Safeguarding Australia
Emerging viral diseases: what are the threats and how should we respond?
Tuesday 4 September 2007
Professor John Mackenzie
Professor of Tropical Infectious Diseases
Curtin University of Technology, Perth
John Mackenzie is an international expert in tropical infectious diseases and a member of various World Health Organization committees concerned with disease surveillance and response. In 2003, he led the WHO team into China during the SARS outbreak and convened the SARS Research Advisory Committee. In 2005, he traveled to Banda Aceh as a member of the WHO tsunami relief team and liaised between WHO and the Indonesian Ministry of Health. John is particularly interested in zoonotic and mosquito-borne viral diseases, and is of the view that early detection of disease outbreaks is essential to enable control procedures to be initiated.
Emerging viral diseases: what are the threats and how should we respond?
Thanks very much indeed for the invitation to come and speak tonight on possible Australian responses to threats that I certainly perceive, and I think a lot of other people perceive, as being on our doorstep and waiting for the right conditions before they might emerge here and present us with problems in the future. We also need to be aware and prepared for possible new, previously unrecognised diseases arising either in Australia or elsewhere in the world – as we now belong to a global village, anything arising elsewhere today can be here tomorrow!
I am not trying to do this as an alarmist; please don't think that in any way at all. I am also not going to talk about international surveillance or response. That is another area which I think tonight I will try and leave aside – although I will pick up one little point from the introduction by Professor Lambeck. We had a polio case recently. Now, you would know that when you arrive in Australia you have to put your address on the back of your arrival card, just in case there is a problem in some way and you have to be contacted. Well, all the people on the same flight as the person who had developed polio had filled in their landing cards, and the information about their probable whereabouts from these cards was made available on a disc a few weeks later when the polio case was recognised, and was used to trace about 90% of the passengers. So the system does work! However, it appears that if the health authorities had wanted to trace passengers arriving on a flight four days previously because a passenger became ill after arrival here, it might not have been so easy. The flight manifests are only kept for 24 hours, and information on the passenger cards would probably have been processed and sent for storage and not be readily available. So the possibility of obtaining the information from their cards, should there be an emergency a few days after the arrival of the flight, might not be so simple or easy. It would also be very useful for this kind of emergency if passenger manifests could be retained for at least two weeks. Hopefully, all this is going to change before the next emergency event of this kind, whether it is polio or some other exotic disease.
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I want to talk about emerging diseases. 'Emerging diseases' is really a very broad title, because it covers almost everything that is either currently threatening us or likely to threaten us in the future. So first of all emerging diseases may be new diseases we have never seen before – totally new ones – and these might come from some wildlife niche or some part of the globe we haven't been into before; or, secondly, they may be known diseases which are increasing, or which threaten to increase, either in incidence or in geographic spread.
That covers a large variety of different diseases. But those that are of most concern to us are those that have international significance, either because of their importance because of tourism or trade, or because they threaten to become a pandemic, that is, spreading around the globe. So these are the ones which we consider to be most important.
I just want to sow the seed, if you like, that the concept of emerging diseases is a fairly broad topic and does, in fact, cover many kinds of disease. If there is any chance it might increase in incidence, it is considered to be an emerging disease. So it's a rather broad brush.
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In the context of the new millennium and new century, we have a number of diseases which have emerged for the first time. We saw SARS-coronavirus four years ago; we have seen other ones like Ebola and Marburg appear in the last 20 years; we have seen other equally nasty viruses, like Nipah virus, which have never been seen before, suddenly appearing only 8 years ago.
There are also other diseases that we have known about for a long time, and many of which we thought we had conquered or controlled to some degree, but they are now recurring – in different formats, sometimes, in different guises, but nevertheless they are coming back to haunt us in many different ways. The types of disease I am talking about here are things like meningitis and measles (measles we could have got rid of long ago as there is an excellent vaccine, but it is still causing problems), and yellow fever. One of the best vaccines available is to the yellow fever virus, but in the last decade we have had more cases of yellow fever in Africa and South America than we had seen in the previous 90 years. In other words, despite having all the vaccines available, we don't always control these diseases as we would like. There are many different reasons for this, some being financial, especially in developing countries, others being due sometimes to lack of political will or to poor public health services.
There is also the accidental – and deliberate – release of organisms which could be a problem to us. Accidental release often happens through bad training or through handling errors in laboratories, or because laboratories are not being properly maintained in terms of the filters and so on, so that disease agents escape. But deliberate release is more of an international worry as a means of terrorism, and certainly one that I think is engaging a number of people's minds at present.
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In the presentation I want first of all to talk a little bit about emerging diseases, followed by a short discussion on the factors which are associated with disease emergence – I don't want to spend too much time on that – and then a more detailed look at some examples of emerging diseases which are of particularly concern to Australia. Here I am looking at ones which are bat-borne (by the fruit bat, in this instance) and some which are mosquito-borne. Finally, I will look at what we can do to detect and prepare for potential threats in the future: what kind of response should we make, and what kind of plan should we have to mitigate the threats beforehand?
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It is very important to remember that about 70 per cent of what we call novel, emerging viruses over the past two decades have been zoonoses. That is, they have come from an animal source. Most of these viruses have come from bats, particularly fruit bats (as we'll see in a moment), but rodents and birds have also been important reservoirs for other viruses. Some we still don't know the hosts for, although we may have suspicions. Thus we think that fruit bats are the probable reservoirs for Ebola and Marburg,but in fact we are still not totally sure.
What is really important is that if we are serious about wanting to do good surveillance and being able to detect these things early, we have to have surveillance that includes wildlife. There is no point in having a surveillance system unless wildlife diseases are included. This is a very, very strong message that we cannot ignore and really have to get across to people: wildlife disease surveillance is a crucial component of any surveillance system if we want to try and understand as well as predict and control emerging diseases.
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This slide shows some of the viruses that have emerged in the past 15 or so years. It doesn't show all of them; it is just a selection of them.
The colour is an important part here. First of all, those that are in red are ones which have a zoonotic background – ones which are zoonoses, and come from an animal source. Those that are in yellow can also transmit between people, but they have an initial zoonotic event. In other words, the first transmission is zoonotic, and then it can be human-to-human transmission thereafter. Those that are in white are human diseases without any involvement of wildlife.
You can see right away that the reds and the yellows far outnumber the whites. This again shows how important wildlife is in terms of disease emergence.
A few of them also have a little blue asterisk. These are the novel, totally new viruses we have never encountered previously. And, in fact, you will see two of those for this year already, 2007.
There has been a new LCM-like virus. LCM, lymphocytic choriomeningitis virus, is a virus which occurs in house mice around the world. But a new virus suddenly appeared in Melbourne in a patient who had recently returned from Europe, was sick, and later died in hospital. His organs were transplanted into three recipients, and those three recipients died from encephalitis some weeks later. And from one of those patients a totally novel LCM-like virus was isolated, one we had never seen before. This was done, in fact, with great difficulty by Professor Lipkin's laboratory in the US working with Dr Mike Catton's laboratory in Melbourne – they not only discovered the virus but were able to totally sequence it.
Another one, Melaka virus, is one that has come from fruit bats and causes acute respiratory disease. It appears to be transmitted from fruit bats to people. It was discovered earlier this year by Dr Chua in Malaysia working with Dr Linfa Wang and colleagues here at the CSIRO Animal Health Laboratory.
So here are two totally new viruses discovered or reported this year.
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These emerging diseases – not just viruses but bacteria as well, and other parasites – occur everywhere. This slide is to show you that it is not only Africa, for instance, where we see most emerging diseases, but examples are also from North America, South America, and Asia. Thus diseases may emerge from any part of the globe, and there is no particular part of the world where this is more common.
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What is also important to remember is that these diseases can cause enormous economic problems. Here we see, for instance, that the outbreak of SARS-coronavirus, in Asian countries alone, cost somewhere about US$60 billion. This amount does not even include Canada and other countries that also had suspected cases.
I will be talking about the disease called Nipah in more detail in a moment, but Nipah cost the Malaysian government somewhere about US$400 million to eradicate. We saw plague in India not long ago: this cost the Indian government about US$1.7 billion. We have seen BSE (bovine spongiform encephalopathy or mad cow disease) in the UK, and over about a 12 year period it cost US$34 billion to the industry there.
So another take home message is that these emerging diseases can cost a country a large amount of money as well as resulting in loss of life.
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Here are some examples of emerging zoonotic diseases from different animal sources. There are some rodent-borne ones, such as hantaviruses and arenaviruses. (The LCM-like virus which I just mentioned, in Melbourne, is an arenavirus.) They are all from various species of rodents from around the globe, and interestingly may have evolved with their particular rodent host.
We have henipaviruses, rubulaviruses and lyssaviruses from bats. Particularly here in Australia, we have got a new bat virus that causes rabies-like disease in humans, called Australian bat lyssavirus. In fact, the disease it causes is rabies. We don't call it rabies, but to all intents and purposes it is rabies by every definition, and indeed rabies vaccine will protect you against it. This particular virus may be transmitted by fruit bats and at least one species of insectivorous bat.
I have put question marks against filoviruses such as Ebola and Marburg. There is more and more evidence suggesting that fruit bats are their probable reservoir hosts, but most human index cases catch the virus not from fruit bats but from eating infected bush meat.
We also see viruses emerging from insectivorous bats. In fact, SARS-coronavirus looks now as if it might have emerged from an insectivorous bat.
And then we have emerging viruses from birds, such as the highly pathogenic avian influenza H5N1, which we are all so concerned about as the possible next influenza pandemic, and which is currently causing human deaths on our doorstep, so to speak.
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In our region, a large number of viruses have appeared in the last few years, such as SARS, Nipah and one that is not zoonotic, called human enterovirus 71, HEV71 on the map, which causes hand, foot and mouth, usually in children, but has recently been associated with a much more serious neurological infection in some children. There are a number of different viruses here, and some of these I will talk about today, some I won't.
So why and how do new viruses emerge? What is the background? What are the mechanisms, what are the factors?
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I think the essential message here is that human intervention and human activities are the most important causes of viral emergence. .
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Here are some human activities which can lead to emergence. One such is demographic changes exemplified by population growth. As the population increases in size, shanty towns and slums develop; diseases then emerge, such as dengue, a disease of increased urbanisation due to rural people moving to the cities, which, in the case of dengue, happened especially in the years following the second world war. Changes in land use are important, such as deforestation where we cut down native trees to plant new paddy fields, or other forms of agriculture. Or we build dams for irrigation – again changed land use. Both these changes can lead to disease emergence, such as Japanese encephalitis which I will talk about later. Another example of human activity influencing disease emergence is in animal husbandry. Have you looked at the battery hens, or seen chickens in large sheds of 200,000 chickens, each in close confinement? Or, the way we produce veal these days? These are examples of changes to animal husbandry, and I believe are really quite horrific, but the density and close proximity of the different animals to each other provide the ideal conditions for virus spread
Changed animal husbandry was also important in the emergence of bovine spongiform encephalopathy, where there was a change in the process of the production of the feed which was given to the cows. Instead of treating the carcasses and other ingredients of 'cow cake' with heat as had been the norm, it was done chemically, with the result that the prions responsible for the disease were not inactivated but could still be transmitted resulting in the emergence of this particular prion disease in cattle.
There have been enormous changes in transportation, both in the speed at which we are transported around the globe and in the increasing passenger numbers. Whenever an outbreak happens today anywhere in the world, it can re-emerge in Australia or New York tomorrow, thanks to the speed of aircraft travel. In other words, the world now is a global village, not just for people but for trade and for animals.
So these are different reasons and methods by which diseases can emerge and spread.
Natural occurrence does occur too. For example, vertebrate host movements or migratory bird movements can help viruses emerge and spread. But most of these activities reflect human behaviour or human involvement in some form or another, whether it be technology, whether it be agricultural change, transportation of people or goods, or whatever.
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Underlying all these changes, there are other factors which are important too, such as viral evolution, vector biology and host factors. Virus evolution is particularly important for the emergence of new strains of influenza virus. The importance of vector biology: can be demonstrated by whether different mosquitoes species or even genotypes can transmit a particular virus, by breeding sites specificities, and so on. So, obviously, vector biology is a very important component of arthropod-borne virus emergence.
This has been a very quick look at some of the factors which contribute to virus emergence, but the most important message is that human activity is a crucial component.
What are the threats? This is where I want talk now about some particular diseases.
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Initially I will show you some of the exotic diseases which are of particular concern just now to Australia. This is my list; it is not an official list, but one which I believe really demonstrates some of the diseases on our doorstep which are of concern.
I will talk about Nipah virus in a moment. To me, this is perhaps the most important and most dangerous virus facing us just now.
I will maybe show three slides on avian influenza. I don't want to talk too much about avian influenza today except to mention it in passing.
Of the next few virus, Rift Valley fever I won't mention, other than to say that it is a mosquito-borne disease of humans and livestock found in Africa and more recently in the Middle East, but I will spend a bit of time on Japanese encephalitis, because it is one that my laboratory has been particularly involved with. I will also say a little bit about West Nile, which is of interest in the way it has spread from Europe to the Americas – it has caused havoc in North America in the last six or seven years, with over 100 deaths a year. Dengue I won't mention again, but I will say a few words about Chikungunya. This is a virus you may never have heard about but it is one that has been causing more and more problems in the last two or three years, and that currently is causing massive outbreaks in India, with several million people being affected.
There are other ones that we might mention in passing later on, like SARS-coronavirus, Dandenong (the new name for the LCM-like virus) and Chandipura, another virus that is important in terms of insect transmitted disease in India, but only if there is time.
Again there is a hidden message in this slide, in that all the viruses shown are zoonoses, but those shown in blue font have a vector – a mosquito vector, or an arthropod vector – that contributes to the transmission cycle.
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I said I would mention bird flu. I will, but only very briefly.
With H5N1 avian influenza on our doorstep, are we at any greater risk now than at this time last year or the year before? I don't know, but what I can tell you is that the number of cases in Indonesia has been increasing over the last two years, and so has the case fatality rate. In other words, the virus strains circulating in Indonesia appear to be getting more and more virulent for humans.
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So far this year (up to last week) 30 cases have been diagnosed, and 26 of those died. In other words, we are certainly seeing more and more human cases of avian influenza on our doorstep.
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This slide is a map of Indonesia showing, in green, where avian influenza has been found in poultry, so you can see it really is throughout our closest neighbour, and thus very close to us. So, yes, it has to be thought about as some kind of risk.
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Globally, over the last four years, the number of cases of avian influenza in humans, is about 322 with 195 deaths. That is a case fatality rate of about 60 per cent. It is not as high as we have been seeing in Indonesia, but nevertheless still high enough to warrant grave concern should this virus become pandemic.
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So there is little doubt that the current strain of H5N1 influenza is a great risk to all of us as the possible cause of a new pandemic. But will there be a pandemic? It has been hovering for several years now and nothing has happened. I think only time will tell whether it does, in fact, become a pandemic virus. However, I must admit that the longer it hangs around without emerging as a pandemic strain, the more I am beginning to doubt if it actually will.
Will the virus spill over into Australia? I think almost certainly it will do, sooner or later. We have been lucky, because we don't have any migratory waterfowl that cross the Equator into Australia. Migratory waterfowl are the major vectors which have been sending the virus around the globe, but migratory waterfowl don't come to Australia. We do have trans-equatorial migratory waders that come in in large numbers, but it is most unlikely they would bring in H5N1 influenza as the stresses of migration would make them too susceptible to a fatal infection.
We get vagrant movement of waterfowl – grass whistle ducks and so on in northern Australia that stray into Indonesia and Papua New Guinea – and it is quite likely that these might bring avian influenza back, but also my suspicion is that we might not even know it if it came in, because it could be contained in northern Australia and would probably die out there. I don't think that it would cause a problem, but nevertheless, 'famous last words' and all that.
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That's all I want to say about influenza, but I am happy to talk about it later in questions. I will talk a little bit now about new viruses that have been emerging for the first time from fruit bats.
In 1994, a virus appeared for the first time in Brisbane which killed a number of race horses and also a well-known trainer, Vic Rail. This is the virus that was later called Hendra virus. Since then a number of viruses have been found from fruit bats, particularly here in Australia. Australian bat lyssavirus, which I mentioned earlier as the one that is really a kind of rabies virus but we don't call it rabies; and Menangle, a virus that appeared on a pig farm near Sydney, again transmitted from fruit bats. It caused problems in pigs such as mummified fetuses and other malformations in fetuses, and also an influenza-like disease in humans. A virus very closely related to Menangle was found in Malaysia and named Tioman, but it hasn't yet been linked to disease. Another is Nipah virus, which I want to talk about in some detail in a moment, particularly with regard to recent events in Bangladesh and India. And, finally most recently, Melaka virus was discovered earlier this year.
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I would like to talk about Nipah virus first. It is a novel virus, from pteropid bats – bats belonging to the genus Pteropus. It first came to light in 1999 as the aetiological agent in a very, very severe outbreak of disease in both pigs and humans, in peninsular Malaysia. It is one of two viruses that make up the Henipavirus genus, the other being Hendra virus, the one we found first of all in Brisbane. They are the only two members of this genus, and both are transmitted from these pteropid bats.
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To look at them in terms of their phylogeny , and in terms of their relationships to other viruses in the paramyxovirus family: here we see the henipaviruses Hendra and Nipah, quite distinct from morbilliviruses such as measles (MeV) or the rubulavirus Newcastle disease (NeV), an important virus of chickens. The main thing is that genetically they are quite separate from the other members of the family. In fact, they are very different in many ways: they have much bigger genomes and they have an additional protein that some other members don't have. So there is quite a distinct difference between these two new viruses and other members of the family.
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The outbreak started initially with a few sporadic cases up in Perak, in northern Malaysia around Ipoh. This had gone on for over a year, and there was an occasional fatal human case or pigs would die. Nothing was really coordinated; no-one suspected anything unusual. Then the cases increased a little bit and the health authorities decided that there was probably an outbreak of Japanese encephalitis occurring, so they organised to immunise people with JE vaccine. It had no effect. People were still dying; pigs were still getting infected. In fact, had the medical fraternity talked to the veterinary fraternity – which they didn't – things might have been discovered much earlier. Unfortunately there was no such discussion. We knew that Japanese encephalitis never kills pigs. But pigs were dying, so it couldn't have been Japanese encephalitis, for that reason alone. But it is all very well to say this in hindsight! Thus, there was a major problem in terms of communication.
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This is where the index case came from, the person from whom the virus was first identified, a farm near Ipoh. There were many other large farms close by but it wasn't intense farming.
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This is one of the old farms, which is no longer in use.
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The outbreak then exploded in about March–April 1999. Infected pigs had been brought down to the very intensive piggery area in the province of Negeri Sembilan, just south of Kuala Lumpur. When that happened, the outbreak really took off in a big way.
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You can see the epidemic curve of the outbreak here. This shows occasional cases happening in December 1998, but it wasn't until the huge outbreak starting in late February, March and April 1999 that we saw the large number of cases. Overall the outbreak was a very severe.
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Thus the outbreak started off in Perak, in northern peninsular Malaysia. Pigs were brought down to the very intensive pig-farming area in Negeri Sembilan, and to piggeries in Selangor. The outbreak also extended to Singapore when pigs were taken down to an abattoir in Singapore.
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Overall, there were 282 human cases and 105 deaths in Malaysia, and a further 11 cases and one death in Singapore. Interestingly, no cases occurred after the outbreak. There were further deaths, but these were mainly in people who had recovered and suffered relapses or people who had late-onset encephalitis, as happened once or twice – people had a very mild disease and suddenly they had a late-onset, fatal encephalitis. Nevertheless, no-one was infected after the outbreak ended, and there has been no case in Malaysia since the end of the outbreak.
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The other important observation I want to share with you is in the demographics. It was mainly in the Chinese ethnic group – they were the people who were usually looking after the animals – or they were in occupations which brought people into contact with the farms. They might have been lorry drivers taking pigs to the abattoirs, abattoir workers and so on. But the main group that were infected were the Chinese ethnic group.
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To control the outbreak, 1.1 million pigs were culled on 946 farms in the outbreak area. Overall there was enormous loss in jobs and infrastructure, and the total cost of the outbreak is estimated at somewhere in excess of US$450 million. So it really was a major undertaking to control it.
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We believed that the source of the virus was most likely to be pteropid bats, based on our knowledge of Hendra virus. It was already known that fruit bats from the genus Pteropus were the main reservoir hosts for Hendra. And, sure enough, when pteropid bats were investigated by my colleague Hume Field and his associates, they were also found to be the reservoirs hosts for Nipah. The virus was first isolated, in fact, from the urine of these bats on Tioman Island by Dr Kaw Bing Chua, just off the coast of Malaysia, and since then other isolates have been obtained.
So we do know the virus is from bats. We don't know how the virus gets from bats to pigs. And then it is quite easy to see how it is transmitted as a respiratory disease in pigs to humans. There is no human-to-human transmission thereafter. In other words, there was the virus from bats to pigs as the first event – how that happened we are not sure. There are a lot of different theories; most of the theories centre around fruit spats from a bat landing in the pig pen, bat urine contaminating the pen, or contaminated fruit landing in the pen. Pig-to-pig transmission is very easy to visualise by the respiratory route as the virus causes an acute respiratory infection in pigs, and then from pigs to humans. But from humans there is no further transmission; we are a dead-end host, if you like.
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That was in 1999. In 2001, though, the virus reappeared. It appeared in two places. It reappeared in West Bengal, in a little town called Siliguri, about 80 miles from Calcutta and close to the border with Bangladesh; and also it appeared in various sites in Bangladesh. And over the following few years there have been more outbreaks.
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This shows all the outbreaks we have had so far, beginning with the Malaysian one in 1999. Then in 2001 we saw the outbreak in Siliguri, in West Bengal. First of all it was thought to be an abnormal measles outbreak – in fact many of the cases appeared to be nosocomial and even the doctors were leaving town. They felt too unsafe to practise in the hospitals, so it became quite a big problem.
At the same time we had two outbreaks in Bangladesh: one in Meherpur, another one in a town about 30 kilometres from Meherpur. These were just a few cases, but what is interesting here is the increased case fatality rate compared to the big outbreak in Malaysia.
And even up to this year, we had further outbreaks again in Bangladesh and West Bengal.
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Two aspects of these outbreaks are particularly interesting. One is that there is now very good evidence for human-to-human transmission. While we had suspected this for a while, it was confirmed this year that human-to-human transmission had definitely occurred in a number of instances. And if we look back now at information being released by the Indian government, it appears that there had been a number of nosocomial infections in hospitals, and the same thing was evident in Bangladesh in the last few years. In the outbreak this year, at least five consecutive nosocomial transmissions were observed. So there is definitely a change in the properties of the virus resulting in human-to-human transmission.
Another thing that happened is there is no evidence of any intermediate host – no evidence of a pig involvement in either Bangladesh or India. There is even no evidence, certainly in India, of any involvement by bats, although bats were implicated in some of the cases in Bangladesh. Presumably there must have been bats involved initially in India, but we can't trace far enough back in the outbreaks to demonstrate this.
The big risk now, I believe, is that as the virus appears to have gained the ability to transmit from person to person, perhaps by the respiratory route, it has the potential to be a new pandemic virus – a little bit like the SARS-coronavirus was. I think Nipah is of equal concern now, with a significant potential for it to burst out from Bangladesh or India, or wherever it might be, to cause a global problem. This is, I think, something we need to keep a very close eye on.
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There is also a possibility, though only by hearsay, that Nipah may have been involved in other parts of India and elsewhere. Certainly a Nipah-like virus has been isolated from fruit bats in Cambodia; we have found antibodies to Nipah virus in pteropid bats from Thailand, from East Timor (Timor-Leste) and also way over in Madagascar. We also find antibodies to Hendra virus in bats in Papua New Guinea and Madagascar. And if you look at the range of these bats, which I will show you in a moment, you see that they really do cover large parts of the globe, extending from islands off the east coast of Africa through to islands in the Pacific.
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This is where we find fruit bats belonging to the family Pteropodidae.
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If we look at the Pteropus bats, as shown here, we see them throughout South-East Asia and Australia, and then a little group around Madagascar, Pemba, Réunion – a long way from connecting with the other ones in India and Sri Lanka. Yet these bats in Madagascar have similar viruses, suggesting strongly that they must probably have evolved with their host.
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We are pretty certain that Hendra virus emerged because native trees, where they got their blossom, the nectar and the fruit that made up their normal diet, were being cut down for land clearance or timber. And so they started invading orchards, and people's gardens to get the nectar from ornamental shrubs and trees, and the fruit they required for their diet. So for Hendra we are pretty certain it is due to deforestation and the bats seeking food from alternative sources.
Nipah might have emerged for similar reasons too, but there is also a suggestion that ENSO-mediated forest fires caused aberrant fruit bat migration. I don't believe that this theory holds true; I think the more you look into it, the less and less likely it is. Nevertheless, I suspect that its eventual emergence was due to an interface between bats and piggeries, and the subsequent outbreak very much influenced by intensive piggeries.
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We also don't know very much about how these viruses in bats move. We know that some of the bats in Australia move into Papua New Guinea across the Torres Strait, and back again. But do they move, for instance, from East Timor into northern Australia? There is some evidence to suggest they probably do. We still don't know enough about this, so my colleagues Hume Field, Peter Daszak and Andrew Breed have started tracking these bats using radio collars.
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This little fellow here was trapped down in southern peninsular Malaysia. As you can see, it went into Indonesia and back up past Tioman Island, up the east coast. Another one moved around between southern Thailand and northern Malaysia. So they do move, following food, but not over long distances. Nevertheless, there are overlapping populations that form an open conduit for these viruses to actually move from country to country.
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Now we move to insectivorous bats. I mentioned earlier that there is increasing evidence that bats seem to be the host for SARS-coronavirus-like viruses. This slide reports work from last year carried out both by a group from Hong Kong with colleagues in China, and by Lin-Fa Wang, from CSIRO in Geelong, and his colleagues, also with China. These two independent studies both found these SARS-like viruses in horseshoe bats in China.
I think bats are a lovely subject, but nevertheless we will move on and talk now instead about mosquito-borne diseases. There are a number of these which are very important and which are spreading in different ways.
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I don't want to spend too much on any of these other than Japanese encephalitis, because that is the one which I think is our biggest threat at present. I will talk a little bit about that and then West Nile, and also say a little bit about Chikungunya.
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Japanese encephalitis is a virus that belongs to a serologically-related group of viruses with several important members. The members of the serogroup are shown here. Thus the Japanese encephalitis serogroup includes Japanese encephalitis, as well as our own Australian encephalitis virus, called Murray Valley encephalitis, which very very occasionally causes outbreaks, as its name suggests, in south-eastern Australia, but more frequently in northern Australia. The group includes Alfuy, which is very closely related to the two above viruses but seems to be a separate virus in its own right. West Nile virus is the virus that has suddenly spread from Europe into the Americas, causing a number of deaths in humans and also in horses and various wild bird species. We have a subtype of West Nile here in Australia which we call Kunjin virus but which in fact is very closely related to the West Nile virus strain in the Americas. Another one is Usutu, which I will mention a little about in a moment. There are a few which are not very important, like Koutango and Yaounde, but in the Americas, St Louis encephalitis is one of the most important mosquito-borne viruses in North America, Central America and South America.
So there are quite a number of viruses in this group, some of them very unimportant and some really significant. It is also interesting to note that we are finding more and more members of this serogroup, with a new one in Austria, called Rabensburg virus, and another one in Russia, from a tick, called Rus98. I shall mention these in a little bit more detail later.
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This map shows where we find the most important members of the JE serogroup viruses. In blue, from Australia, through southern Asia and Africa, southern Europe and then to the Americas, we have West Nile. West Nile has now by far the biggest geographic distribution. St Louis encephalitis virus is found in North, Central and South America. Then we see Japanese encephalitis in the areas coloured pink on this map, and in yellow we see Murray Valley encephalitis, which is found in Australia and parts of Indonesia.
Japanese encephalitis is a virus that is emerging and spreading through a combination of changes in land use and vagrant bird movement between different areas where these changes have taken place.
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This slide shows you where we currently find Japanese encephalitis. This map has changed quite markedly over the last 10 or 15 years, and the parts I want to emphasise are its spread into Pakistan in the west – just to mention it – and particularly its movement into Papua New Guinea, the eastern archipelago of Indonesia and also the Torres Strait and even down to Cape York.
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Most cases of Japanese encephalitis, like Murray Valley for that matter, are asymptomatic. Only about one in 30 to one in 300 infections develop into actual clinical cases.
The clinical disease is usually an encephalitis. It can present as meningitis or myelitis, but encephalitis is the most common serious clinical disease.
Of these clinical cases, about 25 per cent or thereabouts are fatal, about 50 per cent recover but may have severe psychiatric-type disease or sometimes quadriplegia or paraplegia, or various types of neurological disease, and only about 25 per cent fully resolve. The most important thing, though, is that it mainly affects young children in endemic areas – again like Murray Valley encephalitis.
JE is a zoonosis. Normally it transmits either between avian hosts (certain species of heron) and mosquitoes, or between pigs and mosquitoes. Pigs are particularly good hosts, and very much the amplifying hosts, so large amounts of virus enter the environment through infections of pigs.
There are about 45,000 cases reported each year in South-East Asia, but this is probably just the tip of the iceberg. It could be nearer 150,000 to 200,000 cases, but we don't know enough about the burden of disease in regional countries.
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It has been long recognised that this virus has a real propensity to spread, and whenever it spreads it seems to be able to colonise new areas very readily. This happens on a regular basis, particularly where you have deforestation to provide new paddy fields – an ideal environment for the virus to spread.
It has moved to a number of different areas over the past decade or so: through Haryana State, in India, in 1993; Pakistan in 1994; Torres Strait, Australia, in 1995; Kerala State, India, in 1996; and Cape York in 1998. So far, though, it has not become endemic in northern mainland Australia– to the best of our knowledge – but it might be endemic now in the central Torres Strait island of Badu.
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Japanese encephalitis virus exists in four, and maybe five, topotypes – defined as genetic types which are associated with certain geographic areas. I use the word topotype and genotype here interchangeably.
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As we can see here, topotype 3 is found mainly in India and Sri Lanka; topotypes1, 2 and 3 are found in central parts of South-East Asia down from southern Thailand, through Malaysia, and then Indonesia, and here in Indonesia we find all four types with the addition of topotype 4 which is only found there; there are at least two topotypes in China and Japan; and now we have two topotypes in our part of the world, in the Australasian area.
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For a long time we were unconcerned about Japanese encephalitis; we thought it would never happen here. We thought the virus only infected animals and mosquitoes belonging to the Asian zoogeographic area defined by Wallace's Line, which divides the Asian zoogeographic area from the Australasian zoogeographic area. But in fact we were totally wrong about this, and certainly very naïve in our expectations.
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Sure enough, in 1995 we had some cases on a little island in the middle of Torres Strait, Badu, which were shown to be due to Japanese encephalitis. There were three human cases and two of them were fatal.
This was the first time Japanese encephalitis had been seen in our area, and until then the closest known activity of Japanese encephalitis virus had been in Indonesia, in Bali, about 3000 kilometres to the west. So how it got to the Torres Strait is another question.
In the next couple of years the virus reoccurred in the north of the Torres Strait, and then in 1998 we had a big outbreak – again in the Torres Strait, but with a case, for the first time on mainland Australia, about 200 kilometres south of Cape York.
So now it appeared that the virus was tending to re-emerge annually in the Torres Strait, certainly in the last part of the 1990s. And the genetic type of virus was topotype 2, one that probably came from South-East Asia.
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To demonstrate where the virus occurred in the Torres Strait in 1995 and 1998: each of these red pigs shows there were serologically positive pigs found on these different islands in the Torres Strait. You see here the coastline of Western Province of Papua New Guinea, demonstrating how close some of the Toores Strait islands are to Papua New Guinea. The most important islands were Badu, where the three human cases occurred, and Saibai, close to PNG. You see here, at the bottom of the map is Thursday Island and Cape York. As you can see, the occurrence of Japanese encephalitis was quite widespread in the northern and central islands.
In 1998 the virus moved down into Cape York for the first time, infecting pigs near Bamaga and at a little place called Seisia. We also saw it both in pigs and one human case at the mouth of the Mitchell River, between two little townships called Kowanyama and Pormporaaw. The human infection was relatively mild, and the patient fully recovered.
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To look at this on another map: here is where we saw the human case and sero-positive pigs, right at the mouth of the Mitchell River between Kowanyama and Pormporaaw. As you can see it's getting pretty close to our tourist industry, and not all that far from Cairns. We wouldn't want to start asking our tourists to have a JE vaccine to come to Australia, but this is what might well happen in the future.
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We also found the virus in Western Province of Papua New Guinea, and we were able to show that this virus was genetically the same as the virus in Australia. It is almost certain, then, that this is where the Australian outbreak came from when it first emerged in the Torres Strait.
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This is shown in the dendrogram of the genetic sequences of the viruses, where we can see that the Australian and Papua New Guinea viruses are almost identical and belong to topotype 2.
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This is how we think the virus came to Papua New Guinea and then to the Torres Strait. We think it island-hopped, with localised transmission cycles between birds and mosquitoes - or perhaps between pigs and mosquitoes – on each island, as it moved through the Indonesian archipelago, finally coming to Papua New Guinea and then down to the Torres Strait. This is what we think happened, and there is quite a bit of evidence for it from serological studies carried out over the past 20 years or so by colleagues working with livestock on these islands.
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In 2000 we had a recurrence of Japanese encephalitis, and every year since then we have seen Japanese encephalitis back again. But what is really astonishing is that the genotype now is different. From 2000 onwards there has been a different genotype, genotype 1 or topotype 1 – and closest to a virus from Korea. How it got to Australia we just don't know. The previous genotype has disappeared; we no longer see it. So here we have a new genotype and it continues to cause problems.
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Here it is listed in genotype 1. So Japanese encephalitis virus is in the islands of the Torres Strait and in Western Province of PNG, and it looks as if it is here to cause us problems for quite a while to come.
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We believe it could become established in Australia. Everywhere else it has gone in the past it has always established – why should we be any different? Certainly it has now become endemic in Papua New Guinea, and much of the ecosystem in Papua New Guinea and northern Australia is similar. So again there is very good reason why we should think it would eventually establish here.
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Would it go further afield? I believe other parts of Oceania are at risk: Solomon Islands, possibly as far as Fiji. They certainly have the right vector species, and also the right vertebrate hosts to be able to establish. We saw how West Nile virus moved between continents; the same could possibly happen with Japanese encephalitis.
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As described earlier, West Nile virus is found all the way from Australia through to Africa, southern Europe and across to North America.
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I won't say much about the history, other than the fact that it is a virus very closely related to Japanese encephalitis, and although for much of the time it appeared to be a relatively minor cause of febrile disease, sometimes with a rash, it suddenly became much more serious in terms of neurological disease in outbreaks in the late 1990s. We saw big outbreaks in Russia, in Romania and also in other parts of the Mediterranean with cases of encephalitis. Then suddenly, in 1999, it emerged unexpectedly in North America.
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This phylogenetic tree shows where these viruses genetically fit in. You see here that West Nile virus occurs as two distinct lineages and that the main lineage is lineage 1. The New York strain in 1999 is identical to a virus that was isolated the year before in Israel – absolutely identical, down to the last nucleotide.
Also in the same lineage, lineage 1, we have the Australian Kunjin viruses and the Indian viruses, which are slightly more divergent. The second lineage is quite distinct – and includes the initial virus from Uganda from which the name, West Nile, was derived.
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This slide shows how West Nile has moved in the US. The four states coloured pink were the first it reached, in 1999; the green states, in 2000; in 2001 and 2002 it moved to the Midwest; then further west in 2003 and to the rest of the west coast in 2004.
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By 2006 the virus had spread into all states of the US except Alaska and Hawaii, and into seven provinces of Canada, 11 countries in Central America and the Caribbean. We have seen the first cases now in humans and in animals as far south as Argentina. Interestingly, the virus seems to be losing its virulence in Central and South America.
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This slide shows the number of human cases and deaths, and the number of horse cases, too, in North America. The number of horse fatalities is decreasing because of the use of vaccine, but nevertheless it is still a serious disease of horses in North America.
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How did West Nile virus get from the Middle East to New York? We don't know. We believe it was most likely that it was either through a mosquito being carried by a plane, or through an infected human arriving who possibly had some other medical problem leading to an immunosuppression – resulting in a much higher titre of virus than normal.. If this was the case, a high viraemia might be more likely to infect mosquitoes, with the result that it initiated a transmission cycle. We don't really know, and this is all supposition.
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What has been very important with West Nile, though, is that we have learned (thanks to major studies because it has been so common in the United States) that these viruses do not have to be transmitted by mosquitoes; they can be transmitted also by transplantation, by transfusion, by breast feeding, by transplacental transmission, by occupational exposure and perhaps also through urine. So we don't have to be bitten by a mosquito to transmit these viruses.
This is a very new concept to us. Now we have to consider that the same may be so for Japanese encephalitis and other similar viruses, maybe Murray Valley encephalitis. We have just never studied them enough to be aware of these other modes of transmission.
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Just very briefly: this slide from Norbert Nowotny shows the phylogenetic relationships of the Japanese encephalitis sero-group members. Here are all of the JE serogroup members, with Japanese encephalitis (JEV) in the centre at the top. We have Murray Valley encephalitis (MVEV) over on the right, and near the bottom of the diagram we have totally new viruses, Rus98 from a tick in Russia, and Rabensburg (RabV) from Austria. They are quite distinct, even from West Nile – you see here West Nile lineage 1 and West Nile lineage 2. So they are all quite distinct. And even in the most unlikely places, like Austria, we are finding totally new viruses belonging to this group. There is not yet any link of these newer viruses to human disease, but I think time will tell. I mentioned Usutu virus earlier – this is a minor African virus, perhaps causing a febrile disease very occasionally – but recently it has suddenly appeared in central Europe where it has caused fatal infections in various songbirds, especially blackbirds. Nowotny and colleagues have shown that the virus has become established in Austria near Vienna, and it appears to comfortably over-winter there! Another example, if you will, of the ability of this subgroup of viruses to move and establish in new ecosytems.
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We are getting very short of time so I will not discuss Chikungunya in detail, but it is a virus that suddenly reappeared as a major epidemic virus over the past 3 years. We had known about Chikungunya in Asia and Africa for many years, but it suddenly reappeared in the south-west of the Indian Ocean and caused massive outbreaks over the last two years.
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This should give you an idea. On Réunion, for instance, the attack rate was 29 per cent – that is, 29 per cent of the population were infected. And also there were quite a number of deaths with chikungunya recorded on the death certificates, although there is some doubt about whether the deaths were really due to the virus or not.
As I mentioned at the beginning, there are outbreaks in India at present, causing millions of casualties. The last number I heard from Kerala alone was about four million cases.
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I don't want to take too much time on this slide, but Chikungunya is a risk. We now have had a number of outbreaks over the past 24 months in Asia, including Timor East (Timor-Leste), Malaysia, India, Bangladesh and Sri Lanka. And so it is on our doorstep again.
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It is a virus about which we know very little. We don't know if we have mosquitoes that can transmit it (although recent work carried out by Dr Andrew van den Hurk suggests that we may have several mosquito species able to transmit it); we don't know much about its vertebrate hosts; we don't know much about whether the commercial kits that our laboratories use will diagnose it. It is very closely related to Ross River, for instance, and also quite similar to Barmah Forest, two viruses that we already have in Australia that cause human disease.
So at this moment it is certainly a risk to us. I should also mention that it is often difficult to distinguish clinically from dengue, so it is of concern for that reason.
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There are many other viruses which we could talk about and from which I believe we are also at risk, but in a sense it is like a catalogue.
I just want to talk a little bit about other threats. The threats might not be from natural agents but might be from how we work with them.
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I think accidental release and deliberate release of infectious agents are always going to be threats to us in our neighbourhood, particularly when you think back to SARS. In 2003 and 2004, we had laboratory accidents with SARS-coronavirus in Singapore, in Taiwan and in China. One death occurred in China when a person died following a laboratory accident. I believe it is possible that some of the regional laboratories may not have the containment facilities that are necessary for dealing with very highly pathogenic viruses, or do not have the wherewithal for the upkeep of these laboratories. So I do have a concern about the potential for further accidental releases. This is one area we need to do something about, and I think Australia should play a role in this area through education on safe handling procedures for highly pathogenic agents and through helping to establish national guidelines for building and maintaining containment laboratories.
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We also have other things happen in our region. We have major natural disasters such as the tsunami in Banda Aceh. And these may also provide situations that can lead to outbreaks of disease.
So we have a number of things in our region – not just ordinary diseases that we think of, like Nipah or avian influenza, but other natural disasters that can lead to disease outbreaks too.
While there may be a number of diseases which could be thought of as posing a potential threat, perhaps the biggest threat, to me, is a disease that we don't even know about yet, like SARS, like Nipah – some new virus still in its wildlife niche that hasn't yet spilt over into humans. It is probably lurking in a niche we haven't yet gone into. This to me is the biggest worry. This is also why we need to have much better intelligence, much better information about what is going on in Asia, so we know about these potential risks when they first occur, before they can cause a problem for us and possibly for the world.
Therefore I really believe the biggest problem is likely to be something which is still unknown. Therefore what we do need is to have some way of being able to detect it very early when it first emerges.
So, how should we respond to these threats?
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I think the most important responses we can make are really to develop better intelligence, through linkages and networks, particularly through person-to-person linkages, and also through capacity building to improve the diagnostic and epidemiological facilities in our neighbouring countries.
With respect to improving our international disease intelligence, the Department of Health and Ageing does that for us already, and does it very well, but nevertheless it is very often government-to-government, and very often central governments don't know about some outbreaks occurring, believe it or not, in their countries. We see this every so often at the World Health Organisation, that there is an outbreak and you phone up the ministry and say, 'You may have a problem up in the highlands with a severe outbreak of respiratory disease. Did you know about this outbreak?' 'No?' 'Well, can we provide assistance, and help you verify it?' 'Yes, please do.' In other words, countries don't always know what is going on in their backyard. And I think the trouble is that we need to have better and more detailed intelligence. So we need to establish these networks where we can find out about things much more readily, and that is done best, I think, by person-to-person contact, perhaps through joint research programmes.
We also should be much involved in training laboratory scientists and infectious disease physicians in the region, and assisting in countries' compliance with the new International Health Regulations. These will also have a big, big effect on knowledge about disease outbreaks. The new International Health Regulations are a legally binding instrument of international law that will require a country to be able to diagnose, to understand and to assess a new disease or an infectious disease threat and report it to WHO within 24 hours. Thus, once countries are compliant and able to respond in the way expected – and many countries may find it difficult to be fully compliant in the time available – we should know much more about disease outbreaks and much more rapidly. But until that happens – I think there is much more we can do, especially in helping are regional neighbours to become fully compliant.
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I have said that we need to improve our knowledge and intelligence of outbreaks. We do this first of all by current mechanisms. The WHO has various systems in place, through WHO country offices and collaborating centres, but especially the Global Public Health Information Network of Health Canada – these are the more formal systems of intelligence. We need to look at more informal linkages, and it is the informal ones which I think many people in Australia can progress through personal interactions with their colleagues in South-East Asia.
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We can set up various types of international networks, particularly networks of laboratories, networks of different interest groups, for instance. We have different societies, such as the Australian Society for Microbiology, with a link to Asia through the Federation of Asia Pacific Microbiology Societies and through the International Union of Microbiological Societies. There is also the Asian–Pacific Society for Medical Virology which meets every three or four years, and which strongly endorses cross border research programmes. All these different groups are ones which we have to be part of, ones which we can utilise as part of our intelligence-gathering process. The Academy of Science has also been involved with building research linkages, one example being the joint Academy and Department of Education, Science and Training meeting with the Indonesian Academy of Science last year, and with a second such meeting being planned.
On the animal side we have had very good links, particularly with Indonesia, over many years. The Department of Agriculture, Fisheries and Forestry (formerly known as AFFA) had a mandate whereby they had people in Indonesia working on animal diseases that were a threat to Australia, such as bluetongue and so on. We have never had the same mandate in Health, so we have never had the same linkages on a government-to-government basis as had been built up with AFFA. So we have a lot of catching-up to do, in a sense, and I think we can do this very much better now that we know what we need to do, but particularly through these types of informal linkages rather than the more formal ones.
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Capacity building is also a very major issue in our region at present. I mentioned the International Health Regulations. In the next four years, countries are expected to become compliant with these regulations. It means an enormous amount of capacity building for laboratories to be able to detect and diagnose new diseases, and an enormous amount of capacity building in being able to undertake epidemiological investigations. So these are things which they need to do, and we must be involved – very much so – in helping with the training, providing resources and assisting both the World Health Organization and the countries themselves.
I know that AusAID is very much involved now with supporting a group called APSED, the Asia Pacific Strategy for Emerging Diseases, a bi-regional strategy of the World Health Organization, leading to improved diagnosis and control of emerging infectious diseases. This is another way that we can also help build capacity in regional laboratories.
So I think if we are much more proactive through AusAID, ACIAR [Australian Centre for International Agricultural Research] and other aid-funding mechanisms, they can help provide a basis for building these different networks and other linkages which are going to be so important, I believe, in the future.
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To summarise, there is little doubt that emerging infectious diseases are a threat to the health and prosperity of our country, and that early knowledge of these potential disease threats is crucial in being able to undertake a risk analysis of any new threat, and to make contingency plans early enough to be able to do something about that threat, should it actually materialise. There is little doubt also that early knowledge may be gained through better international linkages at the person-to-person level, particularly through common research interests but also through increased capacity building and training in regional laboratories to better detect, diagnose and respond to new, potential threats.
Much of this rests in Australia's participation in regional research, participation in diagnostic and research networks, in assisting with training and capacity building, and in the provision of well-placed aid. I would ask all of you who have any interest in any of these areas to make sure that we do play an effective and suitable role in South-East Asia. It is the best way, I believe, that we will be able to detect, early, any new emerging threat.
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I would like to acknowledge all the people who have been involved in my laboratory and my flavivirus colleagues, and also other colleagues who provided some of the slides, friendship, and many stimulating conversations on emerging diseases and global health security.
Discussion
Deputy Chair:Are there any questions of Professor Mackenzie?
Question 1: You have mentioned the trade and economic implications of emerging diseases. I wonder if, to your knowledge and experience, the Asia–Pacific Cooperation (APEC) group have ever asked to be involved.
John Mackenzie: Yes, they have. There was a meeting of APEC Ministers and senior administrators in science and medicine earlier this year, in Sydney. Discussions included the importance of emerging diseases, problems with vector control and other aspects which are important in terms of how diseases emerge.
Question 1 (cont.): And is that complementary to what you consider to be the right strategy?
John Mackenzie: It is complementary in part. A lot of the agencies that link in to APEC – the Asian Development Bank, and so on – are very keen to be involved. The last meeting we had of APSED was quite amazing: we had the Asian Development Bank, we had the Japanese aid organisation, the Canadian aid organisation, AusAID – everyone seemed to have open chequebooks ready to provide resources to assist in capacity building. So I think there was a lot of understanding that we need to build capacity in the region, and do so rapidly, but it was perhaps a little early at that particular time as many of the strategies had not been fully detailed.
Question 1 (cont.): My second point leads from that. You mentioned the need for intelligence. To what extent – and just say this very quickly – does this work on the ground? That is to say, are there enough people with the right technology so as to be able to identify these diseases as they emerge, quickly enough? You mentioned the inability of some nation states to do this. What exactly is needed? Is it more feet on the ground? Is it more laboratory equipment, made in the United States, transported here, made in Australia, exported there? What is the practical?
John Mackenzie: There are two things. There are no where near enough people with the right technology on the ground. Further training, and also provision of good diagnostic equipment in terms of laboratories is needed badly. Some countries now have bilateral agreements with the US through CDC [Centres for Disease Control]. The CDC are there to help them when they need help, and they will put a team in the field within a matter of hours.
But there is a quid pro quo, of course, in all of this, in that whatever they isolate goes back to the US. If it is then deemed to be a level 3 or level 4 agent, Homeland Security will not let it out again. So this may present a problem, in the sense that they are not always available thereafter for international use.
Yes, there are ways it can be done at present, not always the best ways. But there are big gaps, certainly in the training and in the provision of equipment. I can think of certain countries, like Papua New Guinea, Laos, Cambodia, Burma, where a lot of work needs to be done to build up their capacity.
Question 2: You talked about some of the things that humans are doing to stir up these viruses. I was wondering whether you think that there are any features in the human populations they are finding themselves in that aren't just making those populations susceptible, and might actually be explaining some of the changes in virulence and transmissibility you have described with Nipah virus and AI and some of those.
John Mackenzie: With Nipah I don't know of any things that could be going on to do that. Certainly, obviously, there are lifestyle changes that people have had in various ways which have had a big influence on transmissibility for certain agents – as you know, with STDs and so on, HIV. But in most instances here, no, I don't know of any good evidence to suggest there have been changes of other sorts.
With the avian influenza there are changes in terms of both host and the virus – the virus can mutate very readily, and there are other things which may become important, such as culling diseased birds, which brings in other questions, such as the ability to adequately recompense farmers and families for whom the birds were a livelihood..
Question 3 (Professor Frank Fenner): John, I was a malariologist in New Guinea during the war, and dengue was very common but deaths from it were virtually unknown. Just for general information: there are four serotypes of dengue virus, and I am sure that just one was operating in that part of lowland New Guinea. But after the war, with air travel, the phenomenon of enhancement of virulence occurred when a person who had a certain serological level of, say, type 1 got infected with type 4. There is a death rate, from my memory of it, that runs about 10 per cent now. It was air travel, essentially, that created that difference in dengue.
John Mackenzie: I think you are quite right: it is a combination of travel and urbanisation, and more and more people got together under adverse, slum conditions where vectors could breed readily. Probably those two things had enormous effect, more so on dengue than on any other disease. If you look at the increase in dengue in countries where dengue has become endemic and epidemic since the end of the Second World War, is the numbers are absolutely incredible, that is the number of cases and the number of countries where it is now endemic.
I think during the war you saw very few deaths; as you say, in Papua New Guinea there was probably only a single type. Now we know all four types are there, and they are endemic. But we don't know much about what is happening in Papua New Guinea, unfortunately. It is one of the countries where we have little good information about diseases like dengue. We know it exists, but we have no idea of the incidence, no idea of the number of deaths due to it or anything. There are big gaps in our knowledge of what is on our doorstep.
Question 4: I was wondering about the control of the movement and population development of mosquitoes in Australia, and whether the current moves to increase water storages with household tanks and so on poses a threat in that regard. I think I heard that water tanks were moved out of Brisbane at some stage because of the threat of malaria. Is that a true statement? And what can we do if that is the case?
John Mackenzie: I don't think it was so much for malaria but certainly for dengue, more particularly. It is funny, you know: 100 years ago dengue was quite common in large areas of Australia, all the way down to Bunbury in Western Australia and the New South Wales border on the Eastern seaboard. For some reason, the mosquito that used to transmit it gradually retreated. We think it is partly because we got rid of steam locomotives and went across to diesels, so you no longer had fire buckets and big tanks to fill with water for the locomotives in country areas, and also because of other issues like the use of scheme water rather than tanks. You are quite right, this had a big effect.
Now we are building more tanks, but I think we are taking more precautions. Every tank we sell now has to have netting on it to prevent entry of mosquitoes. I'm not saying it is going to work, and there is a risk, I believe, but I think just now the need for water conservation probably slightly outweighs the risk of mosquitoes, providing those tanks are kept mosquito-proof. That is where the problem will always be, of course.
It is like dengue breeding around the house. We always say that dengue breeds in old icecream containers or car tyres or gutters that have too many leaves in them, but to try and get people to make sure their backyard is tidy and gutters are free, and so on, is very difficult. I suspect it will be the same, in time, with these new tanks. In another 30 years, although they might have had very nice netting initially, these nets may have deteriorated, and I can see problems in the future. But that is being a bit of a Jonah, I suspect.
