A few comments on pandemic influenza
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.
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April 27th, 2009 at 2:40 pm
Could you expand on “Facemasks have an interesting history” ?
Usefull or useless ?
April 28th, 2009 at 7:07 pm
Hey There, In Reading the book, The Great Influenza by John M. Berry, the reason why that flu was killing the young an healthy is because their immune systems were stronger and as such their immune systems over reacted causing them to drown in their own fluids.
April 28th, 2009 at 8:07 pm
Hey There, In Reading the book, The Great Influenza by John M. Berry, the reason why that flu was killing the young an healthy is because their immune systems were stronger and as such their immune systems over reacted causing them to drown in their own fluids.
April 28th, 2009 at 7:59 pm
Hi Beverly
Yes, that’s the currently accepted hypothesis at least as far as I know. You can read about cytokine storms on Wikipedia: http://en.wikipedia.org/wiki/Cytokine_storm
Thanks for dropping by! The Barry book is pretty good – and pretty scary / sobering. People tend to dismiss the flu as a mundane disease we’re all familiar with. But a pandemic strain is something else entirely….
Terry
April 28th, 2009 at 8:59 pm
Hi Beverly
Yes, that’s the currently accepted hypothesis at least as far as I know. You can read about cytokine storms on Wikipedia: http://en.wikipedia.org/wiki/Cytokine_storm
Thanks for dropping by! The Barry book is pretty good – and pretty scary / sobering. People tend to dismiss the flu as a mundane disease we’re all familiar with. But a pandemic strain is something else entirely….
Terry
April 29th, 2009 at 3:03 am
I agree that people should be required to stay home when their sick to stop the spread. I work in a daycare center and in addition to that I think parents should be obligated to keep the children home when their sick. Yes we have policies as do all childcare centers however parents are terrible about giving their children tylenol/ motrin before they bring them to daycare. Then by time it wears off so their temp rises so we know their sick, they have already been there for atleast 3-4 hrs exposing it to the whole center. It drives us teachers CRAZY!
April 29th, 2009 at 4:03 am
I agree that people should be required to stay home when their sick to stop the spread. I work in a daycare center and in addition to that I think parents should be obligated to keep the children home when their sick. Yes we have policies as do all childcare centers however parents are terrible about giving their children tylenol/ motrin before they bring them to daycare. Then by time it wears off so their temp rises so we know their sick, they have already been there for atleast 3-4 hrs exposing it to the whole center. It drives us teachers CRAZY!
April 29th, 2009 at 5:23 am
Good news for now, the WHO has stressed that ,so far, only seven of the deaths in Mexico have actually been ‘confirmed’ as having been caused by this flu. The other thing I’ve ‘picked up’ (excuse the pun) is that these things generally tend to reduce in virulence over time, rather than escalate. That is no guarantee that the bloomin virus won’t re-assort into a worse killer, particularly if it does become very widespread, but it’s a happy thought.
April 29th, 2009 at 6:23 am
Good news for now, the WHO has stressed that ,so far, only seven of the deaths in Mexico have actually been ‘confirmed’ as having been caused by this flu. The other thing I’ve ‘picked up’ (excuse the pun) is that these things generally tend to reduce in virulence over time, rather than escalate. That is no guarantee that the bloomin virus won’t re-assort into a worse killer, particularly if it does become very widespread, but it’s a happy thought.
April 29th, 2009 at 6:51 pm
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April 29th, 2009 at 11:12 pm
Terry
Making any comparison between the present situation and the pandemic of 1918 is totally nonsense. In that times people died even of a normal flu. There were no antibiotics. The salubrity was poor to say the least.
And your comments on the ineffectiveness of existing vaccine is plainly wrong: it is working. Period.
I don’t see the point on panicking people talking about this as if it were the doom day! C’om a little of perspective.
April 30th, 2009 at 12:12 am
Terry
Making any comparison between the present situation and the pandemic of 1918 is totally nonsense. In that times people died even of a normal flu. There were no antibiotics. The salubrity was poor to say the least.
And your comments on the ineffectiveness of existing vaccine is plainly wrong: it is working. Period.
I don’t see the point on panicking people talking about this as if it were the doom day! C’om a little of perspective.
April 29th, 2009 at 11:22 pm
Hi Pablo
Making comparisons is valid – that’s one way of seeing that what happened in 1918 could not happen today. It’s good to know about history.
I’m afraid you might be confused with respect to the vaccine. There is no vaccine, yet. Go read the WHO announcement from today at http://www.who.int/mediacentre/news/statements/2009/h1n1_20090429/en/index.html which says “I have also reached out to influenza vaccine manufacturers that can contribute to the production of a pandemic vaccine.” Having contributed directly to the process of designing human influenza vaccines with the WHO, I’m on fairly solid ground here :-)
There are antivirals though. 2 of the 4 antivirals are working. The evolution of antiviral resistance is a concern, as always, but for the moment we’re in good shape on that front.
In any case, thanks for dropping by and reading. My purpose is not to panic people, just to write up a few comments on things that perhaps aren’t that well known. BTW, I’m writing more at the moment, and it’s much scarier – but still designed to educate and calm rather than frighten and panic. I’m leaving out all the blood and guts, you’ll be pleased to hear!
April 30th, 2009 at 12:22 am
Hi Pablo
Making comparisons is valid – that’s one way of seeing that what happened in 1918 could not happen today. It’s good to know about history.
I’m afraid you might be confused with respect to the vaccine. There is no vaccine, yet. Go read the WHO announcement from today at http://www.who.int/mediacentre/news/statements/2009/h1n1_20090429/en/index.html which says “I have also reached out to influenza vaccine manufacturers that can contribute to the production of a pandemic vaccine.” Having contributed directly to the process of designing human influenza vaccines with the WHO, I’m on fairly solid ground here :-)
There are antivirals though. 2 of the 4 antivirals are working. The evolution of antiviral resistance is a concern, as always, but for the moment we’re in good shape on that front.
In any case, thanks for dropping by and reading. My purpose is not to panic people, just to write up a few comments on things that perhaps aren’t that well known. BTW, I’m writing more at the moment, and it’s much scarier – but still designed to educate and calm rather than frighten and panic. I’m leaving out all the blood and guts, you’ll be pleased to hear!
April 30th, 2009 at 1:51 am
[…] I mentioned in my earlier post, under normal circumstances (even in a pandemic), flu doesn’t kill you. It leaves you […]
April 30th, 2009 at 7:01 am
“Making comparisons is valid – that’s one way of seeing that what happened in 1918 could not happen today.”
Whoa, hold on. Terry, did I misunderstand you? Are you saying that what happened in 1918 could not happen today or are you saying that making comparisons is a way to understand *whether* it could happen today?
@Pablo: What happened in 1918 is certainly highly exceptional, but recurrence on that scale is absolutely *not* out of the realm of possibility. Sure, we have antivirals now but how long will those last before a new strain attains resistance making them as useless as some of the first created antibiotics are today? Sure we have modern medicine and modern worldwide communication of information but we also have ubiquitous and near instantaneous (relative to 1918) global travel (read: vehicle for pandemic contagion) and more urban overcrowding than ever before.
More importantly, the 1918/Spanish Flu isn’t even the *upper bound* of potential mortality. It may not be in our lifetime, but nature gives us a near infinite number of examples that clearly show that a larger and more devastating pandemic is in the cards…eventually. It’s the absolute height of folly and narcissism to believe that we as a human race have this whole “War on pathogens” licked. It’s precisely the type of foolish confidence that would cause it to occur sooner rather than later.
If that thought scares you, well… Good. It’s a scary thought. Then again, you should be calmed by the fact that I’m talking about geologic time here. You and I probably will never see anything on the scale of 1918. But that doesn’t mean it’s not possible.
April 30th, 2009 at 8:01 am
“Making comparisons is valid – that’s one way of seeing that what happened in 1918 could not happen today.”
Whoa, hold on. Terry, did I misunderstand you? Are you saying that what happened in 1918 could not happen today or are you saying that making comparisons is a way to understand *whether* it could happen today?
@Pablo: What happened in 1918 is certainly highly exceptional, but recurrence on that scale is absolutely *not* out of the realm of possibility. Sure, we have antivirals now but how long will those last before a new strain attains resistance making them as useless as some of the first created antibiotics are today? Sure we have modern medicine and modern worldwide communication of information but we also have ubiquitous and near instantaneous (relative to 1918) global travel (read: vehicle for pandemic contagion) and more urban overcrowding than ever before.
More importantly, the 1918/Spanish Flu isn’t even the *upper bound* of potential mortality. It may not be in our lifetime, but nature gives us a near infinite number of examples that clearly show that a larger and more devastating pandemic is in the cards…eventually. It’s the absolute height of folly and narcissism to believe that we as a human race have this whole “War on pathogens” licked. It’s precisely the type of foolish confidence that would cause it to occur sooner rather than later.
If that thought scares you, well… Good. It’s a scary thought. Then again, you should be calmed by the fact that I’m talking about geologic time here. You and I probably will never see anything on the scale of 1918. But that doesn’t mean it’s not possible.
April 30th, 2009 at 8:07 am
Hi Jay
Well, I meant it as I wrote it, but I wrote it carefully. I mean that the same thing could not happen. But that does not rule out other things that could be just as bad or worse. Just as some things that happened in 1918 could not happen today, there are some things that could happen today that could not have happened in 1918 – as you point out with respect to travel. I do think it’s important for people to be as well informed as possible, including about the past :-)
I think I share with you the feeling that people take the stability of our world too much for granted. One thing that’s completely different from 1918 is the degree of interconnectedness. You have only to consider the level of panic and inconvenience that comes from having the mobile phone network go down for a few hours to see the tip of that iceberg. There’s a book called Normal Accidents by Charles (I think) Perrow. It details the chain of events leading to major catastrophes. They’re very different, but a common theme is the chain reaction of extraordinary things caused by linked systems that no-one thought could fail, or that no-one had considered might fail at once, etc. But seeing as most of us have spent our entire lives with food, water, heat and myriad other conveniences I think we tend to take them for granted.
I don’t know what to conclude or what to recommend, etc. But I find the whole thing fascinating and have spent years thinking about the flu full time. To see this unfolding is really something.
Anyway, we’ll see. I agree with your last paragraph. Thanks for taking the time to write.
April 30th, 2009 at 9:07 am
Hi Jay
Well, I meant it as I wrote it, but I wrote it carefully. I mean that the same thing could not happen. But that does not rule out other things that could be just as bad or worse. Just as some things that happened in 1918 could not happen today, there are some things that could happen today that could not have happened in 1918 – as you point out with respect to travel. I do think it’s important for people to be as well informed as possible, including about the past :-)
I think I share with you the feeling that people take the stability of our world too much for granted. One thing that’s completely different from 1918 is the degree of interconnectedness. You have only to consider the level of panic and inconvenience that comes from having the mobile phone network go down for a few hours to see the tip of that iceberg. There’s a book called Normal Accidents by Charles (I think) Perrow. It details the chain of events leading to major catastrophes. They’re very different, but a common theme is the chain reaction of extraordinary things caused by linked systems that no-one thought could fail, or that no-one had considered might fail at once, etc. But seeing as most of us have spent our entire lives with food, water, heat and myriad other conveniences I think we tend to take them for granted.
I don’t know what to conclude or what to recommend, etc. But I find the whole thing fascinating and have spent years thinking about the flu full time. To see this unfolding is really something.
Anyway, we’ll see. I agree with your last paragraph. Thanks for taking the time to write.
April 30th, 2009 at 4:29 pm
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April 30th, 2009 at 5:29 pm
The importance of vaccine and preparedness has become more obvious in wake of the “swine flu virus”. The CDC has developed a healthcare hand book to help combat a variety of Vaccine Preventable Diseases.
The CDC’s Epidemiology and Prevention of Vaccine-Preventable Diseases, 11th Edition (The Pink Book) – Just Released!
The new, 11th edition of the Centers for Disease Control and Prevention’s (CDC) Epidemiology and Prevention of Vaccine Preventable Diseases (The Pink Book) is now available from the Public Health Foundation (PHF). “The Pink Book” provides physicians, nurses, nurse practitioners, physician assistants, pharmacists, and others with comprehensive information on vaccine-preventable diseases. The new 11th edition contains the latest information and updates on immunization, including:
Revised principles of vaccination
Updated recommendations on immunization
New immunization strategies for healthcare practices and providers
Guidelines on vaccine safety
This essential resource is now available for ordering online by visiting the PHF online store at http://bookstore.phf.org. Ordering via mail, phone, fax, and purchase order is also available by calling PHF toll-free at (877)252-1200 for full instructions
April 30th, 2009 at 6:46 pm
Terry, thanks for responding. I completely agree with you. In fact, I just saw this quote today: “If you’ve seen one flu pandemic…you’ve seen one flu pandemic”
Quite true. Was that yours? :-) I’m glad to see someone else who is scientifically fascinated by this. Of course, I dread the spread of this and the lives lost, but as a former researcher in microbiology/immunology (mostly enterotoxic e. coli, dysentery, etc) my intellectual curiosity is peaked by this thing. I guess it’s the mobid fascination that comes with scientific training and understanding full well the very tenuous string onto which we hold the dominance of this planet.
April 30th, 2009 at 7:46 pm
Terry, thanks for responding. I completely agree with you. In fact, I just saw this quote today: “If you’ve seen one flu pandemic…you’ve seen one flu pandemic”
Quite true. Was that yours? :-) I’m glad to see someone else who is scientifically fascinated by this. Of course, I dread the spread of this and the lives lost, but as a former researcher in microbiology/immunology (mostly enterotoxic e. coli, dysentery, etc) my intellectual curiosity is peaked by this thing. I guess it’s the mobid fascination that comes with scientific training and understanding full well the very tenuous string onto which we hold the dominance of this planet.
May 1st, 2009 at 9:26 pm
Just found this nice site with flu data.
Some useful stuff there.
http://www.mexicaninfluenza.net
I don’t think that thsi thing will go pandemic! It will be gone within a month.
May 1st, 2009 at 10:26 pm
Just found this nice site with flu data.
Some useful stuff there.
http://www.mexicaninfluenza.net
I don’t think that thsi thing will go pandemic! It will be gone within a month.
May 5th, 2009 at 4:28 am
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May 18th, 2009 at 6:39 pm
I actually make fun of this flu outbreak on my site.
Future twitters of the famous and infamous
May 18th, 2009 at 7:39 pm
I actually make fun of this flu outbreak on my site.
Future twitters of the famous and infamous
May 21st, 2009 at 5:13 am
Terry, Thanks for taking the time to help educate the broader community. I live in Japan which has witnessed, in the last 10 days, an extraordinary incursion of the virus, especially the Kansai area, where I live. Many schools (nearly all in some cities) schools have been closed, and many business trips and conferences canceled. However of the 200-odd Japanese infections, none (fortunately) has proved fatal. I’m trying to understand if the reaction to the disease here — school closures and widespread disruption of normal business — isn’t an over-reaction. I understand that there is a potential for virus mutation, and the parallels with previous deadly epidemics, but given that the mortality rate for the new virus as of now, do you think it makes sense to close schools, cancel conferences, and in general limit travel? And will those measures really slow the spread of the virus? (The in-flight health inspections Japan implemented at 3 major airports evidently did little to stop the virus from entering the country). Thanks for any comments.
May 21st, 2009 at 6:13 am
Terry, Thanks for taking the time to help educate the broader community. I live in Japan which has witnessed, in the last 10 days, an extraordinary incursion of the virus, especially the Kansai area, where I live. Many schools (nearly all in some cities) schools have been closed, and many business trips and conferences canceled. However of the 200-odd Japanese infections, none (fortunately) has proved fatal. I’m trying to understand if the reaction to the disease here — school closures and widespread disruption of normal business — isn’t an over-reaction. I understand that there is a potential for virus mutation, and the parallels with previous deadly epidemics, but given that the mortality rate for the new virus as of now, do you think it makes sense to close schools, cancel conferences, and in general limit travel? And will those measures really slow the spread of the virus? (The in-flight health inspections Japan implemented at 3 major airports evidently did little to stop the virus from entering the country). Thanks for any comments.
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April 20th, 2012 at 10:51 am
The
importance of vaccine and preparedness has become more obvious in wake
of the “swine flu virus”. The CDC has developed a healthcare hand book
to help combat a variety of Vaccine Preventable Diseases.
The CDC’s Epidemiology and Prevention of Vaccine-Preventable Diseases, 11th Edition (The Pink Book) – Just Released!
The new, 11th edition of the Centers for Disease Control and
Prevention’s (CDC) Epidemiology and Prevention of Vaccine Preventable
Diseases (The Pink Book) is now available from the Public Health
Foundation (PHF). “The Pink Book” provides physicians, nurses, nurse
practitioners, physician assistants, pharmacists, and others with
comprehensive information on vaccine-preventable diseases. The new 11th
edition contains the latest information and updates on immunization,
including:
Revised principles of vaccination Updated recommendations on immunization New immunization strategies for healthcare practices and providers Guidelines on vaccine safety This essential resource is now available for ordering online by visiting the PHF online store at
SY0-301
.
Ordering via mail, phone, fax, and purchase order is also available by
calling PHF toll-free at (877)252-1200 for full instructions