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Thimerosal Containing Vaccines, Part II

WHO


by F. Edward Yazbak MD, FAAP



The featured article on the World Health Organization (WHO) web site on March 15, 2011 was, as expected, about the “Japanese government taking appropriate protective measures” by asking people living within 20 km of the Fukushima Daiichi nuclear power plant to evacuate and those between 20 km and 30 km to stay indoors in unventilated rooms. The detailed information about the catastrophe was presented as several well written pages of questions and answers starting with the all-important: “What is the current risk of radiation-related health problems in Japan to those near the reactor at the time, and those in other parts of Japan?”

WHO was doing what it was supposed to do!

It was responding to a health threat and informing everyone in a balanced scientific and timely fashion!

It was acting responsibly!

***

In Part I of this series, I discussed the history of thimerosal in pediatric vaccines in the United States. In this second part of the three-part series, I will review the role played by the World Health Organization (WHO). Please note that WHO uses the English name thiomersal (lower key) even though the product is a trade name and should be capitalized. To avoid confusion, I did the same.

The World Health Organization was established on April 7, 1948, and has been headquartered in Geneva, Switzerland ever since.

The present Director-General of WHO is Dr. Margaret Chan who was appointed November 9, 2006 and will be serving through June 2012. Dr. Chan was suddenly thrust into the limelight in 2009-2010 when a widespread outbreak of H1N1 influenza became a pandemic.

Even though WHO had promoted vaccination since the late forties without difficulty, Dr. Gro Harlem Brundtland, the Director General in 1999, felt the need to urgently create not one but two new committees that year:

  1. The “Strategic Advisory Group of Experts” (SAGE) to provide guidance on vaccines and biological agenda
  2. The “Global Advisory Committee on Vaccine Safety” (GACVS) “to respond promptly, efficiently, and with scientific rigour to vaccine safety issues of potential global importance.” [http://www.who.int/vaccine_safety/en/]
Just having a SAGE committee must have been wonderful and comforting!

As to GACVS, it did respond to some vaccine issues and crises but as far as doing something about the thimerosal in pediatric vaccines, the committee labored to do nothing and to maintain the status quo.

It took until January 2000 for WHO to endorse the US PHS / AAP July 1999 statement “regarding prospective phasing out of thiomersal – a chemical compound containing mercury used in trace amounts in certain vaccine manufacturing processes and as a vaccine preservative”

Unfortunately even that first sentence did not ring true! Pre-1999 vaccines contained substantially more than trace amounts of thimerosal for the simple reason that trace amounts would have been useless as a preservative.

In the next sentence that started with "However", WHO mentioned the 1930's and frankly outlined its stand:  “However, the Organization underlines the importance of continuing to use currently available children vaccines containing thiomersal. Thiomersal (also known as Thimerosal or mercurothiolate) has been used since the 1930’s …”.
[http://www.who.int/docstore/wer/pdf/2000/wer7502.pdf]

GACVS members are appointed to 3 year-terms but the very first team served from September 1999 to December 2003. Members are not compensated but WHO pays their expenses to get to and stay in Geneva, Switzerland for the meetings.

The present 13-member committee includes a Chairman from Switzerland and a Vice-chairman from the UK. The other members are from France, Guatemala, UK, Philippines, South Africa, India, Canada, USA, Finland, Indonesia and Italy.

The 23rd GACVS meeting in 11 years was held on December 8-9, 2010 to examine:

  • new data related to the risk of intussusception after rotavirus vaccination
  • new data on the safety of pandemic influenza A (H1N1) 2009 vaccines
  • the experience of using yellow fever vaccines among HIV-positive people
  • the experiences of 3 West African countries which are monitoring the safety of a new meningitis A conjugate vaccine.
        [http://www.who.int/wer/2011/wer8605.pdf]

Thimerosal was not brought up!

***

GACVS first “assessed” the issue of thimerosal in vaccines in August 2000.

The committee reviewed the subject several times after that but always reconfirmed its early assurances that “the pharmacokinetic profile of ethyl mercury is substantially different from that of methyl mercury”, “that the half-life of ethyl mercury was short” and “that therefore the exposure to ethyl mercury in blood was comparatively brief.”
[http://www.who.int/vaccine_safety/topics/thiomersal/statement_jul2006/en/index.html]

2002

In the United States, 2002 was a busy year, second only to 1999, when it came to mercury and vaccines: Much of the thimerasol had been removed from pediatric preparations; people were upset about its past use and many families were filing for compensation for vaccine injury. The Subcommittee on Human Rights and Wellness, Committee on Government Reform, US House of Representatives was also holding meetings and its no-nonsense chairman was rattling higher-ups in the regulatory agencies trying to know how and why they allowed mercury to be injected into infants, since the 1930’s …
[The subcommittee reported in May of 2003-http://vaccines.procon.org/sourcefiles/Burton_Report.pdf]

In Geneva, Switzerland WHO was also busy. Parents with or without children with autism were openly questioning how come mercury-containing pediatric vaccines that had been nearly phased-out in the United States were being shipped to “third-world” countries.

WHO needed to do something convincing and the Quality Assurance and Safety of Biologicals Team called a big meeting for April 15 and 16 (2002). Invited were directors from several “National Regulatory Authorities”, executives from the vaccine industry and higher-ups at the WHO Secretariat.

April is lovely in Geneva and the meeting was well attended. Guest participants included executives from nine vaccine companies from as far away as the Far East, in addition to vaccine regulators from Brazil, Belgium, Cuba, France, Germany, India, Indonesia, Italy, Switzerland and the United States. Eleven directors represented the Secretariat.

The meeting’s comprehensive report was published under the peculiar title: “WHO Informal Consultation on the impact of thiomersal on quality, safety and efficacy of vaccines: Regulatory Perspective”
[https://apps.who.int/biologicals/Meeting-Reports/Doc/TM_REPORT.pdf]

Reading the detailed, official and authoritative 11-page report, one had to wonder how such a meeting could be described as an informal consultation. At the time, I thought that an informal consultation was a quick exchange at the 19th hole that started: “By the way Joe, I have this kid with a rash and a swollen ankle…”

A month later, WHO released another much shorter document titled “WHO Informal Meeting on Removal of Thiomersal from Vaccines and its Implication for Global Vaccine Supply.”
[https://apps.who.int/vaccines-access/quality/vmc/thiomersal/Thiomersal_manuf_meeting_May2002.pdf]

Here again one must wonder how “informal” a meeting about “removal of Thiomersal” and “Global Vaccine Supply” between higher-ups at the World Health Organization and executives of vaccine companies can be?

The conclusions that were reached included phrases such as:

  • “The safety of vaccines containing thiomersal as a preservative has been well established over 60 years…”
  • “Thiomersal has proven to be highly effective…”
  • “The demands by regulatory and other health authorities in industrialized countries that thiomersal be removed from vaccines are not believed to be based on scientific facts …
  • “Obtaining regulatory approval for … involves complex activities …
  • “WHO is concerned about the current situation whereby manufacturers in developed countries have been forced to lower the thiomersal content of their vaccines, and is now considering the implications of changing from proven safe and effective practices, …”
  • “The option of using single dose vaccine is not feasible for WHO…”
The report went on: “On analysis of the Pros and Cons of the various alternatives, the group considered that the best option would be to maintain acceptance of thiomersal in vaccines for the global market.”

The committee then listed the required actions necessary to ensure continued availability of vaccines:

  • Clarify the regulatory situation
  • Lobby Ministry of Health and senior regulators.
  • Continue dialogue with EMEA, Korea and Canada
  • Learn about the potential use of the USA export provisions
  • Contact potential recipient countries (of bulk) to see if they would play a bigger regulatory role and become finishers of the vaccines
  • Develop a strong advocacy campaign to support ongoing use of thiomersal
  • Involve developing country regulatory agencies in all these decisions.”
At the end, the committee members not surprisingly “supported WHO’s plan to recommend continued use of thiomersal in vaccines.”

Nine years later, it is clear that those two “informal” meetings killed any chance for anyone to ever bring up the subject of thimerosal-free vaccines … again.

On June 13-14, 2002 the Strategic Advisory Group of Experts (SAGE) met for its fourth annual meeting and decreed that “Two expert groups, the Global Advisory Committee on Vaccine Safety and the US Institute of Medicine have reviewed the data on the safety of thiomersal in vaccines, and have found no scientific evidence of toxicity from thiomersal-containing vaccines. Therefore, SAGE strongly affirms that vaccines containing thiomersal continue to be used for maintaining safe immunization.”
[https://apps.who.int/vaccines-access/quality/vmc/thiomersal/SAGE02Thiomersal.pdf]

On June 20-21, 2002, GACVS met to supposedly discuss the “Safety of thiomersal-containing vaccines”. The report of the meeting was published in the November 22, 2002 issue of WHO Weekly Epidemiological Record and strangely started with a review of the whole charade …!

In 1999, concerns were raised in the United States of America regarding exposure to mercury following immunization with thiomersal-containing vaccines. This was based on the calculation that the cumulative amount of mercury in infant immunization schedules potentially exceeds the recommended threshold set by a USA government agency for methyl mercury. However, thiomersal contains ethyl mercury, not methyl mercury.

Expert advice and data presented to GACVS indicate that the pharmacokinetics of ethyl and methyl mercury are quite different. In particular, the half-life of ethyl mercury is short (less than 1 week) compared with that of methyl mercury (1.5 months). Thus, exposure to ethyl mercury in blood is relatively brief. Ethyl mercury is actively excreted via the gut, whereas methyl mercury accumulates in the body. Two independent epidemiological studies have recently been completed in the United Kingdom. One was funded by WHO (analysis of the General Practice Research Database (GPRD)), the other by the United Kingdom Department of Health (analysis of the data set of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). The GPRD analysis suggests that there is no association between developmental delay, particularly adverse neurological developmental outcomes or behavioural problems, and thiomersal-containing diptheria–pertussis–tetanus (DPT) vaccines given at 2, 3, and 4 months of age. These findings are supported by the ALSPAC results. These studies give further support to the safety in infants of thiomersal-containing vaccines in the amounts used in existing vaccines.

On this basis, GACVS concluded that there is currently no evidence of mercury toxicity in infants, children, or adults exposed to thiomersal in vaccines. It also concluded that there is no reason to change current immunization practices with thiomersal-containing vaccines on the grounds of safety.
[http://www.who.int/vaccine_safety/topics/thiomersal/June_2002/en/index.html]

I should not be alone to question:
  • How two studies, one funded by WHO and the other by the UK DOH can be called “independent”
  • How a study that just suggests that there is no association between adverse neurological developmental outcomes and thimerosal- containing DTP can be considered “irrefutable” and
  • How solely based on those two limited studies, GACVS can absolutely conclude that there is “no evidence of mercury toxicity in infants, children, or adults exposed to thiomersal in vaccines.”

It seemed also disingenuous for the committee to mention in 2002 “concerns” raised in the United States in 1999, when in fact US health authorities had acted on those concerns, yanked thimerosal out of pediatric vaccines and had almost totally achieved that purpose, much before that GACVS meeting even started.

Between 2002 and 2008, the function of the Global Advisory Committee on Vaccine Safety mostly involved shooting down research attempting to prove that thimerosal-containing vaccines were in any way problematic.

In June 2003, the “vaccine safety” committee met and reported that:

“GACVS is maintaining a watching brief on the safety of thiomersal-containing vaccines. There is insufficient evidence to reach definite conclusions regarding the safety of thiomersal in possible special risk groups, notably malnourished infants and premature or low-birth-weight newborn infants. It is important to determine whether such individuals are at special risk, and WHO should encourage further research on the matter relevant to the developing world. Based on the most recent evidence, GACVS reported to WHO that there is no scientific basis for changing current WHO recommendations for thiomersal-containing vaccines, including administration of a birth dose of hepatitis B vaccine and vaccination of low birth- weight infants where indicated.”
[http://www.who.int/vaccine_safety/topics/thiomersal/June_2003/en/index.html]

As if one needed “definite conclusions” regarding safety of thimerosal before providing already developed and available mercury-free vaccines to malnourished or low-birth-weight preemies!

In December 2004, GACVS met to consider whether animal models could be applied in order to better understand the association, if any, between thimerosal in vaccines and neurobehavioral disorders in infants, children and adults. The committee stated:

From an expert presentation made to the Committee and from several publications, it is clear that: (i) no precise animal model exists that closely mimics autism in humans, although animal models of deficit in social play do exist; (ii) in the models available, susceptibility to neurobehavioural disorders has a genetic basis; (iii) there are experimental data to suggest that there is a link between autoimmune deficiency and predisposition to autism (although this remains conjectural); and (iv) mice born to mothers infected with human influenza virus have developed neuropathologies similar to those described in association with autism.
[http://www.who.int/vaccine_safety/topics/thiomersal/Dec_2004/en/index.html]

So the committee traveled to Geneva, listened to “a presentation”, read “several publications” and decided that:
  • No animal model existed anywhere on earth to test a link between autism and TCV
  • Neurobehavioral disorders had a genetic basis and no other etiologies
  • Autoimmune deficiency and mercury toxicity were mutually exclusive
The same thing happened in June 2005.

Committee members flew in to review a recent pharmacokinetic study on the mercury preservative and agreed that “the findings confirmed the view that methyl mercury is not suitable for risk assessment of thiomersal” because “brain concentrations of total mercury were threefold lower with thiomersal, compared with methyl mercury.”

Not surprisingly, the committee decided that it remained “of the view that there is no evidence supporting a causal association between neurobehavioural disorders and thiomersal-containing vaccines.”
[http://www.who.int/vaccine_safety/topics/thiomersal/June_2005/en/index.html]

In June 2008, GACVS met once more to consider a study about the pharmacokinetics of mercury in premature and low-birth-weight infants who received a birth dose of hepatitis B vaccine containing thimerasol and another about neuropsychological performance 10 years after immunization with TCV. The latter study showed that higher thimerosal exposure through vaccines caused lower scores on neuropsychological testing but the committee discounted it because the differences in mean scores were small and only detected in girls.

The committee explained that the studies were of “doubtful clinical relevance” because they were not consistent with results from other ethyl mercury studies. Three years later, I am still bewildered by the logic of that statement.

The members also claimed that the observed associations simply reflected “the effect of chance”, an old cliché we seem to hear quite often in the United States.

At the end, the GACVS concluded that it maintained “the view that there is no evidence supporting any change in WHO’s recommendations for thiomersal-containing vaccines and the vaccination of low-birth-weight infants where indicated.”
[http://www.who.int/vaccine_safety/topics/thiomersal/Jun_2008/en/index.html]

As will be evident in Part 3 of this series, there were many relevant studies during that long period that were never reviewed by the committee.

Of course, there is no assurance that the committee would have found in any of them the evidence it estimated to be enough “to support any change.”

***

In 2009 and 2010, GACVS was busy with the H1N1 “pandemic”.

When it had the chance, GACVS reviewed the “safety” of the HPV and rotavirus vaccines among others.

The members evidently felt by then that the issue of mercury in vaccines for “developing countries” had been discussed enough!

***

The Worlds

Many talk about the third world but few ever mention the first and second worlds.

So what are those worlds?

As much as I can tell, the "First World" refers to the developed industrial countries within the “North American” and “Western European” sphere of influence. These include obviously Canada, the United States and Western Europe, in addition to Australia, New Zealand, Japan and Israel.

The “Second World” includes the old Eastern Bloc (Russia and Eastern Europe) and China.

The “Third World” includes the remaining countries of Asia, Africa, Oceania and Latin America, possibly 70% of the world population and … growing.

***

In the United States, we are usually referring to huge populations in the poorest and least developed countries of Africa when we discuss health, hygiene, nutrition and vaccine policies in the Third World.

Even though OPEC countries are considered part of the third world, their “Petro-Dollars” make them quite distinct.
 
Similarly prosperous countries in South America such as Brazil, Peru, Uruguay and Argentina can hardly be compared to truly “underdeveloped” and near-destitute nations when it comes to health.

For these countries, procuring a slightly more expensive unit dose vaccine for their little ones cannot possibly be a big problem. It seems therefore strange that representatives from those nations’ vaccine regulatory agencies regularly meet in Geneva and still agree that thimerosal-containing vaccines in multi-dose vials are best for infants regardless of size, for pregnant women and for everyone!


In Memoriam: Philip B Rudnick PhD ~ December 23, 2010


F. Edward Yazbak, MD, FAAP
Falmouth, Massachusetts




Thimerosal Containing Vaccines, Part I - In the Dark by F. Edward Yazbak MD, FAAP

Thimerosal Containing Vaccines, Part III - The Convincing Evidence by F. Edward Yazbak MD, FAAP