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Last Updated: Sunday, 13 November 2005, 20:33 GMT
Jeremy Farrar

Jeremy Farrar
Jeremy Farrar is the director of the Oxford University's Clinical Research Unit in Ho Chi Minh City, which is based at the city's main Tropical Diseases Hospital. The following is an edited transcript of interview with Panorama's Jane Corbin, recorded in Hanoi, Vietnam, on 18 October 2005.

Jane Corbin: Doctor Farrar, Vietnam has had an outbreak of H5 N1 virus for the last 2-3 years every winter. What's the scenario as we approach another winter? Are you concerned there'll be another outbreak?

Jeremy Farrar: Yes, in 2004 and 2005, particularly from November to April, we had an increasing number of cases both in Hanoi and in Ho Chi Minh City in the south of the country. So whether this is related to farming practices or to climate, or to a change in behaviour, none of us know. But coming into November, December and January of next year, I think all of us are worried that we're going to see an increased number of cases again.

Jane Corbin: Now tell me what happened in the H5N1 patients that you began to see at your hospital. How did they come to you, how did they present themselves and what course did the illness follow, what were its, if you like, its characteristics?

Jeremy Farrar: It starts with common, non-specific symptoms, which is very important because at that stage its impossible to tell the difference between a very nasty Avian influenza and a common cold or pneumonia, a chest infection, fever, cough, headache, people not wanting to eat, feeling unwell, muscle ache, and interestingly a lot of patients had diarrhoea associated with their early phase of the illness.

They then, in Vietnam, usually have gone into another vicinity, another provincial hospital, or a district hospital, and from there they have been referred to hospitals in Hanoi and Ho Chi Minh City. By the time they've come to central hospitals they've been most very sick, very severe changes on their chest X-ray, very sick, difficulty breathing, sometimes unconscious, and at that stage very close to death in many cases.

Jane Corbin: And is this the disease that takes hold and progresses very quickly?

Jeremy Farrar: Yes, it does, there are first few days when probably you have few symptoms, maybe a slight fever, maybe a cough, maybe a headache, and then that seems to progress and then very rapidly you can deteriorate, so that I remember one case here in Ho Chi Minh City who, in the morning was sitting up having breakfast, talking normally. In another hospital in the Mecong Delta seen by a colleague of mine, and by the evening she was dead. So the progression, once you get to that level of severity, is very rapid, and very nasty. Jane Corbin: And what does this disease actually do to the body? What happens to the body?

Jeremy Farrar: Well the virus probably invades through the mouth or through the nose, and then invades the lungs, and from there spreads to the rest of the body. That's one of the differences between this influenza and what we commonly regard as the flu. In the very severe patients, it's not just their lungs that are affected but many parts of the body, so we've had patients with liver damage, with kidney damage, damage to the brain indeed. So it's a much more widespread infection than is the case with normal flu.

Jane Corbin: So effectively the whole body collapses, as it were, under the strain of this virus.

Jeremy Farrar: That's a good way of putting it. In the end, all of the organs of the body are affected, and in the past and in historical records we've assumed that that's because they have a very nasty viral infection and then superimposed on that they get a bacterial infection. In fact at least in our patients we found no evidence of a super added bacterial infection. Now we may have missed it, and we accept that, but I think there is some evidence that the damage is primarily caused by the virus and of course that's very worrying because it suggests the virus can actually affect the whole body and that's unlike other influenzas.

Jane Corbin: Now we've had some interesting cases and we've looked at some of them here, and perhaps you could just give us some comments on them. We looked at a so-called cluster case here in Vietnam of a young man who caught avian flu, his younger sister also caught it to a lesser extent. Another sister didn't catch it at all. Do these cluster cases give us perhaps a clue as to whether or not this virus is more likely to jump human to human?

Jeremy Farrar: Yes, I think if you were guessing what would happen with an avian influenza coming across into a human population, I think you would predict that you would have lots of chickens, lots of ducks, dying of an avian influenza, spread over a very large geographical area, and then within that geographical area, occasionally you would see a human case, on its own, isolated.

Maybe in a family and no other family members affected. The next stage would be you would maybe start to see clustering occur, and by that I mean more than one patient occurring within a family. At the moment that may well represent common exposure to a virus. Let's say there are chickens within their homesteads were infected and two of them within the family both prepared those chickens for dinner, or for sale, and both of them were exposed to the same virus, then you would. If you were looking for human transmission you would see not just two cases within a family but more loosely associated with a family.

So maybe a family that came to visit and then went back to their own house, or maybe to neighbours getting infected, and it's this clustering of cases which everybody is terrified of because that suggests that instead of humans catching it from chickens and poultry, people are catching it from one another and that's the start of an epidemic happening and then a pandemic, i.e. spreading across the world.

Jane Corbin: There have been cluster cases in Vietnam. Do any of them show yet that we are closer to that human to human transmission?

Jeremy Farrar: My personal interpretation is that at the moment the clusters represent common exposure within a household. You can imagine in Vietnam or anywhere in rural Asia, if you can imagine the scene of a family preparing a chicken and killing it, plucking it, preparing the meat to eat, and many people in that family will be exposed to the feathers, to droplets, the aerosols, to maybe the faeces of the chicken, we don't know. And I think that the cases in Vietnam that currently cluster represents common exposure to the virus.

Jane Corbin: Rather than one human being catching it from another.

Jeremy Farrar: Rather than one human being but I'm a natural optimist and you could interpret the same data and say this is inefficient limited human to human transmission, and you cannot tell the difference at the moment.

Jane Corbin: In other words, the first sign that human to human transmission is possible and therefore worrying.

Jeremy Farrar: That's what you would see if there was human to human transmission. You would see clustering in a family and then looser clustering with the family, and then clustering within a village, in a town, and then it would spread in exponentially after that.

Jane Corbin: Another case was of a man who died leaving a widow and a young daughter. He had, so the story goes in the village, he'd been involved with slaughtering a fighting cock. Now what's the significance of that, especially given those kind of traditions here in places like Vietnam?

Jeremy Farrar: Fighting cocks are part of a way of life. They're part of a culture, not just in Vietnam but actually in many parts of Asia and indeed the Americas. The person looking after the fighting cock has an incredibly intimate relationship with their chickens. They caress them, they take out some of the spit from the chicken after it has fought to help it fight. I'm not an expert in fighting cocks but this is what happens.

Jane Corbin: They actually suck out the mucous.

Jeremy Farrar: They do suck out the mucous from the chicken, and there have been I think two or three cases of people involved in fighting chickens who have caught avian influenza, it's clearly a huge risk for catching the disease. What is interesting though as well is that in fact we've had no cases of people coming from very large chicken farms. There have been, as you know, a massive cull of chickens throughout Asia, and so far we've had no individual whose been involved in that culling process coming in with the infection, and of course that raises the possibility that these people are somehow protected, either from previous influenzas that they may have been exposed to in their flocks of chickens, or minor occasional previous exposures, and that's actually quite encouraging because that suggests that there may be some possibility of developing a reasonably efficient vaccine in the future.

Jane Corbin: To give people immunity against this flu.

Jeremy Farrar: To give people immunity against this influenza, that's right.

Jane Corbin: Now the human to human transmission, as you've discussed, is something that we need to look at in terms of efficiency, for it to happen. Do you think that that is likely, given what we've seen so far? What are the precursors, if you like, for a more efficient human to human transmission?

Jeremy Farrar: Well the virus at the moment is essentially a bird virus and it has to bind to a human tissue in order to infect a human being, and clearly the virus is very bad at doing that, there are billions of chickens, many of them have got the virus, and yet we've only had 120 or so cases that we know of. So the virus is clearly, at the moment very bad at infecting human beings. Two things could happen. One is the virus can change a little bit and it can develop the capacity to bind to my lungs and then it would cause a very nasty infection and I might pass it on. That's what happened essentially in 1918 as the incredibly elegant work that's just been published shows, that the virus was a purely bird virus and it developed the ability to infect human beings and caused horrendous pandemic in 1918.

The other way it can happen is that the bird virus can infect a human being at the same time as that human being is infected with a normal flu. And those two viruses can get together and they can exchange their genes and then you've got a partially avian, partially bird flu and a partially human flu, and if you get the right combination you've got what you need for human pandemic, and that's what probably happened in the 1950s and 1960s, and that recombination event can go on in a human being or it can actually probably also go on in a pig, because a pig can hold both viruses at the same time, and anybody travelling around South East Asia or indeed parts of Europe will know that chickens and pigs often live very closely together in people's farms, and that's also a great worry.

Jane Corbin: Do you think you're seeing all the cases that exist? I mean is there a case for saying that at the moment this thing is so pathogenic it kills its host, but what could be really worrying is if it became less dangerous, survive and therefore became more transmissible. What could happen there?

Jeremy Farrar: Yes, we should learn from history. We often don't but we should learn from history, and in 1918 the mortality rate was actually very low, it was probably 1 or 2 percent. One or two people in a hundred who caught the infection died, and probably 25% of the people were infected. In this virus so far 50 or 60 percent of people who get the infection die, and of course that virus dies with that patient and it's absolutely tragic for the patient and their family but in terms of spreading the virus to other people it's actually very good news at a population level because that virus can't go on. The worry would be if the virus started killing slightly fewer people but infected more, then we have what we had in 1918 and then we have the chance for a global pandemic.

Jane Corbin: So in other words, the virus becomes less strong but more capable to jump from person to person.

Jeremy Farrar: Yes, that's right. Of course the real nightmare is the virus learns the ability from me to you and retains its virulence, but that's very unlikely to happen. I think everybody agrees that if it develops the ability to go from one individual person to another, it will probably become less virulent, but if 25%, if one in four people in the United Kingdom were to be infected, and you had a 1% mortality, that's an awful lot of deaths.

Jane Corbin: Now one of the things that we can do, or we're told we can do, if this flu becomes a reality is to use antivirals, so-called Tamiflu. Is this a realistic answer?

Jeremy Farrar: Yes, I think Tamiflu, Oseltamivir, is not the only drug for influenza but I think it's the most appropriate at the moment. It can be taken by mouth, it's very safe and it has some antiviral activity. So if you have the normal flu and you take Oseltamivir it shortens the period you're ill. We don't know in a nasty influenza, like we are dealing with now, what effect Oseltamivir will have. Of course every patient in Thailand and Vietnam and in Indonesia has been treated with Oseltamivir, but we've still had a 70% mortality. 70% of people have died, and Tamiflu, Oseltamivir may be working but it's not a miracle cure for an incredibly nasty influenza.

Jane Corbin: And is there a danger that we could see resistance to that drug developing the more it's used in answer to an outbreak of flu?

Jeremy Farrar: Yes, I think there is. There is in fact already evidence published in the last few weeks that there is resistance in the virus to Oseltamivir. When a virus becomes resistant to Oseltamivir, in theory that virus will be less virulent. It won't be as fit. I don't share that optimism. I think it doesn't matter whether it's a bacteria or a virus or a malaria parasite, these organisms are fantastically able to adapt and I think as soon as we apply widespread use of Oseltamivir, we will start to see resistance developing inevitably, and I think we do have to pay attention to other drugs other than Oseltamivir, and in the longer term developing new antiviral agents, but that's ten or twenty years away.

Jane Corbin: What about the possibility of developing a vaccine for this flu?

Jeremy Farrar: Yes, I think developing a vaccine for an influenza is actually not complicated, it's not rocket science. You could develop a vaccine for H5 N1 relatively easily, but it takes months to develop it. We are still using what is a very good technology in the sense that it gives you very good immunity and protects people, but it does still require injecting the virus into eggs, and that is a time consuming process. From the day you decide to make a vaccine, until you can actually have enough vaccine to vaccinate a population is months, and the problem with influenza is that the virus changes. So by the time that you've created your vaccine, you're not sure if it's going to offer you any protection against the virus that's causing the epidemic.

Jane Corbin: Do you think governments worldwide have been vigilant enough, have put the money, the research, the time into developing a vaccine?

Jeremy Farrar: I think with hindsight you would argue that we've been too reliant for too long on a technology which is based on a 1950s or 60s technique for developing vaccines. And I think if you look forward, one of the lessons that we must learn from this, whether there was a pandemic or not, is that we do need to invest what will be large sums of money to create a modern vaccine that will hopefully protect you against all types of influenza. Now that's going to be incredibly difficult, but I think the fear that's been generated from this massive outbreak in poultry and the small number of people that have died, has to be a stimulus for us to generate that.

Jane Corbin: There's a great deal of fear about this virus. Do you think the answer to those in Western Europe is to look after themselves, or does the answer lie in helping the developing world which, after all, has seen the largest number of cases so far?

Jeremy Farrar: Yes, I'm biased because I live and work in Vietnam. I think with one or two exceptions, and I think increasingly people are doing what you suggest, of investing here in Vietnam and a number of governments and a number of organisations, the Wellcome Trust, National Institute of Health from the States and a number of other organisations, have invested here and both in Ho Chi Minh City and in Hanoi and I think that's hugely appreciated.

But we need to do more, of course, and if the epidemic reaches Western Europe, whatever preparations we undertake, and of course we should do all of that, but the way to stop this happening is to stop it happening in Asia, and that's going to require a huge investment in terms of money, and resources, and most important of all is the investment of people because that's what you ultimately need.

Jane Corbin: Is it realistic that we could contain an outbreak here in South East Asia and prevent it ever reaching Western Europe, America, etc?

Jeremy Farrar: I really honestly am an optimist, but I think if there were a cluster of cases in any country, it doesn't matter that it's Vietnam, it could be China, it could be Russia, it could be Greece, it could be Edinburgh or Bristol, or London, or San Francisco. If there is a cluster of cases which spread beyond a few cases - and by that I mean 10 or 20 or 30 cases of flu that goes from one person to another - once you've got to that stage, I think it's impossible to contain it, yes. I think once it spreads beyond 20, 30, 40 cases, it's going to be incredibly difficult to control, even in a highly developed country with unlimited access to money and resources.

Jane Corbin: What about the difficulty of preparing against a disease that spreads, or could spread so fast?

Jeremy Farrar: It's incredibly difficult. I think of all of the infectious diseases we know about, of course Malaria, tuberculosis, HIV AIDS and a number of other diseases, devastate huge tracks of the world every year, and we should not neglect those. But if you ask me which is the most infectious disease that should most worry the whole world, I think it's influenza because that is the one that in the 20th century in global pandemics claims enormous number of lives. And the problem with influenza is there's very little in the middle.

There's a few very tragic events like we are experiencing in Vietnam and Thailand and Indonesia of deaths due to H5 N1 virus. And then there's a Pandemic, and there's very little in the middle, and the time scale between the tragedy of this very small number of cases that we are currently dealing with in those three countries and global pandemic, the time scale between those two is very small, and there's very little grey area. So you've either got one or the other, and what we have to try to avoid is this one becoming this one.

Jane Corbin: Do you think the world has perhaps has been slow to wake up to this, particularly given that the developing nations have very little and yet are being expected to cope with this very much on their own?

Jeremy Farrar: We've been living through this outbreak in poultry and in humans since the end of 2003 so that's very close now to two years. If you count up the number of laboratories in the region that are capable of making a diagnosis, you can still count it almost on two hands. That's two years into a major animal and human problem, that's been too slow a response. I think in the future we also have to move into a situation which will encourage openness. We have to accept that we have to generate some sort of mechanism through world bank, through the IMF, to enhance the possibility of getting compensation if things like this occur. In the European Union, if there's an outbreak of foot and mouth disease of course the British Government can compensate farmers, but outside the European Union and the States and the rich counties, there is no mechanism in place to compensate farmers in rural Asia and we have to, I think, learn some lessons from this and develop a mechanism by which to encourage openness and to relieve the economic burden that does occur when outbreaks like this happen.


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