I don’t really get why people are chatting about Tamiflu as if it’s all that

May 1st, 2009 by Ben Goldacre in bad science, big pharma, evidence, systematic reviews | 52 Comments »

By-the-by I don’t really understand why the Guardian subs gave this piece, about how Tamiflu isn’t so great, a headline saying “the drugs do work”. I mean they kind of do work a bit, and we don’t know if they do in a pandemic since they’ve not been tested in those circumstances (which probably won’t come to pass) but we hope they will and so they’re recommended.

Ben Goldacre

The Guardian

Saturday 2 May 2009

Look I don’t want to freak you out, since Tamiflu is the one thing which everyone believes will save us from Parmageddon, but I’ve been reading through the published trial data on the drug, and I’m not sure it’s all that great.The Cochrane Library is one of the greatest inventions of modern humankind. It’s all very well to do a trial, or lots of little trials, but one trial, simply by chance, might give a false negative, incorrectly missing a true benefit from an effective treatment; or one trial might falsely find a benefit from an ineffective treatment, either by chance, or because the study was designed so badly that it not longer represented a “fair test” of the intervention, against whatever you were comparing it to.

The Cochrane Library is an international non-profit collaboration of academics that brings together all the evidence on a given question, using a predetermined standard method for seeking out information, assessing its quality, and combining it into one giant report. They’re slightly turgid, and they are considered by medics and academics to be pretty much the best quality evidence available, because they look at all the relevant trial evidence on a given question, although you will very rarely hear about Cochrane reviews in mainstream media, because journalists are seduced by baubles and novelty.

Handily, there is a Cochrane review on Tamiflu, and a similar drug called Relenza. In reality the drugs’ names are oseltamivir and zanamivir, but for some reason the media always use the original manufacturers’ brand names instead of the generic, a bit like calling all ibuprofen tablets “nurofen”, or all aspirin tablets “dispirin”. After a few years all medicines come out of copyright patent, at which point anyone can manufacture them, but if everyone is used to the brand name rather than the generic then the original company has an advantage. Anyway.

The review on oseltamivir and zanamivir was done several years ago, but reviews are frequently updated in the Cochrane Library, because evidence changes. This review was properly re-done in 2006, and also checked as being up-to-date in May 2008. They asked two questions. Do these drugs treat flu? And do they prevent it?

The time to alleviation of flu symptoms was assessed by nine trials, and the pooled hazard ratio for zanamivir was 1.24. Sorry, that was gibberish: what I meant to say is that the group treated with zanamivir are 24% more likely to have their symptoms alleviated than the placebo group, at a given time-point. For oseltamivir the figure was 20%. It’s alright. I’d take it. It’s just not amazing.

The NICE review from February 2009 looks at similar data, and analyses it in a different way, giving you absolute time to recovery, which is a little easier to understand. Overall, oseltamivir reduced the average (“median”) time to alleviation of symptoms by 0.68 days. For zanamivir the figure was 0.71 days. So you get better 16 or 17 hours sooner if you take these drugs.

The prevention studies are a bit more exciting. Patients had less virus on board, and less in their noses, but neither drug actually stopped patients being infectious. In fact, neither drug had a protective effect at all against influenza-like-illness, or asymptomatic influenza, even at higher doses. (“Influenza-like-illness” is symptoms that look like flu but might be a bad cold: it can take days to get blood tests back, so you treat it as flu, and in a pandemic, you can be more certain that you’re seeing real flu, because there’s more of it about).

For preventing symptomatic influenza, the results are more impressive. Oseltamivir 75mg daily was 61% effective compared with placebo, and 73% effective at 150mg daily, while Relenza was 62% effective. In trials looking at preventing influenza in people who were living in households where someone was already infected, the drugs were also pretty good.

I’d take these drugs if I needed to. Things might be different in a pandemic, and the Cochrane review recommends them in this situation. If they make my symptoms less severe then I’m guessing I’m less likely to die, for example, and they might reduce the spread through a country.

But they’re not miracle cures, and if this is worrying to you, then that just shows how ill-equipped we are to think about risk. For the question of whether we’ll see a pandemic, things are so up in the air that it’s not even possible to give a number defining that risk (which many people seem to find incomprehensible). For the efficacy of the treatments, we do have numerical risk data on the chances of getting better, but for all interventions we have to accept that modern medicine is all about shaving risks and probabilities, in lots of different ways, to achieve the best possible outcome, rather than absolute certainty. And after all that, it’s true, if you got swine flu, you might still die. Which would be seriously rubbish.

Neuraminidase inhibitors for preventing and treating influenza in healthy adults. Jefferson T et al. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001265.

NICE Technology Appraisal Guidance No 168 – Amantadine, oseltamivir and zanamivir for the treatment of influenza.


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52 Responses



  1. Romeo Vitelli said,

    May 2, 2009 at 12:23 am

    Of course Tamiflu has also been linked to some less common side effects including delirium, depression and even suicide. Doctors prescribing the meds need to warn users about potential health risks, which may outweigh the actual benefits.

    drvitelli.typepad.com/providentia/2007/11/does-tamiflu-ca.html

  2. JFM said,

    May 2, 2009 at 12:46 am

    Tamiflu is a lot easier to pronounce than oseltamivir and zanamivir, which I can’t even spell.

  3. Wireman said,

    May 2, 2009 at 12:58 am

    I’m with the subs on “Parmageddon”. It’s good but a bit of a two-steps-away pun. Is “Hamageddon” not better?

    Anyway… can somebody explain the difference between symptomatic and asymptomatic flu to this seeker after simple truths?

  4. NelC said,

    May 2, 2009 at 1:46 am

    Sure, the brand name has been designed to be easy to pronounce and remember, whereas the generic name is, what, assembled from bits of biochemical suffixes and prefixes as a description of the chemical? So, as a journalist, are you going to write or say 2-acetoxybenzoic acid, or are you going to say aspirin?

  5. RTomsett said,

    May 2, 2009 at 1:57 am

    I still reckon “the aporkalypse” is teh bestest.

  6. sarahnz said,

    May 2, 2009 at 2:44 am

    Here in New Zealand we are able to buy Tamilflu over the counter from a pharmacy but…only if you are the person with the flu symptoms. You are not able to buy it for a family member or on behalf on any other person. So with 401 people in voluntary isolation, we are encouraging them to go out in public and spread AN1H1 as widely as possible. And we do have confirmed cases. And this is the result of all the great and good with their pandemic response planning. Bring on the bird flu.

  7. lilacsigil said,

    May 2, 2009 at 4:43 am

    I work in pharmacy. It’s been a long week of explaining about face masks and Tamiflu. Thanks for the review!

  8. SteveGJ said,

    May 2, 2009 at 6:53 am

    I’m not sure using the original brand name gives much of an advantage in the long run. There’s a line between when it goes from being useful, free publicity to just another generic names. At that point brand owners hate it as they’ve lost control.

    As examples of brands gone generic, not necessarily to the advantage of the owners, you could consider Biro instead of ballpoint of Hoover instead of vacuum cleaner. Adobe do there best to stop Photoshop becoming a generic and if you go to their website you’ll find they are very picky at pointing out Photoshop is a noun and a registered trademark. That it can’t be used as a transitive verb as in “to photoshop”, or as the past participle “photoshopped”. Of course this is all to no avail, and the name is becoming generic and associated with all sorts of underhand activities. The use of phrase “image manipulation” is outnumbered by “photoshop” about 15:1 on a Google search.

    The real reason that brand names get used in place of generics is probably more likely down to a combination of laziness, convenience and simply being more memorable. Generic drug names are often, difficult to remember and not catchy. Marketing names are, for obvious reasons, designed to be memorable.

    In simple terms, some brand names win out through natural selection.

  9. maria102 said,

    May 2, 2009 at 7:41 am

    www.journals.uchicago.edu/doi/abs/10.1086/591708?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov

    Anthony Fauci, a world authority in this area said that most flu deaths in 1918 were due to bacterial pneumonia, a disease that can be largely prevented by the pneumonia vaccine which is widely available. The situation today is still the same. The research article from 2008 is available at the link above. Why are the government not recommending this be used as a frontline anti-flu preventative? Currently in this country, it is only given to people with compromised immune systems or over 65. One shot works for at least 10 years, or some think for life.

  10. manigen said,

    May 2, 2009 at 8:27 am

    Great article.

    “After a few years all medicines come out of copyright, at which point anyone can manufacture them”

    It’s a minor point, but Ben is talking about patents in this sentence, not copyright. The distinction can become important; patents die after approximately 20 years (stretching up to about 26 years for a medical treatment in some circumstances), and when the patent dies the manufacturers will rely upon other intellectual property like trademarks and copyright to protect the brand and try to maintain their monopoly. News services use Tamiflu, the trademark, because that’s the name that the manufacturer is lobbying them to use. They want it fixed in everyone’s mind for when the patent runs out.

  11. cosmictrout said,

    May 2, 2009 at 8:28 am

    I don#t mean to nitpick (OK, yes I do) but:

    “After a few years all medicines come out of copyright..”

    you mean they come off patent – there’s no copyright in a medicine

  12. cosmictrout said,

    May 2, 2009 at 8:30 am

    ooh – I see manigen beat me to it ;-) IP nitpickers of the world unite! Er, or something…

  13. patently said,

    May 2, 2009 at 8:37 am

    After a few years all medicines come out of copyright…

    Oops; I just lost all respect for the writer’s grasp of detail.

    Copyright medicines? Whatever next! I look forward to the day when the patent expires on the Coca-Cola trade mark, and we can all use it freely…!

  14. SubMoron said,

    May 2, 2009 at 10:21 am

    Bloody good article. From within I can tell you that GSK are issuing Relenza to sites for free distribution to staff so it looks as though the company thinks it’s worthwhile. Yes, I’ll take it too!

  15. HolfordWatch said,

    May 2, 2009 at 10:35 am

    Well, now that Tamiflu has been exposed as ‘Not all that’ you must be relieved to learn that there is a way to treat Swine Flu, Bird Flu, pretty much any sort of flu: it’s vitamin C and elderberries. I know this because Patrick Holford told me.

    If we develop symptoms, we should take up to 100g of vitamin C a day, find a doctor to give us intravenous vitamin C and take some supplements. Skipping lightly over the fact that taking that much vitamin C by mouth might involve drinking from 3-6.5 gallons of water a day we must alert you to another panacea that Holford discusses.

    The panacea is a Rath Foundation formulation of green tea extract, vitamin C (of course, lysine, proline, N-acetyl cysteine, selenium among other micronutrients. This amazing formula might also work for cancer, Aids (of course), and various other banes.

    Some homeopath/nutritionists such as Jayney Goddard advise against boosting the immune system with elderberries for fear that it will contribute to a cytokine storm in response to the flu.

    You choose your health guru and make your decision.

  16. muscleman said,

    May 2, 2009 at 2:10 pm

    @NelC
    Acetylsalicylic Acid is much easier on the tongue than 2-acetoxybenzoic acid. Depends which way you squint at the molecule of course which chemical moniker you prefer. Just saying there is another one.

    Reminds me of doing histology and using salicylate for clearing specimens, which is why it is the one that leaps to my mind.

  17. Daibhid C said,

    May 2, 2009 at 3:34 pm

    8, SteveGJ – I believe Google are a bit antsy about genericism as well, which has led to New Scientist’s Feedback page using the term FWSE (Famous Web Search Engine).

  18. Sili said,

    May 2, 2009 at 4:57 pm

    “Acetoxybenzoic acid” is wrong anyway – it misses out the phenol bit of the the salicylic acid. “Acetoxy-oxy-benzoic acid” might work, but it’s been too many years since I last worked with IUPAC nomenclature. Pity. I used to be pretty good at it.

    Thank you for the reminder on elder. It’s been a gorgeous Spring, so I prolly should start checking the trees so as not to miss their blooming. I’d like to make some more elderflower cordial this year.

    Not that it’s gonna save me from Parmageddon, but I’ll enjoy sipping it while watching the rioting.

  19. henrywilton said,

    May 2, 2009 at 5:29 pm

    @HolfordWatch

    When I took my manflu to my entirely un-woo-ish doctor earlier in the year, she prescribed elderberries, to my great surprise. Apparently this year’s flu was resistant to Tamiflu, and she pointed me in the direction of this quite positive study:

    www.jimronline.net/content/full/2004/47/0445.pdf

    Of course, as usual “These findings need to be
    confirmed in a larger study”. Any ideas on whether a larger study was ever done?

  20. Sili said,

    May 2, 2009 at 8:11 pm

    Bugger! Of course “acetoxy” is correct! I was thinking “acetyl”. Sorry. I’ll pipe down now and go back to yard sweeping instead of trying to play with the big boys.

  21. HolfordWatch said,

    May 2, 2009 at 8:33 pm

    @henry wilton – NCCAM updated their listing on elderberries as recently as April 2008, and despite their usually generous interpretation of the evidence, they say this about :elderberries:

    *Although some small studies show that elderberry may relieve flu symptoms, the evidence is not strong enough to support this use of the berry.
    *A few studies have suggested that a product containing elder flower and other herbs can help treat sinus infections when used with antibiotics, but further research is needed to confirm any benefit.
    *No reliable information is available on the effectiveness of elderberry and elder flower for other uses.

    The study to which you refer is the one that Holford belatedly edited in and appeared after our complaint that he had given no reference for his claims about elderberries. It is an interesting study but, as far as we can tell, there hasn’t been a larger study. Plus, we are a little unclear as to whether or not the participants were able to guess whether or not they had been taking the elderberry preparation or the placebo syrup (the authors don’t mention whether or not they asked the participants that question).

    On top of that, I’m not sure how they ended up enrolling only people who had influenza as opposed to flu-like symptoms (did they randomise all 80 and then, conveniently, only 10 had to be discarded from both the active and placebo groups – how quickly did the local labs turn around the results of the flu ID tests?). They mention that they had 80 candidates – if 60 of those ended up with lab-confirmed flu, I’m a little surprised. In addition, the authors don’t describe the randomisation method which is a little sloppy of them.

    Nonetheless, for those who can purchase the formulation that was used in the study – it sounds interesting enough (and I am very partial to elderberry syrup as well as rosehip).

  22. henrywilton said,

    May 2, 2009 at 10:37 pm

    @HolfordWatch

    Thanks for the reply!

    …how quickly did the local labs turn around the results of the flu ID tests?

    For what it’s worth, the test that confirmed I had ‘flu took about two minutes.

  23. Robert Carnegie said,

    May 2, 2009 at 11:27 pm

    The brand name is written big on the front of the packet. The science name is in the small print. Anyway, a brand name can represent a pill or product with multiple chemicals. I think, but I’m not sure, Snopes.com said that the recipe for Coca-Cola has changed several times, not only removing the near-homeopathic quantity of cocaine originally included. That the one time that a change actually was announced, great fuss. Every other time, not.

    Whether there’s a flu pandemic appears to be something that we can’t affect as individuals, although… did you know so many people visit Mexico from Britain? Taking a medicine – it’s something that we know how to do.

    How good or bad do elderberries have to be to provide ambiguous results in a trial? Is there a reason to expect them to be any good, besides someone having a warehouse full of elderberry products to sell? I mean, why isn’t it strawberries?

  24. henrywilton said,

    May 2, 2009 at 11:31 pm

    Is there a reason to expect them to be any good, besides someone having a warehouse full of elderberry products to sell? I mean, why isn’t it strawberries?

    I think there is a proposed mechanism. Something to do with cytokines. Of course, I have no idea what a cytokine is, so I daresay it’s all bunk.

  25. pv said,

    May 3, 2009 at 12:12 am

    Can we report Pilltrick Holford to the FDA?

    www.fda.gov/oci/flucontact.html

    And

    A few studies have suggested that a product containing elder flower and other herbs can help treat sinus infections when used with antibiotics

    In conjunction with antibiotics?
    Did I read that correctly?
    ANTIBIOTICS?
    I suspect chewing cardboard might also work in conjunction with antibiotics. But a larger study is recommended!

  26. peterd102 said,

    May 3, 2009 at 12:13 am

    Its something at least, in the face of a possible pandemic. Though it appears rare that this objective veiw of tamiflu appears, The main veiws I have seen are that it is a saviour or completly useless – which seemed to often degenerate into claiming its a conspiracy.

    Still its odd where discussions of Swine flu appear – www.crymod.com/thread.php?threadid=47889&sid=8e5bc1b4fc7087d7c2ccfcb780136f91

    People want answers, it seems odd that they don’t seem to care whether what answers they get are true or not.

  27. HolfordWatch said,

    May 3, 2009 at 9:39 am

    @henrywilton – sure, I was just surprised that they mentioned that they were using local labs and were using 3 washes etc. – and a +ve result was returned within 1-7 days. You can have a rapid, on-the-spot test but a clinically confirmed one may have taken longer back in 2000 – and, as you see, the samples were given up to 7 days to return a +ve result – by which time, most of those in the elderberry group had already recovered so the confirmation came after the recovery.

    The authors provided this information about the randomisation but I’d have liked a little more, especially as all of the candidates were from the office of the one investigator:

    Individual, computer-generated randomization envelopes were kept sealed throughout the study. The randomization code was only broken once all the data had been collected.

    Again -the reduction from 80 candidates to 60 enrolled with a confirmed diagnosis – doesn’t indicate to us when people were randomised. Because, it seems to me that all 80 candidates must have had received either the active or placebo intervention and that at some (unspecified time) they were discarded because they did not have clinically confirmed flu (some may have been discarded because they didn’t meet the inclusion criteria – it’s not clear how many of these made up the 20 who are disparu).

    @pv -to be fair to Patrick Holford, he is recommending elderberries rather than elderflower but yes, this is par for the course for these studies.

    For the mechanism of action, there are several ideas but these are only mentioned in the paper and the details are in papers that I haven’t seen. ‘Flavonoids as immune-boosting by enhancing production of cytokines'; disrupting various processes preventing the virus moving into cells and being unwelcome house guests or the anthocyanins behaving like aspirin.

    Overall,yes, it would seem that taking an appropriate formulation of elderberry syrup would be easier than downing enough water to take 100g of vitamin C a day if symptomatic (and less likely to flirt with hyponatraemia and death). However, you will see there is no mention of the actual amount or grade of the elderberry in the paper so it is not necessarily appropriate to think that any formulation of elderberries would do. There is, of course, a Biocare-Patrick Holford product that contains vitamin C, elderberries etc.

    BioCare – Patrick Holford ImmuneC®

    ImmuneC contains optimum amounts of the vital nutrients vitamin C and zinc, which support the body’s natural defences. Plant extracts of black elderberry and ginger may also assist immune function.
    BioCare Vitamin C and Black Elderberry with Bilberry, Ginger and Zinc
    Contains potent antioxidants to help maintain a healthy immune system
    Contains vitamin C and zinc with plant extracts
    Now contains double the strength of elderberry and added ginger…

    1800mg Vitamin C

    100mg Black Elderberry Extract (4% total flavonoids)

    40mg Ginger

    20mg Bilberry Extract (2% anthocyanidins)

    6mg Zinc

    However, no guidance on how much of that to take if afflicted but, by his standards, it is a comparatively affordable £30 for a supply for 120 days at 2 a day. Not a cheap way to take his recommended 100g of vitamin C a day but there you have it.

  28. timheyes said,

    May 3, 2009 at 12:37 pm

    @muscleman

    This ia part fo the problem wiht the public understanding of science. Jargon.

    Making “in-jokes” about the nameing of chemical compounds does not advance your cause unless you make a point of telling the reader that Acetylsalicylic Acid is the (or one of the) chemical names for Aspirin. I hope that not everyone who reads BadScience is a scientist!!

    If you are all scientists then what’s the point of BadScience?

    Nuff sed.

  29. Ciaran said,

    May 3, 2009 at 7:59 pm

    It’s hardly surprising that poeple refer to a drug by the manufacturer’s name when the generic term sounds like a Sigur Ros track.

  30. JFM said,

    May 3, 2009 at 8:57 pm

    @timheyes:

    Yes and no… people seem to be fine with mega/giga bytes, which are really an ‘in-joke’ – bits, nibbles, and bytes.

    The problem is that the scientific/medical ones are unpronounceable. Products like “kodak” were named for their simple phonetic combination, as are all the manufacturers names. No one really says “disprin” any more – aspirin is a perfectly pronounceable name – all a generic name has to do is have a pronounceable shorthand assigned to it for it to be accessible.

    Of course, that’s what the manufacturers name is, so there’s not really any motivation to change this.

    Unreadable/unpronounceable names (whether they’re in-jokes or not) used on products really do damage the understanding of science. If I were some sort of benevolent overlord, I’d mandate that all ingredients that had generic English names should include them in brackets along with the latin name on all packaging and documentation.

    SO it would be Aqua (Water),….

  31. pv said,

    May 3, 2009 at 9:25 pm

    “Disprin” was a brand of soluble aspirin.
    It seems that “heroin“, like “aspirin” was also a brand name belonging to Bayer.

  32. penglish said,

    May 3, 2009 at 10:48 pm

    I need to re-read the Cochrane reports, but…

    IIRC, one of the key points was the timing. As I remember it, the drugs work better, the sooner they’re given. A cut-off of 48 hours is usually recommended for treatment – although in reality the efficacy will decline according to some sort of curve, They won’t be that much less effective at 49 hours than they were at 47 hours; but they’d probably have been much more effective given within 12 hours of onset of symptoms…

    I can’t remember how much account of these factors was taken by the Cochrane reviews.

  33. lenny law said,

    May 4, 2009 at 12:20 am

    Parmageddon?

    I don’t think so. How about Flupocalypse?

    And as for the old generic / brand names thing.. It’s simple. The generic names are always shorter and simpler in order to encourage busy GPs to write them on the prescription pad, especially when out of patent. Amoxil or Amoxycillin? Augmentin or Co-Amoxiclav? Flagyl or Metronidazole? (I’m a dentist.. we only get to prescribe generic antibiotics..)

  34. Robert Carnegie said,

    May 4, 2009 at 3:20 am

    Influerno?

    Trotterdammerung?

  35. HolfordWatch said,

    May 4, 2009 at 11:00 am

    Just to say that Patrick Holford has updated his post with yet more references about elderberries but still nothing more about the logistics of taking 100g of vitamin C by mouth.

    Viruses get into body cells by puncturing their walls with tiny spikes made of a substance called hemagglutinin. According to research by virologist Madeleine Mumcuoglu, working with Dr Jean Linderman, who discovered interferon, an extract of elderberry disarms these spikes by binding to them and preventing them from penetrating the cell membrane. ‘This was the first discovery,’ said Mumcuoglu. ‘Later I found evidence that elderberry also fights flu virus in other ways.’ In a double blind controlled trial she tested the effects of the elderberry extract, called Sambucol, in people diagnosed with any one of a number of strains of flu virus. Their results, published in 1995, showed a significant improvement in symptoms – fever, cough, muscle pain – in 20 per cent of patients within twenty-four hours, and in a further 73 per cent of patients within forty-eight hours. After three days 90 per cent had complete relief of their symptoms compared to another group on a placebo, who look at least six days to recover. In another double-blind controlled trial it cut recovery time in those with influenza by four days. So this is an added bonus.

    So, good to see that some parts of that post are improving.

  36. S said,

    May 4, 2009 at 11:05 am

    @Wireman

    Seeing as no-one seems to have answered your question, I think:
    Symptomatic – is when you have the flu virus and are displaying flu symptoms
    Asymptomatic – when you have the flu virus but don’t exhibit any flu symptoms

  37. Pain relief said,

    May 4, 2009 at 4:11 pm

    Really(Exactly), to increased the number of cases, and we must see that type of incident will improve the way of helping the people, for it in www.findrxonline.com will find the solutions and other ways of offsetting it.

  38. drgoodhead said,

    May 4, 2009 at 5:36 pm

    Interesting work at the end of 2008/beginning 2009 possibly in Science (?) on the emergence of oseltamivir resistant seasonal influenza strains, including H1N1. Somewhat astonishingly the vast majority of circulating strains were totally resistant to the drug, in the absence of selective pressure, i.e. even when the drug had not been in use. Nuts!! Doesn’t seem to compromise viral fitness. So, looks like the drugs won’t work anyway. Nice.

  39. Filias Cupio said,

    May 5, 2009 at 1:48 am

    (I’m working purely from Ben’s article – I’m to lazy to look up the full report.)

    Taken proactively, there is no reduction in the chance of contracting asymptomatic flu or flu-like. There is, however, about a 2/3 reduction in symptomatic flu.

    What that probably means is that 2/3 of what would have become symptomatic flu become asymptomatic or flu-like, and about the same number of asymptomatic or flu-like are prevented entirely.

    People with the milder forms are still infectious. Are they just as infectious as those with full flu?

    It looks to me like the most useful applications are proactive. Give it to medical staff during an outbreak, so they will be back on their feet as soon as possible after they (as is likely) get sick themselves, and to reduce the odds of them becoming vectors.

    In an incipient outbreak, give it to contacts of possibly-infectious people. Say an exposed person taking the drug has 20% less chance of becoming infectious in turn, and we manage to dose 50% of the people who get exposed. This means a 10% reduction in the infection growth rate. Say the ‘generation time’ of the virus is 3.5 days, or 100 generations per year, and we start with 1000 cases.
    If the ‘natural’ growth rate is +5% (I.e. each infectious individual infects on average 1.05 other people), with no drugs there are 130,000 cases in a year, with the drug there are 6.
    If the natural rate is +10%, with no drugs there are 14 million cases in a year, with drugs there are 1000.
    If the natural rate is +15%, no drugs gives 1.2 billion cases, drugs gives 130,000.

    So, either we quash the outbreak entirely, or we very considerably slow it, giving us time to develop a vaccine.

    My maths was very crude: 0.95^100 (to-power-of 100) compared to 1.05^100. In a pandemic, eventually the growth rate falls because most of an infectious person’s contacts have already had the disease and are now immune. However, the major point remains: even a comparatively small change in the growth rate (-10% in my example) has a huge effect over many generations, and for the flu, the generation time is fast.

  40. Wireman said,

    May 5, 2009 at 2:42 am

    @S

    Cheers. My (old media dictionary) research seems to indicate the following:

    Symptomatic: You are displaying signs of having [flu].

    Asymptomatic: You think you have [flu].

    I’m loving “trotterdammerung”.

  41. JoanCrawford said,

    May 5, 2009 at 12:12 pm

    @39

    You know it’s swine flu when you come out in rashers.

  42. DrJG said,

    May 5, 2009 at 6:58 pm

    @8,maria102:

    I’m not surprised at the suggestion that a lot of flu-related deaths involved bacterial pneumonia – antibiotics are a standard treatment for those with severe respiratory complications of flu.

    But I am afraid that the “pneumonia vaccination” is in fact only a vaccination against pneumococcus (streptococcus pneumoniae), which is far from the only bacterial cause of pneumonia. The abstract linked to only mentions “common upper respiratory tract bacteria”, and though I am not a microbiologist, I do not think that everyone would include pneumococcus in that category.

    In clinical terms, broadly speaking pneumococcus is a common causative organism in acute lobar pneumonia. In endemic influenza, however, the more common respiratory complication in flu, at least in frail elderly patients, is bronchopneumonia, where it is often harder to identify a causative organism without invasive investigations. So far, fortunately, I have seldom had to treat the fit young adults who make up a disproportionate number of deaths in pandemics, so I cannot comment from first hand experience on what type of pneumonia they tend to get, but again, the term used in the abstract “secondary” tends to sugegst bronchopneumonia.

    I have no doubt that widespread pneumococcal vaccination could prevent some flu-related deaths, but it is unlikely that it would be any sort of pancetta – sorry, panacea. In addition, in the scenario of a secondary bacterial pneumonia, it may well be that if one possible causative organism is excluded, another will only take its place.

  43. liquidcow said,

    May 6, 2009 at 10:34 am

    By the way Ben, you needn’t worry about turning down the opportunity to debunk the Swine Flu fears, looks like The Guardian have found someone to do it in your place:

    www.guardian.co.uk/commentisfree/2009/may/05/swine-flu-panic

    Is it me or are articles like this, and the associated denial, the middle-class form of panic?

  44. Norman said,

    May 6, 2009 at 1:37 pm

    @41 JoanCrawford
    You know it’s swine flu when you come out in rashers.

    That was bad, really really bad! I love it.

    However, on a more serious note, I called the NHS helpline to get advice on swine fly. All I got was crackling.

    Cheers,
    Norm.

  45. SteveGJ said,

    May 6, 2009 at 8:42 pm

    You also need to look out for symptoms of scratchings.

  46. andyb123 said,

    May 7, 2009 at 9:28 am

    so generic names are deliberately named with something difficult, and give it a swish brandname so people learn the brand name and will always ask for it!

    there is conventions though, monoclonal antibodies all end in mab, aptamers end in nib etc. but would you remember or even try and ask for bevacizumab when avastin?

  47. Squander Two said,

    May 7, 2009 at 7:49 pm

    Aspirin is an interesting episode in trademark law. As pv said above, it’s a brand name owned by Bayer. Non-German firms started using it for their generics during the Second World War, on the grounds that there was no way Bayer could take them to court at the time. Once the War was over, the trademark was thoroughly diluted and could no longer be enforced in those jurisdictions.

    It is still a trademark in Germany, though, and the other manufacturers call their generics something else.

  48. jsymes said,

    May 7, 2009 at 9:30 pm

    Never mind this blather about tradenames, trademarks etc: Ben, how about a comment on the constant misuse in the media of “pandemic” as a synonym for “epidemic”. Pandemic refers to its spread, epidemic to its intensity. And yet hacks in serious papers refer to, eg, “A mild pandemic of H1N1 would be expected to cause at least three times more deaths and illness than typical seasonal viruses” (Mark Henderson, “Science” Editor, The Times May 6, 2009). A couple of problems there, Mark: what is a “mild pandemic”? One that only spreads to countries with an “R” in them? No, that would preclude Mexico. And New Zealand (although it has an R if you use its Maori name of Aoteoroa). Second problem: “what are the “seasonal viruses”? Last time I Iooked, Mexico is closer to the Equator than the UK, so I would doubt it has the Spring-Summer-Autumn-Winter cycle we have in the UK. Perhaps in Mexico’s case, it’s something to do with the earthquake seasonal cycle. I don’t mean to be too cynical – well, maybe I do – but I am getting pissed off with the non-science being peddled by even the “serious” media – starting with the misuse of pandemic and epidemic.

  49. SimonW said,

    May 9, 2009 at 8:21 pm

    A little reading around suggests that the current seasonal H1N1 flu is resistant to Tamiflu. I’d be interested to know how resistant, as these things are seldom all or nothing.

    The Avian flu that hasn’t happened yet also hung around long enough to pick up a mutation to the Neuraminidase in one human which would potentially render some antivirals impotent (including Tamiflu). This specific mutation has been known to happen before.

    The (UK) government was thus wise to stock both drugs in large quantities, rather than just one or the other.

    And yes they do seem to be presented as some sort of invisible forcefield that stops death and illness by influenza.

    I heard that if you chant the generic names with the correct pronunciation you are also protected.

    I already made my prediction of Tamiflu resistant Swine flu being found by the end of the year, I hope I’m wrong but I was fairly conservative because I hate actually being wrong.

  50. quiact said,

    May 10, 2009 at 8:17 pm

    Some facts about Influenza Viruses:

    Virus is a Latin word, meaning ‘poison’.

    A virus is more of a very well organized molecular parasite than an actual life form, such as a bacteria.

    The virus cannot grow or reproduce without a host cell. That means it needs a bird or mammal, such as humans, in order to exist and thrive.

    And the virus has the potential to completely destroy the host in the process in order to exist.

    The influenza viruses are of what are called orthomyxoviruses, which is a group or family of RNA viruses that are categorized into A, B, and C.

    The Influenza A virus is the one that historically has caused pandemics that have developed in the past.

    About eighty percent of flu cases in the U.S. are type A influenza viruses.

    Influenza vaccinations are the only available method of prevention at this time from the potentially deadly effects of influenza.

    Influenza is the virus responsible for the disease that has its name, and it is spread easily to other humans.

    This virus can be deadly to a greater degree when the virus creates a pandemic, which did happen in the United States and other parts of the world less than 100 years ago.

    Other influenza pandemics primarily have occurred in countries in Asia.

    For an influenza pandemic to occur, which means a global disease existence and presence, the virus must emerge from another species to humans without a strong immune system- as well as the ability to make more humans ill than normal due to the constant mutation of the influenza virus.

    Also, the virus must be highly contagious for a pandemic to occur.

    This particular virus that has been identified is just that.
    That pandemic caused around a half a million deaths in the United States alone.

    This event is now known as the Great Influenza Epidemic.

    Understandably there was panic among people worldwide, as the influenza virus itself was not identified until the year 1933.

    So, the mystery was rather frightening of what was happening at that time.

    The etiology for the deaths that were happening so rapidly was complete mystery to everyone.

    Clearly, at times these influenza viruses are more dangerous than others, and this was one of the strains that clearly very most toxic during that particular epidemic.

    Presently, influenza is once again a very concerning sub-microscopic infectious agent, and we are their potential hosts in order for these viruses to survive.

    The potentially deadly effects of the influenza virus is due to this virus penetrating the host, such as a human being

    Once infected and established in the host, the virus replicates within the cell of the host in the cell’s cytoplasm.

    To survive, the influenza virus targets an enzyme called polymerase, which is what directs the content of this cell to produce proteins the virus needs to exist.

    Unlike coryza, influenza expresses symptoms more severely, and usually lasts two weeks until one recovers who has the flu.

    Influenza, however, poses a danger to some with compromised immune systems, such as the chronically ill.

    So the risk is greater in such populations, along with women who may be pregnant during the flu season, residents of nursing homes or chronic care facilities.

    If unprotected by an effective influenza vaccination given to such patient populations, influenza has a greater ability to penetrate hosts and create complications.

    These complications may include deadly diseases, such as bacterial pneumonia or encephalitis.

    Symptoms of influenza usually start to express themselves symptomatically about two days or so after being infected with the virus.

    Over 10 percent of the population is infected with this virus every year- resulting in about 200,000 hospitalizations and nearly 40,000 deaths, according to the Center For Disease Control (CDC).

    Those who do survive an influenza infection allow others to obtain antibodies from them to develop other antibodies for future viral outbreaks.

    The antibodies are used to produce vaccines to prevent acquisition of the damaging effects of influenza.

    Yet this is only if the antibodies contained in the influenza vaccine are effective against the suspected particular influenza strains that are present during the influenza season.

    Specifically, it is usually what is known as strept pneumo bacteria that kill those due to an infection of these microbes due to being invaded by influenza, ultimately.

    This is the type of bacteria that typically infect a person suffering from influenza who may have compromised immune systems, as mentioned earlier.

    In these cases, the bacteria are allowed to thrive at a higher and more deadly rate.

    On average, it takes over a week for one to die after being infected by influenza that has the power to cause death in particular human populations.

    Pandemic flu outbreaks, such as the one that happened that was mentioned earlier was an influenza strain so powerful that it overkills the cells of its host.

    The influenza virus has this ability on occasion, and its efficacy is dependent on its mutations that have developed over time that make it more powerful than other influenza viruses.

    The flu vaccination is trivalent- meaning it contains three viral strains of suspected viruses for flu outbreaks during a particular winter season.

    The viral strains are determined by the World Health Organization, as well as the Centers for Disease Control, and other organizations.

    Yet one should keep in mind that these three strains of influenza may not even exist in a particular flu season.

    The vaccination is a guess, at best, yet is certainly better than the absence of a flu vaccination.

    Unfortunately, the influenza vaccine administered last flu season was believed to be largely ineffective due to unsuspected strains of the virus infecting others.

    Although about 140 million injections of this vaccine were administered, this proved to be pointless for preventative medicine for influenza during this season.

    The most recent flu season was fairly mild, according to the CDC.

    After giving the vaccination dose to one, it takes about 10 days for that person to build up the immunity for the disease of influenza.

    The months of October to December are recommended to receive this vaccine.

    And the vaccine is about 50 percent effective in offering protection from influenza, according to others, if one calculates the previous flu seasons with flu vaccinations.

    Vaccines are a catalyst for antibody production in humans, which protect them against the virus, if the influenza virus happens to present itself within them.

    The influenza vaccines can be given by injection or nasally.

    The flu season that is now occurring was supplied with 150 million vaccines in the United States.

    However, some studies have shown that this vaccine is rather ineffective based on incidences of the acquisition of the influenza virus by others, initial reports have indicated.

    The influenza season peaks between the months of January and March.

    The vaccine for this influenza season is manufactured by 6 different companies in preparation for this timeframe of the influenza season.

    Also, it takes manufacturers about 6 months to make and formulate the influenza vaccination.

    The influenza vaccine is produced every year according to which type of virus types that may be prevalent during a particular flu season.

    The presence of influenza can be widespread in certain states, yet not others. The vaccination is recommended to be administered to those who are at high risk, such as the chronically ill.

    Also, it is recommended that those under 18 years of age get the vaccine, as well as those people over the age of 50.

    Pregnant women should receive the immunization. Health care personnel are always encouraged to get a flu vaccine as well.

    Such populations of those recommended to receive the flu vaccination are those believed to need the protection the vaccine may offer the most.

    This is of concern, as influenza can progress rapidly into the more serious illnesses mentioned earlier that can lead to death.

    Anti-virals, on the other hand, decrease greatly the ability for viruses to reproduce once established in a human.

    That seems like it should be a focus during viral seasons instead of any vaccination that exist today regarding the disease of influenza.

    Yet, as with antibiotics, viruses can become resistant to anti-virals as well.

    Yet the strains chosen for the influenza vaccine contain what are speculated influenza viruses.

    So the vaccine is ineffective if a new and dominant influenza viral strain that possibly could cause a pandemic happens to be present during an influenza season.

    With the influenza virus, again it can have the ability to kill mammals, as well as birds, along with humans at times.

    The concern that there is an influenza strain that exists that has the ability to mutate.

    If this happens, the viruses have the ability to share genetic data between separate life forms as they, multiply within each one of them with ease.

    This is the case with what is known as the Avian Flu, as well as the Swine Flu.

    The most recent avian influenza virus was identified in China in 1997. Called the H5N1 virus subtype, it has the potential to be the next flu pandemic.

    The last Swine Flu outbreak occured in the United States during the mid 1970s.

    However, the virus responsible for the pandemic mentioned earlier was an avian influenza, which was called the H1N1 influenza virus.

    This virus, unlike the human influenza virus, has a longer incubation period- about 5 days.

    Also, H5N1 has the ability to mutate more rapidly, as well as replicate at a similar speed.

    Avian influenza viruses are highly pathogenic. No one fully understands the influenza virus and its rapid ability to mutate.

    This is because this particularly malicious virus is the result of two separate influenza viruses acquiring the same host at the same time.

    As a result of mutual sharing of genetic material between the two viruses, novel attributes are allowed to develop and create a H5N1 that obviously prove to be rather deadly.

    The H5N1 Avian influenza virus seems to have become progressively more pathogenic in the past decade, according to others.

    The letters H and N, by the way, stand for the antigens HA and NA-and are the letters of proteins that protrude from the viral shell.

    It is these proteins that mutate so often with the influenza virus, and which is why we continue to be infected with this virus.

    With the Avian Influenza existing with the H5N1 strain, millions of birds have been slaughtered due to the danger and unpredictability of this strain.

    The first recorded incidence of human-to-human transmission of the H5N1 virus was believed to be in Thailand in 2004.

    There have been outbreaks of Avian flu in about 10 or 20 countries in the world so far- with Indonesia appearing to be the worst.

    Migratory birds spread this influenza virus between continents.

    The pathogenic strength of the H5N1strain varies due to constant re-assortment or switching of genetic material between the viruses.

    This essentially creates hybrid modifications of what it was before this occurs due to this re-assortment that makes this virus much more virulent.

    So far, nearly a half a million people worldwide have been infected with this strain.

    Also, about half have died from the infection caused by this H5N1 influenza virus.

    Vaccinations are being developed and reformulated constantly at this time due to the pandemic threat of the H5N1 Influenza virus, and most recently, the swine flu virus.

    www.cdc.org/flu/weekly

    Dan Abshear

  51. anotherfakeid said,

    May 14, 2009 at 12:21 pm

    Comedy is all about timing. I’m sorry to say that if you have swine flu, you won’t cure it with elderberries: well not until September-ish when they will be out and about. Probably going to have to make do with the tried and tested remedy for colds and flu. Cap-full of whisky, lemon juice (only the freshest lemon now), honey (or if you are vegan, agave nectar), and hot water. Well won’t cure you but enough whisky will make everything seem alright. In fact, leave out everything else and just use the whisky. Probably get into trouble mixing whisky with something else anyway. Do vegans get swine flu?

  52. blue said,

    June 26, 2009 at 5:31 pm

    I have not read through all the replies, but here’s a thought:

    The effectiveness of any medicine is summed up like this.
    Total effectiveness = (positive trials results)% + placebo effect%

    If the media hype is positive, and sufficiently big, the placebo effect increases because people beleive that the stuff works.

    So after reading this article I have just made the stuff less effective :/

    Even with that, its still a great and informative article thanks. I thank you.