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:
- The “Strategic Advisory Group of Experts” (SAGE) to provide
guidance on vaccines and biological agenda
- 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
