Contagion calculation: Forecasting and tracking outbreaks of influenza

Melbourne University. Australia: Epidemiologist Assoc Prof Jodie McVernon discusses research into tracking and predicting the spread of influenza and other viral diseases like Ebola.


I'm Dr Shane Huntington. Thanks for joining us. Viruses have an extraordinary impact, not only on humans, but on the majority of the world's plant and animal species. Some viral infections go by almost unnoticed, while others can lead to serious illness or death. Arguably, the most well known virus is influenza. Most of us, at some stage in our lives, have been infected by a type of influenza. As viruses go, influenza is one of the smarter ones. It rarely kills its hosts. It spreads at high rates across the globe, and it's been difficult to contain. On top of that there are numerous strains of influenza that are, for now, restricted to animals, but may yet pose a significant threat to humanity. On the positive side influenza is an excellent virus to use for modelling purposes. Its seasonal nature and global distribution enable us to better understand how viruses and other infectious diseases work and spread, potentially giving us new insights into how to control them. Today on Up Close we are joined by an international expert on influenza and the modelling of emerging infectious diseases. Associate Professor Jodie McVernon is an epidemiologist in the Melbourne School of Population and Global Health. Welcome to Up Close, Jodie.

JODIE McVERNON
Thanks for inviting me.

SHANE HUNTINGTON
Jodie, what are the properties of a really successful infectious disease?

JODIE McVERNON
So I think you've already touched on a couple. One is that an infectious disease shouldn't be too deadly. If you kill your host very quickly you don't have many opportunities to get out and about and spread to other people. The other thing that makes influenza very effective is that it actually is incubating, it's growing up in an individual before they even have any symptoms. So there's probably a one or two day window where individuals are shedding virus, can walk around, do their usual things and infect other people before they actually get a fever and start to feel unwell. So at that point the horse has already bolted, if you like.

SHANE HUNTINGTON
 And does influenza actually meet all of these conditions?

JODIE McVERNON
So influenza generally is a very mild virus. We estimate that between one in five and one in 10 people might get the infection every year; children more than adults. But as a result of that infection maybe a quarter to half a million people a year die every year just from seasonal influenza, and that's separate from the burden of pandemics. So that mildness certainly does allow the virus to persist well and to spread through the community. But we do see sometimes more severe infections in some years than others and, obviously, when viruses that have been circulating in birds - for example, we're aware of avian influenza strains or some recent swine influenza strains that can cause pandemics - where viruses that humans are relatively inexperienced cross over into human populations their characteristic is to cause more severe disease.

SHANE HUNTINGTON
Do we have an understanding at this point of what the goal of a virus is? I mean what's it trying to achieve as an entity?

JODIE McVERNON
So viruses aren't cognizant beings. They just want to live. And to be able to live they need to be able to grow up in cells and define more cells. They need to spread to someone else. So at that point viruses that tend to kill people quickly are selected against, and viruses that don't kill people quickly and are able to get out and spread further will tend to survive in the wider population.

SHANE HUNTINGTON
We hear a lot about certain diseases being the next big pandemic globally. There's a few recently that we've heard: SARS, bird flu, at the moment Ebola, in 2014, are all mentioned in this particular context. Are these statements actually valid?

JODIE McVERNON
So the chief characteristics of a virus that is able to cause pandemics are that there is little immunity against them in the human population. So the viruses you're describing are all things where there's been very little human population experience of these infections. Very few people will have made any kind of protective immunity against them, and so, in that sense, we have a lot of people who are potentially susceptible who might become infected. Whether or not a virus causes a pandemic depends on how good it is at spreading between people. So this concept of infectiousness is really important. Flu is very infectious because it can spread in droplets around the place, in airborne particles. It's quite easily spread from one person to another through fairly non-intimate acts. We can cough or sneeze or touch a door handle that somebody might have sneezed or touched themselves with a virus on it, and that makes the probability of spreading the infection high. So transmissibility is really important.

SHANE HUNTINGTON
Does Ebola sit in that category of potentially a very successful virus, as it seems to have been contained for a very long period of time until recently?

JODIE McVERNON
Ebola doesn't have characteristics we'd normally equate with pandemic viruses. Ebola is actually quite difficult to transmit. It is transmitted through close contact with bodily fluids. And people, particularly in the late phases of disease - particularly if they develop any bleeding complications with the infection - are highly infectious. What we've seen in Africa is a lot of events particularly associated with burial rituals, where people would be involved in washing and handling bodies and preparing them for burial, where many people may be infected by one person. Otherwise, it's actually quite a difficult disease to transmit, and it seems to become more infectious late in the disease, at which time we know that someone is sick. Obviously, the other issue with Ebola is that it is a very severe disease and there's a very high fatality rate in those countries that are affected. I think the biggest concern about Ebola at the moment - it's not so much that it's been contained in the past. It's what we call a spill-over disease. So it's a disease of bats. They tend to not get sick with it. There are some intermediate species like primates and some types of deer that can get the virus and be sick with it, but in the past the crossover infections that have involved humans have been relatively few. They've been well contained and then it's died out. So it hasn't been an ongoing infection of humans. What people are worried about with the current scope of the Ebola outbreak in Africa - which has exceeded any previously - is that the virus may start adapting, becoming less severe and more effectively persist and spread between humans. So it might go from being an epidemic to what we call an endemic infection, something that persists in the human population without the need for that spill-over from animals.

SHANE HUNTINGTON
In the same vein, when we speak about bird flu, there is this scenario at the moment where human to human transmission seems to not have been achieved by this virus. Is this something that you think is inevitable for something like bird flu, that sooner or later enough people will be infected that this change in the virus's genetics will enable it to do this extra leap in human to human transmission?

JODIE McVERNON
The issue with bird flu - the reason that we're so aware of the threat of bird flu is that flu is innately a disease of birds and the global population of agricultural poultry has grown by thousands over the last couple of decades. So we have enormous numbers of birds that are able to be infected with viruses that are in close contact with humans. The saving grace of bird flu from the human point of view is that it's actually really difficult for viruses to cross between species, and birds are a long way away from us in the species order of things. So the viruses that infect birds bind well in the airways of birds. They don't bind well in the airways of humans. So that, on the whole, has meant that we see remarkably few cases of human infection, given just the bird viruses that have got to be out there that humans are in contact with all the time. So that's a good thing. The issues about viruses becoming adapted to humans is that there are some species - and particularly pigs - that are able to bind viruses both that infect birds and humans. If a pig happens to have both of those infections going on at the same time, viruses can re-assort. They can swap bits of themselves around and emerge as viruses that might be capable of infection humans more effectively. So as more and more of these events happen - even if the chances are small - the actual numbers that could occur increase. That said, there are probably many infections of humans that occur all the time that just never go any further, that we don't hear about. That's great news, but we need to remain vigilant and aware of these viruses. So the World Health Organisation stockpiles viruses that are thought to be imminent threats for that purpose; but we're very fortunate.

SHANE HUNTINGTON
We hear sometimes these terms H1N1 and various other configurations of the titles of these viruses. Can you pull those apart? What does the H and the N respond to, and the numbers? How are they related to the particular virus we're talking about?

JODIE McVERNON
 So the way we classify influenza viruses, broadly, is on the basis of these two proteins that they show on the surface of the virus, and our bodies make immune responses to those. So the HA is something called hemagglutinin. There are 16 kinds of hemagglutinin that have been described in birds. Of those there are only three types that have ever widely circulated in the human population. So those are H1, H2 and H3 viruses. At the moment, globally, H1 and H3 viruses are circulating in humans together all around the world. The N part is called neuraminidase, and there are fewer kinds of neuraminidase, but N1 and N2 type of viruses have circulated in humans. So at the moment most of the viruses we have are H1N1 or H3N2. We have had mix ups of those in the human and animal populations, and sometimes we get H1N2 viruses, for example, but less frequently.

SHANE HUNTINGTON
One of the things that it is hard to argue with is the success of certain vaccination programs against certain disease of the past; so smallpox, for example. We can think of a number of others, like measles and so forth, where they've, essentially, almost been eliminated. In the case of smallpox, I mean this has been very successful. Why is it that we've been unable to achieve the same goal with something like influenza or even some of the other viruses that stick around?

JODIE McVERNON
 I love to tell the story of smallpox. I think smallpox is a furphy. I always tell students that when they think about any vaccine. It's probably one of the rare examples of something that's worked so well. It comes back to what it is that makes infectious diseases different from each other. So smallpox was one of these infections that had a very high mortality rate. You either died or smallpox or you survived. If you survived your immunity was lifelong. In the 18th century having smallpox scars made you more marriageable because it meant you'd been through it, you were robust and you weren’t going to be wiped out in the next epidemic. For many other infectious diseases we can become infected. We develop some immunity that protects us, maybe, for a year or two, but then that immunity wears off a bit or, in the case of influenza, the virus is constantly changing in the human population. So we have the same - maybe H1 and H3 - viruses, but they're changing a little bit all the time. When they reproduce they don't copy themselves perfectly, so there are all these different possible variants that go out there. And if there are variants that people are already immune to - they're less likely to succeed than the ones that have already moved a little bit away from that - immunity will be more successful. So we see something called antigenic drift in influenza viruses. And so each year the viruses will change a little bit from the ones before. The World Health Organisation monitors that and, usually, over a period of three to five years the viruses will change sufficiently that the World Health Organisation decides they're going to need to update the vaccine so that it will protect more effectively against these new viruses that have moved away from where the previous virus vaccine strains were. If your own immunity can't protect you against influenza for life, how will a vaccine do it? At the moment our influenza vaccines are limited by the fact that they work on this approach of making antibodies against the HA and the NA. So as those antigens are changing and drifting over time, the vaccines become less relevant.

SHANE HUNTINGTON
I'm Shane Huntington and you're listening to Up Close. We're discussing infectious diseases with epidemiologist, Jodie McVernon. Jodie, let's move now into the modelling of some of these diseases. Any model that you use in science requires a range of assumptions and a range of inputs. What are the key ones that you need when you're building models for infectious disease outbreaks?

JODIE McVERNON
So we've touched on some of the issues already that make influenza and other infectious diseases different. Those sorts of concepts are important to build into models. So when we make a model it's just a way of writing down everything we know, and we need to incorporate information from basic biology, from what we see in epidemiology and, often, from sociology, to be able to understand how infections grow up in individuals and how they spread between individuals, and then we can think about how to control them better. So the basic way we think about any infectious disease is, you know, we characterise people in a population as either being susceptible to it - they haven’t had it yet, but they could get it. They're either actively infected and, in that state, they might still be incubating a virus and not know about it, or they might have symptoms. Then there's a stage where they're infectious. At that point they can spread infections to other people. And at the point where people clear an infection and recover, they might have some protection for a while. With many infections that will last for a while, but that protection can wear off over a period. So we build in all these concepts about what we know about how infections grow up, spread, shed, recover, and we put that into some mathematical equations. There's a paper dating back to 1927 that describes this theory of epidemics, and so this cutting edge method has been remarkably effective since then of understanding why infections take off and then resolve in a population.

SHANE HUNTINGTON
When we think back to 2009, I remember, myself, I was sitting in the LAX old airport terminal when the swine flu outbreak was hitting its peak - a very disturbing time. It didn't seem to end up being quite as big as people were predicting. Was there something about the modelling that wasn't quite right there, or some of the parameters not correct?

JODIE McVERNON
So I think prior to 2009 we'd all been looking to the birds. We'd been looking at bird viruses and thinking about the risk of some of those viruses to which humans had had no exposure becoming humanised and being able to spread. So a lot of the early modelling about pandemics was assuming that everybody would be vulnerable. The H1N1 pandemic in 2009 caught us all by surprise. In the first place it didn't come out of Asia, where everybody was looking. It came out of the Americas, and it came out of pigs, not birds. And the thing that we increasingly recognise now is that pigs are very susceptible to human influenza viruses. Pigs have been being infected by human influenza viruses over the years, and the viruses don't change in pigs at the same rate they change in humans. Pigs have fairly short life spans before they turn into bacon, so the viruses don't evolve as much in pigs. What we see is if we go around do surveillance of pigs - and this happening more and more in the US and in China - pigs are a bit of a walking library of old human viruses. So when the 2009 H1N1 swine virus emerged it was an H1N1 virus. We have H1N1 viruses in the human population, but it actually was like a really old H1N1 virus. It was more like the 1918 Spanish flu type viruses which caused a pandemic in the early 20th century. What we found was that particularly older people in the population had some cross-protection against that virus. It wasn't acting on a blank canvas. There was some pre-existing protection because the viruses that had come out of the pigs were actually humanlike viruses.

 SHANE HUNTINGTON
Now, whenever you're doing some of this modelling, presumably you have to incorporate some of the intervention mechanisms that are commonly used around the world. How do you go about that, and what ones do you focus on? And why do you choose those ones over others?

JODIE McVERNON
So in the response, initially, to a pandemic we have a fairly limited suite of options. As we said before, the vaccines that we make - and we'll come back to vaccines - are against the flu types that we know to be circulating. So in the first response we can only really think about generic measures to limit the spread of infection, and we do have some specific measures in the form of antiviral drugs that are effective against pretty much any influenza type. So we can certainly think about strategies to limit movement of people. One of the challenges in that is that complex human behaviour means we can't exactly predict what people will do. In the context of pandemics people often talk, for example, about school closures being a great measure to reduce the spread of infection, and many modelling studies have looked at this. To be effective, school closures really need to be proactive. So before you know the virus is spreading they need to be prolonged. They need to go over months. We've seen in practice that in some settings - for example, Hong Kong - that was a very effective strategy to reduce the spread of infection between young children. But those sorts of measures have enormous social and economic implications. And studies that have looked at economic evaluation of those measures - so that unless people are dying in the streets it's never going to be a cost effective thing to do this. It's going to be politically very challenging - and, societally, we have a high proportion of dual working families - it's a very difficult thing to implement, so some of those things are useful. We can try to pre-empt how well measures will work, but as many studies in the pandemic found also, when schools were closed kids just all hung out at the mall together; so how well can you really reduce the spread of infection becomes a complex question of human behaviour.

SHANE HUNTINGTON
Does the modelling give you any insights into how to go about that, because I can imagine things like closing down the airlines, closing the ports, as you say, closing the schools and so forth, would only be socially accepted for a short period unless, as you say, people were literally dying in the streets. So what do the models tell us about how we should go about that if we have this storm on the horizon coming towards us?

JODIE McVERNON
So I think an interesting avenue that people are pursuing - since the pandemic there have been a lot more detailed studies of contact patterns in school settings, particularly in the US. And the CDC - the Centers for Disease Control - has invested funds in going out and finding more about how this happens. So are there ways that you can reduce the mixing of school levels or school children within school settings? I think there's been a lot more interest in, perhaps, more nuanced approaches to reducing risk rather than saying we have these blanket measures of closing schools, for example; so it's driven a lot more study of human social interactions and behaviours, which I think is important to appreciate.

SHANE HUNTINGTON
 We seem to have two ways which we can go in a drug sense. We have the antiviral path and we have the vaccine path. How do the two compare in terms of successfulness in actually bringing together an end to some of these particular spreads? And is it likely that we're going to preference one over the other in terms of research in the future?

JODIE McVERNON
So each of them has a distinct role to play. So the issue about antivirals is they're a finger in the dyke, if you like. They're a way of stopping or limiting the spread of infection at a stage where you don't have what we could a more definitive intervention. So the issue there is someone who has been given an antiviral drug will be less likely to pick up an infection from another person, but they will only work as long as they're taking the drug. And the standard course of these sorts of drugs is in the order of a week or so. If there is a local outbreak, for example, in a school you could go around and give the drug to people in the school. That might protect them for a week, but as soon as someone else comes in with an infection you would have to start the treatment all over again. So we see antivirals as of use in, potentially, reducing the spread of infection early on, but they're not a permanent stopgap because once people stop taking the drug, they're still susceptible to infection. Much of the pandemic planning that's been done around antivirals really is then focussing on this role of delaying, of slowing down the spread, of making the disease more manageable. We're aware in pandemic events there's the potential for a big burden on health services, so slowing down the spread, reducing how many cases appear on a given day - if we can reduce the number of cases per day that can just stop hospitals, for instance, being completely overwhelmed, so we will have capacity to treat the people that we need. So those are the kinds of end games of an antiviral strategy, is slowing things down, reducing the peak. All of that is about buying time to have a more definitive intervention, which in this case is a vaccine; because once you've had a vaccine that's targeted against the pandemic strain, it should continue to protect you, and at that point you can actually definitively stop the outbreak if enough people have the vaccine.

SHANE HUNTINGTON
You're listening to Up Close. I'm Shane Huntington, and my guest today is epidemiologist, Associate Professor Jodie McVernon. We're talking about infectious disease. Jodie, in terms of vaccines, let's just unpack that a little bit. What's happening in the body when a person receives a vaccine injection for a particular strain of flu, or whether it's something like measles, which is more long term? What's going on in the human body? JODIE McVERNON Vaccines usually contain components of the disease we're trying to protect against, so most influenza vaccines are what we call split virion vaccines. So if someone has grown up a virus - usually in an egg, or sometimes in a cell line - and they've broken down the viruses so they're not alive anymore - they're dead, but they still have the various components we're talking about - the HA and the NA we talked about earlier - that the body can make antibodies to. And so injecting those particles means the body can make an immune response, antibodies will be developed that are then able to spot and kill viruses, should the person become infected. And the first time we give a vaccine against something that is completely unknown - so one of these new viruses - it takes seven to 14 days for that first response to come. And the challenge with many of these pandemic strain viruses that are completely novel is that two doses of vaccine are usually needed to develop a level of antibody that we would consider should protect against infection. So that's significant in a population level because it means even if you have your vaccine on day one, it's not actually potentially working until people have had two doses, and that could be 21 days, 28 days later, depending on how quickly you can get those two doses in.

SHANE HUNTINGTON
You described, in the case of influenza, the reason for the drift in what's happening with the virus and the fact that you need multiple vaccines year after year to make sure you keep up with that. With some of the other ones though, where there isn't that drift, we do hear that you still need to get a booster after sometimes 10 or 20 years. Why is there a need for that to be re-established? Is the body not learning at the original point how to deal with that particular virus and then having that knowledge for your entire life?

 JODIE McVERNON
 Again, it comes back to looking at the natural histories of many infections, and also how well we expect vaccines to do compared with a natural infection. In the case of measles it was classically accepted that once you had had a measles infection - usually in early childhood - your immunity would be lifelong, you would never get measles again. We have a significant issue in many parts of the world at the moment about waning measles immunity from vaccines. We are increasingly recognising that having measles vaccine in childhood - particularly if you only had one dose, which used to be the strategy many years back - may not actually provide you with robust protection throughout life. And so in some countries we are seeing resurgence of measles as a result, partly, of that and also other factors about population movements and so on. In some sense we probably shouldn't expect a vaccine to do as well as the real thing. That doesn't mean that having the real thing is necessarily a good idea because, clearly, a vaccine is much safer than having measles. The other issue, I think, that is important in thinking about persistence of immunity - where we go back to the case of measles, you know, in a population where all the children were getting measles all the time, you had your measles infection in childhood. As an adult you would be constantly being exposed to children with measles, and so probably the fact that the infection was still spreading in the community meant you could get exposed and boost your immunity. As we become more successful in eliminating infectious diseases to a very low level, people get less opportunities to boost their immunity, and that can be another reason, I think, why we are starting to see, for many infections, a greater need for boosting over time. It's one of the unfortunate by-products of success.

SHANE HUNTINGTON
 I can imagine these two issue are unrelated, but there's also the efficacy or the success of a particular vaccine, so in some people it just doesn't seem to work as well. Do we understand why that's the case?

JODIE McVERNON
So there are different vaccines that are more or less effective. That's based on the vaccine itself. For example, the chickenpox vaccine - I can tell you from personal experience of having had a child with breakthrough chickenpox infection - is less effective than some other vaccines, like the measles vaccine. Just in terms of being able to develop a vaccine, not all will be equal in terms of just their inherent effectiveness. There is then this issue of waning over time, and in some individuals who may have compromised immune systems because of chronic illness or other things, we know that vaccines don't work quite as well, and that's just part of their general weakened immune system. For some individuals we will recommend additional doses of vaccine might need to be given over time, if we can reasonably predict that the vaccines may not protect as well. I'm a member of the Australian Technical Advisory Group on Immunisation, and we spend a lot of time thinking in the handbook about people with special risk conditions and whether they have particular additional immunisation needs for that reason.

 SHANE HUNTINGTON
Now, just to clarify something - and it seems clear from the way you've explained it - but it is not possible for a person to contract the real version of the virus from the vaccination program itself, is it, even though we hear of a lot of people saying I got sick after I got the flu injection?

JODIE McVERNON
The influenza virus as we give in Australia are all killed vaccines. There is no live virus in the preparation at all. In other parts of the world live attenuated influenza vaccines are used to vaccinate mainly children. So that's a weakened version of the virus which has been weakened so that it can actually only grow effectively in colder regions of the body. So it can replicate in the nose, but it can't go down and grow in the lungs because it doesn't like warmer temperatures. So in that situation a live virus is given, but it's a weakened virus. And we don't have those vaccines in Australia.

SHANE HUNTINGTON
 In terms of what the body's undergoing there, you often hear about people being tired and so forth after they have this. Is this because the body at that point is mounting an immune response and is, essentially, using energy to create that response for you? JODIE McVERNON That's it. So in terms of why we feel sick when we have an infection, a lot of it is our own fault. Our body, in mounting a response, will make all kinds of hormones and activate immune cells, and that process of generating an immune response is a lot of what makes us feel a bit off colour. It's reasonable for people to expect that they might feel a bit headachey or a bit unwell. Some people will have a bit of a temperature after getting the flu vaccine. Those things are usually very self-limited and mild side effects and, certainly, generally less in most people than having the full blown disease. So if we have an expectation that that might happen, we can pre-empt it. If you feel a bit off-colour, take some antipyretics and know that that should resolve.

SHANE HUNTINGTON
Now, there does appear to be a worldwide program to, hopefully, eradicate polio. It seems as though the number of cases has dropped quite dramatically on a yearly basis from what it used to be. Are there still barriers to actually doing this? Do you think it's achievable to completely eradicate polio across the world?

JODIE McVERNON
 Polio's an enormous and fascinating challenge. One of the really difficult aspects to it comes from the vaccine side. Then there are a whole lot of other social and political issues. There are two types of polio vaccines that have been used in the world. The first types of vaccines that were developed were actually developed through a huge public campaign called the March of Dimes in the United States. That was an inactivated polio vaccine. So it was a vaccine that contained killed components of the polio virus. It was injected. That vaccine was very effective at stopping people who had become infected with polio from developing the rare, but serious, complications of polio, which were neurological symptoms which could lead to later limb wasting and paralysis. So that was a vaccine - it let you get an infection. It actually let you keep spreading an infection, but stops you getting disease. So that vaccine was quite useful in settings where you could be confident that high proportions of people would become vaccinated, because at that point the risk of still spreading infection was very low because everybody out there would have received their vaccine. In most other parts of the world oral polio vaccines have been used. They were developed a little later. They are live vaccines. They contain weakened polio viruses, and they are able to induce protection. They stop you from getting infected with the polio virus, as opposed to just not developing disease. But even if you do become infected, the risk of shedding polio virus and spreading it to other people is much lower. So particularly in resource poor settings where we can't always be confident of getting high levels of vaccine coverage, these vaccines are much more effective at reducing the ongoing spread of disease. And so around the world there have been two completely different vaccine strategies relevant to setting, depending on what has been achievable in terms of coverage. The one problem with the oral polio vaccines is that even though they are weakened and most of the virus in them is completely safe, the viruses from the vaccine persist in the environment. They're monitored for in ground water and, occasionally, those viruses can revert to cause disease. So in settings where those vaccines are used we can have outbreaks of what's called vaccine-associated paralytic polio; so a virus that's come from the vaccine itself has become dangerous again. If vaccine coverage falls to very low levels we can get small outbreaks of disease from the vaccine. So there's been a global effort to try to eradicate polio, get everybody on to injectable vaccines and get rid of the risk of vaccine-associated paralytic polio, but that clearly requires enormous effort to achieve very high levels of sustained coverage, and that's been difficult. There's also been breakdown of vaccine programs in some parts of the world where there's been political or social distrust in vaccines, and so we still do have ongoing transmission of vaccine in several parts of the world. And while that's happening. people are not confident to take the risk of IPV. So it's something that, globally, is a real challenge and a paradox: how best to solve this problem and achieve eradication.

SHANE HUNTINGTON
Are there any other infectious diseases you'd think in the future we will be able to literally eradicate from the world?

JODIE McVERNON
I'm not a great proponent of eradication. I think the other great challenge with infectious diseases these days - which was not an issue so much even at the time smallpox was eradicated - is our intense global travel and mobility. And that certainly is a real challenge for the sustainability of vaccine programs in many developed countries now as people move around the globe. They come from areas with different vaccination backgrounds, with different levels of risk of other infectious diseases. And I think smallpox was, in my mind, probably the really big success story, but I think we understand now more about the challenges of sustaining that kind of impact over the longer term.

SHANE HUNTINGTON
Jodie, when you say you're not quite a fan of eradication of some of these diseases, or elimination of them, are you referring to the fact that they're just incredibly difficult and it's not an achievable goal? JODIE

McVERNON
I think that it's important to have a achievable end games in sight, yes, exactly. If we are seeking to eliminate, then I think we're perhaps on a hiding to nothing. I think more and more in infectious diseases control we see our primary role as to being able to mitigate or reduce the burden of disease. And in some cases that's about directly protecting the groups who are most at risk of severe outcomes. We certainly can try to what we call eliminate - as opposed to eradicate - so reduce levels of disease spread down to a level that puts everybody at less risk. But eradication, I think, perhaps helps us to focus unhelpfully on one disease where, in fact, we may be able to do more by having a broader, more achievable approach to many.

SHANE HUNTINGTON
 If we come back, just briefly, to influenza and this constant need to update your vaccination each year or two, depending on the strains that are heading around the globe, is it likely we will get to a point where we can crack influenza and be able to have something that is effective for all of these strains? Or is that something that, from a chemical perspective, is just unlikely?

JODIE McVERNON
So my modelling group collaborates with the National Health and Medical Research Council funded program that was led by Peter Doherty, and now by Anne Kelso, that looks at understanding different aspects of the immune response to influenza. We know that there's difficulty in sustainability of protection using these HA and NA vaccine approaches. That program's been looking more at understanding how the body's immune cells respond to more conserved parts of the influenza virus. So there are parts of the virus that are needed for the cell's internal machinery, if you like. If those change a lot the virus actually can't survive. So they're very interested in looking at those more stable parts of the virus and looking at how immune cells respond to that and seeing whether they can be stimulated to provide protection. I think the challenge is there that those kinds of immune responses don't stop infection altogether. They help to clear infection, and they might reduce infectiousness. So this is it. When you have a vaccine, they don't all do the same thing. We've talked about polio and the different types of viruses. These types of vaccines would have a very different action, but when we think about them at a population health level, if they can reduce viral shedding they can stop the spread of infection. If that reduced viral shedding makes people less likely to have severe symptoms, there's reduced need for health care and less burden on health care. And so these kinds of vaccine approaches - if they can be developed and be more broadly cross-protective against both known and unknown strains that might emerge in the future - they could have a really significant public health role to reduce the burden of disease. SHANE HUNTINGTON Jodie, thank you for being our guest on Up Close today. JODIE McVERNON Thanks very much. SHANE HUNTINGTON Associate Professor Jodie McVernon is an epidemiologist in the Melbourne School of Population and Global Health. If you'd like more information or a transcript of this episode, head to the Up Close website. Up Close is a production of the University of Melbourne, Australia. This episode was recorded on 12 December 2014. Producers were Kelvin Param, Eric van Bemmel and Dr Daryl Holland, audio engineering by Jeremy Taylor. Up Close is created by Eric van Bemmel and Kelvin Param. I'm Dr Shane Huntington. Until next time, goodbye. - See more at: http://upclose.unimelb.edu.au/episode/331-contagion-calculation-forecasting-and-tracking-outbreaks-influenza#transcription