Planning for Pandemics (repost and update)

by John Q on May 19, 2009

As governments and the WHO wrestle with the decision on whether to divert resources from the production of seasonal flu vaccines to develop a vaccine against H1NI (swine) flu, I thought I’d repost this piece from 2005, suggesting an expansion of vaccination against seasonal flu, in part to expand production capacity to prepare for problems like this.

Thinking a little more, and with the idea of global public goods in mind, it seems obviously in the enlightened self-interest of developed countries to go beyond domestic vaccination programs and contribute both vaccine supplies and organisational resources to encourage routine vaccination in poor countries, as well as ensuring a further expansion of production capacity.

The same goes, I think, for more extensive use of antivirals like Tamiflu, which apparently have the nice property that the flu virus does not develop resistance to them.

Planning for Pandemics

The news of deaths from bird flu in Indonesia is pretty scary. Although, as I’ve mentioned recently Indonesia has made a lot of progress in many respects, the handling of this threat so far seems to show the worst of both worlds: all the ill ffects of authoritian habits combined with the timidity of weak politicians. There have been a lot of coverups, and an unwillingness to tackle the necessary but unpopular task of slaughtering affected flocks of birds. Things seem to be improving now, but there’s a long way to go.

It seems very likely that, sooner or later, bird flu will make the jump that permits human-human transmission, and quite likely that a major flu pandemic will result. The world, including Australia, is very poorly prepared for this. One thing we could do to prepare is to adopt a national program encouraging annual flu vaccinations for everyone, instead of just for limited categories of vulnerable people.

The main benefit of this is not that the shots would provide immunity against a new and deadlier flu variant (though there might be some limited benefit of this kind) but that we would have the infrastructure, production facilities and so on to undertake a mass vaccination against such a variant if it arose. As it is, it seems likely that many countries will be scrambling to get access to an inadequate world supply of vaccines, but if Australia and other developed countries ramped up normal levels of production, it would be much easier to generate extra supplies for our neighbours.

I haven’t looked into it, but my guess is that, even without considering the possibility of a pandemic, the benefit-cost ratio from such a measure would be pretty high. Flu is very costly in economic terms, and I suspect that, if pain and suffering were thrown into the balance, a program of universal free vaccination would come out looking pretty good.

Update There’s lots of good background in Foreign Affairs. A piece by Michael Osterholm reprinted in the AFR Review section recently, is very good and stimulated my thinking on this topic.

Further update, 2009The FA links now appear to be paywalled, but commenter Helen at my blog points to this useful piece by Jim McDonald at Making Light. And here’s a link to a study supporting my intuition that universal vaccination against seasonal flu would be economically beneficial..



Glen Tomkins 05.20.09 at 12:31 am

Swallowing camels and straining at gnats

Yes, one benefit of having everyone vaccinated for annual flu would be that this would create a much greater reserve production capacity to deal with contingencies like this swine flu we have now. But surely a much greater reason to vaccinate everyone every year against annual flu is that annual flu produces a higher death toll, predictably, year after year, than swine flu is even remotely likely to even get within several orders of magnitude of attaining, ever.

My point is not that we shouldn’t be concerned about this swine flu, or other infectious diseases with the potential to kill many people, but that it seems strange to expend efforts to control a disease that has only the remotest possibility of getting anywhere near the death toll of a related disease that will, in an almost dead certainty, kill >30,000 Americans alone (I am not familiar with the figures for Australia) this year and every year succeeding. It’s not that 100 dead of swine flu in Mexico should not cause us concern, it’s that 30,000 dead every year in America alone would seem a more pressing focus for any diversion of resources from other needs to controlling flu that we might feel is warranted.

That a measure like universal annual flu vaccination might also help our response to the very remote possiblility that some swine or avian flu might some day suddenly acquire the ability to achieve as high an attack rate on humans as annual human flu, without it thereby also losing the higher case fatality rate we often see in sporadic cases of animal-to-human flu crossover events, should be a distinctly secondary consideration. 30,000 dead a year is plenty enough to convince me that more should be done against annual flu. Universal vaccination is only one such measure we could and should take. Even easier and less costly would be simply moving our annual school holiday from the summer, where it does no good against this annual scourge, to the flu season, when emptying the schools would disable one of the flu’s great engines of contagion.


John Quiggin 05.20.09 at 2:17 am

Glen, I made both parts of the case, and I think both stand up. I’m glad you agree on one part, and I’ll try to restate the other.

Given a 2 per cent annual chance of a pandemic with 2 million US deaths (both conservative in my view), the expected saving in lives from having an effective preparation for such an event is comparable to that from an effective program against seasonal flu.

The 1918 pandemic caused over 500k deaths in a much smaller US population, and the Asian and Hong Kong pandemics another 100k, so for the 20th century as a whole, pandemic deaths and seasonal deaths were comparable.


Tom T. 05.20.09 at 2:27 am

Isn’t the problem with flu, though, that the vaccine takes months to culture? That’s why the annual vaccine is always essentially an educated guess made in the spring as to which strains will appear that winter. Once a strain is identified as a pandemic, even with more infrastructure, what are the odds that a specific vaccine can be generated in time to do any good?


John Quiggin 05.20.09 at 3:12 am

According to the reports I’ve read, the seed vaccine should be ready in June, which would allow large-scale production for the NH winter. Supply is a real constraint


Zamfir 05.20.09 at 6:42 am

I thought oone reason not to worry too much about the seasonal deaths was that a very large part of them were old, weak people who wer going to die of something soon anyway, and it just happens to be flu. Massive vaccination will, for seasonal flus, not necessarly save as much lives as the death toll suggest, since a significant part of those people will simply die within moths of something else.

But I don;t have reliable numbers for this, so it might a more minor effect.


Matt Kuzma 05.20.09 at 6:43 am

Nit pick: It’s probably not 100% accurate to say that influenza doesn’t develop resistance to Tamiflu. It hasn’t, and it seems unlikely, but evolution is not predictable.

To play devil’s advocate for a minute, why is it in a country’s enlightened self-interest “to undertake a mass vaccination against such a variant if it arose”? If half the world’s population is wiped out by the bird flu but my country has an efficient vaccination machine to protect it, how is the result likely to be counter to our self-interest? Sure, the global economy will need to be restructured which is inconvenient, but with human populations as dangerously high as they are, the resultant reduction in demand for food, water, and energy, and in production of pollution and greenhouse gasses, as well as the reduced destruction of vital habitat causing anthropogenic extinction could lead to a much higher quality of life for the survivors. When the restructuring of the world economy finished, natural resources and land would undoubtedly be a lot cheaper and more widely available. More people on this planet is not, given a strict accounting, good for our quality of life. History bears this out with the Black Death leading to the enrichment of the following generation and ultimately to the Renaissance.


Zamfir 05.20.09 at 10:17 am

Matt, a vaccination program doesn’t have to be 100% perfect, or even 90%, as long as it is applied so widely that it hurts transmission speeds for the epidemic enough to have it die out quickly. Having loads of people infected also increases the odds that the virus mutates into something your vaccin doesn’t protect against at all. So having a lot of other people protected does increase your own survival rate.

For your scheme, you need to have an incredibly reliable vaccin before you can safely relax and see the spoils roll in.

And given that the economy is now less reliant on agriculture than in the 14th century, it’s not obvious that a black plague would nowadays have the same wage-increasing effects as in those days. If the choice is between more resources and more people to trade with, the second might well trump the first.


Glen Tomkins 05.20.09 at 2:01 pm

Why lean on the weak reed?

Even if your theory were correct, that there is a 2% chance every year of something you call a “pandemic” killing 2 million Americans, that still means that this Swine Flu is overwhelmingly likely to turn out to be Swine Fizzle, just like the last Swine Flu panic. How often do you think the public will tolerate you crying wolf before it sets its mind against responding, ever again, to alarms over this or any other emerging illness? I wouldn’t try to put a quantitative probability on that, but the qualitative answer is that the public will almost certainly lose patience long before we hit that negative jackpot, and we will therefore not be able to goad them into action when the real “Next Black Death” shows up on our doorstep. Even worse, when our attempts to get the public to support public health measures is focused on The Big One, what we tell them is that annual flu and its mere 30K+ dead every year is dog bites man, not really news, move along, nothing to see here.

And the idea that there is a 2% chance per annum of 2 million dead from flu in the US alone is pure fantasy. Not that I can posit a different, lower, set of figures, though I think that your figures are about as high as the risk of such an event, if we could know that actual risk, could possibly be without our having to appeal to an excessively fortunate run of good luck on our part. My point is that medicine in particular, and the biosciences in general, despite the fact that it contains many very small subdivisions that are developed enough that we do understand the mechanics of what we observe very well, is still mostly and overall in the stage of systematic observation and description. This question, like most questions in medicine, is simply not ripe for quantitative methods.

If your 2%/2million figure is derived from virologists who claim to be
able to project attack and case fatality rates from genomics, you’ve been listenting to overeager virologists who don’t appreciate the big picture limitations of present knowledge. We simply don’t understand the mechanics of how flu A does what it does, certainly not to the point of being able to say that a certain genotype, which has a certain probability of being reached by mutation, will achieve a certain attack and case fatality rate.

If your 2%/2million theory is derived more modestly and appropriately from doing statistics on observed events, you’re still overprojecting our knowledge of these events. You can’t do such science from an N of 1, but the 1918 flu is the only one that should be counted in a separate category from annual flu, in the same category as what we are worried this Swine Flu will prove to be. The 1957 and 1968 flu seem to have been simply tail events of annual flu, in that 5% zone that we see in the tails of the normal distribution. They did not seem to involve an unusually high case fatality rate (though such rates can never be calculated with much accuracy, since we do not know the underlying attack rate from any reproducible methodology), they did their damage in the usual demographics, the old and very young, and the magnitude of killing was just in the tail, not off the charts. The 1918 event, in contrast, was qualitatively different, even, but not only, in the magnitude of destruction. There were so many deaths that the case fatality rate could not have been, by any means of projecting an attack rate, anywhere close to that of annual flu. It wasn’t the case that it was so virulent that even the young died, rather, it preferentially killed the 18-50 year-old demographic. This was a different disease than annual flu A, and lumping this event with any annual flu event, just to give yourself an N>1, is simply not valid.

We could have another Black Death magnitude event tomorrow. Swine flu could be the causative agent of this event. We could never again have such an event. We could have such an event, and it have nothing to do with any sort of flu. All of these assertions, and many more similar on the topic of such “Next Black Death” events, cannot be assigned a probability of truth or occurrence. We simply do not understand how these singular events happen, we don’t have really reliable observations except for the one 1918 flu event, and have no reason, other than hope, to think that there even is any underlying or unifying factor common to all these events in history, that would ever allow us to predict, before the event has done its destruction, what emerging agent is going to be the Next Black Death. Yes, there is hope that we could identify such a factor, but the task of identifying such is pretty clearly a basic research problem in a very preliminary stage, and is clearly not an issue to present to the public as anything that bears on the immediate situation. What’s in front of us now, and every year, is a disease that takes 30K+ of us, a disease whose behavior we can predict enough to know what measures are likely to help reduce that toll. That disease is ripe for more effective public health measures, and we should not cripple our chances of achieving that by linking its very real threat to threats that we do not understand well enough to have any useful advice to present to the public.


eudoxis 05.21.09 at 7:39 pm

“One thing we could do to prepare is to adopt a national program encouraging annual flu vaccinations for everyone, instead of just for limited categories of vulnerable people.”

This, indeed, is a good idea. Experts are encouraging vaccination of the “not at risk” population, especially children, as well as an extension of the usual 3 month vaccination period. The bottleneck is not production, millions of doses of vaccine go unused each year, but rather anticipation and production of the right vaccine mix and timely delivery of vaccine to the right population.

Unfortunately, even the most efficient top-down workable solution to a flu pandemic is going to fall short of being one step ahead of unpredictable biology. Tamiflu is directed at an enzyme that can mutate. In fact, do a search on Science or CDC + antiviral resistance and you’ll find that there are already populations of flu virus resistant to Tamiflu, including H5 containing bird flu strains.

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