A FEW COMMENTS ON PANDEMIC INFLUENZA
By Terry Jones
fluidinfo.com
Sunday, April 26, 2009

Original Link

Here are some thoughts on the current swine influenza outbreak. These are just off the top of my head -- I will undoubtedly think of more to say and add it in the comments or another posting. I apologize for the lack of links. I may come back and put some in.

I am both unqualified and qualified to make a few comments. I’m unqualified because I no longer work on influenza virus, because I’m not a virologist, because I have no inside information at all about the current outbreak. OTOH, I have some claim to know what I’m talking about. I worked on influenza virus as part of the Antigenic Cartography team at the University of Cambridge for a few years. We helped the WHO choose the H3N2 strain for the human vaccine. I’ve met the heads of the 4 international flu centers and even been in the WHO Situation Room in Geneva -- a self-contained underground fortress. I spent a lot of time hanging out and talking to influenza virologists, many from the Erasmus Medical Centre in Rotterdam. I was even an author on a Science paper on the global spread of epidemic influenza. Plus I’ve read all the books on the 1918 pandemic, which gives some (largely retrospective) insight into what happened back then, and perhaps some insight into what could be about to happen.

I also feel it’s good for someone like me to comment because I’m outside the flu world and the people inside it will be unlikely to say much. Flu is a highly political issue, to put it mildly. People working in the flu research community will be reluctant to speak up. So I should make it very clear that the comments below are just my opinions, and don’t represent anyone else’s thoughts.

I’ll try to just make a few points that I think are fairly sober -- neither alarmist, nor dismissive - and to keep speculation out of it.

Apart from the details of the actual virus, the social side of a potential pandemic is extraordinarily interesting. Very few people will have really concrete information, and those that do will still only be making their best guesses.

In a pandemic, or something that looks like it might be one, wild rumors sweep through the population. That will happen on an unprecedented scale this time round.

The virus has, as far as we know, not spent much time in humans yet. Once it does, it will begin to adapt itself in unpredictable ways. It may become more virulent, or less virulent. It may develop resistance to the antivirals that are currently effective. Antiviral resistance has been a topic of great concern for at least a couple of years. The current virus is already known to be resistant to both amantadine and rimantadine, though oseltamivir is still effective.

If you ask virologists what the probability is that there will be another pandemic, they’ll tell you it’s 1.0. It’s just a matter of time until it happens. it’s like a non-zero probability state in a Markov process. When it does happen, what you do in the first phase is critically important. In the case of the avian influenza they would try to immediately cull all potentially infected birds, to stop the virus spreading and mutating and becoming more likely to enter the human population. When it did get into the human population, there would be swift action to isolate it, again to reduce the spread and the time the virus has to adapt. In the case of the avian influenzas in humans, there has been very little airborne transmission, and we’re lucky for that. But the current virus seems to already have that property, which is of great concern.

It would be a miracle if the current epidemic vaccine provided any protection against this virus. The human vaccine does contain a strain against H1N1, but that’s a strain picked based on sampled human viruses from many months ago. The epidemic vaccine is aimed at thwarting what’s known as antigenic drift -- the relatively slow accumulation of point mutations in the virus. Pandemic strains arise through antigenic shift in which large chunks of viral genetic material, sometimes whole genes, are mixed between influenza viruses from different species. In a pandemic strain some of the genetic material and the proteins it expresses will very likely never have been seen by a human immune system.

The current WHO standard influenza test kit is not very useful in identifying this strain. They have issued instructions warning against false negatives.

Some aspects of the current outbreak are, to my mind, cause for great concern.

The acting-director of the CDC has already said: “There are things that we see that suggest that containment is not very likely.” That is a remarkably candid statement. I think it’s very clear that the cat is out of the bag. The question is how bad is it going to be. That’s impossible to tell right now, because we do not know what the virus will look like in the future, after it has had time to mutate and adapt inside humans.

In normal circumstances it takes about 6 months to make the world’s supply of epidemic vaccine. It’s a long and difficult process requiring tons of virus to be grown in chicken eggs. A canidate vaccine strain has to be identified, it has to be one that grows well in the chicken egg (including not killing the chick). Even under the high pressure of a potential pandemic, making a new vaccine is going to take months. By then the virus may have moved on (via mutation) and the vaccine’s efficacy may be less. Note that the 1918 virus killed tens of millions of people over a period much shorter than this.

Diverting the world’s influenza resources to covering a pandemic threat necessarily diverts them from work on epidemic vaccines. Epidemic flu kills roughly 0.5M people a year as it is. Not being able to pay due attention to the epidemic strains is also a bad thing.

The new virus has been popping up in various places in the US in the last days. I expect it will go global in the next couple of days, maximum. What’s to stop it? The virus has been isolated in several diverse areas and in many cases is genetically identical. The 1918 virus also popped up, in many cases inexplicably, across the US. The book America’s Forgotten Pandemic is worth a read.

There were 3 waves of the 1918/19 pandemic. The first was in summer of 1918 - very unusual, as influenza normally falls to extremely low rates during summer. Note that the current outbreak is also highly unseasonal.

The 1918 pandemic killed with a very unusual age pattern. Instead of peaks in just the very young and the very old, there was a W shape, with a huge number of young and healthy people who would not normally die from influenza. There are various conjectures as to the cause of this. The current virus is also killing young and healthy adults.

The social breakdown in a pandemic is extraordinary. If you read The Great Pandemic by John Barry, you’ll get some sense of it. America’s Forgotten Pandemic also helps give some idea of what it must have been like.

No-one knows just how many people died as a result of the 1918 pandemic. Estimates generally range between 40M and 100M, and have trended upwards over the years. Influenza is not the easiest to diagnose (hence the category ILI -- influenza-like illnesses). It also strips the throat of protective epithelial cells, leaving you susceptible to opportunistic follow-on infections, such as pneumonia, which often do the killing.

No-one knows how bad another pandemic might be in terms of mortality. Low estimates are in the single digit millions. Someone from the WHO suggested a significantly higher number about 4 years ago in the context of avian influenza and that number was quickly retracted. Jeff Taubenberger, who was responsible for resurrecting and sequencing the 1918 virus (an extraordinary story, related in a couple of books) has published work saying 100M might be possible. No-one knows, and it depends on many factors, including the characteristics of the virus, how early it is detected, how easily it spreads, how virulent it is (obviously), the social measures taken to combat it, antiviral resistance, and many other factors.

I don’t think anyone knows how the balance between vastly increased medical knowledge and vastly increased national and international travel will play out. If this virus is not popping up all over the world within a week’s time, I’ll be surprised. Airports are already screening people arriving from Mexico, but I imagine it’s too late and it’s certainly not being done globally.

History dictates that you should probably not believe anything any politician says about pandemic influenza. There has been a strong tendency to downplay risks. All sorts of factors are at work in communicating with the public. You can be sure that everything officially said by the WHO or CDC has been very carefully vetted and considered. There’s no particular reason to believe anything else you hear, either :-)

Facemasks have an interesting history, and have made it into law several times. In 1918 we didn’t even know what a virus was, let alone how tiny they are, so the gauze on the masks was likely totally ineffective.

In conclusion, I’d say that the thing is largely out of our hands for the time being. We’re going to have to wait and see what happens, and make our best guesses along the way.

The influenza people at the CDC and the other international labs are an amazing team of experts. They’ve been at this game for a very long time and they work extremely hard and generally get a bad rap. It’s no wonder flu is such a political issue, the responsibility is high and the tendency towards opaqueness is understandable. Despite all the expertise though, at bottom you have an extremely complex virus -- much of whose behavior is unknown, especially in the case of antigenic shift, especially when it is so young, and especially when you don’t know what nearby mutational opportunities may exist for it in antigenic space -- spreading in a vastly more complex environment (our bodies), and with us moving and interacting in odd ways in a complex and extremely interconnected world. It’s a wonder we know as much as we do, but in many ways we don’t know much at all.

...........

NHNE Epidemics & Pandemics Resource Page