Flu Vaccination

Abstract

The research presented in this article exposes a wide gap between evidence and public policy with regard to influenza vaccination in the context of the 2009 pandemic and with regard to yearly seasonal epidemics. It shows that the World Health Organization and health authorities worldwide failed to protect the interests of the most vulnerable during the 2009 flu pandemic and demonstrates a lack of scientific base for seasonal flu vaccination campaigns. Narrowing the gap between scientific evidence and public health policies with regard to influenza is a serious and urgent matter, one that implies confronting the interests of big pharmaceutical corporations and their allies at academic and government levels. The credibility of science and the well-being of many are at stake.

Keywords

flu vaccination public policy pharmaceutical companies vaccination campaign pandemic flu

The 2014 official webpage on influenza of the US Centers for Disease Control and Prevention (CDC) opens with a categorical statement: “The single best way to protect against the flu is to get vaccinated each year.”¹ The CDC guidelines for flu vaccination further clarify: “All persons aged 6 months and older are recommended for annual vaccination, with rare exception.”² Exceptions are specified as: “People with severe, life-threatening allergies to flu vaccine or any ingredient in the vaccine.”²

Current guidelines in Europe are somewhat more cautious. The British National Health Service introduces its webpage on influenza as follows: “For most people, flu is an unpleasant illness, but it's not serious. If you are otherwise healthy, you will usually recover from flu within a week. However, certain people are more likely to develop potentially serious complications of flu, such as bronchitis and pneumonia. These people should have a flu jab each year.”³ It then specifies who is eligible for a flu shot covered by the public health service: “You are eligible to receive a free flu jab if you are 65 years of age or over, are pregnant, have certain medical conditions, are living in a long-stay residential care home or other long-stay care facility, receive a carer's allowance, or are the main carer for an elderly or disabled person whose welfare may be at risk if you fall ill, are a health care worker with direct patient contact or a social care worker.”³ Medical conditions that make one eligible for the shot are further clarified: “Chronic (long-term) respiratory disease, such as asthma (that requires inhaled or tablet steroid treatment or has led to hospital admission in the past), chronic obstructive pulmonary disease (COPD) or bronchitis; chronic heart disease, such as heart failure; chronic kidney disease; chronic liver disease, such as hepatitis; chronic neurological conditions, such as Parkinson's disease or motor neurone disease; diabetes; problems with your spleen—for example, sickle cell disease, or if you have had your spleen removed; a weakened immune system due to conditions such as HIV and AIDS, or as a result of medication such as steroid tablets or chemotherapy.”³ The National Health Service also recommends the flu vaccine for children over the age of 6 months with a long-term health condition and for healthy children aged 2, 3, and 4 years.³ Most European countries have guidelines similar to those of the British National Health Service.

Does the current knowledge of the effectiveness and safety of the flu vaccine support current public policy in the United States and Europe?

To answer this question, I will analyze relevant aspects of the 2009 flu pandemic and present the evidence available regarding the effectiveness and safety of the seasonal influenza vaccine.

The Flu Pandemic in 2009: A Fake Pandemic According to the Parliamentary Assembly of the Council of Europe

The Parliamentary Assembly of the Council of Europe (PACE) is dedicated to upholding human rights, democracy, and the rule of law and oversees the European Court of Human Rights. (The parliamentarians who make up PACE come from the national parliaments of the Organization's 47 member states. They meet 4 times a year to discuss topical issues and ask European governments to take initiatives and report back. These parliamentarians speak for the 800 million Europeans who elected them. They broach the issues of their choice, and the governments of European countries – represented at the Council of Europe by the Committee of Ministers – are obliged to respond. They are Greater Europe's democratic conscience. [www.website-pace.net/en_GB/web/apce/functioning]). On December 18, 2009, 14 members of PACE, led by the epidemiologist Wolfgang Wodarg (then chair of the Health Committee in the European Council), issued a motion for a recommendation entitled Faked Pandemics – a Threat for Health.⁴ In their document, these European parliamentarians stated: “In order to promote their patented drugs and vaccines against flu, pharmaceutical companies have influenced scientists and official agencies, responsible for public health standards, to alarm governments worldwide. They have made them squander tight health care resources for inefficient vaccine strategies and needlessly exposed millions of healthy people to the risk of unknown side-effects of insufficiently tested vaccines.”⁴ In an interview for the Danish press, Wodarg called the 2009 pandemic “one of the greatest medical scandals of the century” and pointed to the change in the definition of pandemic implemented by the World Health Organization (WHO) in May 2009⁵:“From June 2009 it is no longer necessary, that ‘an enormous amount of people have contracted the illness or died’—there simply have to be a virus, spreading beyond borders, and one that people have no immunity towards.”⁶ On March 23, 2010, the final memorandum of the PACE concluded that the H1N1 crisis had been handled without transparency and that the WHO and other public institutions involved in public decisions regarding the pandemic had “gambled away” the confidence of the European public.⁷ Let us analyze the causes of such a serious accusation.

On April 29, 2009, ie, only 12 days after the 2 first cases of H1N1 had been diagnosed (The 2 first cases appeared in California and were diagnosed on April 17, 2009. See Zimmer SM, Burke DS. Historical perspective: emergence of influenza A (H1N1) viruses. NEJM. 2009:279.) WHO Director Margaret Chan declared a worldwide alertness level 5 for a danger of pandemic and recommended that all governments declare a national health emergency and activate the pandemic emergency plans that had been approved during the 2004–2005 avian flu alarm.⁸ In accordance with these WHO recommendations, on April 26, 2009, the US government declared a national health emergency, despite the fact that there had been only 20 people infected in the United States and none had died.⁹ By then, it was already known that the H1N1 virus was more benign than the usual seasonal flu viruses.¹⁰ Moreover, only the strain (S-OIV), not the type (H1N1), was new,^11–13 and up to one third of the elderly population (the population that accounts for >90% of flu-associated mortality¹⁴) had protective cross-immunity.¹⁵ On June 11, 2009, less than 2 months after the appearance of the first cases, Dr Chan declared a worldwide pandemic level 6 (the highest level) caused by the flu virus A/H1N1 S-OIV.¹⁶ How could WHO authorities announce the maximum level of pandemic alertness with such a mild infection? It was first necessary to change the criteria that define a pandemic. As we have already seen, this happened in May 2009.^{17
18}

While alarming the population with the possibility of having millions of people die from the new flu strain, WHO, together with the responsible health regulatory agencies in the United States (CDC, US Food and Drug Administration) and in Europe (European Medicines Agency), allowed that only 4 pharmaceutical companies successfully claim and hold exclusive patents for the pandemic flu vaccine (The US Food and Drug Administration approved the nonadjuvanted vaccines from Novartis (Focetria/Celtura), Sanofi Pasteur (Panenza/Humenza), and CSL. It also approved the live vaccine from Medimmune for intranasal delivery. [www.fda.gov/newsevents/newsroom/pressannouncements/ucm182399.htm]), (The European agency approved the vaccine from GSK [Pandemrix] and the vaccine from Novartis [Focetria]. Both used oil-in-water adjuvants: ASO3 in Pandemrix and MF59 in Focetria. European Medicines Agency press release, European Medicines Agency recommends authorization of 2 vaccines for influenza pandemic (H1N1) 2009. September 25, 2009.) In the midst of such a severe health crisis as they announced, why did they not require that all equipped laboratories worldwide be allowed to produce the vaccine with the upmost urgency in order to be as efficient as possible in the attempt to save millions of lives? (Interview in Danish done by Louise Voller and Kristian Villesen for the journal Information [www.information.dk/219754]. A full English translation of the interview can be found in Dr Wodarg's personal webpage [www.wodarg.de/english/3013320.html]. Wodarg claimed in this interview: “A vaccine which is that important should not be patented. Everyone who technically is capable of doing so should produce vaccines as quickly as possible when an emergency arises. In that way we can save more lives when a true pandemic arrives.”) In October 2009, news channels around the globe announced a shortage in vaccine supplies.¹⁹ In the midst of a world health emergency of the highest degree and having a medical intervention (the vaccine) that allegedly could successfully control it, health authorities at local and international levels put at risk millions of people in order to uphold the economic interests of 4 of the most affluent private companies in the world.^20,21 These 4 pharmaceutical companies, taking advantage of exclusive patent rights, increased the price of the pandemic flu vaccine. Governments around the world allowed this to happen and outlawed the production of generic versions of the vaccine. Some countries had to cut their social budgets in order to buy enough vaccine for their entire population, especially because early in the flu season, the same pharmaceutical companies that benefited from selling the vaccine announced that, contrary to what is the case for the seasonal flu vaccine, the pandemic flu vaccine would probably need to be administered in 2 doses.^22,23 This announcement, together with alarm about the shortage of the vaccine, prompted governments worldwide to rush into signing contracts with the pharmaceutical companies to secure a double dose for each of their citizens. Later, when health authorities announced that only 1 dose would be required,²⁴ these governments had to honor these contracts and were obliged to purchase millions of doses of the extra-expensive pandemic flu vaccine, most of which ended up being destroyed a couple of years later.

Adverse Effects of Adjuvanted Pandemic Vaccines and Immunity of the Pharmaceutical Companies

The negative consequences of the alleged “fake pandemic” were not only financial. Two of the 4 pharmaceutical companies that held exclusive patents for the pandemic flu (Novartis and GSK) requested to change the composition of the vaccine to speed up its production: the amount of antigen was decreased and the adjuvant was changed. The WHO backed up this initiative: “In view of the anticipated limited vaccine availability at global level and the potential need to protect against ‘drifted’ strains of virus, SAGE [WHO's Strategic Advisory Group of Experts on immunization] recommended that promoting production and use of vaccines such as those that are formulated with oil-in-water adjuvants and live attenuated influenza vaccines was important.”²⁵ The United States did not approve adjuvanted vaccines. Europe did. The vaccines that contain oil-in-water adjuvants are those with the lowest amount of antigen: some of these vaccines contain as little as 1.875 mg of antigen, whereas typically a nonadjuvanted flu vaccine contains a minimum of 7.5 mg.²⁶ According to the most comprehensive study on H1N1 vaccines among those published in 2009, a nonadjuvanted vaccine with 15 mg of antigen was able to mount a satisfactory immune response in the majority of subjects between 12 and 60 years of age.²⁷

Given that the security of the pandemic vaccines was insufficiently studied, the pharmaceutical companies requested that the governments sign a binding immunity deal with them in order to free these companies from all responsibility in case of unexpected adverse effects.²⁸ WHO supported their claim while confirming the experimental nature of the new adjuvanted vaccines: “Since new technologies are involved in the production of some pandemic vaccines, which have not yet been extensively evaluated for their safety in certain population groups, it is very important to implement post-marketing surveillance of the highest possible quality. In addition, rapid sharing of the results of immunogenicity and post-marketing safety and effectiveness studies among the international community will be essential for allowing countries to make necessary adjustments to their vaccination policies.”²⁸ With the sole exception of Poland, all governments signed the immunity deal demanded by the pharmaceutical companies. Family doctor Ewa Kopacz, then the health minister of Poland, publicly denounced the medical and political contradictions of the WHO pandemic management and refused to sign such an abusive contract.²⁹ This fact provided a rare and precious opportunity to assess the efficacy of the pandemic vaccine: how did the incidence and the mortality of the 2009 pandemic flu in Poland compare with those in the surrounding countries that had implemented mass vaccination? The comparison is not easy to do, given uncertainties in the diagnosis of the H1N1 infection and in the attribution of the cause of death, but the official numbers available show that Poland had a relatively lower number of H1N1 infections and of H1N1-related mortality than some of its most heavily vaccinated neighbors: Poland (≈38.10⁶ population) reported 2 024 cases and 181 deaths; Italy (≈59.10⁶ population) reported 3 333 cases and 244 deaths; France (≈66.10⁶ population) reported 5 000 cases and 344 deaths.³⁰

In October 2009, a team of concerned researchers from Germany warned of the potential dangers of using vaccines adjuvanted with oil-in-water emulsions for mass vaccination: “Evidence from animal experiments in conjunction with clinical epidemiological data indicates that, quite irrespective of cause, stimulation of the immune system may accelerate atherogenesis.”³¹ The mechanism of action of water-in-oil adjuvants (MF59 in the vaccine Focetria from Novartis and ASO3 in the vaccine Pandemrix from GSK) was and still is not properly understood: “MF59 induces macrophage recruitment to the injection site and appears to promote uptake of antigen by macrophages and dendritic cells … . Injection of adjuvanted flu vaccine frequently causes local pain and occasionally fever, an indication that proinflammatory cytokines are generated in appreciable amounts … . In addition to squalene, the GSK vaccine also contains the non-ionic detergent polysorbate 80 (Tween 80), with uncharacterized pharmacokinetic and immunological properties, and alpha-Tocopherol.”³¹ MF59 and ASO3 both contain squalene; the lipidic structure of squalene strongly stimulates macrophages and can cause nonspecific immune-mediated collateral damage, thus aggravating most chronic diseases, such as atherosclerosis, inflammatory bowel disease, demyelinating diseases, and noninfectious arthritis. It is well-established that atherosclerosis can be aggravated by unrelated immunological events, such as acute and chronic infections, stress, smoking, and diabetes.

In October 2009, these authors recommended honoring the precautionary principle and decreeing a hold on the mass vaccination programs given the rather benign nature of the H1N1 pandemic flu in comparison with the seasonal flu. The vaccines would then be used only in case of an increase (highly unlikely) in virulence of the circulating H1N1 viruses. Facing the probability that health authorities would decide to go ahead with the mass vaccination despite the forewarned risks, the authors' emphatic recommendation was to use nonadjuvanted vaccines. In the case that the vaccines adjuvanted with squalene were administered despite all warnings, it would be of utmost importance to set up an accurate surveillance program capable of detecting the aggravation of the widely spread chronic diseases mentioned above. Given the widespread and chronic nature of these diseases, their aggravation would be impossible to link to a mass vaccination unless epidemiological studies were specifically designed and implemented to examine this link.³¹

The United States refused to approve the vaccines adjuvanted with squalene for mass vaccination, but both pandemic vaccines approved in Europe (Pandemrix and Focetria) contained squalene (ASO3 in Pandemrix and MF59 in Focetria). No surveillance program was set up, but one adverse effect of the ASO3-adjuvanted vaccine Pandemrix was severe enough to cause its emergency withdrawal in some European countries.³² In August 2010, clinicians in Finland and Sweden identified an apparent increase in the incidence of narcolepsy in children vaccinated with Pandemrix.^33,34 Narcolepsy is a chronic disorder presenting with excessive daytime sleepiness, often accompanied by a transient loss of muscle tone triggered by strong emotion (cataplexy). The narcolepsy associated with Pandemrix showed an abrupt onset and an unusual severity.³⁵ The cause of narcolepsy is the loss of hypocretin cells in the hypothalamus. It is thought to be an autoimmune disease with a strong HLA (human leukocyte antigen) association (DQB1*0602) triggered by environmental factors.³⁵ That oil-in-lipid adjuvants, by their very design, could trigger immune-mediated diseases is what Bhakdi, Lackner, and Doerr,³¹ the concerned researchers from Germany, had predicted in October 2009.

The European Medicines Agency confirmed the association between Pandemrix and narcolepsy in England, Ireland, France, and Norway and recommended avoiding the use of Pandemrix in persons under 20 years of age.³⁶ Taking into account that the interval between onset of narcolepsy and diagnosis can be long, with a median up to 10.5 years,³⁷ and that the diagnostic delay is typically less in younger patients,³⁸ why did the European Medicines Agency not apply the precautionary principle and recommend, following Finland's lead, the withdrawal of Pandemrix in all European countries for all age groups?³⁹ A retrospective analysis done in England between August 2011 and February 2012 found an odds ratio of 14.4 (4.3–48.5) for narcolepsy after Pandemrix vaccination,⁴⁰ a result consistent with the relative risk of 13 reported from Finland in its retrospective cohort study.⁴¹ By November 2013, approximately 800 children and young adults in Europe had been affected from post-H1N1 narcolepsy–cataplexy and their condition remained heavily disabling and incurable.⁴²

A meta-analysis of all randomized clinical trials (RCTs) on the H1N1 vaccines in April 2011 showed a 0.013% rate of serious adverse effects, defined as life-threatening events or events resulting in persistent disability, hospitalization, or death.⁴³ Taking total population size into account, the expected number of people experiencing serious adverse effects after a 100% successful H1N1 mass vaccination campaign would be 7 670 in Italy and 8 580 in France. Contrast this number with the fact that – as we shall see in the next section – there is not enough evidence to prove that seasonal flu vaccines are effective in healthy adults⁴⁴ and with the fact that rates of H1N1 infection and mortality in Poland compared to those in Italy and France showed no effect of the pandemic vaccine. Mild to moderate adverse reactions self-reported during the first 7–10 days after vaccination (fever, any systemic reaction, injection-site pain, and any local reaction) were more (and very) frequent for oil-in-water adjuvanted vaccines (fever in up to 15% of cases, other systemic reactions and local pain in up to 84%). According to the European Medicines Agency's assessment of the safety of the ASO3-adjuvanted vaccine Pandemrix: “The most common side effects with Pandemrix (seen with more than 1 in 10 doses of the vaccine) are headache, arthralgia (joint pain), myalgia (muscle pain), swelling and pain at the site of the injection, shivering, increased sweating, and fatigue (tiredness).”⁴⁵ The authors of the meta-analysis highlight that adverse effects were only monitored short-term and warn that 15 out of the 18 RCTs published were financed by the pharmaceutical industry, suggesting potential sponsorship bias. Moreover, fewer than one third (21 out of 68) of the registered RCTs on H1N1 vaccines had been published in peer-reviewed journals (potential publication bias); the published subset included only 48.1% of the total randomized sample size (19 875 of 41 329). They state also that the degree to which the immunological measures used in these RCTs can be considered markers of vaccine effectiveness is at present unknown, given that live attenuated vaccines have demonstrated their clinical effect without causing an increase in specific antibodies. It is today clear that existing immune correlates such as serum hemagglutination-inhibition antibodies may be unsuitable to estimate vaccine immunogenicity and protective efficacy.⁴⁶

As Poland's then Minister of Health Ewa Kopaj noted, the governments, not the pharmaceutical companies, carried the financial burden of compensation for all serious adverse effects associated with the pandemic mass vaccination.^{47
48} Great amounts of public money were invested to pay for the vaccines when the pharmaceutical companies announced that a second dose would be needed; governments were not compensated by these companies after the decision was finally made that one dose would suffice. Public money was also invested for compensation of severe vaccine-related adverse effects. The extraordinary financial benefits of the H1N1 pandemic vaccination campaign remained in private hands, whereas its financial costs (compensation money) were transferred to governments.

The Cochrane Collaboration Assessment of the Seasonal Flu Vaccine Efficacy

The Cochrane Collaboration is an international, nonprofit, independent organization that promotes evidence-informed health decision making by producing high-quality, relevant, accessible systematic reviews, and other synthesized research evidence.⁴⁹ The Cochrane researchers evaluated the efficacy (preventing confirmed influenza) and effectiveness (preventing influenza-like illness [ILI] (ILI 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. ILI does not have documented laboratory isolation of the causative agent and is the syndrome that most commonly presents to the doctors (‘the flu’).⁵⁶ Influenza A and B represent about 10% of all circulating viruses (more than 200) that can cause ILI.)) of parenteral inactivated and live aerosol influenza vaccines in healthy adults (including pregnant women), healthy children, the elderly, healthcare workers who work with the elderly, people with asthma, people with COPD, children and adults with bronchiectasis, people with cystic fibrosis, children being treated with chemotherapy for cancer, and immunosuppressed adults with cancer.

Effectiveness of the Vaccine in Healthy Adults (Including Pregnant Women)

Influenza vaccination of pregnant women is recommended internationally, whereas healthy adults are currently targeted only in North America. In March 2014, the Cochrane Collaboration published a review demonstrating that the preventive effect of parenteral inactivated influenza vaccine on healthy adults is small: at least 40 people must be vaccinated to prevent 1 ILI case (95% confidence interval [CI]: 26–128) and at least 71 to prevent 1 influenza case (95% CI: 64–80). Live aerosol vaccine had an overall effectiveness (prevention of ILI) comparable to that of the parenteral vaccine: NNV (NNV: number needed to vaccinate. This number indicates how many subjects need to be vaccinated to prevent 1 single case of the disease.) 46 (95% CI: 29–115) and neither of the 2 (parenteral inactivated or live aerosol) showed any appreciable effect on the most relevant public health items associated with the flu among healthy people: working days lost or hospitalization.⁵⁰ The studies reviewed included 69 clinical trials with more than 70 000 people, 27 comparative cohort studies with about 8 million people, and 20 case–control studies with about 25 000 people. The authors warned that the large majority of these studies (70%) could not be properly evaluated due to insufficient reporting details and very different scores among the items evaluated, and that another 20% were clearly biased. The alarming fact is that overall, only 10% of the relevant studies were found to be methodologically sound. Furthermore, despite the international consensus in recommending flu vaccination for pregnant women, no RCTs assessing the safety or effectiveness of vaccination in pregnant women have ever been conducted. The only evidence available comes from observational studies with, at best, modest methodological quality. The studies reviewed (23 reports with a total of 1.6 million mother–child couples) showed very limited effect: NNV 92 (95% CI: 63–201) against ILI in pregnant women and NNV 27 (95% CI: 18–185) against laboratory-confirmed influenza in newborns from vaccinated women.

Effectiveness of the Vaccine in Children

Particularly worrisome are the results of the Cochrane review with regard to vaccination of children under the age of 2 years. Vaccinating healthy children from 6 months of age is recommended in the United States, Canada, Australia, and parts of Europe, but there is no reliable evidence to support efficacy or effectiveness of the vaccine in this population or to rule out harmful side effects.⁵¹ For children between ages 2 and 6, the live attenuated vaccine (intranasal administration) seemed to work (only 6 children would need to be vaccinated to avoid 1 case of influenza). For children ages 6–16, the numbers needed to vaccinate were 28 for influenza and 8 for ILIs. However, the review could find no evidence of effect on relevant public health items: secondary cases, lower respiratory tract disease, drug prescriptions, and otitis media and their consequences and socioeconomic impact. The researchers concluded that the evidence in favor of vaccinating children for influenza is sparse. They denounced a widespread manipulation of the conclusions of the available studies and warned that any positive findings should be interpreted with caution.

It is worth noting that in 2007, a Cochrane systematic review of 274 studies on the influenza vaccine found that studies funded by pharmaceutical companies yielded more positive results than studies that were publicly funded, and that studies funded by pharmaceutical companies were published in higher impact journals that were cited more frequently, regardless of their objective methodological quality.⁵¹

Effectiveness of the Vaccine in the Elderly and Their Caretakers

After reviewing all existing studies on influenza vaccination among the elderly, the Cochrane reviewers concluded that the available evidence is of poor quality and provides no guidance regarding the safety, efficacy, or effectiveness of influenza vaccines for people aged 65 years or older. They recommend a publicly funded and adequately powered RCT run over several seasons to resolve the uncertainty.⁶² Although confirming the usefulness of simple and low-cost interventions, such as hand washing, to reduce the spread of epidemic respiratory viruses,⁵³ the Cochrane reviews do not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older residing in long-term care institutions. Also in this regard, high-quality RCTs are required to avoid the risks of bias in methodology and conduct.⁵⁴

Effectiveness of the Vaccine in Patients With Respiratory Diseases or Immunosuppression

There is tenuous evidence of benefit in patients with COPD and in immunosuppressed adults with cancer. There is no evidence to support vaccination of patients with asthma, bronchiectasis, or cystic fibrosis. There is no evidence to support vaccination of children being treated with chemotherapy for cancer.⁵⁵

The Striking Selection Bias of the Studies Behind the Seasonal Flu Vaccination Campaigns for the Elderly

In 2006, policies recommending vaccination for the elderly (defined as people aged 60 or 65 and older) were in place in 40 of the 51 developed or rapidly developing countries.⁵⁶ This practice started in 1960 in the United States, when, for the first time, the influenza vaccine that had been developed in the 1940s to protect soldiers was offered to the general public, with a particular recommendation for high-risk groups.⁵⁷ The elderly were targeted because 90% of all influenza-related deaths occur among people who are over 65 years of age, with 75% among those over age 70. Numerous cohort studies performed since the introduction of the influenza vaccine have reported a reduction approaching 50% in all deaths in vaccinated compared to unvaccinated seniors during the influenza season.⁵⁸

However, in 2005, epidemiologist Lisa Jackson⁵⁹ suspected that a heavy selection bias was distorting the results of these cohort studies. She noted the logical contradiction of stating a 50% reduction in overall mortality after influenza vaccination, while knowing that influenza accounts for at most 10% of all winter deaths.⁶⁰ Jackson set up to evaluate a cohort of 72 527 elderly followed during 8 years and compared the risk of death from any cause and the risk of hospitalization for pneumonia or influenza of those who had received the influenza vaccination with the risks of those who had not.(The study cohort included 72 527 seniors, who contributed a total of 338 264 person-years of observation during the 8-year study period. During each year, approximately 44 000 seniors were evaluated, and influenza vaccine coverage ranged from 68% to 74% during the study years.) Jackson's assessment included the periods before, during, and after influenza seasons. She found out that the relative risk of death for vaccinated persons compared with unvaccinated persons before, during, and after the influenza season was 0.39, 0.56, and 0.74, respectively, and that of hospitalization for pneumonia was 0.72, 0.82, and 0.95. The fact that stronger differences in risk between the 2 hemi-cohorts were found before the influenza season reveals the presence of a confounding variable. That the risk of dying before the influenza season was found to be lower among those who will be vaccinated indicates a preferential receipt of the vaccine by relatively healthier seniors. The relative risks of death and hospitalization for pneumonia during the influenza season found in this study were very similar to those in comparable cohort studies.⁶¹

Only one prior study had analyzed the relative risks of the 2 hemi-cohorts before the influenza season.⁶² This prior study did not observe differences between the vaccinated versus the unvaccinated hemi-cohorts, but it had methodological flaws that invalidate its results (eg, it recruited the case patients retrospectively, after the end of the influenza season, thus making it possible that participants' survival and health status at the time of recruitment influenced the likelihood that they would be recruited).⁶³

By demonstrating that the greatest reduction in risk of death and pneumonia hospitalization occurred in the period before the influenza season, Jackson discovered a striking selection bias in the previous studies. The existence of such a deep and obvious bias calls into question public health policies that advocate for routine yearly vaccination of the elderly, because the magnitude of the identified bias is sufficient in itself to account entirely for the association between vaccination and the reduction of mortality/hospitalization previously stated. Jackson claimed that further studies were urgently needed, studies that included prospective ascertainment of influenza-specific outcomes, in order to improve the sensitivity to detect a true vaccine effect. These studies have yet to be done.

Three years after Jackson's landmark study, Lone Simonsen (Department of Global Health, School of Public Health and Health Services, George Washington University, Washington, DC.) and Jackson teamed together to demonstrate the persistence of a profound confounding frailty selection bias. They claimed that the flawed nature of the evidence supporting the policy of yearly influenza vaccination for the elderly needs to be acknowledged and that a new generation of unbiased studies with laboratory endpoints needs to be undertaken.⁵⁸ In contrast to the 10% of all-cause mortality attributable to influenza accepted by Jackson in her 2006 study, Simonsen and Jackson's 2009 study took advantage of another study carried out by Simonsen and colleagues⁶⁴ in 2005 to affirm that influenza causes a maximum of 5% of all-cause mortality during the influenza season. This result highlights even more the blatant contradiction of basing a public policy on the alleged 50% overall mortality reduction attributed to the vaccine.

A calling into question of the current policy of influenza vaccination is strengthened by the following facts:

Since 1980, there has been in the United States an increase of 50% in influenza vaccination coverage among the elderly. According to prevalent accepted knowledge about the effectiveness of the vaccine, a reduction of 35–40% of both excess pneumonia/influenza and excess all-cause mortality were to be expected as a consequence of this 50% increase in vaccine coverage; no such reduction has been observed or documented.⁶⁴

A 2003 study by CDC epidemiologists found that in the 1980s and 1990s, as the senior vaccination coverage quadrupled, national influenza-related mortality rates actually increased among seniors.⁶⁵

In 1968 and 1997, none of the viral strains in the seasonal influenza vaccine matched circulating viruses: a major antigenic shift occurred in 1968 when H3N2 (Hong Kong) influenza appeared and completely replaced the type A strain (H2N2, or Asian influenza) that had circulated throughout the world for the prior 10 years, and in the last half of the 1997–1998 influenza season, a drifted variant (A/Sydney/5/97) of the circulating influenza virus (A/Wuhan) appeared and was different enough from A/Wuhan (which had been included in the 1997–1998 vaccine) that the vaccine did not provide much protection.⁶⁶ In both years (1968 and 1997), an increase of both excess pneumonia/influenza and excess all-cause mortality was to be expected; no such increase was observed.

These 3 well-substantiated epidemiological observations suggest a lack of efficacy for the influenza vaccine: significantly increasing vaccine coverage does not correlate with decreased influenza-related mortality and accidental vaccine mismatches do not correlate with increased influenza-related mortality.

Final Remarks

The research presented in this article exposes a wide gap between evidence and public policy with regard to influenza vaccination in context of the 2009 pandemic and yearly seasonal epidemics. This is both hard to accept and difficult to ignore. It is hard to accept because it shows that the WHO and health authorities worldwide failed to protect the interests of the most vulnerable during the 2009 flu pandemic, fostering instead the interests of a few big corporations. It is also hard to accept because it calls into question seasonal flu vaccination campaigns, a well-established practice recommended for decades by the WHO and by most public health authorities worldwide.

At the same time, the data presented are difficult to ignore because the lack of a scientific basis for seasonal flu vaccination campaigns has been repeatedly attested since 2006 by epidemiologists from top-tier institutions, including Tom Jefferson from the Cochrane Collaboration, Lisa Jackson from the Group Health Center for Health Studies in Seattle, and Lone Simonsen from the School of Public Health at George Washington University, to name a few. Why have their recommendations not been heard? Why do health authorities at local, national, and international levels ignore their solid, evidence-based expert advice? Margaret McCartney, elected in 2013 to the Royal College of General Practitioners (United Kingdom), in a brief and pointed contribution to the British Medical Journal at the start of the present influenza season, raised the question of what use is mass flu vaccination and concluded that, in view of the available evidence, the current policy is impossible to justify.⁶⁷

The case of flu vaccination exemplifies what researcher Alan Cassels has named the dilemma between “eminence-based medicine” and “evidence-based medicine.” Cassels defines “eminence-based medicine” as “relying on the opinion of a medical specialist or other prominent health official when it comes to health matters, rather than relying on a careful assessment of relevant research evidence.” Narrowing the gap between scientific evidence and public health policies with regard to influenza is a serious and urgent matter, one that implies confronting the interests of big pharmaceutical corporations and their allies at academic and governmental levels. It won't be easy, but the credibility of science and the well-being of many are at stake.

Footnotes

Author's Note

The content of this article was delivered at a conference at the Johns Hopkins Bloomberg School of Public Health on March 18, 2014.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Author Biography

Teresa Forcades i Vila (1966) is an MD (U. Barcelona, 1990) with a specialty in internal medicine (SUNY at Buffalo, 1995) and a PhD in Public Health (U. Barcelona, 2004). She is also a Benedictine nun with a Master of Divinity (Harvard, 1997) and a doctorate in Sacred Theology (Facultat de Teologia de Catalunya, 2007). She lives and works at the monastery of St. Benet de Montserrat (Spain).

References

Centers for Disease Control and Prevention. http://www.cdc.gov/flu/protect/keyfacts.htm. Accessed December 7, 2014.

Centers for Disease Control and Prevention. http://www.cdc.gov/flu/protect/whoshouldvax.htm. Accessed December 7, 2014.

National Health Service. http://www.nhs.uk/Conditions/vaccinations/Pages/who-should-have-flu-vaccine.aspx. Accessed December 7, 2014.

Faked Pandemics – a threat for health. Motion for a recommendation presented by Mr. Wodarg and others. Doc. 12110. 18 December 2009. http://assembly.coe.int. Accessed December 10, 2014.

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