April 07, 2006

Why H5N1 isn't to be taken so lightly

DON'T PANIC (A la Hitch hiker's guide)

I've noted a lot of people over the past couple of days talking on blogs about avian influenza and the spread of the H5N1 virus around the globe, now confirmed also in the UK. Most people seem to be rubbishing the media coverage as being panic inducing, pointing to the facts that H5N1 and other strains of avian influenza are only spread to humans in rare cases, and even then only with direct contact with infected or dead birds. While there's some truth to this, it doesn't paint the whole story.

If you do a little background reading on avian influenza then you quickly learn an awful lot more than you do from the media coverage. Check out Wikipedia's section on it and also the Department of Health information page on avian influenza. There are a number of facts that stand out to me here, which make it very different from previous health scares such as BSE and SARS, which I believe have made us immune to media coverage in a manner analogous to the story of the boy who cried wolf:

  • The current variation of H5N1 is highly pathogenic, and rapidly spreading across the globe

  • Like all viruses, it mutates with ease. We know what factors make a flu virus a human virus (easily passed from one human to another human), and from this knowledge we know that H5N1 is the biggest pandemic threat of all stains of influenza in circulation. It is just one antigenic shift mutation or a couple of antigenic drift mutations from being an avian influenza virus to a human influenza virus

  • The difference between an epidemic (such as the regular outbreaks of influenza we have yearly) and a pandemic is that a pandemic threatens a global population, compared to an epidemic which is concentrated on one population

  • In order for a flu pandemic to occur from H5N1, it must first mutate into a form in which it can transmit easily between humans. This rapidly will then turn into an epidemic if not caught, and then from an epidemic it will become a pandemic. Experts widely believe that it will not be possible to prevent any of these stages from happening with H5N1

  • Pandemics have the capability to kill millions, if not hundreds of millions of people. The current worst case projection for H5N1 is somewhere around 150 million

  • This has happened before. In 1918 and 1919, an avian influenza became pathogenic and killed between 50 and 100 million people worldwide (called "Spanish flu"). And compared to today, world travel was minimal.

  • There are serious technical problems with combatting a pandemic with vaccines. Once the virus it identified, the development takes several months. H5 appears to require relatively large doses of vaccine to be effective. A large trial found two injections at 6 times the strength of a seasonal flu jab (which you only get once a year, if you have one) gave protection in only 54% of a population. Currently, the world has the capability to produce around 900 million does at a strength for the seasonal flu jab; therefore we would need at least 12 times this production capacity just to immunise less than a sixth of the world population with 54% success rate. Furthermore, there are two different clades (like branches) of virus in circulation. Research is focused on clade 1 viruses; the clade 2 virus is antigenically distinct and a clade 1 vaccine will be unlikely to offer protection against a clade 2 virus pandemic

  • About the only bit of positive news on H5N1 is that it currently hasn't mutated into a human virus, so as yet we have little to fear from it. Most experts believe it's not a matter of if but when this happens though. There's no need to panic right this instant, but taking it seriously would be wise

I would like at this point to explain why I'm making these points. Firstly, I'd like to educate people beyond the media hype; I believe the readership here has more than enough brains to grasp more than the basic facts you can hear on the 10 o'clock news. Secondly, I want to make it clear to people that it's not a case of the authorities crying wolf, there is a very real danger here for a huge virus outbreak. I don't however write this with the view of initiating mass panic. Rather, I think it's important to approach the facts with a level head and accept the reality of a possible outbreak, but when that outbreak happens (it could be tomorrow, it could be in a year, it could never happen) we have prepared ourselves for it, that we don't panic, and that we have well thought out contingency plans to put into place.

Awaiting corrections on the technicalities from Craig and other biochemists/geneticists etc.

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  1. Christopher Rossdale

    Interesting thoughts. I don't think people on the blogs aren't taking it seriously though. I think the main focus of conversation seems to be about the fact that, as you rightly said, it isn't time to panic. There's a difference between recognising the threat, and creating something not far from hysteria. Articles such as yours do the former, the Daily Mail etc do the latter. You're right though – it needs to be taken slightly more seriously. Maybe however the only way for our minds to genuinely calm themselves from the widespread fear and panic is to make fun of it though – reassurance is important in this type of situation.

    07 Apr 2006, 19:33

  2. People like to panic.

    I remember the panic buying at the millenium. As if milk and bread wouldn't get made because the year changed. rolls eyes.

    07 Apr 2006, 19:39

  3. Chris – for sure, ridicule the media some; however the coverage I have seen isn't terribly panic-inducing. There's that stuff which was pointed out on the BBC website, which is Joe Public being typically unable to grasp the facts and placing comments on unmoderated forums, but apart from that the coverage I've seen on the television (haven't read the papers recently) is very much a case of "it's here, but unless you come into contact with diseased uncooked birds you're pretty much safe". As you said, it's important to be reassured, but I am a little concerned that reassurance is going too far into complacency/denial of the situation and a treatment of H5N1 as another "it's just another silly health scare being blown out of proportion", which it very much isn't.

    Victoria – I remember that too. Panicing is a very human thing as you've identified. A good quote from of all places the original Men in Black "People are smart, they can handle it" "A person is smart. People are dumb, panicky, dangerous animals and you know it". Not one of human nature's best points that.

    07 Apr 2006, 19:50

  4. I completely agree with you on this. Reading Ben Keates's entry on this topic illustrates the point. While a lot of people seem to believe that H5N1 as it is today is going to kill everyone, which simply isn't true, these tend to be readers of tabloids and to be honest you kind of expect it.

    However, the others, who tend to be more educated and should know better seem to believe that there is no threat at all, including the vast majority of commentors on that entry. This is more worrying. The New Scientist magazine has been ranting on about the threat for at least several months now, probably in the hope of bringing the whole issue to the forefront of everyone's minds. I agree that we don't want to panic people, but if that's really what it takes to get the govenments of the world to react, then maybe its not such a bad thing in the long run.

    08 Apr 2006, 10:08

  5. H5N1 is dangerous, in that if you get it, there's a good chance you'll die. However the chance of getting it is currently very low. If it mutates to increase that chance, then it's time to panic.

    08 Apr 2006, 10:14

  6. The current variation of H5N1 is highly pathogenic, and rapidly spreading across the globe

    Define pathogenic. It's very bad news if you're poultry, not so much if you're waterfowl. Estimates of pathogenicity in humans vary because there's not really a good measure of what proportion of infected persons present to a doctor.

    The most important thing to bear in mind at the moment is that the current avian H5N1 genotypes are diseases of birds. It's extremely unlikely that anyone in europe is going to catch it directly. The problem is that every infection of a person is a new opportunity for the virus to reassort or drift into a form which is considerably more infectious in humans.

    A while back, I wrote in some detail about what governments don't want to tell you; there's nothing that they can do now other than plan. It will all come down to slowing down the global spread once it (or whatever the next pandemic influenza is) becomes established in people, long enough to develop a functional vaccine. That means some serious restrictions on personal freedoms. Developing vaccines for H5N1 is difficult, because chicken eggs are used in the production, and H5N1 kills them.

    An influenza A pandemic will come. Perhaps not this year, or next year, or this decade. But it is only a matter of time. If we're lucky, by that time medical science will have progressed to a point where we can deal with it, but that seems unlikely.

    08 Apr 2006, 12:25

  7. Craig

    Yup, H5N1 is spreading across the globe but as Max said its not really a problem for the majority of waterfowl that carry it. In birds influenza rarely causes problems and most will carry a variety of influzena strains their entire life without being affected. So really a few dead birds carrying H5N1 isn't all that big a thing.

    In terms of how leathal it is to humans that currently sitting around the 50% mark I believe, for comparison the 1918 flu was around the 4% mark. Of course the 1918 version was much more easily spread between humans hence the high death toll. World travel was minimal in 1918 but then again so was healthcare, sanitation (in large sections of the world) and just general understanding of the virus so drawing comparisons is rather difficult.

    You mention that its only a single antigenic shift away from becoming but an antigenic shift is actually quite a big event. There were a couple of articles published last month about the reasons why H5N1 has trouble spreading from person to person, which appears to be primarily down to the location of receptors in the human airways. Even if this mutation did occur and allowed for easy transfer between human hosts I expect a couple of other mutations would still be required to make it highly infectious in humans.

    Overall yes I agree that its going to cause a pandemic at some point though as a lecturer pointed out H5N1 has been in circulation since the mid 90's (think the first outbreak was 1997) and birds were probably carrying it will before that. Despite this its not made the required jump yet. Vaccines against the strain that does make the jump will take time to prepare but until they're ready existing vaccines are likely to offer some limited protection, which if used correctly combined with isolation of population groups etc should be able to slow the spread of any outbreak. Also tamiflu can now be produced synthetically which is always a bonus.

    08 Apr 2006, 14:18

  8. In terms of how leathal it is to humans that currently sitting around the 50% mark I believe,

    Mortality is high for those who present, but there's some debate about whether there is a larger population who never suffer severely enough to be treated; that is a major unknown in trying to work out the overall population mortality.

    WHO have stacks of information and a detailed factsheet here if anyone's really interested.

    08 Apr 2006, 14:42

  9. I read that too Craig – something to do with it infecting deep in the lungs as opposed to more exposed locations in the respiratory system where it can be spread into expelled air more easily if I remember correctly. With regards to drawing comparisons, a lot of the world's population today has little or no access to good healthcare or sanitation, and it is undoubtedly them that will suffer the most. Looking at how it is currently rampaging through Africa, I would say the chance of an infected human giving rise to a mutated form of influenza in a form easily transmissable between humans is only a matter of time. There's nothing that says the disease can't mutate quite wildly, for example changing HA antigen subtypes. According to Wikipedia on Hemagglutinin, single amino acid changes in H5 hemagglutinin have been found in human patients that can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses. Without a great deal of knowledge of biochemistry, I'd say that means that there's nothing to suggest that it can't mutate into a form where it will affect receptors in humans that make it much more transmissible.

    According to Max's article he linked above, tamiflu is only effective within 48 hours of infection, and even then it's not a cure, it merely increases your chances of survival and, I quote, "its effectivity against such a potent killer is hard to judge." From what I've gleaned from his article though, our ability to synthesise tamiflu and our response to treating the infected quickly in the case of a pandemic is likely to play a key role in controlling such an event.

    Max – it might be what governments don't want to tell us, but I think the government should put a lot more effort into telling us, instead of letting the facts become distorted by the tabloids. The main message I've been hearing is that you're not going to catch H5N1 unless you come into direct contact with infected living or dead birds, but the discussion about a pandemic hasn't happened at all that I can see and I think it should. Discussion of contingency plans and reduction of civil liberties in the event of a pandemic should be widely published and understood now, and we should be looking to bolster our ability to make vaccines and ensure that sufficient medical supplies and production capability is in place for when it happens. If we're properly prepared, the actual event when it comes will be a lot less of a panic to deal with.

    08 Apr 2006, 14:49

  10. Hmm. Interesting. My comment here was going to be something about you reading the Daily Mail…
    However, you do have a point. As I'm not feeling particularly coherent today, I shall sum up my thoughts in handy bullet points (me? A consultant? Never…)

    • People who don't sit down and read the whole of this post will panic more, and thus maybe you should have put the bit about not wanting to cause that at the beginning not the end
    • People will always panic
    • Fewer people are panicking about this than BSE (a big pile of bollocks and completely unfounded) or other similar things, because, as you say, the general public has become immune to it. The Government have fucked up on so many minor/non-existent scares that most people (myself included) just turn the TV off whenever it's on. This is because it's being portrayed in exactly the same way. I think if The Powers That Be ™ realised the boy crying wolf thing, they should be making an effort to really grab peoples' attention. They are not. ITV are saying "we're all going to die" in exactly the same way they always do, with shitty special effect graphicy news sets and special helpline numbers/emails.
    • It's going to happen. Yes, there is a case for making people realise that it is actually serious this time, but equally, there's absolutely nothing we can do about it, so why make a big fuss? All that's going to do is convince people that stopping their chicken consumption is actually going to save their lives, and that is when the panic rollercoaster starts.
    • I would be much happier if this potential pandemic hadn't started under the rule of the party which made such a complete and utter fuck up over FMD. I'm not worried about the virus – I'm worried about the people who are supposed to be protecting me from it.]



    08 Apr 2006, 22:18

  11. Lorna – firstly, I've made a nice little edit for you at the start :-)

    Secondly, with regards to your fourth point, there's not absolutely nothing we can do about it. Firstly, we can be made aware beforehand of potential measures that may need to be enforced during a pandemic. There are individual precautions and preparations that can also be taken, see Wikipedia for a nice little list of these. Just being aware of these in some form of public information campaign would be useful. Of course, precautions such as planning on a national level for strategies in the event of an outbreak and stocking up with the right vaccines/increasing vaccine production capability etc would also help.

    And with regards to your last point, yes I'd be much happier and I'm as worried about this bungling government as you are. But even they are likely to do a good job compared to where the stuff is likely to come from and spread around the most – in Africa – where standards are so low and resources so small that there's so little that can be done anyway.

    And just to clarify, aside from when I'm at home I don't read the Daily Mail. Aside from scanning it when I've been home once or twice, I haven't read copies at all this year. And none of my information in this post has been written following reading of a Daily Mail article about H5N1. So there :-P


    08 Apr 2006, 22:37

  12. The Government have fucked up on so many minor/non-existent scares that most people (myself included) just turn the TV off whenever it's on.

    Better than the last government claiming that there was no risk from BSE, and so on. (and it's really not an unfounded fear. There have been relatively few cases of nvCJD most directly because measures were [reluctantly] taken to control the disease in cattle. It's like the millennium bug. Everything was ok because the problem was fixed, not because there wasn't a problem)

    The problem in this country is that the governments (all of them) have treated the citizens as if they couldn't understand the issues. "Trust us, it'll be OK". There's no room for uncertainty, or for letting people make up their own minds. So when the government has gotten it wrong, it makes people much more cynical.

    Of course, the flipside is that with some issues (the one that really springs to mind is MMR), most people really cannot understand the material to the degree necessary to make a reasoned judgement.

    08 Apr 2006, 23:51

  13. Loved that Wikipedia page… wonder how many people will soon be stocking their basements full of tinned food, toilet rolls and soap in case travelling to the shops is banned.

    Seriously, there's pretty much nothing we can do except wait and see what happens, keep eating our 5 a day, and getting on with normal life. I don't see the point in preparing now for something that might not even happen for 10 years or more.

    10 Apr 2006, 13:39

  14. Max,

    Point taken about MMR etc, but the BSE/nvCJD issue is one close to my heart. I come from a farming family, and it was quite obvious to those in the industry, as 'twere, that the two are not directly linked. More likely a hypothesis, that was never circulated nationally, is that CJD is linked to organophosphates, which is used in dipping (disinfecting, if you like) livestock. It was nothing to do with insane cows and all that nonsense – there are a large proportion of CJD sufferers who were exposed to OPs during their life, but nobody made that link public. The two things I had a problem with were a) The phrase "the human form of mad cow disease" because it is more likely that BSE and CJD were both caused by the same thing but one could not contract the disease from diseased beef, and b) the fact that men and women in their 80s who had been eating beef for their entire lives suddenly stopped in case they caught it.


    I entered the young farmers' public speaking competition (bless me, I know) with a speech about this – I wish I could find it…


    PS - sorry if this is incoherent – I've had a very long day at work…!

    10 Apr 2006, 21:19

  15. a) The phrase "the human form of mad cow disease" because it is more likely that BSE and CJD were both caused by the same thing but one could not contract the disease from diseased beef,

    Don't confuse CJD with nvCJD. nvCJD is interesting because it appeared suddenly, and had very different clinical and demographic behaviour to the well-established "normal" CJD.

    There are a number of pieces of evidence which, whilst not conclusive, are certainly strongly suggestive that BSE is the cause of nvCJD, viz:

    • Monkies can be directly infected with bovine brain tissue
    • The prions recovered from nvCJD sufferers show similar properties to those recovered from BSE infected cows, mice, and cats, but different to those of normal CJD sufferers
    • Mice infected with nvCJD developed a disease indistinguishable from mice infected with BSE (it's a bit more complicated than this, but the jist is there)
    • The epidemiology of nvCJD is consistent with BSE being the causative agent, but there are so many unknowns about the disease that that's still up for debate.

    This is all in a recent review, E. Beghi et al., Neurological Sciences 2004 25 122-129, and a very readable paper D. A. Hilton, J. Pathol. 2006 208 134–141

    Basically, prion disease is becoming more and more well understood; whilst organophosphates have some nasty neurological effects, CJD is not one of them.

    11 Apr 2006, 00:22

  16. hero

    Funny how all the people making a 'scientific' case for how we should panic and how we (i.e. the (not tory) government) are 'unprepared' are rabid blind tories!

    11 Apr 2006, 15:08

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