My understanding of the safety of anthrax vaccine and its role in GWS
Meryl Nass MD
Oct 2004
Recent UK studies
What questions should be resolved regarding the contribution of anthrax
vaccine to GWS, and what data exist to answer them?
1.. Did the vaccine alone, in the absence of other noxious exposures,
cause GWS?
2.. Did the anthrax vaccine, in conjunction with other administered
vaccines, cause or contribute to GWS?
3.. Did the anthrax vaccine in conjunction with other toxic exposures
(other than immunizations) contribute to GWS?
4.. What information is available regarding specific reactions following
vaccination?
5.. Which component(s) of the vaccine are responsible for illness?
1.. Microbiological contamination is a possibility.
2.. Intrinsic toxicity of PA is another possibility.
3..
Excessive amounts of PA and other (expected but uncharacterized)
anthrax fermentation products may be contributing to toxicity.
4.. Might other vaccine components be responsible for toxicity?
5.. Might there be problems with storage, shipping or shelf life
of vaccine?
What research should be done to resolve whether and how anthrax vaccine
causes chronic illnesses?
Other thoughts on GWS exposures
My name is Meryl Nass. I practice general internal medicine in a community
hospital in the US, and also see patients with the diagnoses Gulf War
Syndrome (GWS), Fibromyalgia, Chronic Fatigue Syndrome, and
vaccine-associated illnesses. I have been a student of anthrax and
biological warfare for the past fifteen years. I try to apply the tools of
medicine, microbiology, immunology and epidemiology to investigate
phenomena that are hidden or poorly understood. I am known for having
analysed a major anthrax outbreak, which occurred in Rhodesia during its
civil war. I showed that none of the explanations for why it was a
"natural" event stood up to scrutiny, and that the epizootic was due to
biological warfare.[1] My work was discussed in a 1994 Royal Society
publication titled "Scientific Aspects of Control of Biological Weapons."
My goal was to make it riskier for perpetrators to employ such agents, by
showing that science could be used to distinguish between natural epidemics
and deliberate dissemination of disease. My interest had been to promote
biological arms control, but I was sidetracked into scrutinizing
bioterrorism vaccines several years ago.
Being familiar with the anthrax literature, I was aware that, at the time
the US' Anthrax Vaccine Immunization Program was announced in late 1997,
published evidence for both safety and efficacy of the anthrax vaccine was
lacking. Dr. Peter Turnbull, formerly head of anthrax research at Porton
Down, and others had made this information available in the open
literature. Rodent challenge studies showed poor efficacy of the UK and US
killed human anthrax vaccines against highly virulent strains, and there
existed no published safety data, save from a study of an earlier,
unlicensed "Brachman" (aka "Merck") anthrax vaccine. It contained little
information on systemic adverse effects.[2] I later found that the
unpublished, CDC 'open label' study of the licensed US anthrax vaccine,
used to affirm vaccine safety, had employed report forms that only
collected information on local reactions. Although a nurse at the Alabama
factory where the bulk of the study's anthrax vaccinations were
administered had expressed concern about the adverse reactions, and these
concerns reached the CDC, she was overruled by the local doctor and the
documentary evidence suggests the matter was then dropped.[3]
I wrote a short piece for an internet mailing list of infectious disease
professionals, ProMed Mail, in late December 1997.[4] It suggested that in
the absence of existing vaccine safety data, and in the absence of a cause
or causes for Gulf War Syndrome (GWS), the US military should not begin a
program to vaccinate 2.4 million troops against anthrax until further
research had been performed. At the time I didn't know that the vaccine
was a cause of GWS; it simply seemed unwise to begin a massive peacetime
vaccination program for a disease that did not occur naturally, using a
vaccine that had no track record.
My short piece grew legs. It bounced around the Internet, and if you read
The Lancet on-line, you could 'hot key' directly to my post.[5]
Before I knew it, I was contacted by large numbers of people who had
concerns about taking the anthrax vaccine, and then from soldiers and their
families who contacted me to ask whether illnesses that had developed in
temporal relationship to vaccination were due to the vaccine. I was also
asked to write a review of the issue.[6]
After telling the first 50 or 100 people who contacted me that their
episodes of malaise, fever, diarrhea, joint pains and an enormous number of
odd complaints were unlikely to be due to the vaccine, I began to see
patterns in the complaints they were reporting, and realized there might be
something to their suspicions after all. So I then set out to investigate
the safety of anthrax vaccine.
I reviewed the reports of several panels[7] [8] [9] in the US that had been
charged with investigating GWS, and had said the vaccine had nothing to do
with it. I was surprised to learn that the evidence they relied on to draw
conclusions about the role of anthrax vaccine was shaky at best. The
reports either cited no references to support their vaccine conclusions, or
cited only briefings by military officers, not scientific studies.
Furthermore, despite the finding by a Senate committee in 1994 that anthrax
vaccine was being considered as a possible cause of GWS,[10] and the
statement by the Persian Gulf Veterans Coordinating Board that "all
potential causes [of GWS] that have been identified are being
investigated,"[11] when I reviewed the full portfolio of federal research
on GWS in 1999, I was surprised to find that of 166 studies listed, none
looked specifically at anthrax vaccine.[12] Only because the Wessely/Unwin
study was designed to investigate all potentially noxious exposures that GW
soldiers had faced, had data on anthrax vaccine been captured. It seemed
suspicious that so many of the federally funded studies were designed to
investigate psychological issues, and none the anthrax vaccine.
The 1999 report states that, "the RWG [Research Working Group] established
the development of treatment protocols for unexplained illnesses as a
research priority for future years." [13] And in that same report was a
discussion of two proposed treatment trials for GWS. Yet since those trials
commenced, not one treatment trial for GWS has been sponsored by the
federal government.
Both treatment trials, you may already know, were conducted by the same
group, and studied the effect of cognitive behavioural therapy, and of
doxycycline use for one year (for mycoplasma infection diagnosed by PCR).
As I understand the mycoplasma trial, after speaking with the principal
investigator, Dr. Sam Donta, approximately 450 veterans were enrolled and
given either doxycycline or placebo for one year. At three months there
was a treatment benefit, but by 12 months there had been a high number of
dropouts, and so no benefit was demonstrated statistically.[14] Instead of
enrolling more veterans (there had been a lot of interest on the part of
veterans nationwide during initial enrollment) in order to achieve a valid
sample size, the authors instead concluded "Long-term treatment with
doxycycline did not improve outcomes of GWVs at one year." The VA sponsored
this trial, and in the report I cited above, it says the trial was
projected to cost $12.4 million dollars, or $27,500 per subject. Yet
Pfizer donated the doxycycline and a matching placebo. The 1999 report
states, "The estimated size of this donation will exceed $5 million."
I purchased generic doxycycline for a small number of uninsured patients,
and it cost $8.00 per month for the dose used in this study. Assuming that
the placebo pills cost the same, a one-year course of medication for each
subject would cost $96.00. The total cost for all trial participants would
be $43,200, or less than one per cent of the cost estimated by the Research
Working Group. The subjects were followed for a few visits during 18
months. It is hard to understand why this trial was so expensive. Yet its
cost was used to justify the claim that additional treatment trials were
too expensive to undertake.
The low rate of GWS in French troops, who were unvaccinated, had used
prophylactic doxycycline and consumed cleaner, bottled water, needed
explanation. The issue of whether small numbers of French troops who did
develop GWS were in liaison positions, and were vaccinated alongside US and
UK units, has been raised by the French Ministry of Defense, but to my
knowledge has not been resolved.[15]
Meanwhile, I met with several vaccinated but nondeployed, Gulf War 'era'
soldiers in the US, who had developed similar multisystem illnesses as the
deployed soldiers. Dr. Lea Steele was able to analyze this intriguing
finding in a study of Kansas Gulf War veterans.[16] She found that nearly
4% of the veterans who had not been deployed, nor vaccinated in preparation
for deployment, met her GWS case definition. (She later concluded that
this number is approximately the prevalence rate of a similar condition in
civilians. Since it has been estimated that 3% of the US population has
fibromyalgia, her conclusion has some support.) But those who were
vaccinated in preparation for deployment, but never actually deployed, had
a rate 3 times higher, nearly 12%. In her study, the overall rate of GWS
in those deployed ranged from 20% to 40%, depending on a range of variables
such as rank, branch of service, and time spent in theater.
The US Institute of Medicine (IOM) committee on GWS under Dr. Harold Sox
was asked to review only published, peer-reviewed literature, and did a
credible job looking at the published literature on anthrax vaccine. In
September 1999 the committee concluded that no evidence existed to either
support or refute anthrax vaccine as a cause of chronic adverse health
effects, including GWS.[17] (Since then, a 2003 Cochrane review of anthrax
vaccines drew the same conclusion: "Further research should be carried out
on the short and long term safety effects of available vaccines and if
possible their effectiveness."[18])
However, the IOM committee overlooked several studies that linked anthrax
vaccine to GWS. The first study was performed by a contractor to the
Canadian Department of National Defense (DND), Goss-Gilroy, and was
published on the DND website in 1998.[19] The study used self-reports (as
nearly all the GWS studies have done) and found that immunization with
biological warfare vaccines, which for Canadian troops included only
anthrax and plague vaccines, was associated with chronic fatigue.
Chronic fatigue was a cardinal feature of GWS, as defined by the CDC in a
seminal paper by Fukuda et al in 1998.[20]
In January 1999 a groundbreaking paper by Unwin and Wesseley et al in The
Lancet showed that anthrax vaccine was associated with development of a GWS
syndrome, defined by the authors, in both veterans of the Gulf War, and
also in a small number of anthrax-vaccinated veterans of the Bosnia
conflict.[21] Because of the large number of veterans studied, and good
statistical techniques, this research is very convincing. It furthermore
showed that multiple vaccinations were independently associated with
development of GWS.
During 1999 and 2000, nearly a dozen Congressional hearings were held that
involved anthrax vaccine. The House Committee on Government Reform
published a report of its findings, termed Unproven Force Protection.[22]
Although the Committee recommended that the vaccine be used by the military
as an experimental product, this recommendation was not followed by the
Department of Defense (DOD). Many active and reserve soldiers left the
military to avoid vaccination, and the media were filled with reports of
court martials and other legal challenges to vaccination.
The US Army, the lead vaccine agency for the Department of Defense, was
under the gun on the issue of safety and efficacy of the vaccine. It was
also moving forward to implement a parallel but much larger bioterrorism
vaccine program, termed the Joint Vaccine Acquisition Program, which could
develop dozens of new vaccines and cost many billions of dollars.
In 1999, Colonel John Grabenstein, an army pharmacist who had just
completed a PhD in Pharmacoepidemiology, was chosen to serve as the
clinical head and deputy director of the anthrax vaccine program agency.
He was charged with supervising a portfolio of Army research to show the
vaccine was as safe and effective as DOD had reported to Congress. Col.
Grabenstein was also a consultant and trainer for Merck and Glaxo Smith
Kline, and chaired a committee of the American Pharmacists' Association
whose purpose was to train pharmacists to prescribe and administer vaccines
without a doctor's prescription, and to pass legislation needed for them to
do so in every state. He is on the Board of the Immunization Action
Coalition, an industry-sponsored advocacy organization. Col. Grabenstein
has written, "At present, about 50 serious vaccine-associated injuries
occur each year in the United States, in the course of protecting a
population of 275 million into which 3.9 million children are born
annually,"[23] yet the FDA says that 15% of 12,000 reported yearly
reactions are serious. His remarkable ability to spin even the worst news
has led to his promotion to clinical chief and spokesperson for all
military vaccinations. As quoted in the Washington Post, "Grabenstein said
vaccinations of 524,000 military personnel had found only low risks such as
sore arms, aches and fevers, with the rare serious reaction for 1 in
100,000."[24]
Col. Grabenstein was quoted in the NY Times on December 21, 2001 as saying,
"If people are getting sick, it is not due to the [anthrax] vaccine." He
has misrepresented the conclusions of a number of other studies of anthrax
vaccine, claiming that eighteen studies prove the vaccine to be safe. He
also worked closely with the Institute of Medicine committee that produced
the March 2002 report "The Anthrax Vaccine: Is It Safe? Does It Work?"[25]
He is thanked in the report's acknowledgments.
This report is a cynical whitewash of the safety and efficacy concerns
about anthrax vaccine, and makes a number of unsubstantiated and incorrect
claims regarding both.[26] [27] Furthermore, the report considers the
DOD's Defense Medical Surveillance System database's findings of a
statistical association between receiving anthrax vaccine and
hospitalizations for diabetes, breast cancer, asthma, Crohn's Disease,
thyroid cancer and multiple sclerosis. It acknowledged that these
associations could be signals of a possible causal relationship, especially
for diabetes, Crohn's Disease and multiple sclerosis, and recommends
"additional follow-up" in the text. However, when the report makes its
final recommendations, it recommends against such follow-up, saying, "DOD
should develop systems to enhance the capacity to monitor the occurrence of
later-onset health conditions that might be associated with the receipt of
any vaccine; the data reviewed by the committee do not suggest the need for
special efforts of this sort for AVA."
The National Academy of Sciences division in which this report was produced
is the Medical Follow-Up Agency, and it is 100% funded by the Department of
Defense and the Department of Veterans Affairs. Would this division have
retained its funding had the report provided an honest assessment of the
vaccine?
Under Col. Grabenstein's oversight, the army has published at least four
studies purporting to show anthrax vaccine is safe and effective.[28] [29]
[30] However, the data reported in these studies leave much to be desired.
The most important study, the only one designed to learn about long-term
reactions, was conducted on 603 vaccinated medical staff at Tripler Army
Medical Center.[31] According to the principal investigator, "The
objectives were to provide active surveillance of self-reported side
effects and the duration of symptoms." [32] Soldiers were asked to
complete a questionnaire about symptoms that developed after their last
anthrax vaccination, whenever they presented for a subsequent inoculation,
or within two weeks of vaccination.
One case of multiple sclerosis and two other neurologic reactions developed
in vaccinees. One neonatologist developed a tremor and upper extremity
weakness associated with a CPK level over 1000. A pediatric cardiologist
developed numbness and fasciculations, suggesting a brachial plexopathy,
which resolved. Although the study was designed and initially advertised
to seek persisting adverse reactions, the forms completed by soldiers only
specified whether reactions lasted brief periods less than 72 hours, or
more than 72 hours, and the published paper provides no tables on side
effect duration. The paper notes that only local reactions could be linked
to vaccination, and appears to dismiss vaccine causality for other
reactions without providing a rationale for doing so. The exit
questionnaire used was a general health questionnaire (Health Enrollment
Assessment Review Survey), rather than a questionnaire designed to capture
specific information related to vaccine adverse effects and their duration.
In fact, the questionnaire used made no reference to anthrax vaccine.
Other problems with this study include the fact that although 603 persons
were enrolled and originally reported on,[33] the published paper lists
only 601 subjects. The abstract notes that localized reactions occurred
more often in women, but neglects to mention that systemic reactions did
also, at approximately twice the rate of men. Although the published paper
notes that one reason for enrollees to drop out was pregnancy, it omits
mention that eleven women became pregnant during their vaccine series, and
the outcome of the pregnancies remains unknown.
This is important because navy physician Cdr. Megan Ryan has found that
women vaccinated for anthrax during the first trimester have a higher rate
of birth defects in offspring than unvaccinated women.[34] [35] Apparently
this research was compelling enough, despite an army study to the contrary,
for the FDA in 2002 to change the pregnancy warning on the vaccine label
from a C (no data on risk) to a D (data suggests increased risk during
pregnancy). However, the data have not yet been published.
Dr. Maria Araneta, also associated with the Naval Health Research Center
and University of California, has shown that GW veterans are also likelier
than controls to have children with certain birth defects.[36]
According to the Tripler study authors, "Women in the immunized cohort were
more likely to report (in their exit questionnaire) that their general
health was 'poor or fair' compared with the unimmunized cohort (RR 4.4; 95%
CI: 1.3-15.1).otherwise there were no notable trends or associations."
Regarding the Tripler authors' claim that there were no notable trends in
their data, one would think that the high female reaction rates and poorer
female health at the study's conclusion would be notable, and that a
serious neurologic reaction rate of 0.5% in a vaccine study should have
raised some eyebrows.
Because all the army studies claim to show the vaccine is safe, sometimes
in spite of evidence to the contrary, and all were supervised by the same
individual, while virtually all the research done elsewhere has found that
chronic illnesses are associated with anthrax vaccinations, I have chosen
to disregard the army research, which I believe has put the "mission" to
vaccinate soldiers before the science.
The FDA has similar criticisms of these army studies. In the vaccine's
package insert[37] under the title "Post Licensure Survey Studies" FDA
included the following statement: "In addition to the VAERS data, adverse
events following anthrax vaccination have been assessed in survey studies
conducted by the Department of Defense in the context of their anthrax
vaccination program. These survey studies are subject to certain
methodological limitations, e.g., sample size, the limited ability to
detect adverse events, observational bias, loss to follow-up, exemption of
vaccine recipients with previous adverse events and the absence of
unvaccinated control groups."
Several years ago, in conjunction with the Hartford Courant newspaper, I
reviewed the first 1660 anthrax vaccine adverse events reports to FDA
(found in the Vaccine Adverse Effect Reporting System (VAERS)), and found
that about 160 met the CDC's case definition for GWS. Most of those
reporting had not been to the Gulf. They had reported at least two of the
following three problems: musculoskeletal pain, fatigue, and a cognitive or
emotional disorder. I wrote to the FDA about this, and enclosed the
Fukuda/CDC's case definition from the JAMA. I was later gratified to learn
that the revised January 2002 anthrax vaccine package insert[38] includes
the CDC's GWS case definition in the list of reported adverse reactions,
although the fact that this is the GWS definition is not stated.
As early as May 1999, 14 months after the start of the Anthrax Vaccine
Immunization Program, a group of military clinicians got together to
identify illnesses developing after anthrax vaccination, develop criteria
for waiving further vaccinations in certain ill individuals, and develop
evaluation, prevention and treatment strategies. Col. Grabenstein later
joined this group, which placed him in the interesting position of denying
that chronic illnesses are caused by anthrax vaccine, while also
coauthoring credible reports of vaccine adverse reactions, and coauthoring
clinical guidelines for vaccine-related disorders. The guidelines have
undergone several revisions since 1999, and can be found on the DOD
website.[39]
It is interesting that the unexpected reactions seen by these military
clinicians in 1999, when they wrote the first draft of the guidelines,
remain important and continue to be addressed by the guidelines four years
later: these include neurological reactions, chronic fatigue, chronic pain
syndromes and 8th nerve dysfunction, among others.[40]
One of the clinicians in the forefront of responding to illnesses that
develop following military vaccinations is Col. Renata Engler, MD, the
Army's chief allergist- immunologist. She evaluated severely affected
soldiers at Walter Reed from the beginning, and founded the National
Vaccine Healthcare Center in 2001.[41] Subsequently the military's Vaccine
Healthcare Network has expanded to four sites, and its mission has expanded
to include illnesses developing after any vaccination. The centers have
also treated smallpox vaccine reactions, and developed screening criteria
for waiving both anthrax and smallpox vaccinations. They are involved in
research on vaccine reactions. Over 1,000 in depth case reviews and
patient evaluations have been performed. Despite the centers' successes,
funding was about to be cut off in October 2004, but has been reinstated
for one year as a result of Congressional interest.
According to Walter Reed National Vaccine Healthcare Center authors,[42]
"between May 1998 and July 2001, 82 patients were evaluated for complaints
of prolonged systemic clinical problems whose onset was associated or
attributed to anthrax vaccine exposure by the patient, referring provider
or family member...the spectrum of systemic symptoms in this group is
heterogeneous with the reasons for referral including (but not limited to)
one or more of the following features: non-injection site skin rashes
(15%); persistent headaches (12%); tinnitus (16%); other neurologic disease
or symptoms (21%); prolonged fatigue with 50% functional loss for > 60 days
(21%). Specific diagnoses are diverse with some patients manifesting
prolonged disability...there continues to be a need to improve our
understanding of these clinical scenarios."
In February of this year, Army Surgeon General James B. Peake issued new
guidelines for treatment of soldiers' illnesses that do not respond to
standard treatments.[43] He suggested that vaccine reactions be
considered, that vaccine histories be taken, and that clinicians seek
second opinions from the vaccine healthcare centers. His memo followed
publicity about the death of Rachel Lacy, a 22 year old nursing student and
army reservist who was called up for duty in Iraq, given five vaccines in
one day, including anthrax and smallpox, rapidly became ill, and died 4
weeks later at the Mayo Clinic. Her autopsy revealed adult respiratory
distress syndrome and eosinophilic lymphocytic myocarditis. Another
military case of eosinophilic lymphocytic myocarditis was seen at Mayo
Clinic around the same time, also associated with five vaccines including
anthrax and smallpox, but the soldier lived to have an endomyocardial
biopsy, receive high dose prednisone treatment, and recover.[44]
The Surgeon General may also have been responding to media reports of over
twenty "mystery pneumonias" in soldiers that were non-infectious,
associated with eosinophils in blood or bronchoalveolar lavage fluid, and
resulted in a number of ventilator cases and several deaths.
After years of military physicians failing to report vaccine adverse
reactions to FDA, and failing to acknowledge in the patients' medical
records that such reactions have occurred, the Vaccine Healthcare Centers
have begun to reverse this unfortunate trend. One soldier who I recently
evaluated had been extensively worked up by the Vaccine Healthcare Center.
His record there stated,
"Staff Sergeant ****** was a high functioning, decorated service member
prior to beginning the anthrax vaccine in 1998. He has had no disciplinary
action. He has functioned well in his duty assignments and is highly
regarded even now. Staff Sergeant ******'s life has been significantly
altered due to his current disability, and hope for recovery is uncertain.
The lack of clinical findings is discouraging and leaves his providers
baffled and powerless as to an effective treatment plan. His condition is
not unique for us at the Vaccine Health Care Center. We have treated many
proficient service members with debilitating conditions that cannot be
diagnosed or medically substantiated, conditions that have developed in
close temporal association to having received the anthrax as well as other
vaccines. Hopefully future medical research and discovery will provide
some definitive answers to these perplexing medical dilemmas and allow us
to effectively treat individuals such as Staff Sergeant ******."[45]
This statement was signed by Limone C. Collins, MD, director of the Walter
Reed Regional Vaccine Health Care Center and by Jeannette F. Williams, FNP,
case manager, on January 14, 2004. It is gratifying to finally have these
clinicians, who see the greatest number of patients with post-vaccine
illnesses, acknowledge that they too are baffled by patterns of symptoms in
many patients who are debilitated and treatment resistant, and who have
developed undiagnosable illnesses following vaccinations, usually including
anthrax.
Because the subset of illnesses that are readily diagnosable in soldiers I
evaluate often turn out to be endocrinopathies, connective tissue
disorders, vasculitides, and other autoimmune disorders such as multiple
sclerosis, I have begun to hypothesize that the difficult-to-diagnose
illnesses are also autoimmune, despite not fitting into usual diagnostic
categories, nor having classic laboratory findings of autoimmunity. The
fact that so many GW veterans, and many with anthrax vaccine-associated
illnesses, have become chemically sensitive, suggests that some poorly
understood form of allergy comprises at least part of their illness. I
expect that further appropriate research will yield lab markers, and
accurate ways of understanding and treating these disorders. The
significant cognitive impairment in most of these veterans, which may not
show up on scans, will be shown to have physiological correlates in future,
as will their physical disabilities. Eventually, our understanding of GWS
will shed light on a variety of poorly understood syndromes like
fibromyalgia, chronic fatigue syndrome and chemical sensitivity.
Recent UK studies
Regarding the short-term adverse effects of recent anthrax vaccinations in
the UK, in soldiers vaccinated before the recent Gulf deployment, two small
studies have been done. The UK vaccine is given as a four dose series over
one year, with yearly boosters; the US vaccine is given in 6 doses over 18
months, with yearly boosters.
In the first paper by Hayes and World, 129 soldiers working in a military
field hospital were offered vaccine, and 76% (98 soldiers) accepted and
began the series.[46] Initially, 63% had adverse reactions. "Forty-five
percent of these caused incapacity." Approximately 22% of reactors had arm
pain that prevented lifting or driving for 48 hours. Twenty-one percent of
reactions were designated severe. Only 27 of the 98 soldiers who began the
vaccinations completed the four dose series. The authors noted, "Although
the old vaccine is considered safe, the number of adverse reactions and
incapacity reported by a military medical unit was unexpected."
The second paper looked at vaccine acceptance and adverse reactions in
personnel at five RAF bases.[47] "Those completing the [vaccine] course as
a percentage of those starting it varied from 22% at base 2 to 3.7% at base
4." Yet these authors reported that only 11% of vaccinees had side
effects, and that these were mild.
Neither set of authors was able to explain the dropoff in vaccine uptake.
Both studies were supported by the MOD.
What questions should be resolved regarding the contribution of anthrax
vaccine to GWS, and what data exist to answer them?
1.. Did the vaccine alone, in the absence of other noxious exposures,
cause GWS?
Nondeployed GW 'era' soldiers and recent vaccinees who had no additional noxious exposures should be formally studied for chronic illness effects. However, studies and individual reports from recent US and UK vaccinees, and Wesseley's vaccinated Bosnia cohort are very suggestive that anthrax vaccine alone may cause GWS. Additional support comes from the presence of many ill, vaccinated, nondeployed veterans. There exist no reliable negative studies of which I am aware. What the incidence of GWS is in those with only an anthrax vaccine exposure is unknown, and may be difficult to determine, because veterans had variable numbers of doses, and the composition of the vaccine from lot to lot varies enormously, so reactions rates may also. A recent unpublished study of reactions and their persistence at Dover Air Force Base suggests that in some circumstances, chronic illness rates may be very high, up to 30%.[48] Furthermore, although we have estimates of vaccine uptake (provided by the US and UK governments) in GW veterans, I have seen no documentary evidence that supports the accuracy of these estimates. Therefore in my opinion the number of US GW veterans with anthrax vaccine exposure is unknown, and the information that DOD has produced regarding the vaccination status of a few thousand GW veterans is similarly unreliable. The fact that DOD policies were established at the time of the GW to omit recording certain vaccinations, particularly anthrax, leads to concerns that persisting adverse reactions were anticipated.
The reports by Wesseley, Steele and Cherry on multiple vaccinations are in agreement about this. Is it more dangerous to give other vaccines at the same time as anthrax vaccine, compared to giving the vaccine individually? The US' Armed Forces Epidemiology Board has considered this issue, but decided multiple vaccines were safe with anthrax (in the absence of good data), and the British MOD did establish a policy to inoculate for anthrax without other vaccines being used simultaneously. Whether this policy remains in place and whether it was followed I do not know, nor am I privy to additional evidence, if any, upon which the MOD and DOD concerns were based.
There is no population data or experimental data, to my knowledge, that addresses this question. It is an important question, particularly because chemical and pharmacological exposures can predispose to autoimmune disorders similar to some that appear to be caused by the vaccine alone. Dr. Abou Donia has expressed interest to me in pursuing this in the animal model. From my perspective, it is quite likely that the combination of exposures increased the risk of illness in veterans. Whether combined exposures led to additive, synergistic or other effects is worthy of study.
4.. What information is available regarding specific reactions following vaccination?
1.. The Vaccine Adverse Event Reporting System (VAERS), a joint FDA-CDC undertaking, has collected approximately 3,000 reports from medical professionals and vaccinees regarding adverse events following anthrax vaccination. The database is limited by lack of follow-up for most of the reports, absence of verification using medical records, the fact that reporting is voluntary, use of cumbersome terminology, and the presumption that reactions are under-reported by a factor of 10 to 100. I made the following calculation in July 2002, using data supplied to me by FDA, that one in 250 vaccine recipients had had an anthrax VAERS report filed, and FDA noted then that 25% of these VAERS reports were serious. Subsequently, some of these reactions have been down-coded by FDA and are no longer labeled as serious. This database needs to be mined.
2.. The VAERS database is designed to capture 'signals.' Because it is felt by FDA that causality cannot be assessed on the basis of VAERS reports alone, such signals are then investigated with a directed epidemiologic study. Such a study to establish or refute causality for anthrax vaccine reactions has not been performed, to my knowledge.
3.. Dr. Mark Geier and his son David Geier have manipulated their own copy of the VAERS database, and established a method by which they compare adverse event reporting rates from one vaccine to another, in order to estimate a "baseline" level of symptoms that are not causally related to vaccination. They have shown that levels of reporting for joint[49] and gastrointestinal-related[50] complaints are much higher for anthrax vaccine than for other killed vaccines.
4.. Approximately ten case reports of illnesses following anthrax vaccination have been published in the medical literature. It should be of interest that all these reported reactions could be autoimmune effects.
5.. Which component(s) of the vaccine are responsible for illness?
1.. Microbiological contamination is a possibility.
i. Many
lots had visibly contaminated bottles, which were thrown away without extra
testing of the remaining vials; some lots and sublots had to be destroyed
due to bacterial or fungal contamination.
ii. The
only sterilizing step in vaccine production was filtration. For several
years the manufacturer used a tetanus vaccine filter for anthrax vaccine
that had not been validated for anthrax.
iii. Even
after the manufacturer rebuilt its entire anthrax manufacturing facility,
the bottling suite was not sterile, and the manufacturer has had to ship
all vaccine to a company in the state of Washington, Hollister-Stier, for
bottling since 2002.
iv. Only
two types of plates were used to incubate aliquots of vaccine to determine
whether there was microbiological contamination. The plates were held for
5 days. This was insufficient to identify bacterial L-forms such as
mycoplasma, spirochetes that could pass through the pores of the filter, or
slow-growing bacteria. It was inadequate to identify viruses. It would
also miss many fungi.
v.
Studies of other human and animal vaccines have found viral and mycoplasma
contamination.
vi. A
DOD-sponsored study designed to address the issue of high mycoplasma levels
by PCR in GW veterans, originally found by Dr. Garth Nicholson and others,
identified no mycoplasma in vials of anthrax vaccine;[51] however, because
the DOD has refused to provide vaccine vials for independent study, and
because it would be easy for DOD to inactivate microorganisms in the killed
vaccine, to select an uncontaminated sublot for testing, or refilter the
vaccine, without revealing that such had taken place, I do not believe this
study rules out mycoplasma contamination in anthrax vaccine.
vii. Many
lots were found to have low (out of specification) levels of benzethonium
(phemerol) during supplemental testing of the vaccine stockpile in
1997-1999; Benzethonium was used for its antimicrobial effects; low levels
increased the chance of microbial contamination.
viii.
Microbial contamination (or simply chronic occult infection) is one of the
few theories of the origin of GWS that could explain the transmission of
GWS to some spouses and children of affected veterans.
2.. Intrinsic toxicity of PA is another possibility.
i. Both
the British and US vaccines' primary immunizing ingredient, and main
protein component, is PA (Protective Antigen). The British vaccine seems
to cause similar problems as the US vaccine, even though the two vaccines
use different anthrax strains, a different culture system, and slightly
different adjuvants (aluminum phosphate [alum] in the UK, and aluminum
hydroxide [alhydrogel] in the US). However, both countries have had
manufacturing problems that led to both manufacturing facilities being
refurbished in the past five years, so it is possible that manufacturing
flaws are contributory.
ii. ii.
In the 1960s, prior to licensing the current anthrax vaccine, at least two
studies done at Fort Detrick looked at the effect of PA, in the absence of
lethal factor or edema factor, injected into monkeys. In the first study,
levels of blood glucose and liver glycogen dropped markedly with injection
of PA.[52] In the second study, PA was injected into the monkeys'
cerebrospinal fluid. The authors had the following to say: "Within 30 to 60
seconds, a marked decrease in cortical [brain] electrical activity was
noted, followed in some animals by complete electrical silence at
approximately 3 to 5 minutes."[53] Thus some inherent toxicity of this
compound has been established, but no research has been published in the
open literature to expand on these observations in the intervening
thirty-six years.
3.. Excessive amounts of PA and other (expected but uncharacterized)
anthrax fermentation products may be contributing to toxicity.
i. The
pre-Gulf War I lots were tested by Dr. Bruce Ivins at Fort Detrick, and
found to vary in concentration of PA by a factor of forty. Perhaps the
more concentrated lots caused problems in susceptible individuals.
ii. After
the Michigan vaccine fermenters were changed from glass to stainless steel,
and the filters were changed from three dimensional ceramic filters to two
dimensional nylon filters, Dr. Ivins discovered that the newer lots were
one hundred times more concentrated than the lots made with the earlier
fermenters and filters.[54] You might wonder how FDA allowed this to
occur, but FDA was simply not notified of these changes by the manufacturer.
iii. The
vaccine is manufactured by growing an attenuated strain of anthrax in
culture, heat-shocking it to kill the bacteria, filtering the culture
medium, adding aluminum hydroxide gel, stirring to promote protein binding
by the gel, centrifuging the mixture, discarding the supernatant and
resuspending the pellet, adding formaldehyde and benzethonium, and the
resulting mixture is the vaccine. Thus any components of anthrax,
including cell membrane, DNA, and even undefined virulence factors, may
become part of the vaccine. Because this mix has not been characterized,
and because the concentrations of PA as well as other components vary
greatly between different sublots (each individual fermentation product
becomes a sublot of about 10,000 vaccine doses), other virulence factors
remaining in the vaccine could be problematic. Also, these extraneous
materials probably further stimulate an immune response.
iv.
Recombinant PA vaccines, with very low concentrations of other materials,
were developed even before the first Gulf War, and at least one (rPA102) is
in clinical trials in the US. I have been told informally that high
concentrations of these purer vaccines are needed in order to generate
sufficient immunity in vaccinees. In its initial Phase 1 clinical trial,
the rate of systemic reactions reported for the rPA102 vaccine was 39%,
compared to an 18% systemic reaction rate for Biothrax.
4.. Might other vaccine components be responsible for toxicity?
i. The
level of aluminum in each vaccine dose, and the number of doses used, does
produce a high body burden of parenteral aluminum.
ii.
Rumors of the use of experimental anthrax vaccines at the time of the first
Gulf War abound. Because two Fort Detrick commanders acknowledged in early
1990 that unlicensed anthrax and other vaccines were used in selected
military units,[55] it appears to have been standard practice to use
unlicensed anthrax vaccines in some troops. I have collected several
documents for the Inquiry that relate to the US use of unlicensed
(experimental) medical products in soldiers, and after reviewing this
subject, and the memorandum of understanding about the use of such products
between the FDA and DOD, I have come to believe that clinical trials of
experimental medical products were regularly conducted in the military
without the knowledge of troops. I further believe that use of such
products outside of a clinical trial setting also routinely occurred. (The
US National Strategic Stockpile of drugs and vaccines now includes
unlicensed products, and recent laws passed in the US would allow such
experimental products to be mandated for civilians as well, in the event of
a designated bioterrorism emergency.) How experimental anthrax vaccines may
have differed from the licensed vaccine at the time of the GW is unknown.
iii.
Richard Rettig wrote a formal study for the RAND Corporation about the use
of (eight) unlicensed drugs and vaccines during the Gulf War.[56] At the
time of the GW, the DOD only acknowledged using two unlicensed products,
pyridostigmine bromide (NAPS) and botulinum toxoid vaccine.
iv.
Squalene has been cited as a possible unlicensed adjuvant added to anthrax
vaccine at the time of the Gulf War. Pertussis vaccine is known to have
been used to adjuvant the anthrax vaccine in the UK. Numerous studies by
Drs. Turnbull, Ivins, Welkos and Jones and others explored the use of novel
adjuvants in boosting the efficacy of anthrax vaccines, which was known to
be poor in the face of highly virulent anthrax strains. These researchers
found that a variety of adjuvants, including Bordetella pertussis and
synthetic adjuvants containing squalene and other highly immunogenic
materials, were capable of profoundly boosting vaccine efficacy after only
one dose.[57] However, none of these adjuvants were licensed for human use
in the US. Might they have been used at a time our nation was facing
possible attack with anthrax, when vaccine availability was limited, and
when the FDA gave the DOD the right to use a number of experimental
products on troops?
5.. Might there be problems with storage, shipping or shelf life of
vaccine?
i. We
know that in 1998, some FDA-approved lots of vaccine had been in storage
since the Gulf War, well past their putative 3-year expiration period.
The manufacturer had a policy of simply retesting potency of expired lots
and then redating the lots for an additional three-year period. FDA was
not aware of this procedure until 1997.[58]
ii. The
DOD had a policy in place, apparently approved by FDA, that all vaccine
stored in bulk would have no expiration date. Such vaccine would be tested
only for potency at the time it was bottled, and then issued a standard
shelf life. No testing for degradation of the product, or for toxicity,
took place at the time of bottling. This extended expiration dates by ten
years or more.
iii.
Investigational New Drug (IND or unlicensed) products were covered by a
similar but different policy. They have no expiration date at all, and can
be stored indefinitely either in bulk or in vials and ready for immediate
use, with no potency or other testing required before they are used.
iv. The
alhydrogel adjuvant has only a two-year shelf life, according to the
manufacturer, after which there is increased desorption of protein.[59]
How this affected vaccine subjected to long periods in storage is unknown.
v. The
FDA recalled anthrax vaccine lot 016 due to stopper deterioration; the
problem was discovered by the presence of visible particulates in the
vaccine. Whether other lots contained rubber particles is unknown.
Whether stopper deterioration allowed entry of late microbial contaminants
is also unknown.
vi. No
anthrax vaccine stability testing was done prior to 1998.
vii. No
published studies have addressed any issues of prolonged vaccine storage,
shipping and/or holding of vaccine outside the temperature limits
established in the product license, or other issues of product degradation.
Yet we know that vaccine was shipped by the military using 'polar packs'
only, without refrigeration or climate control, and that it did not always
remain within the temperature limits specified in the product license.[60]
6.. The FDA issued a NOIR (Notice of Intent to Revoke the establishment
license of Michigan Biologic Products Institute) in March 1997, due to a
large number of failures of cGMP by the manufacturer.[61] Possibly other
quality control failures not discussed above led to illness.
7.. Possibly GW 1 soldiers are ill from receiving unlicensed anthrax
vaccines, not the Michigan vaccine product. Possibly they had unlicensed
adjuvant added to what had been an acceptable product. However, the fact
that large numbers of soldiers have become ill after receiving this vaccine
over the past 6 years, during which no convincing evidence has surfaced
that unlicensed vaccines were being used, or that unlicensed adjuvants were
being added to the vaccine, weighs against that possibility being the
complete explanation for anthrax vaccine toxicity.
What research should be done to resolve whether and how anthrax vaccine
causes chronic illnesses?
1. A large prospective case-control active surveillance safety trial
should be done using soldiers who are required to be vaccinated by the US
military, and comparable controls, for as long a period of follow-up as
possible. (I believe it would be unethical to vaccinate volunteers due to
the high rate of serious reactions.) Gulf War veterans often developed
their illnesses slowly, sometimes years after leaving the service. The
recent safety studies of anthrax vaccine, as opposed to studies of GW
veterans, have all been short-term, generally concluding about one month
following vaccinations.
a) The vaccine lot(s) they are receiving should be characterized as
comprehensively as possible; the concentrations of PA, aluminum,
benzethonium and formaldehyde should be measured; and the presence of known
anthrax virulence factors should be identified.
b) Both bottled vaccine and individual vaccine components should
undergo comprehensive toxicity testing in animals, especially pregnant
animals, which according to the package insert has not been done.
c) The VAERS database of approximately 3,000 adverse event reports
should be mined to collect the most common complaints, and develop a
reporting form for this clinical trial that will elicit whether any of
these complaints develop, but also will allow for 'penciling in' of any
other symptoms or illnesses experienced by vaccinees over the period of
follow-up.
d) This entire study must be carried out by independent researchers
who have no ties to the DOD or VA, and no other conflicts of interest.
2. Several rare, serious illnesses have been linked anecdotally to anthrax
vaccine. These include pemphigus vulgarus (currently being investigated by
the Walter Reed National Vaccine Healthcare Center) aplastic anemia,
leukemia, lymphoma, multiple sclerosis, glomerulonephritis, and others.
a) Independent researchers should review the records of all soldiers
who have received a bone marrow transplant in the military, and see if
there is a disproportionate number who have received anthrax vaccine, as
alleged by one marrow recipient.
b) All cases of new onset of multiple sclerosis, glomerulonephritis,
and other serious autoimmune diseases and lymphoproliferative disorders
should be similarly reviewed, to see if the rate of development of these
disorders in the vaccinated is different than the rate in a comparable
unvaccinated cohort.
3. The Institute of Medicine's 2002 report on anthrax vaccine contains
information from the Defense Medical Surveillance System database on
hospitalizations pre and post vaccination in military facilities. One half
million person-years of vaccinees are included. Although overall
hospitalizations in the anthrax-vaccinated are only about 2/3 as frequent
in the unvaccinated, hospitalizations for several diagnoses are
significantly higher in the vaccinated cohort. However, this result is
confounded by the fact that only the healthiest soldiers receive anthrax
vaccine for deployments. Better data would compare the rates of these
disorders in anthrax vaccinees with a matched cohort of non-vaccinated
servicemembers. This comparison should be done by independent researchers
who have access to servicemembers' complete medical records.
4. All US servicemembers have blood serum frozen every 1-2 years. Because
many of the chronic illnesses being reported appear autoimmune in nature,
analyzing stored serum samples to identify if/when autoimmune markers
developed, and whether this occurred in proximity to vaccination, is
important. Examination of stored serum for autoantibodies has been done
for a number of soldiers seen at the Vaccine Healthcare Centers, although a
compilation of results has not been published.
5. Cohorts of nondeployed, vaccinated GW veterans and unvaccinated control
veterans should be examined clinically to determine whether vaccination is
associated with subsequent illnesses, and whether serum markers of
autoimmunity or other markers, such as lower levels of endocrine hormones,
higher rates of mucocutaneous candidiasis, etc. exist that might
distinguish between the two groups.
6. More research in animal models needs to be done using combinations of
exposures. Anthrax vaccine has not yet been included in these studies, and
because the vaccine is impossible to obtain for research, and the entire
vaccine stockpile is owned by the DOD, such research will have to be
mandated by Congress in order to be carried out. Combinations should
include organophosphates, pyrethrin, pyridostigmine bromide, jet fuel,
solvents routinely used by the military, other inhalants, other vaccines,
etc. It is very important to learn whether certain combinations of
chemical or pharmaceutical exposures promote vaccine toxicity.
7. HLA typing of those who develop vaccine-associated illnesses should be
done, to determine whether a genetic predisposition to these illnesses can
be identified. Cytokine release patterns post vaccination should also be
studied.
8. The Defense Medical Surveillance System database tells us that women
who have received anthrax vaccine are several times as likely to be
hospitalized for carcinoma in situ of the breast or genitourinary system
after being vaccinated, as they were before vaccination. Reports of
abnormal PAP tests in female Gulf War veterans abound, and there are
reports that female Vietnam veterans were similarly affected.
Differentiating between a viral and toxic etiology for cervical carcinoma
in situ, and seeking information on synergism between viral and toxic
exposures in military women would be valuable.
Other thoughts on GWS exposures:
1. DU-Reports over the past several years have indicated that
byproducts of fission from nuclear reactors have been mixed with pure
depleted uranium[62] to create munitions and armor that are radioactively
much more hazardous than would be expected from pure DU. This lends
credibility to reports of illness from this exposure. The cancer risk and
other risks, especially in those with high body burdens of inhaled DU, must
be established.
2. I believe the increased accidental death rate in GW veterans is due
to problems of cognition, slowed reaction times and impaired judgment.
These sequellae of their GW service are present in the majority of GW
veterans I have treated. Several who have undergone formal
neuropsychiatric testing showed clear deficits in cognition, especially of
executive function.
3. Certainly the reports from both US and UK soldiers that they
received several more inoculations than are documented in their medical
records raise questions, and neither Rettig's RAND report nor any other
information in my possession answer them.
4. Economic modeling of the costs of vaccine-associated illnesses in
soldiers and veterans should be done, so that society can better calculate
the risk/benefit equation for using anthrax and other new vaccines, and
embarking on massive bioterrorism vaccination programs.
5. The Department of Defense medically retires soldiers who become
chronically ill following vaccinations. This shifts the costs of medical
care and disability pensions to the Veterans Administration, which is
financed through a separate Congressional appropriation. The DOD is thus
protected from the financial pain resulting from its use of highly
reactogenic vaccines. Were the VA to be funded out of a common
appropriation along with the Defense Department, the decision to use
reactogenic vaccines and to expose soldiers to other dangerous substances
would probably be made much more judiciously.
6. Because the DOD is the employer of all those receiving anthrax
vaccine, is the employer of all physicians treating ill vaccinees at
military facilities, owns the entire vaccine stockpile, is the indemnifier
(insurer) of the vaccine manufacturer, is the holder of the vaccine patent,
and has created policies that demand mandatory vaccinations with not only
anthrax but smallpox vaccine (which is no longer given to civilians due to
a high rate of serious adverse events), and a host of new vaccines
sponsored by DOD are in product development, the Defense Department cannot
be expected to change its course on vaccine policy now, despite
overwhelming evidence demonstrating serious safety concerns.
Instead, only the Congress, the Judiciary or the President can apply the
restraint needed to end the mandatory use of dangerous and questionably
effective vaccines by the military. US military medicine has become the
handmaiden of vaccination policies designed by non-medical officers, and
both the DOD leadership and most military physicians have turned a blind
eye to the medical consequences of these policies. So far, neither has
paid a price for doing so. Instead, it is the ill themselves who pay the
price for developing vaccine-induced diseases, which are often impossible
to diagnose or treat. Many of those who develop these disorders lose their
military career, their employability, their health, and even their
self-respect, as they are try to understand what has happened to them, and
then convince an uninformed medical establishment that they are truly very
ill.
We physicians, who are unable to return these soldiers and veterans to
health, must at least believe in them, work to educate our colleagues about
them, and find a place in our textbooks for them. And encourage research
designed to enlighten us about these obscure but devastating syndromes.
Thank you very much for allowing me to make this presentation.
Meryl Nass, MD
Mount Desert Island Hospital
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[1] Nass M . Anthrax Epizootic in Zimbabwe 1978-80: Due to Deliberate
Spread? PSR Quarterly 1992;2: 198-212.
[2] Brachman PS, Gold H, Plotkin SA et al. Field evaluation of a human
anthrax vaccine. Am J Pub Health 1962;52: 632-45.
[3] Centers for Disease Control. Observational study of anthrax vaccine,
1967-72. Report and raw data obtained by FOIA to CDC, August 2000.
[4] Nass M. ProMED Mail post. January 2, 1998. included for Inquiry.
[5] Morris K. US anthrax-vaccine producer saved for now. Lancet Feb 28,
1998;351:657.
[6] Nass M. Anthrax Vaccine: Model of a response to the biologic warfare
threat. Infect Dis Clin NA 1999;13:187-208.
[7] NIH Technology Assessment Workshop Panel. The Persian Gulf Experience
and Health. JAMA 1994;272:391-6.
[8] Institute of Medicine Medical Follow-Up Agency. Health Consequences of
Service During the Persian Gulf War. National Academy Press. Washington DC.
1995.
[9] Report of the Defense Science Board Task Force on Persian Gulf War
Health Effects. June 1994.
http://www.gulflink.osd.mil/dsbrpt/
[10] Senate Committee on Veterans' Affairs. Is military research hazardous
to veterans' health? Lessons spanning half a century. December 8, 1994. S.
Prt. 103-97.
http://www.gulfweb.org/bigdoc/rockrep.cfm
[11] Persian Gulf Veterans Coordinating Board. Unexplained illnesses among
Desert Storm veterans. A search for causes, treatment, cooperation. Arch
Intern Med Feb 13, 1995; 155:262-8.
[12] Research Working Group of the Persian Gulf Veterans Coordinating
Board. The Annual Report to Congress: Federally Sponsored Research on Gulf
War Veterans' Illnesses for 1998, Appendices. Department of Veterans
Affairs. June 1999. pp 7-13. This list of studies is provided to the Inquiry.
[13] Research Working Group of the Persian Gulf Veterans Coordinating
Board. The Annual Report to Congress: Federally Sponsored Research on Gulf
War Veterans' Illnesses for 1998. Department of Veterans Affairs. June 1999.
[14] Donta ST, Engel CC, Collins JF et al.(48 authors are listed). Benefits
and harms of doxycycline treatment for Gulf War veterans' illnesses; a
randomized, double-blind, placebo-controlled trial. Ann Intern Med July 20,
2004;141:85-94.
[15] French to Check Liaison Officers for Gulf Syndrome. Reuters (Paris)
Sept. 14, 2000.
[16] Steele L. Prevalence and patterns of Gulf War illness in Kansas
veterans: association of symptoms with characteristics of person, place,
and time of military service. Am J Epidemiol. 2000 Nov 15;152(10):992-1002.
[17] Institute of Medicine. Gulf War and Health: Volume 1. Depleted
Uranium, Sarin, Pyridostigmine Bromide, and Vaccines 1999. National
Academies Press, Washington DC. p313.
[18] Jefferson T, Demichelli V, Deeks J et al. Vaccines for preventing
anthrax (Cochrane Review). In: The Cochrane Library, Issue 2, 2003.
[19]Goss-Gilroy. Study of Canadian Gulf War Veterans. Never published
except on the DND website.
http://www.dnd.ca/menu/press/Reports/Health/health_study_eng_1.htm (could
NOT be accessed August 28, 2004)
[20] Fukuda K, Nisenbaum R, Stewart G et al. Chronic multisymptom illness
affecting Air Force veterans of the Gulf War. JAMA 1998;280:981-8.
[21] Unwin C et al. Health of UK servicemen who served in the Persian Gulf
War. The Lancet 1999; 353:169-178.
[22] House Committee on Government Reform. Unproven Force Protection.
Government Printing Office 2000.
[23] Grabenstein J and Wilson JP. Are vaccines safe? Risk communication
applied to vaccination. Hospital Pharmacy 1999;34:713-729.
[24] Vaccine offer raises new questions. Washington Post, December 23,
2001. p A20.
[25] Institute of Medicine. The Anthrax Vaccine: Is it safe? Does it work?
National Academy Press 2002. Washington DC.
[26] Nass M. Trampling on the science.
http://www.redflagsweekly.com/nass/2002_march11.html
[27] Schumm W, Webb FJ, Jurich AP et al. Comments on the Institute of
Medicine's 2000 Report on the safety of anthrax vaccine. Psychol Rep
2002;91:187-91.
[28] Lange JL, Lesikar SE, Rubertone MV, Brundage JF. Comprehensive
systematic surveillance for adverse effects of anthrax vaccine adsorbed, US
Armed Forces, 1998-2000. Vaccine. 2003 Apr 2;21(15):1620-8.
[29] Rehme PA, Williams R, Grabenstein J. Ambulatory medical visits among
anthrax-vaccinated and unvaccinated personnel after return from southwest
Asia. Mil Med. 2002 Mar;167(3):205-10.
[30] Wiesen AR, Littell CT. Relationship between prepregnancy anthrax
vaccination and pregnancy and birth outcomes among US Army women. JAMA.
2002 Mar 27;287(12):1556-60.
[31] Wasserman, G, Grabenstein JD, et al. Analysis of adverse effects after
AVA in US army medical personnel. J Occ Envir Med 2003;45:222-233.
[32] Wasserman G. Tripler Army Medical Center Survey. First Annual
Department of Defense Conference for Biological Warfare Defense
Immunizations. Fort Detrick, Maryland. May 26, 1999. transcript.
[33] GAO/T-NSIAD-99-226
[34] MMWR 127 vol 51 No. 6. Notice to Readers: Status of US Department of
Defense preliminary evaluation of the association of anthrax vaccination
and congenital anomalies.
[35] Johannes L. Anthrax Vaccine May Increase Incidence Of Birth Defects
For Pregnant Women. Wall Street Journal. January 16, 2002.
[36] Araneta MRG, Schlangen KM, Edmonds LD et al. Prevalence of birth
defects among infants of Gulf War veterans in Arizona, Arkansas,
Californai, Georgia, Hawaii and Iowa, 1989-93. Birth Defects Res Part A.
Clin Mol Teratol 2003; 67: 246-60.
[37]
http://www.fda.gov/cber/label/biopava0131022LB.pdf page 6
[38]
http://www.fda.gov/cber/label/biopava0131022LB.pdf page 6
[39]
http://160.151.186.52/VHC/providers_management.htm.
[40] Copies of the 1999 and 2003 guidelines are provided for the inquiry.
[41]
http://www.ha.osd.mil/afeb/meeting/051104meeting/Transcript%20-%20May%2011%2
02004.pdf
[42] Martin BL, Nelson MR, Labutta R et al. Anthrax Vaccine Temorally
Associated Systemic Adverse Events Referred to a Tertiary Medical Center.
Abstract presented at the 58th annual meeting American Academy of Allergy
Asthma and Immunology, March 2002. Supplied by National Vaccine Healthcare
Center at Walter Reed Army Medical Center.
[43]
http://www.anthrax.osd.mil/media/pdf/LearningfromAdverse.pdf His memo
is enclosed for the Inquiry.
[44] Murphy JG, Wright RS, Bruce GK, Baddour LM, Farrell MA, Edwards WD,
Kita H, Cooper LT. Eosinophilic-lymphocytic myocarditis after smallpox
vaccination. Lancet. 2003 Oct 25;362(9393):1378-80.
[45] A copy of this soldier's evaluation is included for the inquiry.
[46] Hayes SC and World MJ. Adverse reactions to anthrax immunisation in a
military field hospital. J R Army Med Corps. 2000 Oct;146(3):191-5.
[47] Enstone JE, Wale MCJ, Nguyen-Van-Tam, JS et al. Adverse medical events
in British service personnel following anthrax vaccination. Vaccine 2003;
21:1348-54.
[48] Tanner J. Dover Air Force Base Survey.
http://www.anthraxvaccine.org/report.PDF
http://www.anthraxvaccine.org/data.PDF
http://www.anthraxvaccine.org/data.PDF
[49] Geier DA and Geier MR. Anthrax vaccination and joint related adverse
reactions in light of biological warfare scenarios. Clin Exp Rheumatol.
2002 Mar-Apr;20(2):217-20.
[50] Geier MR and Geier DA. Gastrointestinal adverse reactions following
anthrax vaccination: an analysis of the Vaccine Adverse Events Reporting
System (VAERS) database. Hepatogastroenterology. 2004 May-Jun;51(57):762-7.
[51] Hart MK, Del Giudice RA, Korch GW Jr. Absence of mycoplasma
contamination in the anthrax vaccine. Emerg Infect Dis 2002;8:94-6.
[52] Walker JS, Lincoln RE and Klein F. Pathophysiological and Biochemical
Changes in Anthrax. Federation Proceedings 1967; 26 (5): 1539-44.
[53] Vick JA, Lincoln RE, Klein F et al. Neurological and Physiological
Responses of the Primate to Anthrax Toxin. J Infectious Diseases 1968; 118
(1): 85-96.
[54] Kingsbury N. Anthrax Vaccine: Changes to the Manufacturing Process.
Testimony before the Subcommittee on National Security, Veterans' Affairs,
and International Relations. October 23, 2001. GAO-02-181T.
[55] Takafuji ET, Russell PK. Military immunizations. Past, present, and
future prospects. Infect Dis Clin North Am. 1990 Mar;4(1):143-58.
[56] Rettig R. Military Use of Drugs Not Yet Approved by the FDA for BW/CW
Defense. RAND 2000. Document number RB-7534
[57] Nass M. Anthrax vaccine: Model of a response to the biologic warfare
threat. Inf Dis Clin North America 1999; 13:187-208.
[58] An FDA Memorandum attesting to this is included for the inquiry.
[59] Newman MJ and Powell MF. Immunological and formulation design
considerations for subunit vaccines. Pharm Biotechnol 1995;6:1.
[60] Frank KJ. Monitoring temperature sensitive vaccines and immunologic
drugs, including anthrax vaccine. Am J Health Syst Pharm Oct 15,
1999;56:2052-5.
[61] FDA Center for Biologics Evaluation and Research. FDA warns Michigan
Biologic Products Institute of Intention to Revoke Licenses. March 11,
1997.
http://www.fda.gov/infosheets/mich-inf.htm
[62] Simons M. Traces of Uranium Isotope Found in U.S. Munitions in Kosovo.
NY Times, Jan 17, 2001.
http://www.nytimes.com/2001/01/17/world/17URAN.html
To visit Dr. Meryl Nass's web site, go to:
http://www.anthraxvaccine.org
Anthrax information web site:
http://www.dallasnw.quik.com/cyberella/
http://groups.yahoo.com/group/Anthrax-no/files/VAERS.pdf
DESTROY QUARANTINED VACCINE:
http://www.PetitionOnline.com/mod_perl/signed.cgi?robi2662&1
PETITION TO OVERTURN/REPEAL FERES DOCTRINE
http://www.petitiononline.com/fd1950/petition.html
Also visit: Anthrax Vaccine Benefit vs Risk:
http://www.avip2001.net AND
http://www.MajorBates.com/
Anthrax Vaccine Network
http://www.ngwrc.org/anthrax/default.asp
Military Vaccine Education Center link,
http://www.milvacs.org
Sgt. Sandra Larson's story:
http://www.ngwrc.org/anthrax/heroes/sandralarson.htm
http://www.avip2001.net/CongressionalTestimony.htm
Tom Heemstra's new book -
http://www.anthraxadeadlyshotinthedark.com/index.html
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