Flu Vaccine–where is the evidence?

Several astute observers of the flu, the vaccine, and the government promotional campaign urging the public to vaccinate against the flu, responded by challenging the 36,000 annual death count the CDC attributes to the flu.
 
Below are two articles: one, a meta-analysis of the published flu vaccine reports by Tom Jefferson of the Cochrane Center published by the BMJ. The other, a column by Dr. Edward Yazbak, a pediatrician. 
 
The findings are sobering: There is a gap between evidence and public health policy

"The optimistic and confident tone of some predictions of viral circulation and of the impact of inactivated vaccines, which are at odds with the evidence, is striking."
 
"Public policy worldwide recommends the use of inactivated influenza vaccines to prevent seasonal outbreaks. Because viral circulation and antigenic match vary each year and non-randomised studies predominate, systematic reviews of large datasets from several decades provide the best information on vaccine performance. Evidence from systematic reviews shows that inactivated vaccines have little or no effect on the effects measured. Most studies are of poor methodological quality and the impact of confounders is high.  Little comparative evidence exists on the safety of these vaccines.  Reasons for the current gap between policy and evidence are unclear, but given the huge resources involved, a re-evaluation should be urgently undertaken.

There is NO EVIDENCE to support the number of deaths attributed to the flu by the CDC.
 
We can only conclude that we are in the era of post-evidence-based medicine.
Our public health policies are not even remotely evidence-based. Rather, our public health policies are faith-based decrees by government "authorities"–no better than voodoo medicine.

Underlying this collapse of Western medicine is the collision bewteen science and business: our public health policies are currently shaped by business interests.
As Mr. Jefferson reports, "a messy blend of truth conflicts and conflicts of interest making it difficult to separate factual disputes from value disputes" in the debate about influenza vaccines.

The CDC appears to be acting on behalf flu vaccine manufacturers–even as the evidence shows the vaccine to be worthless at best.

Dr. Yazbak notes that according to both the FDA and the CDC, “The fact that an adverse event occurred following immunization is not conclusive evidence that the event was caused by a vaccine. A VAERS (Vaccine Adverse Events Reporting System) search performed on Oct. 10, 2005 yielded three reports in the past two years of children younger than 23 months of age who died shortly after receiving a dose of influenza vaccine. No other vaccines were administered at the same time and all three children had underlying diseases.” 

Similarly, the FDA denied the link between SSRI antidepressants and the suicide risk—despite a mountain of evidence in its own file drawers.
 
See also: Jefferson T, Smith S, Demicheli V, Harnden A, Rivetti A, Di Pietrantonj C. Assessment of the efficacy and effectiveness of influenza vaccines in healthy children: systematic review. Lancet 2005 Feb 26-Mar 4;365(9461):773-80. Review.

See also: Influenza Vaccination of Infants: A Useless Risk By Red Flags Columnist, F. Edward Yazbak, MD, FAAP http://www.reflagsdaily.com/
  ( Dr. Yazbak, a pediatrician, now devotes his time to the research of autoimmune regressive autism and vaccine injury  (tlautstudy@aol.com) ).

Contact: Vera Hassner Sharav
veracare@ahrp.org  

~~~~~~~~~~~~~~~~~~~~~~

<strong>BMJ  2006;333:912-915 (28 October), doi:10.1136/bmj.38995.531701.80 <br />Analysis and comment<br />Public health <br />Influenza vaccination: policy versus evidence <br />Tom Jefferson, coordinator1 </strong>

1 Cochrane Vaccines Field, Anguillara Sabazia, Roma 00061, Italy <a href="mailto:jefferson.tom@gmail.com">jefferson.tom@gmail.com</a>

Each year enormous effort goes into producing influenza vaccines for that specific year and delivering them to appropriate sections of the population. Is this effort justified?

Viral infections of the respiratory tract impose a high burden on society. In the last half of the 20th century, efforts to prevent or minimise their impact centred on the use of influenza vaccines. Each year enormous effort goes into producing that year's vaccine and delivering it to appropriate sections of the population. Here, I will discuss policies on the use of inactivated vaccines for seasonal influenza; the evidence for their efficacy, effectiveness, and safety ("effects"); and possible reasons for the gap between policy and evidence.

<strong>Policies <br /></strong>Every vaccination campaign has stated aims against which its effects must be measured. The US Advisory Committee on Immunisation Practices produces a regularly updated rationale for vaccination against influenza.1  The current version identifies 11 categories of patients at high risk of complications from influenza (box).

The rationale rests on the heavy burden that influenza imposes on the population and the benefits of vaccination. For example, reductions in cases, admissions to hospital, mortality of elderly people in families with children, contacts with healthcare professionals, antibiotic prescriptions, and absenteeism for children and household contacts are the main arguments for extending vaccination to healthy children aged 6-23 months in the United States.2  Canada introduced a similar policy in 2004.3

 Less comprehensive policies recommending vaccination for all people aged 60 or 65 and over are in place in 40 of 51 developed or rapidly developing countries.4 On the basis of single studies, the World Health Organization estimates that "vaccination of the elderly reduces the risk of serious complications or of death by 70-85%."5 Given the global nature of these recommendations, what type of evidence should we expect to support them and what does available evidence tell us?4

<strong>Which evidence? <br /></strong>When considering the best evidence for vaccination we must take into account the unique epidemiological features of influenza viruses and the rationale for immunisation. The incidence and circulation of seasonal influenza and other respiratory viruses vary greatly each year, each season, and even in each setting. A systematic review of the incidence of influenza in people up to 19 years' old reported a seasonal variability of 0-46%; during a five year period the average incidence was 4.6% in this age group. During a period of 25 years the incidence was 9.5% in children under 5.6  Because of this variability and lack of carryover protection from one year's vaccine to the next,7 especially if the virus changes its antigenic configuration, single studies reporting data from one or two seasons are difficult to interpret. Single studies are also not reliable sources for generalising and forecasting the effects of vaccines, especially when numbers are small. They introduce further instability into already problematic forecasting. Additional limitations to our forecasting ability are imposed by our use (and misuse) of studies assessing the effects of influenza vaccines. Although the effect assessed depends on the aims of the particular campaign, most concentrate on serious effects (such as pneumonia or death) and person to person transmission (table 1 ). Field efficacy studies are only relevant when viral circulation is high, but no one can forecast with precision the impact on next year's influenza. <<a href="http://www.bmj.com/cgi/content/full/333/7574/912#FIG1">http://www.bmj.com/cgi/content/full/333/7574/912#FIG1</a>> 

<br />View this table: [in this window] <<a href="http://www.bmj.com/cgi/content/full/333/7574/912/TBL1">http://www.bmj.com/cgi/content/full/333/7574/912/TBL1</a>> <br />[in a new window] <<a href="http://www.bmj.com/cgi/content-nw/full/333/7574/912/TBL1">http://www.bmj.com/cgi/content-nw/full/333/7574/912/TBL1</a>>

   Table 1 Effects of inactivated influenza vaccines and preferred designs of primary studies to assess them <br />Figure 1 <<a href="http://www.bmj.com/content/vol333/issue7574/images/small/Jeft396234.f1.gif">http://www.bmj.com/content/vol333/issue7574/images/small/Jeft396234.f1.gif</a>>

<strong>Flu vaccination: is the effort justified? <br /></strong>Studies of the effects on influenza-like illness and its complications most closely replicate real life conditions because no one knows what agent (if any) causes this disease. Influenza-like illness is an acute respiratory disease caused by many different viruses (including influenza A and B), which presents with symptoms and signs that cannot be distinguished from those of influenza. Influenza-like illness does not have documented laboratory isolation of the causative agent and is the syndrome that most commonly presents to doctors ("the flu").

In general the most powerful and reliable studies are those that "average" out several years and perform subanalyses by setting, population, viral circulation, and viral-vaccine antigenic match—variables that affect interpretation of the effects of a vaccine. Systematic reviews are the best way to perform such analyses, and provide powerful evidence weighted by the methodological quality of the studies involved. Large datasets containing several decades of observations help us to assess the performance of vaccines more accurately.

<strong>People for whom vaccination is recommended in the United States</strong>1 <<a href="http://www.bmj.com/cgi/content/full/333/7574/912#REF1">http://www.bmj.com/cgi/content/full/333/7574/912#REF1</a>>  <br /><em>People aged 65 or more <br /></em>Patients in institutions who have chronic medical conditions <br /><em>Adults and children with chronic disorders of the cardiovascular and respiratory systems (including asthma but excluding hypertension) <br /></em>Adults and children who have been treated in hospital in the preceding 12 months for a range of conditions (for example, diabetes or haemoglobinopathy) Adults and children with conditions that compromise respiratory function or handling of infected secretions <em>Children aged 6 months to 18 years being treated with aspirin <br /></em>Women who are pregnant during the influenza "season" <br /><em>Children aged 6-59 months <br /></em>Adults aged 50-64 years <br /><em>Carers and household contacts (including children) of those in the above risk categories and of children aged 0-59 months <br /></em>Healthcare workers

<strong>The evidence <br /></strong>I searched for relevant systematic reviews when updating and expanding the Clinical Evidence chapter on influenza (see bmj.com <<a href="http://bmj.com/">http://bmj.com/</a>> )—evidence was plentiful. The examples in table 2  show the strength of the evidence and the contradictions in relation to the stated aims of the vaccination campaign. Whenever possible, I chose evidence gathered in the optimal circumstances (for inactivated vaccines)—high viral circulation and a good match between the viral antigen and the vaccine.

View this table: in a new window] <<a href="http://www.bmj.com/cgi/content-nw/full/333/7574/912/TBL2">http://www.bmj.com/cgi/content-nw/full/333/7574/912/TBL2</a>>   Table 2 Examples of evidence from systematic reviews comparing inactivated influenza vaccines with placebo or no intervention

Three problems are immediately apparent. The first is heavy reliance on non-randomised studies (chiefly cohort studies), especially in the elderly. This makes assessment of methodological quality an important part of data interpretation. For example, of 40 datasets assessing the effects of influenza vaccines in elderly people in institutions, only 26 reported data on viral types in circulation and only 21 gave information on vaccine content. Insufficient data were available in 11 of 17 retrospective studies of elderly people in institutions to allow reviewers to assess the authors' claim of "high" or "epidemic" viral circulation.11   A metaanalysis 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.15, 16 It is impossible for a vaccine that does not prevent influenza to prevent its complications, including admission to hospital.

A more likely explanation for such a finding is selection bias, where one half of the study population (hemi-cohort) systematically differs from the other in one or more key characteristics.14 -16  In this case, the vaccinated hemi-cohort may have been more mobile, healthy, and wealthy than the control hemi-cohort, thus explaining the differences in all-cause mortality.11 14  The same effect is seen in stronger study designs (such as cluster randomised trials) that are badly executed, which introduces bias.10   Its presence seems to be a marker of confounders that persist even after adjusting for known ones, and it makes accurate interpretation of the data difficult. Caution in interpretation should thus be the rule, not the exception. This problem (in the opposite direction—with frailer people more likely to be vaccinated) has been identified before but not heeded.17 The only way that all known and unknown confounders can be adequately controlled for is by randomisation.

The influence of poor study quality is also seen in the outcome of a review of evidence supporting the vaccination of all children to minimise transmission to family contacts.18 Five randomised studies and five non-randomised studies were reviewed, but although data were suggestive of protection, its extent was impossible to measure because of the weak methods used in the primary studies.18 

The second problem is either the absence of evidence or the absence of convincing evidence on most of the effects at the centre of campaign objectives (table 2 ). In children under 2 years inactivated vaccines had the same field efficacy as placebo,8   and in healthy people under 65 vaccination did not affect hospital stay, time off work, or death from influenza and its complications.9  Reviews found no evidence of an effect in patients with asthma or cystic fibrosis, but inactivated vaccines reduced the incidence of exacerbations after three to four weeks by 39% in those with chronic obstructive pulmonary disease.12, 13, 19  All reviewers reported small data sets (such as 180 people with chronic obstructive pulmonary disease13) , which may explain the lack of demonstrable effect.

The third problem is the small and heterogeneous dataset on the safety of inactivated vaccines, which is surprising given their longstanding and widespread use. A Cochrane Database Systematic Review found only one old trial with data from 35 participants aged 12-28 months.8 In the general population of elderly people, despite a dataset of several million observations, safety was only reported in five randomised controlled trials (2963 observations in total) on local and systemic adverse events seen within a week of giving parenteral inactivated vaccine.11  Although there appears to be no evidence that annual revaccination is harmful, such a lack of knowledge is surprising.

<strong>Gap between policy and evidence <br /></strong>The large gap between policy and what the data tell us (when rigorously assembled and evaluated) is surprising. The reasons for this situation are not clear and may be complex. The starting point is the potential confusion between influenza and influenza-like illness, when any case of illness resembling influenza is seen as real influenza, especially during peak periods of activity. Some surveillance systems report cases of influenza-like illness as influenza without further explanation. This confusion leads to a gross overestimation of the impact of influenza, unrealistic expectations of the performance of vaccines, and spurious certainty of our ability to predict viral circulation and impact. The consequences are seen in the impractical advice given by public bodies on thresholds of the incidence of influenza-like illness at which influenza specific interventions (antivirals) should be used.20

The confusion between influenza and influenza-like illness is compounded by the lack of accurate and fast surveillance systems that can tell what viruses are circulating in a setting or community within a short time frame, and after the "season" is finished give an accurate picture of what went on to enable better forecasting of future trends.21  Accurate surveillance must be based on a properly worked out sampling system for cases of influenza-like illness that meet set criteria, with accurate and quick feedback of a presumptive microbiological diagnosis. Without this, we cannot generalise from random sampling.

Another reason may be "availability creep." In their efforts to deal with, or be seen to deal with, policy makers favour intervention with what is available—registered influenza vaccines. A similar philosophy is the "we have to make decisions and cannot wait to have perfect data" approach. This attitude may have an altruistic basis but has two important consequences. Firstly, it uses up resources that could be invested in a proper evaluation of influenza vaccines or on other health interventions of proven effectiveness. Secondly, the inception of a vaccination campaign seems to preclude the assessment of a vaccine through placebo controlled randomised trials on ethical grounds. Far from being unethical, however, such trials are desperately needed and we should invest in them without delay. A further consequence is reliance on non-randomised studies once the campaign is under way. It is debatable whether these can contribute to our understanding of the effectiveness of vaccines. Ultimately non-randomised designs cannot answer questions on the effects of influenza vaccines.

<strong>Summary points </strong><br />Public policy worldwide recommends the use of inactivated influenza vaccines to prevent seasonal outbreaks <br />Because viral circulation and antigenic match vary each year and non-randomised studies predominate, systematic reviews of large datasets from several decades provide the best information on vaccine performance <br />Evidence from systematic reviews shows that inactivated vaccines have little or no effect on the effects measured <br />Most studies are of poor methodological quality and the impact of confounders is high <br />Little comparative evidence exists on the safety of these vaccines <br />Reasons for the current gap between policy and evidence are unclear, but given the huge resources involved, a re-evaluation should be urgently undertaken

The optimistic and confident tone of some predictions of viral circulation and of the impact of inactivated vaccines, which are at odds with the evidence, is striking. The reasons are probably complex and may involve "a messy blend of truth conflicts and conflicts of interest making it difficult to separate factual disputes from value disputes"22 or a manifestation of optimism bias (an unwarranted belief in the efficacy of interventions).23

Whatever the reasons, it is a sobering thought that Archie Cochrane's 1972 statement that we should use what has been tested and found to reach its objectives is as revolutionary now as it was then.

Contributor: TJ designed and wrote the paper and is the sole contributor and guarantor. <br />Competing interests: TJ owned shares in Glaxo SmithKline and received consultancy fees from Sanofi-Synthelabo (2002) and Roche (1997-9).

<strong>References <br /></strong> 1. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbid Mortal Wkly Rep 2006;55: 1-41. <br />2. American Academy of Pediatrics Committee on Infectious Diseases. Recommendations for influenza immunization of children. Pediatrics 2004;113: 1441-7.[Abstract/Free Full Text]  <br />3. Orr P. An advisory committee statement (ACS). National Advisory Committee on Immunization (NACI). Statement on influenza vaccination for the 2004-2005 season. Can Commun Dis Rep 2004;30: 1-32.[Medline] <br />4. Van Essen GA, Palache AM, Forleo E, Fedson DS. Influenza vaccination in 2000: recommendations and vaccine use in 50 developed and rapidly developing countries. Vaccine 2003;21: 1780-5.[CrossRef] [Medline] <br />5. World Health Organization. Influenza vaccines. WHO position paper. Wkly Epidemiol Rec 2002;77: 230-40.[Medline] <br />6. Bueving HJ, van der Wouden JC, Berger MY, Thomas S. Incidence of influenza and associated illness in children aged 0-19 years: a systematic review. Rev Med Virol 2005;15: 383-91.[CrossRef] [Medline] <br />7. Beyer WE, de Bruijn IA, Palache AM, Westendorp RG, Osterhaus AD. Protection against influenza after annually repeated vaccination: a metaanalysis of serologic and field studies. Arch Intern Med 1999;159: 182-8.[Abstract/Free Full Text] <br />8. Smith S, Demicheli V, Di Pietrantonj C, Harnden AR, Jefferson T, Matheson NJ, et al. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev 2006;(1):CD004879. <br />9. Demicheli V, Rivetti D, Deeks JJ, Jefferson TO. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 2004;(3):CD001269. <br />10. Thomas RE, Jefferson T, Demicheli V, Rivetti D. Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database Syst Rev 2006;(3):CD005187. <br />11. Rivetti D, Demicheli V, Di Pietrantonj C, Jefferson TO, Thomas R. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev 2006;(3):CD004876. <br />12. Cates CJ, Jefferson TO, Bara AL, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev 2003;(4):CD000364. <br />13. Poole PJ, Chacko E, Wood-Baker RWB, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;(1):CD002733. <br />14. Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli V. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 2005;366: 1165-74.[CrossRef] [Medline] <br />15. Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ, Miller MA. Impact of influenza vaccination on seasonal mortality in the US elderly population. Arch Intern Med 2005;165: 265-72.[Abstract/Free Full Text] <br />16. Simonsen L, Viboud C, Taylor R. Influenza vaccination in elderly people. Lancet 2005;366: 2086.[ISI] [Medline] <br />17. Hak E, Verheij TJ, Grobbee DE, Nichol KL, Hoes AW. Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications. J Epidemiol Community Health 2002;56: 951-5.[Abstract/Free Full Text] <br />18. Jordan R, Connock M, Albon E, Fry-Smith A, Olowokure B, Hawker J, et al. Universal vaccination of children against influenza: are there indirect benefits to the community? A systematic review of the evidence. Vaccine 2006;24: 1047-62.[CrossRef] [Medline] <br />19. Bhalla P, Tan A, Smyth R. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database Syst Rev 2000;(1):CD001753. <br />20. Harling R, Hayward A, Watson JM. Implications of the incidence of influenza-like illness in nursing homes for influenza chemoprophylaxis: descriptive study [see comments]. BMJ 2004;329: 663-4.[Free Full Text] <br />21. Carman WF, Wallace LA, Walker J. Rapid virological surveillance of community influenza infection in general practice. BMJ 2000;321: 736-7.[Free Full Text] <br />22. MacCoun RJ. Biases in the interpretation and use of research results. Annu Rev Psychol 1998;49: 259-87.[CrossRef] > [Medline] <br />23. Chalmers I, Matthews R. What are the implications of optimism bias in clinical research? Lancet 2006;367: 449-50.[CrossRef] [Medline]

See Related Articles and Rapid Responses on the BMJ website:  <<a href="http://www.bmj.com/cgi/eletters/333/7574/912">http://www.bmj.com/cgi/eletters/333/7574/912</a>> 

© 2006 BMJ Publishing Group Ltd<br />~~~~~~~~~~~~~~~~

Tuesday, November 28, 2006
Dr. Yazbak, a pediatrician, now devotes his time to the research of autoimmune regressive autism and vaccine injury.
Nothing New about Lack of Effectiveness of Influenza Vaccination in Babies
By Red Flags Columnist, F. Edward Yazbak, MD, FAAP
(tlautstudy@aol.com)
 
A friend sent a copy of my recent “Influenza Vaccination of Infants: A Useless Risk” (1) to a pediatrician with whom he had been sparring for a while about the need to administer mercury-containing vaccines to babies. By return email, he received a copy of a study just published in the October issue of PEDIATRICS, which he forwarded to me.
The message from the well-meaning pediatrician, who is convinced of the need for influenza vaccination of infants, with or without mercury on-board, was clear: This important peer-reviewed article in a first-class pediatric journal carries more weight than anything published on http://www.reflagsdaily.com/

That is obviously not true. My articles are always well-researched, fully documented, carefully edited before submission and then “peer-reviewed” by the site’s exceptional editor and Red Flags’ informed readers. Because I am pro-reasonable and careful vaccination, my reviews would never be accepted in “medical journals,” not because of their quality but because of their content.
The title of the recent article in PEDIATRICS (2) — “Effectiveness of the 2003-2004 Influenza Vaccine among Children 6 Months to 8 Years of Age, with 1 vs 2 Doses” — could easily be voted Most Creative Title of the year. With a few words, it turned two negatives into a positive message because, in fact, the 2003-2004 Influenza vaccine was almost totally off the mark, and the CDC and the authors themselves found one dose of influenza vaccine inadequate.

The lead author, Debra P. Ritzwoller, PhD, and three co-authors, Susan Shetterly, MS, Kristi Yamasaki, PharmD,and Eric K. France, MD, MSPH, are employees of Kaiser Permanente Colorado. Two other co-authors Carolyn Buxton Bridges, MD, and Margarette Kolczak, PhD, work for the National Immunization Program (NIP) at the Centers for Disease Control and Prevention (CDC).
Both the Clinical Research Unit and the Department of Preventive Medicine at Kaiser Permanente have had a long and close relationship with the NIP.
In a footnote, the authors declared that some of the data had been presented at the June 23, 2004 meeting of the Advisory Committee on Immunization Practices (ACIP) of the CDC and that they had no conflict of interest.

Déjà vu
In the most recent study, the authors included 29,726 children of whom 17.3 percent (5,143) were 6 to 23 months old. Figures in the thousands or millions in medical writings always raise a red flag with me: Why the razzle-dazzle? Is it just a smokescreen?

As I read the paper, I realized that all the comments and findings related to the vaccination of infants were identical to those of a study from Colorado reported in the CDC’s “Mortality and Morbidity Weekly Report” of Aug. 13, 2004 [53(31); 707-719] — research I was well aware of. (3) The release of the earlier study results in MMWR was perfectly timed between the recommendation to vaccinate 6- to 23-month-old children and the beginning of the flu season.
The 2004-2005 flu season was the subject of many articles on Red Flags (4, 5, 6, 7) and was, by far, the most publicized and interesting to watch after its opening salvo with the Chiron debacle.

The 2004 MMWR study was also authored by Ritzwoller, Shetterly, Yamasaki, France, Bridges and others.…
It essentially revealed that:
§ The predominantly circulating influenza A (H3N2) virus strain was antigenically different from the influenza A (H3N2) strain in the 2003-2004 vaccine
§ The study objective was to evaluate how effective the 2003-2004 influenza vaccine was against “medically attended illnesses” — namely influenza-like illness (ILI) and pneumonia and influenza (P&I) — during the peak influenza activity period of 19 days in the Denver metropolitan area (Nov. 19 to Dec. 7, 2003)
§ A total of 5,139 children were included in the analysis
§ Of those children, seven percent had chronic illnesses
§ Seven percent of the children were fully vaccinated (two doses of vaccine) and 20 percent were partially vaccinated (one dose) on Nov. 19. By the end of the study period, 5 and 27 percent respectively, were fully or partially vaccinated
§ Fully vaccinated children had a 25 percent reduction in ILI and a 49 percent reduction in P&I
§ Partially vaccinated children had no statistically significant reduction in either.

The study was never published in a peer-reviewed journal. 
In her November 2004 article “How effective is the flu vaccine,” (8) Maryann Napoli criticized the Ritzwoller findings: “But the key question is: 49% and 25% of what? Dr. Ritzwoller was not able to provide the answer. Here's why the question is important: If few children in this study got the flu, then these reductions are less than meets the eye. For example, if 10,000 kids belong to a health plan and only four of the unvaccinated kids and three of the vaccinated kids got an influenza-like illness, that's 25% fewer cases.”

Napoli also questioned why the children were not randomly assigned to a vaccine and placebo group and reported that “When asked whether the flu vaccine caused any adverse reactions, Dr. Ritzwoller said there were none, but acknowledged some gaps in her study. ‘Hospital admissions were not tracked, and the parents were not interviewed,’ she explained, attributing this to inadequate CDC funding.”

This last statement by the lead author now creates two real problems for the CDC:
1. If “hospital admissions were not tracked,” then how can the ACIP claim that vaccination of children 6 to 23 months will decrease hospitalization rates?
2. If the CDC funded the study reported in MMWR last year, it certainly — at least in part — funded the recent study just published in PEDIATRICS.

This latter was not acknowledged and raises at least one question: How can a study by scientists employed by a vaccine-promoting agency and others who are funded by that same agency be published with a footnote stating “No conflict of interest declared”? 
The October 2005 publication
The article’s conclusion was as creative as the title — “Influenza vaccine was shown to prevent medically attended ILI among children six to 23 months of age, as well as older children, even with a suboptimal match” — and challenged both logic and definition.

From the point of scientific logic: As much as the authors (and the CDC) believe that the mismatched 2003-2004 influenza vaccine should, would or could have affected clinical illness in the community, it is unlikely that intelligent readership would accept that it actually did.

From the point of simple definition:
§ Optimal means most favorable or desirable, and most favorable should be in the vicinity of  90 percent
§ Suboptimal usually connotes something just slightly less than optimal, perhaps 85 percent and even possibly 75 percent. But it certainly was never ever intended to describe an 11 percent antigenic match between the predominant circulating influenza A virus strain and any strain in the available vaccine. That match can only be described as terrible!
The rest of the article reveals the following:
§ Vaccine effectiveness findings were listed under the subtitle “Estimates of VE”
§ The authors conceded that “because this was an observational study, vaccination status was not randomized.  Therefore, irrespective of the adjustment variables used, selection bias may exist with respect to which patients obtained vaccination.”
§ The respiratory outcomes were not laboratory-confirmed and were based only on available data on the HMO computers. 
§ The analyses and conclusions were limited to a very short period of 19 days from Nov. 19 to Dec. 7, 2003.
§ Only 17.3 percent (5,143) of the 29,726 children included in the analysis were 6 to 23 months old.
§ By the start of the study period on Nov. 19, only 7.5 percent of children 6 months to 8 years old were fully vaccinated and 9.9 percent were partially vaccinated
§ By the end of the study period, children 6 to 23 months of age had vaccination rates of 14.6 percent and 27 percent, respectively for full or partial immunization, the highest rate achieved in the Colorado HMO.
§ “Vaccine effectiveness” for fully vaccinated 6 to 23 months old children was reported again as it was in 2004 at 25 percent for ILI and 49 percent for P&I.
§ One dose of vaccine was useless and did not affect the incidence of both disease categories in any statistically significant fashion.
§ Some 46 children in all, aged five to eight years, received the live attenuated influenza vaccine as the vaccine is contraindicated in children under five

Viral Surveillance 2003-04
1. In the fall of 2003, the population of the United States was estimated to be 292 million.
2. During the complete influenza season — Sept. 28, 2003 to May 22, 2004 — there were 130,577 respiratory specimens for influenza viruses tested in the United States by CDC-approved laboratories. (8)
3. Only 18.9 percent or 24,649 specimens were positive. In other words, almost 80 percent of individuals suspected to have influenza in the United States did not have evidence of the virus on culture and could not be presumed to have influenza.
4. Of the positive cultures, 99 percent or 24,393 were influenza A viruses and 249 were influenza B viruses. 
5. Of the influenza A specimens, 7191 or 29.5 percent were sub-typed. Of these, 7,189 (99.9 percent) were influenza A (H3N2) viruses, and two (0.1 percent) were influenza A (H1) viruses.
6. The proportion of specimens testing positive for influenza peaked at 35.2 percent during the week ending Nov. 29. During the previous four seasons, the peak percentage of specimens testing positive for influenza ranged from 23 percent to 31 percent. The peaks were also later in the season.
7. By June 15, 2004, CDC had antigenically characterized 1,024 influenza viruses collected by U.S. laboratories since Oct. 1, 2003.
8. Of the 949 influenza A (H3N2) isolates characterized, only 106 (11.2 percent) were similar antigenically to the vaccine strain A/Panama/2007/99 (H3N2) and 88 percent or 843 were different.

Looking at the pediatric population of the Colorado HMO, of the 5,143 children aged 6 to 21 months, only 750 (14.6 percent) at most received two doses of vaccine. Of those, only 11.2 percent or 84 children could have possibly acquired vaccine-induced immunity — if indeed the vaccine is effective as the CDC claims and many others deny. (1)
A new, simpler and cheaper study should now be done that could help us all. 

Ritzwoller should get her favorite computer programmer to identify the 750 records of infants under the age of 23 months enrolled in the HMO who received two doses of flu vaccine. She should then exclude infants with pre-existing or chronic conditions and compare the rest of the group with a matched sample of unvaccinated infants. Now those results will be worth publishing on www.redflagsdaily.com.
*          *            *

Safety of influenza vaccines in children
In a letter to the editor of The Lancet on Sept. 3, 2005, T. Jefferson, S. Smith, V. Demichelli, A. Hamden and A. Rivetti expressed their concerns and frustration at the fact that, though they tried, they were unable to get reliable information regarding the safety of influenza vaccines on the market.

This team has written and published several comprehensive publications on vaccination practices.  My most recent article on influenza vaccination of infants 6 to 23 months (1) was mostly based on their impressive review of the efficacy and effectiveness of influenza vaccines in children, a review that included every study they could find in any language.
In the letter to The Lancet, Jefferson and associates expressed deep concern that safety studies were not done, the studies were too old and too small, or the vaccine manufacturer simply refused to allow the team to review the data from the vaccine trials.

The frustrated authors ended their letter stating, “We believe all unpublished trial safety data should be readily accessible to both the regulatory bodies and the scientific community on request. Our evidence gives rise to a concern that lack of access to unreported data prevents published data being put into context and hinders full and independent review. This cannot be good for public confidence in these vaccines.”
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According to both the FDA and the CDC, “The fact that an adverse event occurred following immunization is not conclusive evidence that the event was caused by a vaccine.” 

A VAERS (Vaccine Adverse Events Reporting System) search performed on Oct. 10, 2005 yielded three reports in the past two years of children younger than 23 months of age who died shortly after receiving a dose of influenza vaccine. No other vaccines were administered at the same time and all three children had underlying diseases.
Report # 210764: 8-month-old vaccinated 10/7/2003. Died suddenly 10/8/2003.
Report # 214136: 1.7-year-old vaccinated 11/24/2003. Died suddenly 11/29/2003.
Report # 228987: 8-month-old vaccinated 10/18/2004. Developed symptoms within 24 hours and died on 10/23/2004.
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Procter and Gamble and the Simple Solution
On July 16, 2005, Luby, Agboatwalla, Feikin et al published in The Lancet a simple and convincing randomized controlled study, which showed that hand washing with soap can prevent diarrhea and lower respiratory infections, the two clinical syndromes responsible for the largest number of childhood deaths globally. Four of the investigators, including the lead author, are CDC employees. (10)

Neighborhoods in adjoining squatter settlements in Karachi, Pakistan, were randomly assigned. Three hundred households in 25 neighborhoods were assigned to use plain soap and an equal number of households were assigned to use antibacterial soap with triclocarban. Three hundred and six households in 11 different neighborhoods were randomized as controls. Weekly home visits by trained workers were used to encourage hand washing in the “treated” group and to carefully record illnesses in all groups.

There was a 50 percent lower incidence of pneumonia among children younger than five in households that received plain soap and hand-washing promotion than among controls. Pneumonia was defined according to the World Health Organization clinical case definition. Analysis was by intention to treat.

In addition, children under the age of 15 in the plain-soap group had a 53 percent lower incidence of diarrhea and a 34 percent decreased incidence of impetigo than matched controls.
Incidence of disease was about the same between the soap groups.
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Advantages of the plain bar of soap
§ It really works
§ It is absolutely safe
§ It is competitively priced
§ It is easily available
§ It has never contained thimerosal
§ It has a very long shelf life
§ It does not require refrigerated transport
§ It does not hurt unless you get it in the eye
§ It carries a lifetime guarantee not to cause Guillain Barre Syndrome and intussusception
§ It makes much more sense

Conclusions:
1. A recent study is not convincing as to the effectiveness of the available pediatric influenza vaccine.
2. Other national and international studies have questioned the vaccine’s efficacy and effectiveness in children less than 23 months of age.
3. A smaller simple study was outlined that can provide more reliable and believable results with little effort and without extra funding by the CDC.
4. It is more than likely that there will be a shortage of preservative-free influenza vaccine this season and that the CDC will still assert that any vaccine containing mercury is better than nothing.
5. The FDA should investigate vaccine manufacturers who refuse to reveal the findings of their vaccine safety studies to reputable and discreet researchers.
6. Unbiased vaccine research, free of any conflict of interest, is much needed.
7. Think soap.
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References:
1. http://www.redflagsdaily.com/yazbak/2005_sep30.php
2. Ritzwoller DP, Bridges CB, Shetterly S, Yamasaki K, Kolczak M, France EK; Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses. Pediatrics. 2005 Jul;116(1):153-9.
3. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5331a1.htm
4. http://www.redflagsdaily.com/conferences/vaccines/2004_nov17.php
5. http://www.redflagsdaily.com/conferences/vaccines/2004_dec03.php
6. http://www.redflagsdaily.com/yazbak/2005_feb17.php
7. http://www.redflagsdaily.com/yazbak/2005_feb25.php
8. http://www.medicalconsumers.org/pages/FluVaccineisRarelyEffective.html
9. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5325a1.htm
10. Luby SP,  Agboatwalla M,  Feikin DR, Painter J, Billhimer W, Altaf A, Hoekstra RM Effect of handwashing on child health: a randomised controlled trial. The Lancet 2005; 366:225-233
 

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