The following is an edited excerpt from and interview with Professor Roy Anderson, conducted in late 2005...

How likely is human-to-human transmission of a lethal H5N1 virus?

It is quite difficult to estimate the likelihood of when it will happen. Bird virus has been around at least since 1996; we haven’t had that event despite very close contact between humans and birds in Southeast Asia and China. We have had a nine-year period where no event has occurred. Now, the next nine or ten years, the likelihood is that it will occur. But we are not certain what the product will be that comes out. It could have more pathogenicity and human transmissibility, or it could have high pathogenicity within humans, and very low transmissibility within humans. There is a great deal of uncertainty.

How would the virus become a pandemic?

The virus changes by two scientific prefaces. One is mutation -- a slow accumulation that points on this genetic code of small changes. That can make a bird virus transmissible to humans, but in the past major pandemics, we’ve had about three a century, the key aspect has been what is called “re-assortment.”

Re-assortment is if I acquire a human strain that is circulating, and at the same time acquire the bird virus. The two infect the same cell inside my body, their genetic codes get jumbled and something new comes out.

That new thing that comes out, there’s a small likelihood that what comes out has the high pathogenicity of the bird virus, and the degree of transmissibility within humans. But it is equally likely that what comes out has the low transmissibility of the current circulating human virus, and perhaps sufficient transmissibility within the human population. So there’s huge uncertainty, and very low probability of this re-assortment event occurring.

What would have to happen for the re-assortment event to occur?

Using myself as an example, I would have to have the current circulating human influenza virus, and then be exposed within 12 to 48 hours to the bird virus -- so I get dually infected during those first two days. That’s what’s required for re-assortment.

There is a great deal of uncertainty of the characteristics of the current bird virus with the human transmissibility capabilities.

What would be the extreme outcome, if it were to obtain re-assortment?

A lot of figures have been bandied around about mortality rates, about the fraction of the population that would be infected. The truth is one doesn’t really know what is likely to happen. The question is how transmissible is it? Does it have a replication rate that takes it from human to human easily, or is it quite difficult to transmit? The worst scenario of course is high transmissibility. What typically happens with a new virus is that it starts off with low transmissibility and then as it circulates country by country, it improves its capability of transmitting from human to human

Another attribute which is hugely important is the pathogenicity. H5N1 is very pathogenic to humans, but subsequent epidemics after 1918 were of low pathogenicity to humans. The worst scenario obviously is something totally novel that the entire population has never seen, with high transmissibility and high pathogenicity.

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There are some figures that suggest it could be even worse than 1918, which indicates that its not only a scientific problem, but it would also become a social and political crisis. Can you talk about those two aspects?

Again, I stress that it is uncertain what the future holds, but if a highly pathogenic organism emerged, then we would have highly considerable problems. Influenza is unlike most other infectious diseases in two aspects. First, it tends to have a very short generation time. The generation time is the time from when I acquire it, to when on average I transmit it to somebody else. For influenza, that’s typically a few days, perhaps two to three days. Now by comparison, think about HIV -- the average time from when somebody acquires to when they transmit the virus is many years. The HIV epidemic develops on a time scale of decades, many, many decades, hundreds of years. The influenza pandemic will develop on a time scale from weeks to months.

Within a given country, the epidemic will probably be all over in about four to six months. Worldwide, the epidemic, or pandemic, will probably be over in about a year. Therefore, the first aspect is that speed of action is absolutely vital. We haven’t got time to ponder your contingency plans, you have to have them prepared and put them in place on day one when the infection arrives in your country.

What’s your appraisal of the current preparedness?

Clearly, there is quite a lot of variability between countries and how much they’ve taken this threat into account that relates to both the amount of anti-viral drug that they’ve ordered. There’s a lot of variability, a lot of differences of opinion in key areas. Do you restrict travel from certain countries to, say, Canada or the United Kingdom? Do you screen passengers on entry to an airplane? Do you then screen them again on exit? Quite a bit of scientific work has been done there. And they all point to one rather simple and stark observation: Once this starts, it’s almost impossible to stop from spreading from one country to another, unless your travel restrictions are 99.99 per cent effective. In other words, unless you totally close the borders down instantaneously you are very, very unlikely to restrict the entry.

That leaves you to two conclusions. One, your efforts should be totally focused on trying to help the country of origin of the new pandemic strain, whether that be southern China, Vietnam, Thailand… You help the World Health Organization with your own country’s stock of Tamiflu or an anti viral agent. The second point, since you are very unlike to stop it from entering, your country’s specific contingency plans should be orientated to: ‘how do I respond to when it arrives in a major city?’

Some experts suggest airlines could actually sterilize jetliners.

I think our experience from SARS and from a variety of other examples, is that screening passages at the entry to the airlines, the exits, sterilizing the airlines, is not a sensible expenditure of time and energy. The most sensible expenditure of time and energy is to work up a contingency plan of how you are going to control it when it arrives in the country. Ordering the anti-viral drugs, and preparation for rapid vaccine production, those to me are the most sensible expenditures.

Then there’s the more complicated set of contingency plans: Do you close schools? Do you restrict travel within a country? How do you ensure that the health care front line staff are protected and adequately informed about how to manage it with simple hygiene measures? How are you going to ensure the continued supply of fuel and food to a country which has a very threatening epidemic? These are the key issues, in my view.

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How would you prepare a country?

At the beginning you need very, very good surveillance so that you don’t find out about its arrival you know one to two weeks afterwards. Your surveillance has got to be exceedingly good.

Secondly, in an ideal world you need diagnostic services in a country, to be able to take a suspicious case, elevated temperature and fever and so on, and be able to diagnose whether that is an influenza virus very speedily, within a few hours. At the moment, these diagnostic tests, we still haven’t got that technology sorted out. That is another priority: getting rapid diagnostics developed in advance for influenza virus infections, so you can use your limited supply of anti-viral drugs very effectively by only treating those who have influenza.

I think my greatest worry is the origins of the epidemic may occur in some remote rural area of southern China, or perhaps Russia -- that it won’t be picked up for a number of weeks to a number of months. That because of some poor surveillance in the world, diagnosis will occur late and therefore it will explode on the world scene without adequate warning. That’s the real concern.

I am afraid that silent spread in rural regions is a possibility. Another thing that the WHO and international community can do is to try and improve surveillance capability in Southeast Asia, and in China in particular. And in Russia, so that the world has advanced warning and can try to help those countries suppress the epidemic in its point of origin.

How will we be able to measure our degree of success against a pandemic?

Success is quite difficult to measure, because it’s only in retrospective analysis that you’ll be able to look at the mortality rate from the virus, and by comparison between countries how quickly you managed to suppress its spread.

How would cities, societies enforce quarantine?

My own view, in the case of an epidemic, is that you need tight government control: unified policy applied across all cities and all states. That will happen in the United Kingdom, but the U.K. is a small area in comparison with Canada and central government will play the central role in dictating policy, in different cities, in different health authorities.

President Bush has indicated that there will be military involved in his most recent plan, in your view, how might this look in the UK?

The question of military involvement is not something that is in the contingency plan for the United Kingdom. The Department of Health will take the lead in the case of an epidemic, and it will control the actions determining how to minimize spread, how to minimize mortality, and also with its interaction with other government departments: how to maintain education, fuel supplies, and so on.

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What do you say to the people who are the closest to you, friends, family, about how to cope with a pandemic?

People do ask questions. My initial response at the moment is the risk is low. Number two, keep separate in your mind the avian problem, which is a veterinary problem, keep that separate in your mind from the human problem.

We’ve had this avian virus spreading since 1996 and we’ve had no human problem, except for some direct transmission from birds to humans, but no onward human-to-human transmission. Keep that in your mind. There is no immediate threat at present.

If the worst happened, then a lot of common sense simple things would be important. Minimize your mixing. Perhaps work out a way with your employer where you can work at home via some broadband computer network. Do simple things like wash your hands.

People infected with a respiratory virus, when you blow your nose you contaminate your hands, then you shake hands or contact a door knob or a railing or whatever, you may be leaving virus on those contact surfaces. The virus will survive there from minutes to hours, depending on certain conditions. Try and minimize those sorts of contacts.

When should parents pull their children from school?

There will be guidance from central governments. It will depend very much on the transmissibility and the pathogenicity of the virus. For example, all these influenza viruses have different age specific pathogencities. They may or may not be pathogenic to the elderly or to the very young. Teenagers and young adults may be more resistant to sever effects of the virus. We won’t know that until the epidemic emerges. Guidance in central government about this will be crucial.

Having said that, what was so transparent from the SARS epidemic is that in respect of government guidance, people responded in a manner connected to the degree of hype that was presented to them in the media, sometimes accurately, sometimes falsely. Individuals will respond without government guidance. If you take, for example, Hong Kong during the SARS epidemic, their strong attendance in cinemas, or sporting events, dropped dramatically well before any government announcements.

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