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Flu Vaccine Efficacy

I guess I will be spending the rest the flu season writing about the nonsense that is promulgated about the flu vaccine and the disease. One of the more common laments about the flu vaccine is that it doesn’t work:  I got the flu vaccine and still got the flu. Well maybe. Maybe not.  It takes a few weeks to get protection, so the flu could have developed before the antibody response to the vaccine.  The vaccine does not protect to the numerous other viral infections that circulate each winter, so perhaps you had an adenovirus but thought it was the flu. Then there is the evidence.  Some readers of the blog are worried that the literature does not support the use of the vaccine.

“My research for  good studies on the efficasy (sic) of seasonal flu vaccines so far has left me wondering if I’ve somehow missed the good research. Tom Jefferson of the Cochrane Institute says that Most studies are of poor methodological quality and the impact of confounders is high. I agree.  Please would you refer me to some of the best studies on the efficasy (sic) of seasonal flu vaccines.  After a critical appraisal of the best studies you know of I’d like to submit the same for publication in the interest of science.”

Why some readers think I am a research librarian, I do not know. It is not an uncommon request. As an aside,   I have a full time job and a family to raise.  Don’t be asking me to do your grunt work. It’s called Pubmed. Use it.

But the topic for this post concerns the efficacy of the flu vaccine. I am limiting myself to the use of the vaccine in adults.

The flu vaccine is not out best vaccine for at least three reasons.

First, every year they have to make an educated guess which influenza strains will be circulating 9 months in the future.  The better the guess, the better the protection the vaccine should provide.  Some years they choose better than others. But often the match between the vaccine and the disease is not optimal, so vaccine efficacy can be decreased.  The vaccine works best when there is a good antigentic match between the vaccine and circulating strain of influenza.

Second, response to the vaccine is not 100%.  The older and more immunoincompetent are the least likely to develop a good antibody response to the vaccine. In a bit of medical irony,  the more likely a patient is to need protection from the vaccine, the less likely they are to get a protective antibody response from the vaccine.

Third, vaccination rates are often suboptimal to get benefit in populations, i.e. herd immunity.  The elderly will more likely benefit if they are not exposed to influenza at all rather than relying of vaccine mediated protection. It may be more important if those around them, say their health care provider or family, receives the vaccine and as a result does not pass flu on to more vulnerable people. But we rarely (never, ever, never) get vaccination rates at levels for herd immunity to kick in.

So it’s a suboptimal vaccine.  And that’s a problem. One, because it will make it more difficult to prove efficacy in clinical studies and two, there is a sub group of anti vaccine goofs who seem to require that vaccines either be perfect, with 100% efficacy and 100% safe, or they are not worth taking.

The influenza vaccine is not 100% efficacious in preventing disease, but it is as close to 100% safe, and much safer than the disease.

There are multiple kinds of studies one could do to prove efficacy, each with their own problems.

One kind of study would be direct inoculation of flu into volunteers who received either the vaccine or placebo.  This is the simplest study to do (if you can find volunteers to get the flu) and lends biologic plausibility to the vaccine, but doesn’t reflect the real world.

Another study would be to to give vaccine or placebo to populations and see who develops influenza.  These are not easy studies to do well.  Do you diagnose flu as a flu like illness, i.e. on clinical grounds, or do you do cultures or PCR or both to prove the diagnosis?  Outside of prison or the military, it is hard to capture people through an entire flu season to get the appropriate specimens.

Or do you use other endpoints?  Death? Antibiotic use? Hospitalization?  Perhaps the flu will not be prevented but attenuated, so it is less likely to spread, and overall the secondary complications of influenza will decrease in a population.

Influenza and pneumonia are both associated with acute myocardial infarction. “Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction (PubMed).” Influenza is a risk for developing acute bacterial pneumonia.  Prevent influenza (PubMed) and you would prevent both primary and secondary myocardial infractions.

The best proof of concept of this effect, where vaccination of one population leads to a decrease in disease in another population, has been with the conjugated pneumococcal vaccine used in children, the Prevnar.  This vaccine covers the 7 most common strains of invasive pneumococcus in children and uptake of this vaccine is high.  Use of the vaccine has resulted in invasive disease plummeting in children, and as an side benefit, invasive disease with the same strains has also plummeted in the elderly (PubMed) .

Such an effect may be occurring when children are vaccinated against influenza. “Vaccination of approximately 20-25% of children, 1.5-18 years of age in the intervention communities resulted in an indirect protection of 8-18% against MAARI (medically attended acute respiratory illness in adults > or =35 years of age.” (PubMed)(PubMed).

In the end, almost all clinical studies have limitations.  For a (mostly) good review of the problematic nature of the studies to date, read Influenza vaccination: policy versus evidence.  I say mostly good as the conclusion from this paper is that the data is suboptimal and doesn’t support widespread use of the vaccine.  I conclude, as shall be seen, that while the data may be suboptimal, it does support the use of the influenza vaccine. And, of course, I am the right one.

Sometimes you get unlucky doing clinical trials: plan a big placebo controlled trial with the influenza vaccine and that year you have both a vaccine mismatch and a mild flu season, and you end up with no good data (PubMed).

You have make due with the tools at your disposal. There are 1207 references on pubmed using ‘influenza’ ‘vaccine’ ‘efficacy’ as search criteria.  That’s a lot of papers, that show varying effects.  Like much of medicine, some studies are better and some are worse and they have variable outcomes.

Direct Inoculation

This type of study is the most compelling for proof of concept, but the least “real world”.  Take a population of (one hopes) volunteers and give them either the vaccine or placebo, then squirt them in the nose with influenza. This has advantages and disadvantages, but at least you know exactly when there was an infection, with what strain, and you can measure antibody levels to see if the patients had what should be protective antibodies.  Best of all, you can control the strain of influenza to get a best antigenic match between the vaccine and the pathogen. In the real world none of this is possible. Unless you are fool enough to walk into the room of a known influenza patient without a mask and inhale deeply.

There have been a variety direct infection studies with flu vaccine over the years.

“Protection rate against artificial challenge with influenza A was 96% when vaccine and challenge viruses were homotypic. When the vaccine strain and challenges virus were heterotypic, protection ranged from 70-100%. Protection rate from infection during a homotypic epidemic was, retrospectively, 95%; while 50-87% protection from influenza illness was achieved during a heterotypic epidemic. In all instances, vaccinees experienced mild, mostly afebrile upper respiratory symptoms, unlike controls who had moderate to severe symptoms, often with fever. Infecting virus was shed more often by unvaccinated controls (PubMed).”

Similar results are found for the live attenuated virus vaccine:

“The efficacy of live attenuated cold-adapted (ca) reassortant influenza A H3N2 and H1N1 virus vaccines against experimental challenge with homologous wild-type virus 7 months after vaccination was compared with that of licensed inactivated virus vaccine in 106 seronegative (hemagglutination-inhibiting antibody titer less than or equal to 1:8) college students. The live attenuated virus vaccines induced as much resistance against illness as did the inactivated vaccine. Vaccine efficacy, measured by reduction in febrile or systemic illness in vaccines, compared with that in controls was 100% for ca H3N2 vaccine, 84% for inactivated H3N2 vaccine, 79% for ca H1N1 vaccine, and 67% for inactivated H1N1 vaccine. Less protection was conferred against upper respiratory tract illness; there was 50 and 77% protection in ca and inactivated H3N2 vaccines, respectively, but there was no protection in ca or inactivated H1N1 vaccinees. The duration, but not the magnitude, of H1N1 wild-type virus shedding in both ca and inactivated vaccinees was significantly reduced compared with controls. In contrast, a significant reduction in the duration and magnitude of H3N2 virus shedding was observed in ca vaccinees but not in inactivated vaccines. After wild-type virus challenge, live ca virus vaccinees demonstrated resistance at least as great 7 months postvaccination as did inactivated virus vaccinees (PubMed).”

I find these types of studies compelling.  They also make me optimistic for the H1N1 vaccine in that the match between the virus and the vaccine is excellent and we should get high levels of protection from the vaccine in those that can mount an antibody response.

These are not real world examples of course.  In the real world the vaccine may not match perfectly, the vaccine may not be handled and administered correctly and the patient, for innumerable co-morbid conditions, may not be able to respond to the vaccine.

However, I am still, barely, young and no medical problems yet, and a health care worker who has daily contact with the old and infirm. The data above is enough for me to take the vaccine, if for no other reason that it may prevent me from passing it on to my patients.

Specific Groups

This is the most most difficult study to do for the reasons mentioned above.

What group of people are in the study? What are the endpoints and how are they defined? And, for the study period, how good a match is the vaccine for the circulated strains of flu?  All these and more make the studies for flu efficacy at best difficult to do.

The NEJM this month had a nice study on the relative efficacy of killed vrs attenuated vaccine in a healthy adult population that was allowed to get seasonal flu naturally. The end point was culture or positive PCR.

“A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types A (H3N2) (about 90%) and B (about 9%). Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. The absolute efficacy against the influenza A virus was 72% (95% CI, 49 to 84) for the inactivated vaccine and 29% (95% CI, -14 to 55) for the live attenuated vaccine, with a relative efficacy of 60% (95% CI, 33 to 77) for the inactivated vaccine.”

Perfect?  No. 72% protection from the inactivated vaccine. Not bad.  Other studies have demonstrated the the live attenuated vaccine efficacy rates of 50% or better.  In the elderly, for example, a

“randomized, double-blind, placebo-controlled study investigated the efficacy, safety, and immunogenicity of LAIV in community-dwelling ambulatory adults >/=60 years of age in South Africa in 2001. Nose and throat swabs were obtained for influenza virus culture based on the symptoms of influenza-like illness. A total of 3242 subjects were enrolled, with a mean age of 69.5 years. The efficacy of LAIV against influenza viruses antigenically similar to the vaccine was 42.3% (95% CI, 21.6-57.8%). Efficacy against A/H3N2 viruses was 52.5% (95% CI, 32.1-67.2%); vaccine efficacy was not observed against antigenically similar B strains (PubMed).”

Of course, the weapon of choice in these debates are the meta analysis.  In institutionalized elderly, the vaccine, when given to staff and patients,  did not prevent influenza but did decrease pneumonia and all cause mortality (PubMed)(PubMed). “Staff vaccination had a significant effect on influenza-like illness (vaccine effectiveness [VE] 86%, 95% CI 40-97%) only when patients were vaccinated too.”

So, as a health care worker, you could conclude that a) vaccine doesn’t work it doesn’t prevent influenza. I don’t need it. Or b) the vaccine benefits my patients by preventing secondary complications and decreases their risk for death.

How about the general population?   The most recent Cochrane meta analysis of the vaccine efficacy in 66,248 people (almost Cardiology levels of patient involvement)  from 2004 (PubMed),

“Inactivated parenteral vaccines were 30% effective (95% CI 17% to 41%) against influenza-like illness, and 80% (95% CI 56% to 91%) efficacious against influenza when the vaccine matched the circulating strain and circulation was high, but decreased to 50% (95% CI 27% to 65%) when it did not. Excluding the studies of the 1968 to 1969 pandemic, effectiveness was 15% (95% CI 9% to 22%) and efficacy was 73% (95% CI 53% to 84%). Vaccination had a modest effect on time off work, but there was insufficient evidence to draw conclusions on hospital admissions or complication rates. Inactivated vaccines caused local tenderness and soreness and erythema. Spray vaccines had more modest performance. Monovalent whole-virion vaccines matching circulating viruses had high efficacy (VE 93%, 95% CI 69% to 98%) and effectiveness (VE 66%, 95% CI 51% to 77%) against the 1968 to 1969 pandemic.

AUTHORS’ CONCLUSIONS: Influenza vaccines are effective in reducing cases of influenza, especially when the content predicts accurately circulating types and circulation is high. However, they are less effective in reducing cases of influenza-like illness and have a modest impact on working days lost. There is insufficient evidence to assess their impact on complications.”

Again, those qualifiers. But the overall meta-analysis suggests the vaccine works for prevention of influenza, and the conclusion does bode well for vaccination against H1N1, which has matches the current strain and is in high circulation.

I will say as an aside that the earlier Cochrane review suggested that influenza cases were decreased by 6% from the vaccine. One commenter over at my Medscate blog, drdan23 suggested that a 6% decrease in disease was not worth it.  30,000 direct and indirect deaths from influenza in the US, maybe 500,000 worldwide. 6% of 30,000 is 1800. 6% of 500,000 is 30,000. Only 6% decrease in deaths? I was always wondering who would be sitting on those death panels that Palin was talking about. It’s the anti flu vaccine docs.

Since 2004, clinical trials testing the efficacy of the influenza vaccine have been drifting in:

“A total of 2058 persons were vaccinated in October and November 2005. Studywide influenza activity was prolonged but of low intensity; type A (H3N2) virus was circulating, which was antigenically similar to the vaccine strain. The absolute efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%-77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%), respectively.

CONCLUSIONS: With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates (PubMed).”

Or this:

“We carried out a randomized, double-blind, placebo-controlled trial of inactivated and live attenuated influenza vaccines in healthy adults during the 2004-2005 influenza season and estimated both absolute and relative efficacies.

RESULTS: A total of 1247 persons were vaccinated between October and December 2004. Influenza activity in Michigan began in January 2005 with the circulation of an antigenically drifted type A (H3N2) virus, the A/California/07/2004-like strain, and of type B viruses from two lineages. The absolute efficacy of the inactivated vaccine against both types of virus was 77% (95% confidence interval [CI], 37 to 92) as measured by isolating the virus in cell culture, 75% (95% CI, 42 to 90) as measured by either isolating the virus in cell culture or identifying it through real-time polymerase chain reaction, and 67% (95% CI, 16 to 87) as measured by either isolating the virus or observing a rise in the serum antibody titer. The absolute efficacies of the live attenuated vaccine were 57% (95% CI, -3 to 82), 48% (95% CI, -7 to 74), and 30% (95% CI, -57 to 67), respectively. The difference in efficacy between the two vaccines appeared to be related mainly to reduced protection of the live attenuated vaccine against type B viruses.

CONCLUSIONS: In the 2004-2005 season, in which most circulating viruses were dissimilar to those included in the vaccine, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. (PubMed).”

Or this:

“INTRODUCTION: Influenza vaccine has been shown to be highly effective in temperate regions with well-defined seasonal influenza. Healthcare workers (HCWs) are advised to receive regular influenza vaccination to protect themselves and their patients. However, there are limited data on the efficacy of influenza vaccine in HCWs in the tropics.

MATERIALS AND METHODS: In this observational, investigator blinded cohort study, bi-monthly questionnaires recording influenza-like illness (ILI) episodes and medical leave were administered to 541 HCWs at the Singapore National University Hospital and KK Women’s and Children’s Hospital from 2004 to 2005. ILI was defined according to a standard symptom score.

RESULTS: Baseline characteristics were comparable in both the vaccinated and non-vaccinated groups. Overall, the relative risk of self-reported ILI in vaccinated HCWs was 1.13 [95% confidence interval (CI), 0.98-1.13; P=0.107]; medical leave taken was lower in the vaccinated group [mean 0.26+/-0.6 days per visit, compared with 0.30+/-0.5 days in the non-vaccinated group (P=0.40)]. Because of the reported Northern Hemisphere 2003/04 vaccine mismatch, we stratified the cohort and determined that the group which received a matched vaccine had a relative risk of ILI of 0.49 (95% CI, 0.37-0.66; P<0.001), achieving a vaccine efficacy of 51%. Mean medical leave decreased significantly in HCWs who received the matched vaccine, compared with those who did not receive vaccination (0.13+/-0.3 vs 0.30+/-0.5; P<0.001) and with HCWs vaccinated with mismatched strains (0.13+/-0.3 vs 0.39+/-0.9; P=0.01).

CONCLUSIONS: A well-matched influenza vaccine is effective in preventing ILI and reducing sickness absence in healthcare workers in tropical settings. Efforts need to be made to increase influenza vaccination rates and to improve the currently available vaccines (PubMed).”

Or this:

“BACKGROUND: We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzed for changes in spirometric and functional status, comparing patients with laboratory-documented influenza (LDI)-caused illness, non-LDI-caused respiratory illness, or no illness, and for association with influenza vaccination.

METHODS: Patients received either IM trivalent inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal placebo (TP). We performed spirometry, measured the chronic lung disease severity index (CLDSI) score to assess functional status and well-being, and tested for influenza virus infection.

RESULTS: Worsening in FEV(1), percentage of predicted FEV(1), and CLDSI score (p < 0.001) was associated with acute respiratory illness in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more likely to be associated with worsening in FEV(1) and CLDSI score acutely than non-LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL, 1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute respiratory illness) to be associated with better CLDSI score at the end of the study. Hospitalization was more frequent in patients with acute respiratory illness (p < 0.0001).

CONCLUSIONS: Acute respiratory illness was associated with increased health-care utilization and obstruction to airflow, and worse functional status and well-being. At the end of the study, receipt of TC was associated with improvement and acute respiratory illness was associated with worsening in functional status and well-being (PubMed).”

But wait. There’s more.  If you call now, not only will you get the above studies, we will add, at no additional cost:

“We identified six studies that assessed the incidence of influenza in vaccinated HIV-infected subjects. Four of these studies compared the incidence in vaccinated versus unvaccinated subjects. These involved a total of 646 HIV-infected subjects. In all the 4 studies, the incidence of influenza was lower in the vaccinated compared to unvaccinated subjects with RD ranging from -0.48 (95% CI: -0.63, -0.34) to -0.15 (95% CI: -0.25, 0.05); between 3 and 7 people would need to be vaccinated to prevent one case of influenza. Vaccine effectiveness ranged from 27% to 78%. A random effects model was used to obtain a summary RD of -0.27 (95%CI: -0.42, -0.11). There was no evidence of publication bias. CONCLUSION: Current evidence, though limited, suggests that influenza vaccines are moderately effective in reducing the incidence of influenza in HIV-infected individuals. With the threat of a global influenza pandemic, there is an urgent need to evaluate the effectiveness of influenza vaccines in trials with a larger number of representative HIV-infected persons (PubMed).”

Now it may be file drawer effect and negative studies are not being published.  The studies show benefits from the vaccine, the benefit is variable depending on the  circulating strain, the vaccine match and the population vaccinated. But a benefit none the less.

Population Studies

The most compelling population data comes from Ontario, Canada, where they have had a ongoing attempt to maximize the  vaccination of the whole population against influenza (PubMed). The other Provinces did not see fit to try and vaccinate everyone, continuing with targeted influenza vaccination.

This represents an interesting natural experiment.  If the effects of the influenza vaccine are less in preventing disease but more in decreasing secondary endpoints like death, hospitalizations, or antibiotic usage, it may show up in population studies. There are numerous issues with this kind of study, but are “appropriate for assessing the public health impact of a population-wide intervention.”

During the period in the reference, Ontario experienced greater uptake of vaccine than any other Province:

“Between the pre-UIIP 1996–1997 estimate to the mean post-UIIP vaccination rate, influenza vaccination rates for the household population aged ≥12 y increased 20 percentage points (18%–38%) for Ontario, compared to 11 percentage points (13%–24%) for other provinces (p < 0.001) (Table 2). For those <65 y, the vaccination rate increases were greater in Ontario than in other provinces, while for those ≥75 y, the increase was smaller in Ontario. For all age groups, Ontario always achieved higher vaccination rates than other provinces.”

And the results of all that vaccination:

“After UIIP introduction, influenza-associated mortality for the overall population decreased 74% in Ontario (RR = 0.26, 95% confidence interval [CI], 0.20–0.34) compared to 57% in other provinces (RR = 0.43, 95% CI, 0.37–0.50) (ratio of RRs = 0.61, p = 0.002) (Table 3). In age-specific analyses, larger mortality decreases in Ontario were found to be statistically significant only in those ≥85 y.”

Not Bad.

“Overall, influenza-associated health care use decreased more in Ontario than other provinces for hospitalizations (RR = 0.25 versus 0.44, ratio of RRs = 0.58, p < 0.001), ED use (RR = 0.31 versus 0.70, ratio of RRs = 0.45, p < 0.001), and doctors’ office visits (RR = 0.21 versus 0.53, ratio of RRs = 0.41, p < 0.001). In age-specific analyses, greater decreases were consistently observed in Ontario than other provinces for age groups <65 y. For seniors, greater decreases were observed in Ontario than other provinces for hospitalizations among those aged 65–84 y and for ED use among those 65–74 y.”

A subsequent paper (PubMed) demonstrated that “universal influenza immunization is associated with reduced influenza-associated antibiotic prescriptions.” So it may be the secondary effects of the vaccines that are more important than primarily preventing me from getting flu.

It’s the old rising tide lifts boats effect.

The study that needs to be done would be vaccinate everyone west of the Mississippi and no one to the east. Prevent travel between the two parts of the county.  See who gets influenza.  Now that would be an epidemiological study.

The study is in contrast to the Tom Jefferson paper that several, evidently anti vaccine folks,  have sent me  where is says,

“A meta analysis of inactivated vaccines in elderly people showed a gradient from no effect against influenza or influenza-like illness to a large effect (up to 60%) in preventing all-cause mortality. These findings are both counterintuitive and implausible, as other causes of death are far more prevalent in elderly people even in the winter months. It is impossible for a vaccine that does not prevent influenza to prevent its complications, including admission to hospital.”

Again with the binary approach to the vaccine.  A milder case of flu due to the vaccine will lead to fewer complications and deaths. It is only impossible if you do not recognize that the influenza vaccine, unfortunately, is not like the tetanus vaccine, but its effects are more likely a continuum due to partial effects on the person getting the vaccine and the hard to measure benefits of being less likely to spread the disease.

In my mind that is the true benefit of the influenza vaccines: decreasing the morbidity and mortality of populations.  The benefit for populations is derived through vaccinating individuals. That requires a bit of altruism on the part of those receiving the vaccine, as they may be getting vaccinated more for the benefit of others than for themselves. However, at least in the US, a premium is currently placed on being a self centered narcissist; indirectly helping others, even for MD’s and RN’s, is apparently not on the to do list.

Do flu vaccines work? It depends on what the meaning of is is. If you are simplistic and like binary answers, yes or no, then you can pick yes or pick no, and find studies to support your contention that the vaccine doesn’t work.

If you realize that medicine is subtle and nuanced, and often the answers are filled with qualifiers and uncertainty, that the practice of medicine is messy, I think the answer is that the flu vaccine is of benefit. And that the more people who get the vaccine, the greater the benefit for everyone. You do not know how much it pains me to quote Donald Rumsfeld , but he was partly right when he said “You go to war with the army you have, not the army you might want or wish to have at a later time.”

It is true in medicine as well. My army is the vaccine and the data used to support it. You can conclude that neither the vaccine nor the data is perfect, and decide the vaccine is not useful.

Or you can look at the preponderance of data, with all the flaws,  nuance, subtleties and qualifiers, and conclude the flu vaccine is of benefit.  The vaccine decreases the probability of morbidity and mortality.  It is a good thing.

Posted in: Science and Medicine, Vaccines

Leave a Comment (58) ↓

58 thoughts on “Flu Vaccine Efficacy

  1. skepchick says:

    “indirectly helping others, even for MDs and RNs, is apparently not on the to do list.”

    I take exception. Speak for yourself.

  2. Deetee says:

    Readers may be interested in the BMJ’s coverage of pandemic flu issues, which includes something Jefferson has produced today for Clinical Evidence.

    http://pandemicflu.bmj.com/

    http://clinicalevidence.bmj.com/ceweb/resources/editors-letter-full.jsp?q=w_pandemic_flu

  3. Mark Crislip says:

    I suppose that should have read “not on everyones to do list”

  4. Scott says:

    Could somebody explain to me the ethics involved in direct inoculation studies? My general understanding indicated that a study wherein some set of the subjects would be predictably worse off than if they had not participated would be unethical (“do no harm” and all that).

    But it would seem like the placebo group certainly, and the vaccine group somewhat, would be harmed by the trial (i.e. get the flu when they otherwise might not have).

    So I guess my understanding of the ethics is incomplete. Could anyone educate me?

  5. wales says:

    I’m confused, deetee last dubbed T. Jefferson a “toe rag”, now he is a legitimate reference source? Which is it?

  6. DanaUllman says:

    Well, it comes full circle. This time I am the one who is referencing the largest and most respected body of research from the Cochrane Collaboration, the Lancet, the BMJ, and Clinical Evidence…and the work of Tom Jefferson, MD. Everyone else is simply cherry-picking.

    You may enjoy and benefit from reading my blog at the Huffingtonpost. http://www.huffingtonpost.com/dana-ullman/the-questionable-efficacy_b_311621.html

    People will also benefit from the words that Jefferson asserts today that summarize his thoughts about flu vaccines (it is a “commercial enterprise”).

    You may even enjoy my sense of humor in my article “How to Create Your Own Pandemic”:
    http://www.huffingtonpost.com/dana-ullman/how-to-create-your-own-pa_b_311652.html

    Because you folks are so insistent upon good evidence based medicine, I assume that you ALL agree with me that the “study” that was recently published in the New England Journal of Medicine that supposedly tested the safety and efficacy of the H1N1 flu vaccine was embarrasingly bad and did not prove either safety of efficacy. Heck, it was not even placebo-controlled.

    Oh…are you NOW going to say that it is not necessary to do placebo controlled research?

  7. Mark Crislip says:

    As to whether he is toe rag, I cannot say, my only knowledge is his interesting takes on vaccines. I do not agree with the conclusions, but I am a proud member of the medical industrial complex, so I would.

    Every paper has to be taken in context and everyone who writes on this blog may have a different take on the same material.

    Except that homeopathy is stupid cubed. And then squared.

  8. halincoh says:

    Mark, I’ve been practicing internal medicine and pediatrics for 18 years and never have I seen a more complete ( and since you went FOX NEWS with Rumsfeld I shall too with ) fair and balanced review of the literature than this. Truly, an excellent job. Thanks for your due dilligence.

  9. Mark Crislip says:

    I wonder the same thing about the ethics of those studies as well.

  10. Archangl508 says:

    Mark,

    Really nice article. I linked to it from Ullman’s blog on HP trying to make sure people get both sides of the info. My SN on HP is cable1977, trying to fight the misinformation peddlers. Gave me some great ammunition to use.

    So far as the ethical issue, isn’t it ok as long as you have full informed consent? As long as consent safeguards are in place and endpoints are established to determine if people were getting too sick it should be ok. At least no worse than a Phase I study with a novel compound.

  11. Jayhox says:

    Great article Mark! Thanks for your time and effort to lay things out objectively.

    Quick question: Can healthy, asymptomatic individuals exposed to H1N1 (or any strain for that matter) be “carriers” in the classic sense, or can it be passed on primarily by direct contact? In other words, if I’ve been exposed to H1N1 but am asymptomatic, can I pass it to someone else by coughing or sneezing or the like?

  12. Mark Crislip says:

    I read http://clinicalevidence.bmj.com/ceweb/resources/editors-letter-full.jsp?q=w_pandemic_flu, and found it kinkd of funny.

    He calls 1% incidence of a disease rare. 1% of the US population is 3 million people. That is a ton of people.

    When you look at the recent NEJM article of flu vaccine efficacy, as an example, the end point was culture or pcr proven influenza, 35 of 325 in the placebo group of normal healthy adults got flu during the study period, or 10.8%. Reality appears to be 10 fold higher than his analysis.

    So Jeffersons analysis, while interesting, doesn’t match with reality and remind me of someone proving, based on their calculations, that bumblebee’s can’t fly.
    ===
    People can shed influenza about 24 hours before the onset of symptomatic disease, but Typhoid Mary like conditions are NOT I forgot the NOT known.

  13. Th1Th2 says:

    Get the flu vaccine and you will be a “carrier” of these strains for sure: A/South Dakota/6/2007 (H1N1) (an A/Brisbane/59/2007-like), A/Uruguay/716/2007 (H3N2) (an A/Brisbane/10/2007-like), and B/Brisbane/60/2008. Regardless whether or not you become symptomatic.

  14. wertys says:

    @HCIB

    your serious posts are funnier than your ‘hilarious’ ones.

    Incidentally, why is it that alt.medders are so devoid of a sense of humour (or ‘humor’ if you will)

  15. Prometheus says:

    Th1Th2 states:

    Get the flu vaccine and you will be a “carrier” of these strains for sure: A/South Dakota/6/2007 (H1N1) (an A/Brisbane/59/2007-like), A/Uruguay/716/2007 (H3N2) (an A/Brisbane/10/2007-like), and B/Brisbane/60/2008.

    It strikes me as funny that a person whose ‘nym is based on immunology terminology doesn’t understand basic immunology (or virology).

    The injected influenza vaccine is made up of “dead” (inactivated) virus – they can’t infect you (‘cuz they’re “dead”) and certainly can’t make you a “carrier”.

    However, the nasal vaccine (FluMist), does have live (but attenuated) virus derived from exactly the strains that “Th1Th2″ mentions. In fact, he/she even preserves the parentheses found in the product insert.

    Unfortunately for “Th1Th2″, you won’t become a “carrier” of the unattenuated strains, even after receiving FluMist. Part of the attenuation process is to make them less able to replicate (if they didn’t do that, it would be just like giving you the wild-type virus), so the virus load in your upper respiratory tract is less – much, MUCH less.

    And, even if you somehow did manage to transmit these attentuated strains to another person, you would simply be giving them the attenuated vaccine strains – just as they would have received if they had gotten FluMist.

    If that worked (it doesn’t, sad to say), it would greatly simplify the vaccination process – you could just pass the attenuated vaccine strains person-to-person. But, as I said, it doesn’t work that way.

    Nice try, “Th1Th2″ – better luck next time.

    Prometheus

  16. wales says:

    Dr. Crislip, regarding a recent NEJM paper on vaccine efficacy you say “Reality appears to be 10 fold higher than his [Jefferson’s] analysis.” I don’t understand how the 352 placebo participants in the NEJM study represent “reality” to a greater degree than the study participants in the multiple studies reviewed by T. Jefferson. Am I missing something? Why would the 352 participants be more representative of the population at large than the 1 million+ participants in the 257 datasets contained in the Jefferson studies?

    I do see your point about 1% of the US population, or 3 million people, being a lot of people. By the same token, vaccinating 300 million people (or even half of the population, say 150 million) in an attempt to prevent 3 million cases of influenza is kind of funny too.

  17. wales says:

    According to a recent Reuters article, the US government’s H1N1 vaccination campaign is costing $6.4 billion. Yes that’s 6,400,000,000 dollars. That’s kind of funny too (strange, not humorous).

  18. Mark Crislip says:

    I know I am in trouble when I discuss statistics, but when I read his paper the end point is the number of influnza like disease ie all coughing febrile illnesses that are due to influenza, of which influenza is going to be a small sub set, vrs a population where the end point is influenza only is the NEJM.

    but maybe I am wrong, I do not have access to his data set

  19. Kausik Datta says:

    Psst, Prometheus!

    It strikes me as funny that a person whose ‘nym is based on immunology terminology doesn’t understand basic immunology (or virology).

    The profundity and depth of Th1Th2′s ignorance of anything remotely associated with immunology is a legend around these parts… :)

  20. Oroboros says:

    Thanks for publishing such excellent information and analysis.

    Opposition to this (and other) vaccinations seems to be growing in the general populace at an alarming rate. I encounter more and more people who believe that something is wrong with the H1N1 vaccine.

    Strangely, the fringes on both far left and far right seem united on this one, which may explain why it is becoming so prevalent. Who would think that a a global conspiracy of genocide by the Illuminati was all it took to bridge the bitter partisan divide in this country?

    I believe that Jane Bürgermeister’s rights to free speech end “where my nose begins”, to paraphrase a famous quote. I hope she and the others spreading such ugly disinformation are held accountable. It may be up to people like us to take her on more directly. I wish I could find information about the actual progress of her court case (i.e. has the judge finished laughing and managed to set a trial date).

  21. wales says:

    Yeah, I hear what you’re saying about statistics. I assumed your point was that you were extrapolating from the 352 participants in the NEJM. My point is that 352 is a very small sample and does not accurately represent a random sample of the population.

  22. Mark Crislip says:

    Yeah. Wales is correct. Jefferson also states that the Cochran gives the rates at 7%, closer to the NEJM number, then argues why they are wrong.

  23. albatross says:

    “Why some readers think I am a research librarian, I do not know. It is not an uncommon request. As an aside, I have a full time job and a family to raise. Don’t be asking me to do your grunt work. It’s called Pubmed. Use it.”

    I understand your frustration, but not every reader is a research scientist or doctor. Perhaps they’re looking for a “translation” of the at-times impenetrable to the lay population lingo of the research world.

  24. Oroboros says:

    FYI There is a typo in about the 4th paragraph of the blog post:

    The flu vaccine is not our best vaccine for at least three reasons

    Also, I just ran across flutracker.rhizalabs.com/ which is plotting estimated H1N1 cases via the Google maps API. It is too bad that we can’t vaccinate just half the country and then watch how it develops.

  25. qetzal says:

    I found Jefferson’s editorial quite odd. His conclusion was this:

    In summary, evidence presented here points to influenza being a relatively rare cause of ILI and a relatively rare disease. It follows that vaccines may not be appropriate preventive interventions for either influenza or ILI.

    And yet immediately above that, he has a figure that shows the influenza was the single most commonly identified cause of ILI, and accounted for 11% of all cases (77/700). His numbers might support his claim that influenza is a relatively rare disease overall (77/10,000 or 0.8%), but they don’t support that it’s a relatively rare cause of ILI.

    And even if both of those were true it most certainly does not follow from those data that vaccines may not be appropriate preventive interventions for influeza or ILI. To determine if influenza vaccination is appropriate, we need to consider not just disease frequency, but also the severity of consequences from the disease, whether the vaccine prevents those severe consequences, etc.

    Elsewhere in the editorial, Jefferson says:

    [O]ur aim here is to discuss why influenza inactivated vaccine performance is poor, and why most studies rely on non-specific outcomes, such as death from all causes, and hospitalisations for pneumonia and influenza (which are not usually based on virological testing). One possible answer is that seasonal influenza is a relatively rare and benign condition, with an incidence not exceeding 1% in the general population during autumn and winter months.

    Yet he doesn’t discuss at all why vaccine performance is (supposedly) poor, or even attempt to show that it is! He also ignores the obvious explanation for the reliance on ‘non-specific outcomes.’ Namely, that preventing deaths and hospitalizations is exactly what we hope the vaccine will do.

    All in all, a very strange editorial, IMHO.

  26. hokieian says:

    Th1Th2,

    THe chances of someone who gets the flumist vaccine becoming a “carrier” is 1 in 1,000,000,000,000,000,000,000 (reversion to wt influenza is estimated at 1 out of 10^20 replication cycles).

    So I guess there’s a chance. You’re not entirely wrong.

    http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19453395

  27. Th1Th2 says:

    Prometheus,

    1. “The injected influenza vaccine is made up of “dead” (inactivated) virus – they can’t infect you (’cuz they’re “dead”) and certainly can’t make you a “carrier”.”

    Certainly, you don’t know what an asymptomatic carrier is let alone the understanding that even if vaccines are killed they can still cause the disease. What it prevents or mitigate is the development of signs and symptoms of the disease. Straight from the horse’s mouth it says:

    “Vaccines contain antigens that cause diseases. However, the antigens in vaccines are weakened or killed. This means they cannot produce the signs or symptoms of the disease, but they do stimulate the immune system to create antibodies.”

    http://familydoctor.org/online/famdocen/home/healthy/vaccines/028.printerview.html

    The absence of clinical signs and symptoms does not rule out the disease process especially after the inoculation of disease-specific antigens in the body. This is the reason vaccines are designed to transmute wild-type infectious diseases to become noninfectious, that is, subclinical or asymptomatic.

    2. “Unfortunately for “Th1Th2″, you won’t become a “carrier” of the unattenuated strains, even after receiving FluMist. Part of the attenuation process is to make them less able to replicate (if they didn’t do that, it would be just like giving you the wild-type virus), so the virus load in your upper respiratory tract is less – much, MUCH less.”

    Well, an essential criteria for an effective vaccine is the ability to infect the host cells. Infection takes precedence over replication and is necessary in order to induce immunity.

    “FluMist contains live attenuated influenza viruses that must infect and replicate in cells lining thenasopharynx of the recipient to induce immunity. Vaccine viruses capable of infection and replication can be cultured from nasal secretions obtained from vaccine recipients.”

    3.” And, even if you somehow did manage to transmit these attentuated strains to another person, you would simply be giving them the attenuated vaccine strains – just as they would have received if they had gotten FluMist.’

    Clearly a borrowed concept from naturally-acquired immunity as a result of exposure from natural infection. Hence, vaccines expose naive and non-diseased individuals to become infected and diseased even before any protection could take place. Although, it’s utter nonsense in the first place how vaccine apologists regard vaccination as protection.

    4. “If that worked (it doesn’t, sad to say), it would greatly simplify the vaccination process – you could just pass the attenuated vaccine strains person-to-person. But, as I said, it doesn’t work that way. ”

    Your delusional thinking does not make reality go away. Please enlighten your mind by reading some vaccine package inserts.

  28. wertys says:

    @Th1Th2

    1. This is not even wrong. You are filtering those fairly innocuous words from your linked source through some type of cognitive bias/conspiracy filter and coming up with a breathtaking misinterpretation.

    2. Do you understand how vaccines work ? Stimulating the immune response to a level below that of a clinical infection is, by definition, not an infection. An infection is when a wild-type virus replicates competitively with the immune system trying to shut it down. With a live virus vaccine, the fight is fixed in favour of the immune system, because certain critical abilities of the wild-type virus are deliberately impaired or disabled.

    3. This para ranks you among the foremost non seqitur artists of your generation. I am simply unable to detect what point your trying to make.

    4. You are correct to state that delusional thinking does not make reality go away. I prefer to think that understanding reality might make some of your fallacious thinking go away.

  29. Th1Th2 says:

    wertys,

    Read it again.

    “FluMist contains live attenuated influenza viruses that MUST infect and replicate in cells lining the nasopharynx of the recipient to induce immunity.” (Emphasis added)
    http://www.medimmune.com/pdf/products/flumist_pi.pdf

    Are you dyslexic or what?

  30. wales says:

    I guess it’s all a matter of perspective. I don’t find Jefferson’s editorial conclusions odd. He has apparently uncovered some odd facts, if the data are accurate.

    While some may think that 11% of ILI caused by influenza is not “relatively rare” (after all, the concept of “relatively” is relative). It is rather surprising to think that 68% of ILI has unidentified cause, especially given the name “influenza-like illness”.

    It appears to me that Jefferson’s opinion is that given the questionable efficacy of some/many flu vaccines, and given the expense of vaccines versus other effective preventive methods such as hand washing, it just doesn’t make economic sense to pursue mass influenza vaccination campaigns. At least that’s what I gather from comments such as these:

    “The disparity in effectiveness between the high profile of influenza vaccines and antivirals and the low profile of physical interventions is striking. Public health recommendations are almost completely based on the use of vaccines and antivirals despite the lack of strong evidence. Vaccines work best in those who are universally considered least to need them—namely, healthy adults.”

    http://www.bmj.com/cgi/content/full/339/sep21_1/b3675

    By high profile I assume he means expensive and high tech.

  31. qetzal says:

    @wales

    I’m pretty sure that being responsible for 11% of ILI does not qualify as “relatively rare” by any conventional medical terminology. A minor point, no doubt, but suggestive of a bias and willingness on Jefferson’s part to exaggerate the data to try to make his case.

    Also, I don’t think it’s at all surprising that the majority of ILI can’t be ascribed to a known causative agent, given how non-specific the symptoms are. The fact remains that of all identified causative agents, influenza is the most common, per the data Jefferson cited.

    AFAIK, neither you nor Jefferson has made an adequate case for the claimed “questionable efficacy of some/many flu vaccines.” Jefferson certainly made no such case in that editorial. Nor did he make any case whatsoever that measures such as handwashing are effective, much less more cost-effective than flu vaccines.

    I agree that Jefferson thinks flu vaccines may have little value. He might even be right. However, his editorial did essentially nothing to actually support his opinion. THAT’s what I thought was so odd.

  32. trrll says:

    Well, an essential criteria for an effective vaccine is the ability to infect the host cells. Infection takes precedence over replication and is necessary in order to induce immunity.

    This is false. Killed-virus vaccines are incapable of infecting anything. Live virus vaccines, on the other hand, do produce an infection, but it is a self-limiting infection produces little or no symptoms of illness. If you will re-read the article on which you are commenting, you will see that the inactivated (killed) virus vaccine is at least as effective in protecting against disease as the live-virus vaccine, disproving your notion that infection of host cells is required to induce immunity.

  33. Ed Whitney says:

    For what it is worth, there is an article (Wicker S et al. Infection 2009;37:197-202) which discusses flu vaccine compliance in German health care workers. Reasons for noncompliance included supposition of a low risk of infection, fear of side effects, belief that the vaccine would trigger the flu infection, and scepticism about the vaccine efficacy.

    I wonder if there is the same kind of political lunacy in Germany as there is in the USA. Does Germany have its Rush Limbaugh and Glenn Beck? Germans are used to “government-run health care” and may not be as prone to the kind of insanity we have in America.

    As for me, I got a flu shot last year, and they didn’t even give me a lollipop afterwards! I didn’t cry or anything. So this year I am saying screw’em. They can’t make me and I ain’t going!

  34. Prometheus says:

    “Th1Th2″ responds:

    Certainly, you don’t know what an asymptomatic carrier is let alone the understanding that even if vaccines are killed they can still cause the disease. What it prevents or mitigate is the development of signs and symptoms of the disease. Straight from the horse’s mouth it says:

    “Vaccines contain antigens that cause diseases. However, the antigens in vaccines are weakened or killed. This means they cannot produce the signs or symptoms of the disease, but they do stimulate the immune system to create antibodies.”

    I suppose I’m just wasting my time, but in the event someone else (other than “Th1Th2″) is confused….

    Antigens are substances that can provoke and immune response – they may be intact (live) organisms or fragments of organisms. The hepatits B vaccine, for instance, contains only the surface antigen (a protein) of the hepatitis B virus and is absolutely incapable of causing disease.

    Some vaccines (like the hepatitis B vaccine, mentioned above) contain only purified proteins from the disease-causing organism. Others contain the entire organism, either “killed” (in which case they are also incapable of causing disease) or “attenuated” (in which case they cause an infection, but not a symptomatic – or very symptomatic – disease).

    The source that “Th1Th2″ uses is incorrect on the composition of vaccines. I’d suggest using another.

    The commentary continues:

    Well, an essential criteria for an effective vaccine is the ability to infect the host cells. Infection takes precedence over replication and is necessary in order to induce immunity.

    “Infection takes precedence over replication…”? That doesn’t make much sense at all.

    The “life cycle” of an influenza virus is fairly simple – it infects the host cell (a cell lining the upper respiratory tract), carries its genome (8 segments of negative-sense ssRNA) into the cell and then takes over the cell’s metabolic processes to make copies of itself (replication). Without replication, the infection process stops – if it can’t replicate, it dies with the host cell.

    “Th1Th2″ continues:

    Hence, vaccines expose naive and non-diseased individuals to become infected and diseased even before any protection could take place. Although, it’s utter nonsense in the first place how vaccine apologists regard vaccination as protection.

    Vaccines work by inducing an immune response sufficient to prevent a successful infection by the disease organism (i.e. the “wild-type” influenza). They either do this by presenting a relatively small amount of “dead” virus to the immune system (which cannot, by the definition of “dead” – cause an infection) or by creating an infection by a virus that is attenuated (i.e. does not cause as severe or as symptomatic an infection as the “wild-type” organism) but is sufficiently similar to the “wild-type” that immunity to the “vaccine strain” will protect against the “wild-type”.

    That vaccinations work is a matter of fact, supported by data going back to the late 1700′s (the first “vaccination” was an attenuated smallpox virus). That small-minded, ignorant people have long been afraid of vaccines also goes back to the late 1700′s. People often fear what they don’t understand.

    “Th1Th2″ – as Kausik Datta pointed out – is hopelessly confused about how vaccines work and what they contain. A good source, although a bit technical in parts, can be found at:

    http://pathmicro.med.sc.edu/lecture/vaccines.htm

    Prometheus

  35. Dr Benway says:

    A disease that has no signs or symptoms at any point in time would be indistinguishable from health, Th1Th2.

    Vaccinations give people health.

    I realize that reading the sentence above may make your head asplode. But in the long run, you will be better off without all those naturopathic delusions rattling around in there.

  36. wales says:

    I suppose influenza vaccine efficacy is a matter of perspective. Qetzel states “neither you nor Jefferson has made an adequate case for the claimed “questionable efficacy of some/many flu vaccines.” Jefferson certainly made no such case in that editorial.”

    Perhaps the case wasn’t made in the editorial. However, the various specific Cochrane reviews do make an adequate case by highlighting widely varying rates of influenza vaccine efficacy. Efficacy varies significantly according to the population examined and type of vaccine (live versus inactivated) and match between vaccine and circulating strains. I would like to clarify and amend my earlier statement and substitute “widely varying rates of efficacy” for “questionable efficacy”. The point is that with such widely varying rates of efficacy, the rationale for population-wide influenza vaccination polices becomes questionable.

    The Cochrane review on Vaccines for Preventing Influenza in Children found that from RCTs, live vaccines showed an efficacy of 82% and an effectiveness of 33% in children older than two compared with placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% than live vaccines but similar effectiveness: 36%. In children under two, the efficacy of inactivated vaccine was similar to placebo.

    The review on Vaccines for Preventing Influenza in Healthy Adults found that inactivated parenteral vaccines were 30% effective against influenza-like illness, and 80% efficacious against influenza when the vaccine matched the circulating strain and circulation was high, but decreased to 50% when it did not. Excluding the studies of the 1968 to 1969 pandemic, effectiveness was 15% and efficacy was 73%. This gets more complicated and vaccine efficacy has even less impact on the population if the Jefferson editorial is accurate in claiming that 68% of ILI is of unknown cause and 11% of ILI is attributable to influenza (then vaccines are 30% effective against 68% of ILI and 50-80% effective against 11% of ILI).

    The review on Vaccines for Preventing Influenza in the Elderly found that in homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against ILI was 23% and non-significant against influenza. Again, 23% effective against 68% of ILI and non-significant against 11% of ILI.

    http://www.cochrane.org/influenza/reviews.html

  37. Dr Benway says:

    I’m bored with the vaccine thing. Can we get the alties to pick on multivitamins instead, just for a change of pace? Surely someone can connect-the-dots and draw us up a spooky BigVitamin conspiracy.

    I’m having flashbacks to college dorm life and a suitemate who played Steely Dan’s Aja album several hours daily.

  38. wales says:

    Dr. Benway: Not everyone who questions vaccines and vaccination policy subscribes to conspiracy theories. Perhaps sbm’ers consider T. Jefferson to be an “altie” or a conspiracy theorist?

    Like I tell my kids, those who complain of boredom are boring. Unless you are compelled to participate in this discussion (say for compensation) you must be free to abstain, n’est-ce pas?

  39. Dr Benway says:

    C’mon, wales. How many years of your life you wanna waste on this vax thing. There are books filled with medical facts one might crank upon.

    Biotin. They say you need 300 micrograms daily. I call bullshit.

  40. yeahsurewhatever says:

    “I’m bored with the vaccine thing. Can we get the alties to pick on multivitamins instead, just for a change of pace? Surely someone can connect-the-dots and draw us up a spooky BigVitamin conspiracy.”

    If need be, I can invent such a conspiracy.

    Linus Pauling faked his own death, and is behind the whole thing. He determined that scurvy actually grants ETERNAL LIFE and then sought to keep it a secret by advocating ginormous doses of ascorbic acid to throw everyone off. It’s the perfect crime, or at least it would have been if not for those meddling kids and their dog.

  41. wales says:

    Dr. Benway: I generally do not spend valuable time on things I consider to be either boring or a waste of time. Apparently the blog contributors here do not consider the vaccine topic to be either boring or a waste of time or they would not continue to issue pieces on the subject (unless of course they are paid to do so, which is the only reason I can imagine to spend time writing about something one considers boring or a waste of time).

    I do wonder how physicians have the spare time to spend hanging out at blogs and whining about boredom.

  42. weing says:

    wales,

    Your realize that the efficacy of parachutes in preventing injury or death has never been put to randomized double-blind placebo controlled trials. Clearly the efficacy is questionable and at best variable. Clearly the policy of the mass issuing of parachutes to paratroopers and coercion of skydivers to use them is questionable.

  43. Dr Benway says:

    wales:

    Apparently the blog contributors here do not consider the vaccine topic to be either boring or a waste of time or they would not continue to issue pieces on the subject

    I don’t know the SBM doctors. Maybe they love talking about vaccines. However, knowing doctors generally, I think it’s more likely that they find the need to rebut the anti-vax crowd tedious, in the same way that biologists find the ID proponents tedious. Both “debates” have been going on for a hundred years or more. The arguments against the vaccines never change. The special pleading regarding the dangers of the antigens in vaccines in relation to the sea of antigens everyone swims in every day continues to make no sense. And Generalissimo Francisco Franco is still dead.

  44. skepsis says:

    wales,
    there are two camps in the vaccine debate: the anti-vaccine sect and the pro-vaccine sect. Neither is especially interested in science based facts. As influenza vaccine have never been proven to have any efficacy the debate is based on belief, not evidence, nor a sound skeptical analysis of said evidence.

    That is why they happily rebut all Cochrane studies and Tom Jefferson evidence based reviews by citing flawed studies. While at the same time profess to be skeptics pursuing rationality and reality.

    Tom Jefferson did also make a study called “Relation of study quality, concordance, take home message, funding, and impact in studies of influenza vaccines: systematic review” (http://www.bmj.com/cgi/content/full/338/feb12_2/b354). Where he concludes (especially point 3 is regarded as heresy by the pro-vaccine religion):

    1) Study sponsorship is associated with optimistic results.

    2) Influenza vaccination continues to be recommended globally, despite growing doubts about the validity of the scientific evidence underpinning policy recommendations.

    3) Evidence is of poor quality, and studies with conclusions in favour of vaccines are of significantly lower methodological quality.

    4) Influenza vaccines studies sponsored by industry are published in journals with higher impact factors and are cited more but are of similar size and quality to the others.

  45. wales says:

    wales your superficial analogy is like comparing apples to oranges. dr. benway, most professions require a high tolerance for tedium.

  46. wales says:

    make that “weing” your superficial analogy….

  47. wales says:

    Good points skepsis. Add to that the ghostwriting problem and there is much to be skeptical about regarding medical journal articles.

  48. sheldon101 says:

    To the beat of the old time elixer salesman

    Come close my friends. I keep hearing how those everyday vaccines don’t do the job on the eldrerly and they just keep dying Well, I’ve got the answer for you, a magical elixer. It does things never dreamed of by Tom Jefferson.

    For the only the price of a more painful arm you get – more doses from your virus, better protection against antigen drift and one big kick at the immune system.

    Here’s what we do — take only 3.75mcg of dead virus protein and add the magical (but deadly) AS03 elixer. You get more doses per gallon of vaccine. You get better protection against antigen drift and you kick that immune system real….hard.

    Look what you get:

    http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10119.htm
    These results show that 88.0% of the subjects between 61-70 years of
    age, and 86.7% of those over 70 years of age, demonstrated a response
    that was above the regulatory threshold of 1:40 seroprotection, which
    is considered indicative of protection. Results in the age group 18 -
    60 years of age were similar to previously reported studies in that
    age group, with 97.5% of subjects reaching the 1:40 seroprotection
    level in this trial.

    Now you might get that with a double dose of your standard vaccine (studies show 4x definitely works safely) but you don’t get extra doses and better protection against drift. See US study on double dose for asthmatics
    http://www3.niaid.nih.gov/news/QA/H1N1VacASTHMAqa.htm

    And folks it gets better ..

    You say you’re worried about the infants and the kiddies under 10 because CDC is saying it takes 1/2 dose plus 21 days plus booster plus 10 days to get great protection… that I can’t help you with, I don’t think.

    Up in Canada and in Europe it will probably end up at 1/2 dose plus 21 days is good protection.
    http://www.ctvbc.ctv.ca/servlet/an/local/CTVNews/20091023/who_swine_091023?hub=BritishColumbiaHome

    http://www.pharmanews.eu/gsk/361-experience-of-gsks-h1n1-adjuvanted-vaccine-pandemrix-and-preliminary-paediatric-results

    Next year it should be different. There will be the AS03 results from Canada and Europe and perhaps similar results with MF59. The US has large stockpiles of both adjuvants.

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