Effect Measure

The blogosphere (DemFromCT at DailyKos) and the main stream media (Alan Sipress at the Washington Post) brought us the two faces of the current flu pandemic. Like Janus, one took lessons from the present and past, the other looked worriedly to the future.

Dem’s piece on flu at DailyKos (a regular feature of the world’s biggest political blog) is superb. Most everyone who regularly reads about flu in the blogosphere (and it is a huge readership) knows that DemFromCT is the blog handle of an expert who has been writing about pandemic flu for years (as long or longer than we have and we are coming up on our 5th blogiversary), knows the landscape intimately from both the policy and scientific perspective, and is himself a practicing pediatric pulmonologist, so in his daily practice he is in the eye of the storm. With those qualifications you’d expert the best and that’s what you get. His post on Sunday, “Lessons Learned from the Pandemic” hits every nail on the head, and there are a lot of nails. He extracts 7 lessons and you should read his post in its entirety, but I’ll tease you with the first lesson:

[Lesson] 1. Expect the unexpected

No one saw an H1N1 pandemic coming. Moat of the planning was for a more severe H5N1. This had implications, because a less severe pandemic needed more flexibility in planning. Schools didn’t close, so school buildings could not be used for mass dispensing areas for vaccine and tamiflu or alternate care clinics (and school personnel were busy with their day jobs aqnd not available to help.) HHS and DHS figured out how to get tamiflu to hospitals but not to private pharmacies (how to you give pre-purchased free-to-the-public medicine to retail stores?) While tamiflu shortages didn’t materialize in the fall (spot shortages in children’s preparations were addressed with instructions to pharmacists to compound adult capsules into syrup), they were a problem in the spring. Flexible responses helped to the point where most of these issues were invisible to the public. (DemFromCT in DailyKos)

Everyone says flu is astoundingly unpredictable, but here Dem provides added comment on what that meant in practical terms for this pandemic. The rest is just as good. Read it.

And it’s just that potential for almost anything that forms the nucleus of the Washington Post’s Economics Editor, Alan Sipress. Sipress has been on the trail of pandemic flu since early 2004, following the ups and downs of what many of us thought was going to be the next pandemic, avian influenza (A/H5N1). When I say Sipress has been following it, I don’t mean passively. He has personnally visited the rural and urban incubators of a deadly flu strain (this is one case where the oft misused phrase of the main stream media, “deadly virus” is appropriate), a flu strain that hasn’t gone away (except from the headlines, crowded out by swine flu). It’s still out there bubbling away in a vast human and animal bioreactor that he describes in a WaPo op ed, Playing chicken with a nightmare flu. And now comes swine flu, a virus that seems unusually promiscuous, already transmitting in the wild from humans to animals (and originally from animals to humans). We’re giving it to livestock (pigs), poultry (turkeys) and companion animals (ferrets and cats, so far, but the list will probably extend). And of course we are giving it to each other. It doesn’t have the horrific virulence of bird flu (which kills half or more of its human victims) but it’s much more transmissible. Given the ability of influenza virus to mix and match genetic elements from one strain to the next, Sipress documents the worry of flu scientists that we’ll get the worst of both worlds: an extraorindarily virulent bird flu like virus that transmits as well as swine flu. Given that both viruses can infect the same animals (birds, pigs, humans, ferrets and who knows what else), the potential for co-infection raises the fear of a genetic witches brew:

So far, scientists haven’t found proof that swine and bird flu are about to merge and spawn a deadlier virus. But the prospect is so chilling that health officials have been warning about it since earlier this year. Margaret Chan, director general of the World Health Organization, urged public health experts not to take their eyes off H5N1 bird flu even as H1N1 swine flu was sweeping the globe this spring. “No one can say how this avian virus will behave when pressured by large numbers of people infected with the new H1N1 virus,” she told an assembly of the world’s top health officials in May. Separately, she appealed to Asian health ministers: “Do not drop the ball on monitoring H5N1.” (Alan Sipress, WaPo)

It’s possible this nightmare scenario is impossible. Or it could be likely or even inevitable. Nothing about flu is a certainty at this stage of our knowledge. We don’t know enough about how the genetic elements in the influenza virus have to work together as a team to be able to predict whether this can or can’t happen, or if it can, how likely it is. But it would be foolish for Janus to look neither way. Blinders are not acceptable attire.

Janus is the Roman God of beginnings and endings. Only time will tell how many meanings this has for the swine flu/bird flu story.

Comments

  1. #1 Don S
    November 17, 2009

    By the end of the season it is likely that billions of humans will have been infected with H1N1 and untold numbers of other creatures. How many of those individual humans other creatures will happen to also be infected with H5N1 at the same time? How many cells among those species will contain both both reproducing H1N1 and H5N1′s at the same time? I could not even start the calculation but the number is quite large. Reassortments WILL occur with enough swings at bat and there will be plenty of swings at bat. The issue is what will be the nature of the reassortments.

    Some won’t be able to spread well, some will spread well but be attenuated, and some can be contagious and severe. Maybe all of them, maybe all at the same time.

    One small comforting thought – the deadlier version is really at a competitive disadvantage. If it kills its host cells quickly it cannot reproduce. If it sickens its host too much then its host doesn’t move around and spread it. If it kills the host quickly then even less so. If reassortments are possible then the milder form is at an evolutionary advantage.

    Small comfort that thought but something.

  2. #2 Sean Rushforth
    November 17, 2009

    A new strain of swine flu that is resistant to anti-viral drugs has been discovered in the UK for the first time.

  3. #3 DemFromCT
    November 17, 2009

    Don, because of that, other questions obscured by anti-vax noise need to be asked.

    The rest of the world uses adjuvants. The US does not. Should we? Are they safe and tested? Would that allow for “vax for all”? Why does Germany give unadjuvanted vax to politicans and adjuvant to the population?

    If we introduced a new technology such as recombinant vaccine (brew in a vat without eggs, ready in 6 weeks, make as much as you want), would the public accept it, mid-pandemic?

    Should we make H5N1 and inoculate people now? That flu has a 63% mortality.

    That’s in addition to reasonable questions that have answers (is this current vax safe (yes, decades long track record)), was it rushed (no, it always takes six months and the virus was identified in April), should I give it to my kids if they were sick in spring (yes, because many things look like flu), etc.)

  4. #4 DemFromCT
    November 17, 2009

    Sean, see WHO :

    17 November 2009 — Preliminary tests reveal no significant changes in the pandemic (H1N1) 2009 virus based on investigations of samples taken from patients in Ukraine. Analyses are being performed by two WHO influenza collaborating centres as part of the global influenza surveillance network.

  5. #5 DemFromCT
    November 17, 2009

    Oops, posted too soon… so, in regard to the occasional resistance, not widespread at this time.

    One of the very interesting questions to be addressed is whether large scale use of tamiflu has been beneficial or responsible for more resistance. That’s within the larger question of which of the different responses from different countries was most effective, or was it all luck of the draw?

  6. #6 military wife
    November 17, 2009

    Should we make H5N1 and inoculate people now? That flu has a 63% mortality.

    I’m not sure why we haven’t, really. It’s been 4 years since the first big outbreak in Hong Kong/China, right? It doesn’t take 4 years to create a new flu vaccine, obviously.

  7. #7 M. Randolph Kruger
    November 17, 2009

    Mil Wife….

    It does in the case of H5…. Unlike H1N1 entirely which is made from special eggs. H5 kills those eggs. The best process so far has been to take the virus, genetically engineer it to remove the part that kills the egg. Make the general vax from the newly inserted nearly non lethal virus, then put the part back in as it now has a fighting chance to beat it.

    Webster did it here in Memphis and he is sitting on it because his trials showed the primates would live from it but many would be invalided for months ….Just from the vax. The only other way is molecular level vax… That one Dem or Revere would have to tell you about and that technology is years away. Boutique bug juice….. made specifically for the bug youse got.

    Webster is an acquaintance, he said that this stuff would make you very, very sick in its own right but you would likely survive. It has never gotten to the human stage of testing. I dont know whether it qualifies as having live attenuated virus because its engineered… But it would seem that it does at some level of criteria for that.

  8. #8 JJackson
    November 17, 2009

    Military wife & Randy

    You are missing the point the problem with an H5N1 vax is there is no human H5N1 and it may never come. If it does a vax based on any of the existing clades may not be of any use. The solution is to shift away from egg based production as fast as possible. No government should give any funding – or orders – to any company that has not got a clear plan to transition all of their production to a system with a much faster turn around than the old egg based technology. Production systems for seasonal flu vaccine must be able to produce volume quickly and be scalable for pandemic years. The production system needs to be shown to be safe now so trials and approvals for new strains are quick. Baxter and others that have invested in cell based production facilities that, theoretically, are quick to first vial, and more scalable, are novel and slow through the regulatory phase.
    Frankly we seem to have got lucky so far but this is a wake-up call and the regretful loss of life that is about to occur in the temperate northern hemisphere countries should be used to change systems for next time- and there will be a next time.

  9. #9 Dave
    November 17, 2009

    On Dem’s comment on resistance to tamiflu. The rate of use of tamiflu has previously not been a driver in resistance.
    Because of tamiflu’s mechanism of action, there was some thought that resistant strains would lose their ability to be transmitted. In 2005, Moscona noted “To date, no documented transmission of an oseltamivir-resistant virus has occurred between people.”

    Last year, evolution proved this wrong and suddenly 99% of the strains were resistant.

    A superb paper on the evolution of pathogens is Grenfell et al., Science 303:327-332, 2004.

  10. #10 Eric
    November 17, 2009

    Good post. Our social system is really screwed up as far as risk assessment goes. We’ve optimized everything for such short time horizons (the next fiscal quarter) that it is almost impossible to make needed investments in reducing risks (in public health, emergency management, or even financial) that are remote in the short term, but less remote in your lifetime. I see this over and over in many government and business contexts.

    This is particularly bad for the (hopefully) remote prospect of Swine Flu mixing with Bird Flu. The impact of this won’t be worse just in linear terms, but there are many positive feedbacks (secondary impacts) which could lead to an exponentially worse situation. It reminds of Katrina. A Category 4 storm hitting New Orleans is much much worse than a Category 3 storm, since there are so many tipping points and thresholds that compound damage once the scale of the disaster goes being a certain level.

    What is the probability distribution like for pandemics in terms of severity (high virulence, highly transmissible)? Is something that kills 10-30% of the population an event that happens every thousand years or so (Black Death, Plague of Justinian, etc.)? Does this distribution look like a Power law (as does the severity of earthquakes, asteroid strikes, volcanism, etc.)?

  11. #11 Eric
    November 17, 2009

    Answered my own question. It looks like their may be power-law distributions to the severity of flu (and other transmissible diseases).

    This is a great discussion http://www.practicalethicsnews.com/practicalethics/2009/05/the-flu-paradox-is-the-who-focusing-too-little-on-flu.html about probabilities and under-investment in risk reduction.

  12. #12 cpg
    November 17, 2009

    WEhen you mention antiviral resisitance. Dont put Relenza in there. It’s still good and has shown no signs of becoming resistant.

  13. #13 Paula
    November 17, 2009

    Thanks for this post, Reveres. And thanks, cpg, for the point re Relenza. What is the situation re intravenous, if oseltamivir resistant 2009h1n1 develops? Given the otc Tamiflu now in 1 Scandinavian country (sorry–I forget which) and what may happen in, especially, (unless this is just a US viewpoint of that country) Afghanistan, that seems a serious possibility soon. (So should persons unlikely to get vaccine before such resistance may occur, go out and do a swine-flu party?!)

  14. #14 Phila
    November 17, 2009

    Unfortunately, right after reading DemFromCT’s excellent post, I stumbled on this nonsense.

    Here’s hoping DemFromCT reaches more people.

  15. #15 cpg
    November 17, 2009

    Paula

    If Tamiflu reistance occurs then IV perimivir will likely be resistant. SEE CDC article. IV relenza will still work under this mutation. See Q21

    http://www.cdc.gov/h1n1flu/EUA/pdf/peramivir_qa.pdf

    http://www.dailymail.co.uk/health/article-1228189/Miracle-cure-swine-flu-girl-4-saved-brink-death.html

    PS GSK arent making any IV relenza. Just using the left over trail samples. No money in developing it.

  16. #16 Phila
    November 17, 2009

    Sorry for the broken link.

    On second thought, it’s just as well…no sense giving this stuff more traffic.

  17. #17 Paula
    November 17, 2009

    Re 15–thanks, cpg. I did know some of this but certainly had no idea that GSK’s not making (nontrial) IV relenza. So isn’t it sort of crazy not to be funding the latter, or emergency crash-funding other IV antivirals? Or are the monies needed for surveillance drones?

  18. #18 cpg
    November 18, 2009

    More money in vaccines that will likely have to replaced regularly. I think effective antivirals are the answer to all flus. Both as preventive and treatment. I don’t believe Tamiflu is a effective antiviral because of its engineering. H274K resistance is becoming more widespread by the day. Hell its 99.9% useless againt the previous H1N1 strain today. Matter of time.

    GSKs IV Zanamivir could of been saving hundreds of lives today but they dont give a rats.Show me the money !!!

  19. #19 cpg
    November 18, 2009

    What a coincidence. GSK have just today launched Phase two trials with IV relenza. Look at the oversight authorities. all the major countries. They will fast track this big time and supply that recent US order for 10000 doses under emergency protocols. Lives will now be saved. I’m over the moon.

    http://www.gsk-clinicalstudyregister.com/protocol_detail.jsp;jsessionid=77272DB1B85092E862A100B0FF5420CE?protocolId=113678&studyId=29102&compound=Influenza+B+Virus&type=Medical+Condition&letterrange=G-K

  20. #20 Paula
    November 20, 2009

    Good timing, I guess, cpg (re 19). Just read a couple of news reports re Tamiflu-resistant clusters, possibly direct-transmitted, in Wales and NC hospitals. These may have been contained, but what–if anything–do they indicate re further/extant mutations in this regard?

  21. #21 Pierce R. Butler
    November 21, 2009

    DemFromCT @ # 3: Why does Germany give unadjuvanted vax to politicans and adjuvant to the population?

    What’s German for WTF?

    Does anybody here have more on that one?