Effect Measure

Listening to the earache vaccine

If you have or have had small children you may be all too familiar with earaches. When our kids were small we felt as if we were single-handedly supporting the amoxicillin makers. A major cause of middle ear infection is the organism Streptococcus pneumoniae (S. pneumoniae), which sometimes it invades other tissues and causes bacterial meningitis (not the kind that you read about killing healthy teenagers, but bad enough) and sometimes other body sites. It is also a cause of pneumonia in adults and was a common cause of secondary bacterial pneumonia in the 1918 flu. That was then. Now there is a vaccine for seven of the most common strains of this bug and it has made a dramatic difference in the rates of S. pneumoniae infections in children. In Massachusetts there has been a 75% reduction in severe invasive pneumococcal infections in children since 2001. So that’s the good news.

The news that isn’t so good, although it’s not terrible, is that the existing pneumococcal infections are increasingly being seen in strain 19A (actually a serotype), which is not included in the 7 strain pneumococcal vaccine. In 2000 only about 10% of the cases were 19A. Now they are over 40% 19A in the under 18 age group. The 19A strains are also more drug resistant, although even for the drug resistant variety there are alternative drugs that will work.

So are the 19A infections worse? The CDC report states there was no “significant” difference in outcome for 19A drug-resistant, drug sensitive and non-19A cases:

In addition, no significant differences among the three groups were detected in the proportion of patients with meningitis, pneumonia, or bacteremia without focus, case-fatality ratios, rates of hospitalization (79% versus 68% and 59%, respectively), or longer hospital stay (64% with >4 days versus 40% and 51%, respectively). (CDC, MMWR)

Here I would take issue. The pesky word “significant” is ambiguous in this connection and can mean “clinically or epidemiologically” significant or “statistically” significant in medical parlance. Since the difference between 79% and 59% or 64% and 40% is clearly clinically significant, this can only mean the fairly large differences weren’t statistically significant, which here is a function of sample size. The proper way to say this would be to note that the data didn’t allow a judgment as to whether the differences seen were from sample error, a real difference or some hidden bias (unmeasured differences in risk factors in the compared groups).

The incidence rate for serious pneumococcal disease in the under 5 age in Massachusetts in 1990 was about 56 per 100,000 children. By 2000, when the 7 strain vaccine became widely available, it was down to 18/100,000 or less and has remained there since. Thus 19A seems to be taking the place of other strains, not adding to them. Data from 2005 indicate 95% coverage in the 1-1/2 to 3 year old target population for the three dose schedule.

The vaccine is still doing its job. Prevalent serotypes of various bugs change over time and this change might either be “natural” or one encouraged or revealed by vaccine use. I wouldn’t hesitate to have my children vaccinated today if they were babies and their children — my grandchildren — have or will receive this vaccine. But this is a developing situation we need to keep our eyes on.

The recent reluctance to make public the problem with polio vaccine in Nigeria traces to a fear the news would be grist for a developing and dangerous anti-vaccine movement. Understandable. but very risky. We need to be as clear-eyed as possible about vaccines, their value and the trade-offs they present. Along with the tragic loss of public confidence this strategy invites, comes another casualty of deviating from the truth: we begin to believe our own prevarication.

Comments

  1. #1 Tom DVM
    October 23, 2007

    It is time for the ‘ethical’ epidemiologists to band together and regulate their profession…

    …if not to be found complicit by their silence.

  2. #2 Charles Roten
    October 23, 2007

    The way you fuel things like the anti-vaccine movement is by sitting on your data and not making it public.

    That way, the people who profit it can allege conspiracy and coverup.

    As usual, lack of transparency is the biggest mistake you can make. But this argument always fails to impress petty bureaucrats and other subspecies of the genus “malignant authoritarian”. They have their obsessions, and they’re going to cling to them ’till death do them part.

  3. #3 Tom DVM
    October 23, 2007

    “The way you fuel things like the anti-vaccine movement is by sitting on your data and not making it public.”

    Charles.

    In my opinion, the reason they are sitting on the data…is because they don’t have any data that doesn’t leak like a sieve.

    They have never done a double-blind quality test to prove the efficacy of seasonal influenza vaccine…and an analysis of avaliable screening tests, leads me to believe seasonal influenza vaccine doesn’t work…at all!!

    It seems to me that you could eaily balance a double-blind quality study by following patients personal choice and then offering them a few hundred dollars each directly or as a donation to the charity of their choice to allow diagnostic follow-up paired serology…or pay them only diagnosis based follow-up serology is required.

    Considering the fact that several billion dollars have and are being spent on pandemic vaccine, the relative investment would seem to be small.

    I hope, at the end of the day to be wrong…and we find that seasonal influenza does work and by extension, we will all be protected…

    …but we need a ‘real’ study to decide the issue.

  4. #4 revere
    October 24, 2007

    Tom; There are several RCTs of flu. In an RCT you don’t allow personal choice. Treatment allocations are randomly assigned. It is more difficult than you think, practically speaking. And seriology is insufficient. You need to see disease development.

  5. #5 Tom DVM
    October 24, 2007

    Revere. Thanks. I fully acknowledge that I am not an expert in statistics or epidemiology.

    This is like a twelve step program. First, we must admit to ourselves that we have not proof of efficacy for a more than two billion dollar technology…and we never have had irrefutable scientific proof.

    Then we must admit that a standard double-blind study is unethical with respect to seasonal influenza.

    Then we must come up with a workable compromise.

    There was a study done in Ontario Canada a few years ago where I assume it was estimated that 95% of conditions diagnosed as seasonal influenza were actually food poisoning. I do not know the mechanism used to come to this conclusion and it could be flawed as well…but as a veterinarian and a crop scientist with interest in this area, I am not surprised…

    …the total cost to the economy, in a province with an approx. population of 8 million people from food poisoning, was over 500 million dollars per year.

    So we must compromise and come to a design for a study where the ‘double-blind’ requirement is fulfilled.

    This could be achieved by, after balancing the sample size as to age, income group etc. etc., the family is asked what their choice is for vaccination vs. non vaccination.

    Once that decision is reached, then they are asked to join in the study which will measure influenza vs. food poisoning.

    They have already made their choice so that anyone who does get sick, does so by free choice rather than being arbitrarily placed in one group or another.

    Then to ensure that they will allow acute and convalescent serum blood samples to determine the presence of seasonal influenza…financial payments are offered or other non-cash incentives.

    I don’t see this as a problem…because at the moment, there is no proof their ‘magic pill’ which they now boast that they can produce in the billions of doses works or not…

    …with this in mind…an investment of 2-400 million would seem wise given the potential consequences of a useless pandemic vaccine…

    …and secondly, as a veterinarian, I concluded a long time ago that biosecurity is a figment of a non-agriculturalists mind…it ain’t going to happen.

    In a pandemic, as I’m sure you know, the humans become vectors and are vectors before they know they are vectors…the chickens and eggs in those facilities won’t last a month and their pandemic vaccine will not be produced until after the first wave is completely over and they have no sick employees.

    So we need to:

    1) prove once and for all if seasonal influenza works and then extrapolate to estimate whether pandemic vaccine may work.

    2) We have to seriously re-examine chicken-egg vaccine and come to a conclusion about the potential of the chickens surviving a pandemic first wave.

    3) I also think we need a serious review of the ‘real’ potential for complete resistance to Tamiflu in the first wave…and a review of those neurological side-effects including suicidal tendencies (like the initial reports of suicide in kids on antidepressants that were downplayed by regulators, universities and governments in the past…later to be found true).

    4) Do we have proven off-patent pharmaceutical, non-pharmaceutical alternatives that will lower the CFR and also lower the significant numbers of persons who will live with life long, chronic, life limiting side effects like COPD (Chronic Obstructive Pulmonary Disease – emphysema).

    …but first we must take the first step and design a study to prove the vaccine works or not…and believe I hope it does work…although I don’t think so…at all.

    Thanks

    /:0)

    2)

  6. #6 revere
    October 24, 2007

    tom: Studies like the kind you suggest have been done. they are the ones that show the vaccine works. It is the RCTs that are more equivocal, at least for the older age groups. There have been a number done, including the Dutch studies that were the subject of an earlier post on elderly and the flu. Your design doesn’t work because the people who agree to be vaccinated may also be different: e.g., they may take more precautions, be more concerned about their health, etc., etc. That would make be vaccine look better. On the other hand they might also be frailer or sicker or not as sick, etc. The only thing that would nail this down is a randomized, double blind clinical trial where diagnoses are confirmed as flu. This is difficult to do but there are some in the literature, and the vaccine works for younger ages. The question is whether it works and works well enough for the older, targeted age group.

    I am off on an overseas trip (science, I’m glad to say) but you might try searching the literature and report back what you find.

  7. #7 Tom DVM
    October 24, 2007

    “Studies like the kind you suggest have been done. they are the ones that show the vaccine works.”

    I respectfully disagree. Anecdotal screening studies without acute and convalescent serum have been done and they prove ‘squat’.

    I know the medical profession is confident of their abilities to diagnose infection but the fact is they are often wrong when it comes to seasonal influenza and the vaccine may interfere with one screening blood sample to prove etiology.

    I happen to believe that seasonal influenza is a relatively rare disease as a result of the absolute dominance of H1N1 and its offspring in the twentieth century…which knocked out all competition…

    …I also think the accidental re-introduction of H1N1, from a Russian Lab in the 1970′s, artificially extended this period of quiescence.

    Herd immunity has decreased the incidence of seasonal influenza and a variety of other conditions including massive levels of undiagnosed food poisoning are being confused with it.

    The emergence of so many exotic influenza viruses in the 1990′s and the human cases as a result…I believe are a natural occurence at the end of the all Empires, human or pathogen, as other viruses fill the void and compete for dominance…

    …and the winner is and will be H5N1…and this ‘freak of nature’ has capabilities never seen before.

    We have to prove whether the vaccine works…the consequencies of continued apathy are too great from this virus.

    Thanks

  8. #8 revere
    October 24, 2007

    tom: Please go to the literature and read the studies. They are not “screening” studies. There are a bunch of cohort studies and they are referenced in the literature. Then let’s talk.

  9. #9 Tom DVM
    October 24, 2007

    Revere. I have read every study that I could get my hands on…each one ‘leaked like a sieve’…they were all subjective…

    If you have a study that fulfills the scientific…could you please provide a reference so that I and my friends could read and analyze it.

    By the way, if they will provide sufficient numbers of others to do the double blind study, I will participate…as long as the World Health Organization is not remotely involved.

  10. #10 Tom DVM
    October 24, 2007

    Sorry, that should have read…If you have a study that fulfills the scientific method..

  11. #11 revere
    October 24, 2007

    Tom; I’m traveling so can’t supply exact cites. I am talking about influenza vaccination as protection again seasonal influenza. Is that your reference?

  12. #12 Ryan
    October 24, 2007

    More news from ACIP. The morning session debated the expansion of the CDC recommendations for un- or under-vaccinated children to harmonize with the APA’s recs.

    There is development into more-valent vaccines. Although we’re a few years out from seeing or hearing much about them, it’s reasonable to think that they’ll be here before we have a huge shift to other strains. So we’re probably doing pretty well…

  13. #13 Tom DVM
    October 24, 2007

    Yes I am talking about influenza vaccine.

    Here’s the thing:

    In laboratory animals in double-blind studies they use a virus to produce the vaccine and then they vaccinate the lab animal with the vaccine…

    …that virus goes in the freezer until they want to test the vaccine and then they test the vaccine with the identical strain that they produced the vaccine with.

    In doing this…the researchers have dismissed the one tool that makes influenza different from every other family of viruses…its ability to harness genetic drift.

    As well, H5N1 and other serious pandemic viruses have a many multiples higher replications rate translating I thin into more mutability and more genetic drift…

    …so these laboratory experiments prove that if you artificially remove genetic drift, then the vaccine works.

    They also conveniently come up with excuse and excuse why the seasonal influenza vaccine didn’t work for a particular year…and then they say well of course it won’t work next year because of genetic drift…then they say well you may have to be revaccinated every 3 months for it to be effective when it takes six months to make it…

    …this isn’t science…this is politics…and I apologize to the politicians.

    We need a double-blind study for seasonal influenza that allows natural genetic drift (where the researchers can’t conveniently exclude things cause they can)…

    …and if we can’t achieve even this level of testing…then we have to acknowledge to ourselves that the pandemic vaccine, even if they can produce it, will not work.

    One other thing about vaccines. They can’t produce seasonal influenza for two years in a row without screwing up now…how are they going to do it when they are reverse vectors infecting their chickens or when 50% of their workforce is out consistently over the first wave of the pandemic…

    …oh right…I forgot…they are going to be vaccinated and therefore immune to infection and shedding virus infecting those children…

    …good…what about their wives, childrens, friends, brothers and sisters and their famillies and their communities etc…

    …the bottom line…they are dreaming in technicolour…it ain’t going to happen…they aren’t smart enough to pull it off!!

    One last question and sorry I drifted…

    …they are going to have millions of patients, and they are going to have no way to tell which ones are going to get secondary pneumonias or not…and if they wait till they can tell, their patients are going to die…so they wil have to treat proactively…

    …so the question is…forget the prednisolone…where are they going to get antibiotics to treat 30-60% of the population?

    That is the real question.

    Thanks.

  14. #14 Tom DVM
    October 24, 2007

    Shoot!! Sorry again.

    It should have read…yes, I am talking about seasonal influenza.

    ……and if we can’t achieve even this level of testing…then we have to acknowledge to ourselves that the pandemic vaccine, even if they can produce it, may not work.