Effect Measure

This year’s flu season

This year’s flu season isn’t over, but it’s almost over, and it was fairly typical and much better than last year, which was nasty. It began at the end of September but didn’t take off until early January, peaking in mid Februrary. New cases are still appearing but much less frequently and they are mainly influenza B, which tends to be milder than influenza A. Most of flu/A this year was also of the milder H1N1 sort, which probably contributed to the better outcomes. Here’s where we are (source for all charts here):

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Comparing this year with previous years shows it to be relatively typical of recent mild flu seasons and also shows how bad last year was:

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If we look at it by age group we see again that this was much like three of the past four years except in the older age groups, where it was somewhat better than any of them:

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This year’s flu vaccine got both the circulating H1N1 and H3N2 strains right (A/Brisbane) but missed flu/B, only 20% of which were vaccine strain (B/Yamagata) while the other 80% were B/Florida. Based on current surveillance data, next year’s vaccine will be unchanged for flu/A (A/Brisbane) but changed for flu/B (B/Victoria). Let’s hope they get it right. Almost all of the predominant H1N1 was oseltamivir (Tamiflu) resistant but none of the H3N2 were resistant. None of the H1N1 or H3N2 were resistant to the zanamivir (Relenza). The oseltamivir flu/A picture was reversed for the older adamantane antivirals (which work by a different mechanism). Almost all of the H1N1 and none of the H3N2 were sensitive. No flu/A virus was simultaneously resistant to oseltamivir and an adamantane antiviral. All flu/B viruses were sensitive to both oseltamivir and zanamivir (the adamantanes are not effective for flu/B).

Did influenza vaccination make a difference? CDC certainly thinks so. Since seasons where A/H1N1 and flu/B are the predominant circulating viruses tend to be milder, it’s not possible to say that getting the flu/A strains right is what made this season milder than last year’s flu/A mismatch. Pediatric flu mortality has also been better this year (45 deaths):

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But of the 36 deaths in ages for whom vaccination was recommended (older than 6 months), 5 had been vaccinated, although the data are provisional. No data are given for vaccination rates for comparison. It’s clear that if vaccination is protective, it is not completely so. Bacterial co-infection (primarily with Staph) was mostly in older children (over age 10).

The workings of this enigmatic virus continue to defy us — and sicken and kill us on a regular basis. Meanwhile A/H5N1 is still out there, mainly in poultry and wild birds but continuing to infect and kill humans. Each flu season we wait for the other shoe to drop. So far it wasn’t the year, [although a pandemic can begin at any time of year]. If we are lucky, it won’t ever happen. But better to be prepared than to trust to luck. The cost of being unlucky and unprepared is frightful.

Comments

  1. #1 Path Forward
    April 17, 2009

    In your excellent flu season summary, you wrote:

    Each flu season we wait for the other shoe to drop. So far this wasn’t the year.

    Regarding a pandemic (as opposed to “merely” a severe flu season), that implies that we stop waiting for the other shoe to drop in between flu seasons! I don’t think you meant that.

    An influenza pandemic can begin, and spread, starting anywhere in the world, at any time during the year.

    And of course many of us who read your blog are not waiting at all — we are preparing and trying to stimulate preparedness.

    Again, an excellent summary, Revere.

  2. #2 revere
    April 17, 2009

    You are right. I thought about this and edited it to read “so far” but you point out I didn’t go far enough. I added an additional edit.

  3. #3 Racter
    April 17, 2009

    I saw a pretty significant discrepancy through the season between the level of activity in various states as it was reported on the CDC site and at the Google Flu Trends site. I know the CDC’s approach is rather more scientific, but it’s always bugged me knowing that the surveillance data I’m looking at are a couple of weeks out of date. Besides, not all of the CDC surveillance methods are that much more scientific; “ILI outpatient visits” is (by definition) a net which is going to draw a lot of the very same bycatch. I’m not yet sure how reliable to consider this new tool to be, but it’s kinda fun, and it gives me something to gnaw on while I’m waiting for the weekly CDC update on Fridays.

  4. #4 DemfromCT
    April 17, 2009

    hey, Racter, if you want fun tools, try this:

    http://www.flutweet.com/

    Like google flu trends, it uses whatever people are talking about (no accounting for pandflu chatter, though.)

    Also, CDC’s recommendations on antivirals are ahead of availability of “other than tamiflu”, as relenza and rimantidine can be hard to find.

  5. #5 Racter
    April 17, 2009

    “no accounting for pandflu chatter, though”

    Ain’t it the truth! Twitter as an epidemiology tool is a fun idea, but unfortunately, “Global flu activity” doesn’t contain much information I can apply on a day-by-day basis. What I want to know is what’s going on in my neighborhood. For this purpose, even the CDC’s distinction between “Regional” and “Widespread” is utterly useless; I take it to mean: “widespread in some regions” — but because they don’t specifiy which regions, the only safe assumption to make is that it means essentially the same thing as “widespread”.

    I’m not clear on whether sensitivity to Rimantadine implies sensitivity to Amantadine. I have some Amantadine (though it’s getting a bit old), as well as some Tamiflu, and my default plan has been to go with both. That’s gotta be some kind of a buzz in that deal, at least. But maybe I’d be better off trying to aquire a little Rimantadine to add to my stash?

  6. #6 Jeff D
    April 17, 2009

    I’m a lawyer and science buff, not a doctor, but despite my flu shot last October, I caught what I guess were two significantly different respiratory viruses that presented identical symptoms (sore throat, followed quickly by post-nasal drip, bronchial congestion, and a serious cough that lasted more than a week). Only I caught these two viruses in February and April, with about a month of no symptoms in between. I know more than a dozen colleagues in my office who caught the same bug, very easily. If it was a flu virus, maybe it was the same virus for me each time, and maybe the virus went to Florida in March for spring break.

  7. #7 revere
    April 17, 2009

    JeffD: Alas there are many respoiratory viruses besides flu (see
    this post for an example. You and colleagues probably had one of the many candidates.

  8. #8 Tom DVM
    April 17, 2009

    “But of the 36 deaths in ages for whom vaccination was recommended (older than 6 months), 5 had been vaccinated, although the data are provisional.”

    According to the way I was taught, this data would set off alarm bells…once again this does not indicate that vaccine works.

  9. #9 Ren
    April 17, 2009

    I’m the influenza surveillance epidemiologist for a state health department. As far as being two weeks behind Google Flu Trends, we’re not. The reporting by CDC is, but at the state level, we’re not. (My counterparts in all the states and I are improving our communications, so we know what is going on all over.)

    As for the case definitions, they are the best that we can use to describe the flu activity. People always get confused and think that “widespread” equals “pretty bad”. Our state is divided into five regions, and “widespread” flu activity means that we are seeing flu activity above baselines in three or more regions. “Regional” means that only two regions are being affected, and “Local” means that one region is being affected. “Sporadic” means that flu activity is not above baseline, but positive flu lab results are coming in and/or we’ve detected an outbreak at an institution.

    Like Medicine, Epidemiology is much more of an art than a science… Though we use math. :-)

  10. #10 Path Forward
    April 18, 2009

    Jeff D wrote that he had two episodes of:

    sore throat, followed quickly by post-nasal drip, bronchial congestion, and a serious cough that lasted more than a week

    CDC states that flu

    usually start[s] suddenly and may include the following symptoms:

    * Fever (usually high)
    * Headache
    * Tiredness (can be extreme)
    * Cough
    * Sore throat
    * Runny or stuffy nose
    * Body aches
    * Diarrhea and vomiting (more common among children than adults)

    Having these symptoms does not always mean that you have the flu. Many different illnesses, including the common cold, can have similar symptoms.

    Hallmarks of many or most flu cases include fever, body aches, and severe exhaustion — people often say they “feel like they’ve been hit by a truck,” although there are milder cases of the flu.

    Without a test, it is hard to know if Jeff D had two cases of the flu this season or “just” two other respiratory infections (not to downplay the misery of a serious long-lasting cough).

    But Jeff D does present us with a good example of a well-informed, vaccinated person wondering if he did, indeed, catch the flu despite being vaccinated.

    The vaccine is thought to reduce the chance of getting the flu by 70 to 90% in healthy adults, when the vaccine match is good. So overall, this year the vaccine should have been a bit less effective than that, because of the mismatch with one of the two circulating Influenza B’s.

    Lots of other nasty bugs out there!

  11. #11 revere
    April 18, 2009

    Tom: Weren’t you taught that you would need to know the flu rate in comparable vaccinated and unvaccinated to make that judgment?

  12. #12 Tom DVM
    April 18, 2009

    Revere.

    It is my hypothesis that if vaccine does not work against seasonal influenza, it will be useless in the face of a pandemic…

    …and in fact it will be worse than useless as there is nothing more dangerous than a partially effective vaccine.

    For instance, let’s say that we vaccinate all healthcare workers unknowingly with partially effective vaccine.

    Human nature is such that protected healthcare workers may become complacent. So they do not wear masks and gloves when they should etc. etc.

    They then become infected but more importantly probably become:

    a) carriers,acting as a wick spreading the virus into the community. accelerating the pandemic (surge capacity) and increasing infection efficiency.

    b) you may in addition to carriers, lose a large percentage of your healthcare workers to active infection in the initial stages of the pandemic.

    c) you may greatly increase the porportion of Gullian-Barre syndrome cases as well…because this syndrome is the body attacking itself by an inappropriate immune response..and by definition, a partial immune response may prime you for just this eventuallity.

    In fact, we are currently watching the ‘train-wreck’ caused by partially effective vaccines in poultry and probably pigs etc. in Asia at the moment…so the sign post is there if we are willing to take the time to read it.

    So now we have 5 of 36 dead children vaccinated. To me this clearly indicates poor vaccine although one would never really know at this point in time.

    The porportion of those vaccinated is way-way too high…and I would think when this is extrapolated through probabilities, serious questions as to effectiveness would logically follow.

    So then the question becomes, do we want to prove the existing technologies effectiveness conclusively or not?

    I would think, given the limited financial etc, resources, the answer would be Yes…

    …and although it would be reasonably straightforward to set-up a conclusive study by following the natural choice of healthcare workers (a pathway followed for some of the best study results of the last quarter century) , it seems that we do not have the will…

    …all it seems we do have at the moment is blind faith.

  13. #13 revere
    April 18, 2009

    Tom: My problem with you is that you do have a hypothesis and evidence doesn’t seem to matter to you:

    So now we have 5 of 36 dead children vaccinated. To me this clearly indicates poor vaccine although one would never really know at this point in time.

    You now have it right. Before you did claim to know.

    …and although it would be reasonably straightforward to set-up a conclusive study by following the natural choice of healthcare workers (a pathway followed for some of the best study results of the last quarter century) , it seems that we do not have the will…

    I don’t know who taught you to study things this way, but you should get your money back. Best study results of the last quarter century? Name one. If HCW don’t wash their hands, does that mean that washing hands isn’t of value? If dotors smoke, does that mean smoking is OK?

    You have a belief. That’s fine. But don’t talk as if it is based on evidence. No one has the data at this point, and while you may think such evidence is easy to secure, as someone whose profession it is to gather and interpret such evidence, I can tell you that you are dead wrong.

    You also believe, on the basis of your own field experience with farm animals, that prednisolone will save people with avian flu. The field experience so far of clinicians is that steroids don’t help and may be harmful. That doesn’t seem to matter to you. You perseverate in saying it over and over again. You don’t care about evidence. What you believe is what you believe.

  14. #14 Tom DVM
    April 18, 2009

    Revere.

    You are certainly entitled to your opinion.

    If you have any studies that prove irrefutably that seasonal influenza works (at all) outside the lab…studies based on acute and convalescent blood testing…I would very much appreciate it if you presented it in a logical manner…so that we all can discuss it.

  15. #15 Lea
    April 18, 2009

    Actually revere I appreciate Tom DVM’s responses, especially since he’s a retired doctor of veterinary medicine. And time and time again I’ve witnessed him extend a civil and kind hand to you, yet you rarely, if ever, do the same.

    What I’m curious about is why, as it appears to me to be so, do you dislike him so much? “Health discussion and argument”, those are four words found at the top of this blog’s page. Argument yes, it happens often here but come on, you are nearly cruel everytime with your response to Tom DVM.

  16. #16 revere
    April 18, 2009

    Lea: I don’t dislike him in the least. On the contrary. I like him quite a bit. My responses here are rarely personally motivated (I say “rarely” because I am human and lapse at times). But this site is about science and Tom persistently pushes two ideas for which he has no evidence: that flu vaccines don’t work (we are lacking good data on efficacy for certain groups so neither of us knows for sure); and his claim that prednisolone is the only effective therapy for avian flu. Neither of these are trivial matters and if you are going to make claims about them here — over and over — you need to have better evidence than that you believe it. This site is read by thousands of people and some may take actions on the basis of what they read here, including things I write. So there is an obligation to call him (or anyone or me) on sweeping claims. Tom has commented here on many things and I believe those are the only two where I push back hard. I do it because he deserves to get hammered when he says some of the things he says. I’ll say it again. This site is mainly about science, not about winning an argument or about personalities. Tom does understand that, and you need to also. Science may seem harsh or impersonal to you, but it’s the way we operate. With evidence.

  17. #17 Tom DVM
    April 18, 2009

    Thanks Lea.

    I think one thing we could agree on is that the results are mixed on seasonal influenza vaccine efficacy.

    Some screening studies hint it works. Some screening studies hint it doesn’t. The fact is that neither of these studies has adequate sensitivity and none of them would be accepted back in the 1980′s, let alone pre-1980.

    I don’t remember you providing any evidence to back up your claim that these vaccines are effective…and the tie must go to the runner…if you are right then nothing is lost. If I am right than everything is lost.

    The losses with seasonal influenza are relatively low. The potential losses from an H5N1 pandemic are enormous. We can’t afford to spend limited resources only on antivirals that don’t work and vaccines that won’t work.

    I could make the argument that the reason H5N1 has evolved to the extent it has is primarily because of vaccines in Chinese poultry for the last seven years.

    Partially effective vaccines drive the virus underground (subclinical) where it can’t be detected but allow silent accentuated passages in individual poultry that drive mutation one way, then another…and then every which way…which appears to be exactly what is going on. Partially effective seasonal influenza vaccines are also probably driving mutation as well.

    In veterinary medicine, this is an ongoing argument. There are those that favour test and slaughter…and there are those that favour vaccination. In my opinion, you can’t eradicate a disease of this type with vaccine and the results in China speak for themselves.

    As far as prednisolone goes, by the way an unrelated topic to this thread, I have made the argument several times.

    The fault is not with the drug…the fault is the way in which it is being used. If those with Acute infections are dying of ‘shock’ then there is only one anti-shock option at the moment…and a trusted option whose effets have been well known for more than fifty years.

    Secondly, the drug is cheap and avaliable in oral-tablet form so that it could be used in a pandemic at home under the advice of a healthcare worker…unlike proprietary solutions that leave us at the mercy of pharmaceutical companies…especially since they often don’t turn out to be quite as effective as the internal research indicates.

    If you treat the patient with H5N1 before the ‘cytokine storm’ is fully active then you can head it off…which at least hypothetically would be an option in a pandemic.

    Of course, the truth is that we will have only placebos to treat pandemic influenza because existing stores of medications will be exhausted in the first few weeks and as Dr. Osterholm has explained, the raw materials come from off shore.

    The first thing they might try with the prednisolone and H5N1 is go to intramuscular or subcutaneous treatments because IV treatments for septic type shock does not work in my experience.

    Secondly, the reason the SARS treatments had limited success was because they were using massive off label doses far past the 5-7 day window. At that pont, the law of diminishing returns takes over and you really do have significant, life threatening immunosuppression and other complications from continued steroid use.

    It either works or it doesn’t and you only get one shot at it.

    I have also repeatedly stated that if an effective alternative is developed through new research or old drugs such as statins that I am all for it instead of prednisolone.

    That effective alternative also applies to vaccines…the current technology doesn’t work and won’t work anyway because the humans will infect the laying hens and there will be no eggs anyway to produce the antiquated and largely useless existing vaccine.

    Again…if you would provide an overview of the existing literature-studies that prove otherwise then I would appreciate it.

    So far all I have seen is screening studies based on a doctors visual examination etc….and therefore, a lot of food poisoning is misdiagnosed as influenza…and as you said earlier, there are a lot of respiratory viruses that can be confused with influenza.

    So the way I was trained is that you need acute and convalescent blood samples indicating a rising titre to prove that the animal was infected….so that is probably the studies we need.

    As I said before, laboratory vaccine results don’t mean alot because they come from funding companies that stand to benefit…the laboratory will not share antigen so that the results can be repeated (a basic precept of science) and as I have said, they challenge the vaccinated animal with the exact virus they produced the vaccine with…which doesn’t allow for antigenic drift that occurs naturally.

    So do we have studies of this quality.

    If not all we have to do is get the healthcare workers who choose to be vaccinated and compare them to a similar sample of healthcare workers who choose not to be vaccinated and balance for risk.

    We could have the results in six months and have the answer that we need.

    This is an easy study to work with…why hasn’t it been done?

    Thanks Revere as always. I look forward to any studies you can point me to from the archives on vaccine studies and any that you might provide in the future.

    Since at this point all influenza medication is based on faith…I don’t why your faith is any better or worse than mine.

    And there has been one particular study of healthcare workers over several decades that has without doubt been the nicest piece of research done in the past twenty years. I can’t come up with the name…it is well known maybe someone else can provide it.

  18. #18 Path Forward
    April 18, 2009

    Re:

    “So now we have 5 of 36 dead children vaccinated. To me this clearly indicates poor vaccine although one would never really know at this point in time.

    Until we know:
    1. which influenza strain was involved in the 5 vaccinated children who died, and
    2. whether each of those children was fully vaccinated (i.e. had two flu shots if it was the child’s first season ever being vaccinated),
    we cannot even begin to relate the effect of vaccination on these children’s clinical course.

    If a vaccinated child died of Influenza B from the Victoria lineage (about 80% of this year’s Influenza B, and not included in the vaccine), or if a vaccinated child died but had only ever had one flu shot, that child would not be considered fully vaccinated against this season’s flu.

  19. #19 Tom DVM
    April 18, 2009

    Sorry, one other thing.

    “and his claim that prednisolone is the only effective therapy for avian flu.”

    This is an incorrect statement.

    The treatment protocol would include early steroid-prednisolone intervention with:

    1) concurrent prophylactic broadspectrum antibiotics that would continue for more a week to ten days if necessary. Not all antibiotics are created equal and some classes would work better than others.

    2) oral electrolytes are very important in situations where healthcare may not be an option. Balanced electrolytes,started as early as possible (concurrently with the above treatments) would attempt to head off dehydration in part due to cardiovascular compromise.

    3) Concurrent use of non- steroidal anti-fever drugs such as advil or tylenol such that hopefully, you will be weaned off the steroids by day four or five and be maintained on the non-steroidal alternative.

    This protocol is specifically for a pandemic with no healthcare avaliable at hospitals and under conditions that the person who gets sick could be assumed to have pandemic influenza in the early stages.

    These treatments could be distributed to the general public for probably no more than 20 or 30 dollars and could be stockpiled for future use as the stale dates would be long.

    That is quite a way from…”and his claim that prednisolone is the only effective therapy for avian flu.”

    Thanks.

  20. #20 Tom DVM
    April 18, 2009

    Path Forward.

    I agree…but many of the problems with this antiquated technology form the 1930′s is that there are time delays etc. that allow the virus to mutate away from the vaccine.

    So all of these problems as in time delay for production as well as guessing a year prior to the vaccine production because it takes so long means that the vaccine technology is ineffective for the relative speed of virus dissemination and drift today.

    There are new technologies being studies and in my opinon, our only hope is that a new technology that can be produced in a month rather than six months becomes avaliable…that would go a long way to improve results.

    The unfortunate point is that H5N1 is out of control. It has far passed the threshold of genetic material avaliable to interact with other genetic material that is out there from seasonal and other avian strains. It has widened it’s geographical reach and is revisiting previously affected areas as it turns out several times…which is from a veterinary point of view one of the worst signs…

    …and last but not least, it is now known that it can ciruclate in other mammals without killing them…the last missing link to allow continued passage and opportunity to evolve towards humans.

    The pigs are an expected problem. The raccoons are a major problem because they are a connection between the air-shoreline interface and through the forests-wetlands to barns.

    If it is in the Raccons then it is most likely in rats around barns and mice in houses…and at that point…there is nothing stopping the evolution towards mammals…and since other mammals are not killed…then we appear to be the endhost.

    So we had better not become to complacent and get on with planning and stockpiling medications even if we at some point in the future have to throw them out.

  21. #21 Lea
    April 19, 2009

    that flu vaccines don’t work … and his claim that prednisolone is the only effective therapy for avian flu.

    Well revere, since I cannot tolerate the flu vaccine to begin with then I am greatly interested in secondary treatments. Secondary, from my limited medical knowledge, is the stuff that actually kills the host, NOT the flu its self.

    This site is read by thousands of people and some may take actions on the basis of what they read here, including things I write.

    Then you better include a disclaimer revere as it sounds like you’re paranoid.
    You seem to forget that most who read this site are adults who can make solid and credible decisions for themselves. In other words, I know what my body does and does not tolerate. For me I prefer to deal with the secondary causes of death associated with H5N1 as a means to surviving the curse.

    And you’re welcome Tom DVM, your input is interesting and valuable to me.

  22. #22 victoria
    April 19, 2009

    Ditto Lea.

    Tom DVM,

    Thank you for your logical, common sense approach to this topic. You get no argument from me. Each month that goes by seems to add weight to your argument. I too, choose not to be complacent,

  23. #23 Tom DVM
    April 19, 2009

    Thanks Victoria, Thanks Lea

    One last thing.

    When you are confronted by skeptics and are accused of fear-mongering…there is one counter argument that is irrefutable.

    There has never been a virus or pathogen of any kine, in known history, that has had the real ability to infect and kill all species of animals except for reptiles.

    We as humans face many kinds of daily threats, calculated risks…sometimes we are lucky and sometimes the ‘fickle finger of fate’ gets us…

    …but H5N1 truly represents a rare beast…the equivalent of a biological asteroid. Now, its never going to knock humans off the planet like the real asteroid in Mexico did to the dinosaurs…but it does have the real ability to remove 15% of the worlds population in two years.

    The other thing is the mass of genetic diversity that H5N1 has to interact with. We have had changes in seasonal influenza as well as a number of avian influenza’s that have emerged in the past ten short years…

    …the point being that there is a massive genetic resource avaliable today that wasn’t ten years ago…and H5N1 is a massive genetic raw material in itself as it now has several subtypes in all regions of the world probably including North and South America…

    …the bottom line is that it is a pretty safe bet that history will repeat more than likely repeat itself in the next little while…

    …We probably aren’t going to have one pandemic but will probably have several pandemics in the next thirty years…of course they all won’t present the unique threat of H5N1.

    The good news is that we have the tools avaliable to make pandemic influenza a ‘calculated risk’. All we have to do is ‘completely understand’ the threat and act accordingly.

    Thanks Revere as always!!

  24. #24 revere
    April 19, 2009

    Tom: It isn’t like this is the first time you and I have been on this Merry-Go-Round. Each time I point out that your statements aren’t borne up by the medical literature, that you have no evidence for your assertions and that your claims about evidence are incorrect. You seem impervious, which is why I get exasperated. The literature on vaccine efficacy is fairly large and it isn’t hard to find cites, but for your convenience here’s a recent one that reviews the literature on the kind of randomized control trials you say have never been done (in addition, your use of the term “screening studies” is not comprehensible in this context):

    Rhorer J, Ambrose CS, Dickinson S, Hamilton H, Oleka NA, Malinoski FJ, Wittes J.Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials.Vaccine. 2009 Feb 11;27(7):1101-10.

    Regarding your last comment, I have never accused you of fear mongering, so I assume you are just making a general observation. That aside, I have no idea what you are getting at when you talk about diseases that affect every species. H5N1 doesn’t do that either. As for it being unique — hardly. Plague is estimated to have wiped out a third of the population of Europe in the 14th century. Many isolated populations have been virtually completely wiped out by organisms to which they had little immunity. The less isolated, the less likely this is to happen. You are extremely worried about the potential of H5N1. I agree. Many of us are. That means it is even more important to be clear eyed and keep speculation under control. Regarding steroid use, are you suggesting we stockpile prednisolone for the world’s population? This suggestion isn’t too different in spirit from what Dave Fedson suggests for generics like statins or the glitazones, except that he has a substantial body of science to back up his suggestion and you have only the fact that you think it works because you found it helpful in farm animals, none of which were infected with H5N1. Clinical experience with the steroid blunderbuss has been disappointing, perhaps for reasons suggested in one of our recent posts on TipDC cells.

    Lea: I have no idea what your reference to paranoia means. I take my obligations here seriously, however. And this isn’t about you, your feelings, whether you agree with something politically or whether vaccine agrees with your body. It’s about science. You have a tendency to try to counter statements you disagree with, for whatever reasons, by praising someone else who disagrees with us on any subject, for whatever reasons. It would be good, but probably too much to expect, that if you disagree about something you would say why.

    Meanwhile, I continue to offer the comment thread as a platform for others to say pretty much what they want. I am unusual amongst science bloggers in that regard. But if you wish to take advantage of the venue, you have to expect push back from me or others when indicated.

  25. #25 Tom DVM
    April 19, 2009

    Revere.

    Thanks you for the referene.

    Does the general public recieve live attenuated vaccine?

    How about the vaccine in general use today.

  26. #26 Tom DVM
    April 19, 2009

    Also, is that study avaliable.

    I seem to only be able to read the abstract.

    Thanks.

  27. #27 revere
    April 19, 2009

    Tom: I’ll try to get you a .pdf when I get to the office on Tues. Yes, the public gets live vaccine (e.g., FluMist), but the cite also looks at placebo controlled studies.

  28. #28 Tom DVM
    April 19, 2009

    Thanks.

    I agree that intranasal live vaccine does give the best chance for success, as it stimulates local immunity in the nasopharynx etc.

    In animals, intranasal vaccine was less dangerous from a post-vaccine reaction point of view and seemed to provide both a much more effective and efficient response-protection against infection in animals.

    However, most vaccine is given intramuscularly, and it is specifically that vaccine where I think the greatest problem is…and it is that vaccine that is most commonly used.

    A fine line is walked with live vaccines. In animals, live attenuated vaccines tend to produce post-vaccine reactions…so I am surprised that reports of mild sickness post reaction in humans are taken so lightly. An immune system tied up responding to a live vaccine is vulnerable to some extent.

    Also…if you consider human beings within the scope of the Animal Kingdom…H5N1 is absolutely unique…there has never been a pathogen with the potential to infect and kill virutally all species of animals on one hand and circulate unaffecting others…producing the perfect evolutionary ‘storm’.

    Also…in considering prednisolone (steroid that doesn’t require liver activation) as one potential medication in a pandemic…we should remember that steroids are produced by the adrenals naturally in all stress situations including disease stress…and therefore,we are mimicing a natural physiological stress response in using these drugs. Therefore, they are part of the bodies memory and response to disease.

    If the kids with lethal seasonal influenza could be identified early enough in the course of infection, targeted, moderate dosages of prednisolone given by a route other than intravenously would I am certain prevent death. Of course, effective broadspectrum antibiotics would be given proactively as well as other supportive therapy.

    You are right that I have not treated H5N1…but I have treated a very similar syndrome to SARS (Atypical Interstital Pneumonia). Appropriate targeted prednisolone (all other steroids didn’t work at all) remarkably increased survival rates…and with other supportive therapies mentioned…the animals most importantly survived without chronic sequelae observed with SARS in humans and will be observed in the future with H5N1.

    Intravenous steroids never worked well for disease challenges other than E. coli dehydrations-shock. The analogy I would give is that IV steroids are like crack cocaine. The effect is too short to provide what is needed to prevent cytokine storm. Intramuscular treatments give at least 12 hour levelled blood concentrations and subcutaneous treatments can even up the effect over 24 hours…

    …an ultra-short effect-response falling off a cliff in three hours is almost worse than no treatment at all…and that may be part of the problem currently with H5N1 treatment.

    Thanks

  29. #29 Tom DVM
    April 19, 2009

    Sorry…I should have said ‘Therefore, they are part of the bodies (inherent)memory and response to disease.

    Also, the disease I treated was…’Acute Atypical Interstitial Pneumonia’.

  30. #30 Racter
    April 19, 2009

    >>” An immune system tied up responding to a live vaccine is vulnerable to some extent.”

    Tom,
    That sounds a lot like an argument often heard from members of the anti-vax community when criticizing the practice of administering multiple vaccines simultaneously. Can you expand on that? What exactly is it that makes the immune system more vulnerable? I mean, it seems to me that non-specific (cell mediated) immunity being in a heightened response state would make it more difficult for another pathogen to obtain a foothold, not less. If you’re talking about humoral immunity, then I don’t understand at all what you could be basing that on.

  31. #31 Tom DVM
    April 19, 2009

    Hi Racter.

    The immune system generally and blood cells production specifically is a very energy intensive system.

    Why exactly this happens, I have never read a completely accurate explanation…suffice to say that there is more about the body that science doesn’t understand than anyone would care to admit.

    There are three types of vaccine: natural infection (the best), modified live viruses and killed virus. The killed virus is pieces of dead virus. I favour killed virus vaccine where possible.

    Modified live virus is just that…alive.

    I have repeatedly observed immunosuppression after modified live virus vaccine…many times resulting in having to treat multiple very sick animals. This happens a little too often just to be just a coincidental incubating of another disease as it happens at the exact time the vaccine was administered.

    Cell mediated immunity is more of a blunt weapon cleaning up cellular junk-dead cells or cells identified by attached antibodies etc. It is not as highly energy intensive because it is around all the time.

    Humoral immunity (antibodies etc )is very specific and also very energy intensive. Since modified live virus is ‘alive’…you are being infected with a controlled infection. This is a challenge to the immune system that does tie it up temporarily…

    …in other words, humoral response ability to challenge is limited. It has a limited capacity to respond.

    I have observed some vaccines that appear to make the animal or herd more susceptible to the exact disease you are supposed to be protecting against.

    gs pointed me to one possible explanation.

    http://en.wikipedia.org/wiki/Original_antigenic_sin

    In my opinion, too many persons feel sick post vaccination for it to be coincidence. Sometimes this can be taken as a good thing…you are getting a really good immune response. However, for the very sensitive, the sickness can approach the disease and therefore is not a good thing.

    The fact is that no one really knows for sure…all you can do is observe and then try to explain those observations.

    I guess the bottom line is that every time you stick a needle in your arm, you are taking a calculated risk…so you must be absolutely sure there is a real benefit on the other side.

    Hope that helps.

  32. #32 Racter
    April 19, 2009

    >>”Humoral immunity (antibodies etc )is very specific and also very energy intensive”

    So I’ve heard. The thing is, nobody has ever been able to explain exactly what type of “energy” is being expended. I understand that what you’re saying is that the humoral response has a limited capacity to respond. What I’m asking is for details; what exactly is the nature of these limits? What reason is there to suppose that multiple lineages of B cells cannot replicate simultaneously? The whole system depends on the ability of plasma cells to secrete massive quantities of antibodies. If potential exhaustion of some limited resource is an issue, how does the whole thing ever work in the first place?

  33. #33 Tom DVM
    April 19, 2009

    Racter.

    Maybe if you want to delve into this further, we should do it at Pandemic Flu Information forum (PFI)…but I will try to answer your questions.

    Let’s put it this way. What I see are effects. I don’t see the causes…and I don’t get hung up on the causes if I can find away around that ‘effect’. It’s a trial and error process.

    The source of energy that the human body uses is the same for all uses. Think of it as the animal body always follows the simpliest, least cost pathway…so systems like energy are redundant.

    It’s not that the immune system has a well defined and limited capacity. It’s just that it becomes less efficient by degrees…often you wouldn’t notice the difference…but it seems with novel, not previously seen pathogens it does make a difference.

    For instance, if you only got a partial response then you might get a cold less severe than your last one. In that case, the immune system couldn’t prevent viral replication but it limited it. This is also the best case scenario for partially effective vaccines as well.

    The body can respond with multiple lineages simultaneously, but not as effectively.

    One other thing. The immune system appears highly regulated probably because it can kill you in a hurry if it gets out of whack…so if you have had a bad week and are stressed. The natural response of the adrenal’s suppresses the immune system and often you can end up sick.

    When it comes to H5N1, I guess the point is to somehow find a way around the ‘effects’. So far, all attempts haven’t been to successful but we seem to have time to come up with other solutions.

    Maybe a new vaccine will be effective against pandemic influenza and be able to be produced in time to make a difference.

    Maybe we will find an effective antiviral.

    Maybe statins will work.

    It’s a little late to hope that the virus will just go away.