Archive for April, 2009

OK, it’s a pandemic. Now what?

Thursday, April 30th, 2009

Here are some more thoughts on the (now official) influenza pandemic.

I would like again to emphasize that I’m not an authority and I’m not trying to pass myself off as one.

I’ve already been accused of deliberate fear-mongering. That’s the opposite of my purpose. On the contrary, it’s important to stay calm and there are good reasons for doing so. If you don’t want to know a bit of history and to have some sense of things that have happened in previous pandemics, then you don’t have to read what follows. There’s no harm in staying calm via not knowing. On the other hand, there is harm in being gripped by fear due to ignorance.

If you do read, try to keep in mind that the main point here is that you shouldn’t be overwhelmed by fear or begin to panic. There’s no reason to. Plus it will only make things worse.

On the subject of being an authority and fear-mongering, after I wrote up the first set of thoughts I was invited to be a guest commentator on a radio show. I declined. It feels very irresponsible to say anything about influenza given that I am not an expert and don’t even work in the field anymore, but OTOH it feels irresponsible to remain totally silent given that I know at least some historical things fairly well.

To illustrate the conflict: On April 26 it seemed crystal clear to me that the virus was going worldwide. You only had to have seen the Google map that I twittered about the day before to see that it was going to be all over the place in days. But I didn’t want to point that out, and when I was asked I told the asker to be his own judge. I linked to a map showing Mexico and the US earlier and said “hopefully we wont have to zoom out” – trying to get people to consider that we would probably soon have to zoom out.

So I think I’ve been quite restrained. This post is also restrained. As I said above, there are good reasons not to sensationalize things or to create the impression that people should panic.

So here we go again, a few more thoughts as they come to mind. These are things that I find interesting, with a few scattered opinions (all of which are just guesses). There’s no real structure to this post.

The WHO have announced today that we’re officially in a pandemic. That doesn’t really mean much, but it’s good to have a candid and early declaration – part of the problem historically has been slowness to even admit there’s a problem. The WHO didn’t even exist in 1918.

In case you don’t know, there’s pretty good evidence that humans have been fighting influenza for thousands of years.

The most interesting thing to me in reading about the 1918 pandemic is the social impact of the disease.

One thing to make clear is that the current pandemic is not the 1918 pandemic. I tend to agree with those who say that a pandemic of that nature could not take place today – but note that people, perhaps especially scientists – would have said that at all times prior to and after 1918. We often under-estimate the forces of nature and over-estimate our own knowledge and level of control.

BTW, something like 75% of people who died during World War 1 did so because of the flu pandemic, which didn’t really take off until November of 1918. Amazing.

As I mentioned in my earlier post, under normal circumstances (even in a pandemic), flu doesn’t kill you. It leaves you susceptible to opportunistic follow-on disease. The good news is that we are vastly more informed now than we were in 1918 about the nature of infectious diseases. For example, we know a lot about pneumonia, which we did not in 1918. See the moving story of the amazing Oswald Avery, who dedicated his life to the disease and along the way fingered DNA as the vehicle of genetic inheritance – and never won a Nobel prize.

So the care of people who have been struck down by flu is going to be much more informed this time around. And it will probably be better in practice too. I put it that way because odd societal things happen in a pandemic. I hesitate to go into detail, because some people will assume that things that happened way back when will necessarily happen again this time around.

One of those things is that medical systems get overrun by the sick. Plus, doctors and nurses understandably decide that their jobs have become too dangerous and they stop showing up for work. So there can be a sharp drop-off in the availability of medical help.

So much so that there were reports of doctors and nurses being held hostage in houses in 1918. I.e., if you could get a doctor to visit to attend to your family, the situation was so dire you might consider pulling a gun on him/her and suggesting they make themselves comfortable for the duration.

The problem is not so much that many people are dying, it’s that a much larger number are simultaneously extremely ill and that panic grips them and everyone else. Roughly 30% of all people caught the 1918 flu. I have another post I may write up on that. Normal (epidemic) flu catches 10-15% of people in any give year.

Many of our systems are engineered to provide just-in-time resources, to cut the fat in order to maximize profitability, etc. That means that we’re closer to collapse that would seem apparent. How many days of fresh food are there on hand in a major city?

None of this is meant to be alarmist. But the reality is that alarming things have happened in the past.

Most interesting and revealing to me is that our cherished notions of politeness, of our generosity, our goodwill towards our neighbors, etc., can all go out the window pretty quickly. I’ve long held that all those things are the merest veneer on our underlying biological / evolutionary reality. We’re very fond of the ideas that we’re somehow no longer primates, that we’re not really the product of billions of years of evolutionary history, that somehow the last centuries of vaunted rationality have put paid to all those primitive lower impulses. I think that’s completely wrong. Behavior during a full-scale pandemic is one of the things that makes that very clear.

In a pandemic, if things get ugly, you can expect to see all manner of anti-social behavior. If you read John Barry’s book The Great Influenza or Crosby’s America’s Forgotten Pandemic you’ll get some graphic illustrations.

If I had a supply of tamiflu (which I don’t), I wouldn’t tell anyone. That’s deliberately anti-social. Ask yourself: What would you do if you had kids who were still healthy and your neighbor called you in desperation to tell you that his/her kids seemed to have come down with influenza? Get out your family’s tamiflu supply and hand it over? Lie? What if they knew you had it and you refused to give it or share? What if your neighbor’s kid died and yours never even got the flu? What kind of relationship would be left after the pandemic had passed?

This may all seem a bit extreme and deliberately provocative of me, and yet those sorts of dilemmas (sans tamiflu, naturally) were commonplace in 1918. As you might expect, they don’t always get resolved in ways that accord well with our preferred beliefs about our own natures in easier times. Crosby speculates that the reason the pandemic of 1918 is “forgotten” is due largely to the fact that it coincided with the war, and that people were generally exhausted and dispirited and wanting to move on. I’d speculate further that people en masse frequently behaved in ways that they weren’t proud of, and wanted to forget about it and act as if it hadn’t happened ASAP. That’s just a guess, of course.

In any case, if there’s a full-blown pandemic, societal structures that we take for granted are going to be hugely transformed. Medical services, emergency services, food supply, child care and education, job absenteeism, large numbers of the people who would normally be in charge of things coming down sick and being unable to do their normal jobs, etc. All sorts of things are impacted and lots of them are interconnected. The system breaks down in many unanticipated ways as all sorts of things that “could never happen” are all happening at once.

You might think I’m fear-mongering here, but I’m not. In fact I’m refraining from going into detail. Go read John Barry’s book, or any of the others, and see for yourself.

The important thing to remember in all this is that we are no longer in 1918. BTW, there were also influenza pandemics in 1957 (killing just a couple of million people) and 1968 (killing a mere million).

Apart from the fact that we’ve advanced hugely in medical terms, we are also much better connected. I can sit in the safety of my apartment in Barcelona and broadcast calming information like this blog post to thousands of people. We are better informed. We know that panic and fear greatly compound the impact of a pandemic. They feed on one another and prolong the systemic societal collapse. Because we can communicate so easily via the internet – provided our ISPs stay online – we can help keep each other calm. That’s an important advantage.

So my guess is that this wave isn’t going to be so bad, certainly not in terms of mortality. One thing to keep in mind though is that the virus isn’t going away. It will likely enjoy the Southern hemisphere winter, and we’ll see it again next Northern hemisphere winter. And yes, those are guesses. Because influenza is a single-stranded RNA virus it mutates rapidly (you don’t get the copy protection of a double strand). So this is the beginning, not the end, even if the pandemic fizzles out in the short term. It will be back – probably in less virulent form – but by then we’ll also have a good leg up on potential vaccines, and we’ll also know it’s coming.

OK, I’ll stop there for now. I have tons of other things I could write now that I’m warmed up. You can follow me on Twitter if you like, though I doubt I’ll be saying much about influenza.

If you truly believe I’m fear mongering, please send me an email or leave your email address in the comments. I’ll send you mail with some truly shocking and frightening stuff, or maybe fax you a few pages from some books. Believe me, it gets a lot nastier than anything I’ve described. Things are not that bad, certainly not yet. We’re not in 1918 anymore

So, stay calm, and do the simple things to keep yourself relatively safe. If everyone follows instructions like those, the virus wont have a chance to spread the way it could otherwise. That may sound like pat concluding advice, but there’s actually a lot to it – the epidemiology of infectious disease – in part the mathematics of infection – can be hugely altered depending on the behavior the typical individual. Following basic hygiene and getting your kids to too will make a big difference. There’s no denying that this is going to get worse before it gets better, but we can each do our part to minimize its opportunities.

A few comments on pandemic influenza

Sunday, April 26th, 2009

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.

Sack the golden towns of Montezuma!

Wednesday, April 8th, 2009

“My dear fellow,” Burlingame said caustically, “we sit on a blind rock careening through space; we are all of us rushing headlong to the grave. Think you the worms will care, when anon they make a meal of you, whether you spent your moment sighing wigless in your chamber, or sacked the golden towns of Montezuma? Lookee, the day’s nigh spent; ’tis gone careening into time forever. Not a tale’s length since we lined our bowels with dinner, and already they growl for more. We are dying men Ebenezer: i’faith, there’s time for nought but bold resolves!”

From: The Sotweed Factor, by John Barth.


Tuesday, April 7th, 2009

Coding is what you do when you tire of dealing with other humans. You get to interact with a literal-minded idiot who slavishly follows your every wish. Unfortunately you have to specify *everything* down to the very last detail in order to get anything done. But at least it does what it’s told, which is comforting in a world where everyone selfishly insists on doing what *they* want. You should try it sometime, it’s very relaxing, and nice to be totally in control.