible for large outbreaks.) If any single cell of such an animal is simultaneously infected by a human and a bird influenza A virus, there is the potential for something called "genetic shift." In this setting, all possible combinations of the two virus species can be produced. These new viruses could theoretically contain components of the bird virus which human immune systems would not recognize, as well as components from the human virus that would permit easy transmission between people. We know that such recombinant influenza A viruses can form quite readily, and that's why they're so dangerous.

Because we have no immunity?

We are all exposed to flu viruses almost every year. Most of us have a little bit of immunity from our previous exposures to influenza viruses, because the viruses usually just drift from year to year. As long as there have been no major changes in the virus, I am likely to have partial immunity to a 2005 virus because of my exposure to closely related influenza viruses during 2004 and 2003. However, none of us, except for some people in Asia, have ever seen an H5N1 virus, the principal strain of avian flu. As a result, we are all potentially highly vulnerable to these viruses because our immune systems have no past memory. This is the scenario in which many people could die.

Viruses like HIV have moved from animals into human populations. Is this becoming a more common threat?

There may be more potential for animal viruses to "jump" to humans for several reasons. First, because of overpopulation, more people are moving into once remote parts of the earth's surface. For example, miners and farmers are hacking their way into the rain forests. Second, we are travelling to ever more exotic areas. There weren't very many people kayaking down the Amazon 30 years ago, but now an adventure vacation of this kind is more or less routine. Many more people are putting themselves in the way of potentially dangerous organisms. Third, we've always had zoos, but now people keep all kinds of weird pets in their homes. Look at the outbreak of monkey pox in the American Midwest in 2003; people were keeping Gambian rats as pets. The virus jumped from the rats to prairie dogs, which people were also keeping as pets, and then jumped to people. Finally, we're much better at diagnosing many of these exotic illnesses. In the past, people would have acquired these diseases and died without a diagnosis. Now we can very often find out what happened.

So far, avian flu has killed 45 people. How did they catch it?

Most people believe that they caught it through very close association with birds, either living or dead. Most known cases were associated with domestic birds, but the virus also exists in wild bird populations, so hunters could also be at risk. The majority of the victims of H5N1 influenza to date had clear exposure to chickens, ducks or geese, on farms or in markets. In a very few individuals, no such association with birds can be found, and those are the cases in which the virus may have been transmitted from human to human.

How would it spread if it becomes highly contagious?

By the respiratory route - and it will spread very quickly. About 40% to 60% of influenza is spread before people become symptomatic, which is very different from SARS, for example. SARS is mostly spread by individuals who have symptoms. With influenza, it's terribly difficult to quarantine people because they are transmitting it before they know they're sick. Someone could quite innocently get on an airplane anywhere in the world and infect people all around them. Transmission can occur easily without terribly close contact - in a room, an airplane or an elevator.

Is the spectre of a global pandemic a worst-case scenario, or a likely one?

I think most scientists believe that an influenza pandemic is inevitable, whether it is avian flu or something else. The real question is, how prepared are we going to be when it comes?

What are the prospects for developing a vaccine or other treatments?

I'm an optimist; with the next flu pandemic, we will have a vaccine. However, the speed with which it becomes available may be a critical factor. As soon as a virus jumps from the bird population - or maybe from pigs or cats - into humans, and shows the ability to spread from person to person, the clock is ticking. How long will it take the vaccine industry to gear up and make the right vaccine?

I have letters from colleagues in Tunisia and other countries which say, "What happens to us in the event of a flu pandemic?" Tunisia has no flu vaccine manufacturing capacity. What if a pandemic is causing 10% mortality throughout the world? Does that mean countries like Tunisia have no access to a vaccine until the countries that can make it have finished vaccinating their populations?/

What needs to be done to prevent the spread of avian flu beyond certain areas of Asia?

We'll never contain it; there's no way. That's really a naive hope, that we could contain influenza in a geographic region. It's never been done before. It's impossible because, as I said, around 50% of transmission occurs before people are symptomatic. In order to institute effective quarantine, there could be no movement. Quarantine is not a viable protective strategy for influenza A.

Avian flu was recently found in other animals, such as tigers and cats. Does that indicate a mutation and possible move towards humans?

It's not a good sign. Most people don't cozy up to tigers, but they do cozy up to cats. It's not known whether cats can also be infected by human influenza. There are two possible scenarios here: one is that the cat catches avian influenza from a bird and brings it into the human household. The cat is acting as a conduit for the virus. In the second scenario, a single cell in the cat could be simultaneously infected by both a bird virus and a human virus, and that's where genetic shift could theoretically occur, producing a mixing and matching of all the viral genes.

Most people in the West think of flu as something nasty you get in the winter but recover from after a week or two of bed rest. What is different about something like avian flu?

First of all, that is a misconception. Influenza is one of the reliable causes of winter season mortality and morbidity. Although most healthy young adults will survive, garden variety influenza A kills thousands of elderly people every year. Over the age of 65, the risk of mortality from influenza goes up significantly. That's why we target the elderly specifically for vaccination.

Second, avian flu has a 33% to 66% mortality rate among young, healthy individuals, so it is massively more dangerous. Its lethality in humans to date has been extraordinary.

What should be done in countries that can't afford vaccine programs or to take preventative measures?

There is very little that they can do. There are anti-viral drugs, but they are very expensive, and they won't be available either. Furthermore, some influenza A viruses are resistant to whole families of anti-viral drugs. This is certainly the case for the H5N1 viruses circulating in birds at the moment.

What kind of bug caused the 1918 influenza pandemic? Why did it kill so many people?

That was caused by swine flu. There were no vaccines or effective anti-viral drugs in 1918. However, there probably wouldn't have been enough time to vaccinate even if the technology had been available to generate a vaccine, since so many of the deaths occurred so quickly. We don't yet fully understand what made this particular influenza virus so deadly.

How can we prepare to fight new bugs?

We need to know more about anti-virals. HIV has spurred the development of anti-viral drugs, but we still don't have very many. Clearly, some viruses can be targeted by drugs. We have really had quite phenomenal success with HIV to date. We haven't cured it, but it used to be uniformly fatal in a very short period of time. Today many people have relatively asymptomatic periods measured in decades.

We also need more efficient ways of developing vaccines and of delivering these products in new ways, such as through the nose or mouth. Finally, we need to be able to move quickly from developing and testing a vaccine to mass production and mass distribution. For example, once a vaccine is developed in Canada it would have to be tested in at least 9,000-12,000 people before distribution to the entire Canadian population. How quickly could we recruit, inject and study 12,000 people in Canada? Once the data is collected, how quickly could we analyze it and get it to the regulatory authorities for approval?

Many of us in the vaccine community would like to have all of these steps pre-approved and set up like dominoes. In the event of a pandemic, we wouldn't have to think a great deal - all we would have to do is tap one end of the chain of dominoes and everything goes into motion. We could theoretically shorten that whole process down from months to weeks.

What can people do to protect themselves?

In the event of a pandemic without either a vaccine or effective anti-virals, limiting mobility would make a great deal of sense, as well as discouraging public gatherings, etc. This happened to some extent in the 1918 pandemic: movie theatres were closed and people stayed home. Similar strategies were employed during some of the large polio epidemics as well. Preventing people from getting together can certainly slow the spread of some viruses.

Dr. Brian Ward was interviewed by Montreal freelance writer Sylvain Comeau.

Left: A Vietnamese man transporting chickens has them disinfected at a market in Hanoi. Right: Bottles of flu vaccine make their way along an assembly line at a Quebec City pharmaceutical company.
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