Talk to Anthrax Vaccine Committee, Institute of
Medicine
October 3, 2000
Meryl Nass, MD
In December 1997, when the anthrax vaccine program
was announced, I wrote a short piece for ProMed Mail, pointing out that there
was no published evidence for safety or efficacy of this vaccine in
humans. That piece was cited by The
Lancet, circulated on the Internet, and resulted in my being contacted by
hundreds of people. Within several
months, I began receiving frequent reports of illnesses, which I initially thought
were not vaccine-related. Some began within hours of vaccination, and included
vomiting, diarrhea, severe headaches, and malaise. Months after vaccination people began reporting persistent
fatigue, arthralgias, myalgias, memory loss, difficulty concentrating, sleep
disorders, tremors and various symptoms of autonomic neuropathy. Endocrinopathies (usually hypofunction) were
reported, often but not necessarily in conjunction with the other symptoms I
have described.
I wish I had a perfect review article to explain
these unusual symptoms. It remains to
be written. However, a substantial
number of anthrax vaccine recipients have replicated the Gulf War Illness
symptom pattern. Keiji Fukuda and
Catherine Unwin have separately shown that a complex, multi-system syndrome
exists in many Gulf War veterans, and is not unique to the Gulf War. Gulf War veterans have two to three times
the rate of a large number of symptoms, as non-deployed veterans.
Han Kang of the VA has survey data showing similarly
increased rates of symptom prevalence in Gulf War vets who believe they
received anthrax vaccine, versus those who believe they did not. These studies are a good starting point for
the committee.
There are no comparable articles in the anthrax
vaccine literature, but the confusing multiplicity of symptoms is the same in
anthrax vaccine recipients, and the pattern of symptoms is the same, as seen in
Gulf War vets. Also, patients in both
groups frequently report chronic fatigue and fibromyalgia.
You will be told by others that there is no elevated
rate of illness following anthrax vaccine, and that people who are reporting
illnesses are not reporting the same syndromes. I ask you simply to examine the data that exist, and not to rely
on interpretations provided by myself or anyone else. The VAERS reports, for example, do show a large number of cases
of fatigue, though many are coded as asthenia, myasthenia, or somnolence, in
addition to fatigue. I contend that the
VAERS process, in which an FDA contractor selects terms from a limited list to
code adverse events, is simply inadequate for dealing with complex multi-system
illness. FDA is now updating the system.
Review the anthrax VAERS reports.
It is very difficult to get an idea of the illnesses reported, their
severity and duration.
A study begun at Tripler Army Medical Center in
September 1998, to observe long and short-term systemic reactions to anthrax
vaccine in 603 active duty medical personnel, could be definitive, but the
long-term data have not been released.
Eight per cent of the subjects missed work or sought medical care after
their first vaccination. One physician
developed tremors, and had to stop working.
This was attributed to autoimmune vasculitis by his neurologist.
A very good symptom survey was done at Dover Air
Force base, by a Dover pilot. Her
results show a high rate of new symptoms following vaccination. The raw data and interpretation are included
in your packet.
The original licensing studies, the so-called
Brachman and CDC studies, demand another review. Both focused on active surveillance, ending at 48 hours post
vaccination, for local reactions, thus missing lingering systemic effects. The
report forms from the CDC study, which were used to assure safety for licensure,
omit systemic effects. One nurse who
did report a high rate of reactions at the largest mill in the CDC study, was
overruled by the local physician, who said that anthrax reactions were no more
significant than those for typhoid vaccine. Ironically, injected typhoid is the
most reactogenic vaccine in common use.
The adverse event tables from this study contain
multiple arithmetic errors, and reaction rates from the same vaccine lot vary
widely, from study site to site, and from dose to dose, calling into question
the study's validity.
The Brachman study, of which Dr. Plotkin was a
co-investigator, has similar problems, and used a different vaccine. Four of five, or two of three anthrax
vaccine recipients (the text is contradictory on this point) developed anthrax
during the study, but were excluded from the statistical analysis, generating
an efficacy rate of 92.5%. At least one
of the excluded subjects met the authors' inclusion criteria. A 1960 paper by the group says that
vaccinated subjects at the largest mill worked in lower risk areas of the
factory than those who developed anthrax, and that only 25% of employees
received the vaccine. Thus despite nine anthrax cases in non-vaccine
recipients, the authors did not feel vaccine efficacy had been
established. Yet two years later they
reported the questionable 92.5% figure for efficacy. Dr. Plotkin wrote a third paper describing the risk factors and
clinical course of those who developed inhalation anthrax, four of whom died,
but entirely omitted the fact that the cases he described were participants in
an anthrax vaccine clinical trial, and two had received placebo vaccine. For these reasons, the Brachman/Plotkin and
CDC studies do not establish vaccine safety or efficacy.
Why are chronic illnesses reported by a sizable
minority of patients receiving anthrax vaccine? As far as I am aware, the issue has not been studied. If the committee has concerns about the question
of biological plausibility, I would be happy to meet with you again to discuss
it, and bring another packet of evidence.
I am providing the autopsy report on Richard Dunn, which you will find
interesting. For now, I can suggest the
following:
· The lots are extremely
heterogeneous, and the vaccine contents have never been fully characterized.
· Long-term storage, and
redating of expired vaccines multiple times, perhaps has led to problems. The suggestion was made, prior to licensure,
that duration of storage was associated with increased reaction rates.
· The vaccine only goes through
one sterilization step, filtration, yet the filter was not validated for this
purpose according to an FDA inspection report.
· Therefore, it is possible that unknown viruses or other
slow-growing microorganisms contaminate the vaccine.
I wanted to mention one other important item. There may be more than one anthrax vaccine
in use now or previously, possibly produced at alternate manufacturing
establishments. I enclose documents
which show that other sites were contracted to produce anthrax vaccine, that
two Fort Detrick commanders referred to anthrax vaccine as experimental, and
that the Secretary of the Army indemnified an alternative manufacturer six
months after the Gulf War, in September 1991, directing that their production
be shipped to the Michigan plant.
Perhaps most important, the Defense Department has reserved the right to
use unlicensed vaccines on servicemembers without informed consent. Some study
participants in the CDC trial did not provide signed informed consent, as noted
in study documents I include. I believe
it is within your charge to comment on the issue of using experimental anthrax
or other vaccines on servicemembers or Defense Department employees without
informed consent. Such behavior by
researchers goes outside the bounds of what is ethically and legally acceptable
in our society.
You have agreed to review an
extraordinarily difficult area of medicine, even absent the political
controversies involved. Your
deliberations will be closely scrutinized.
To succeed in achieving the first-class vaccine evaluation for which
this committee was formed, you will need to pay scrupulous attention to issues
of ethics, and be certain the information you are provided is accurate. I believe it imperative that the anthrax
vaccine controversy be settled definitively, or public acceptance of all
vaccines may be tainted by the shadow of this substandard product.
Thank you.
-------------------------------------------------------
Subject:
Text
of my talk to IOM for the Committee's Use
Date:
Wed,
04 Oct 2000 21:31:35 -0400
From:
"Dr. Meryl Nass" mnass@netquarters.net
To:
Lois
Joellenbeck <ljoellen@nas.edu>
Dear Lois,
Here are my remarks on October 4, 2000 for the
Committee's use.
To be clear about the Brachman article, here are the
sections to which I
referred:
1. (p. 634) The authors define "complete"
and "incomplete" inoculees.
"The inoculees referred to as complete include all
those employees who
received the prescribed inoculations at the
scheduled times; incomplete
inoculees include those who missed one or more of
the scheduled
inoculations"
2. (p. 634) "Three of these cases occurred
among individuals who had
received the vaccine..."
3. (p. 635) "One of the "incomplete"
vaccinated cases developed a
"typical" cutaneous anthrax (sic) a day or
two before the scheduled
third inoculation of the initial series." She had received her
inoculations on schedule, and not missed any, so met
inclusion criteria.
4. (p. 644) "Twenty-six cases occurred among
the population during the
evaluation period.
Four cases occurred in individuals who had
incomplete inoculations. Of the remaining 22 cases, 15 occurred in
placebo-inoculated employees, six in uninoculated,
and one in a
vaccine-inoculated employee." This Summary states that 4 persons
received some inoculations and developed
anthrax. Only two of the cases
are specifically described in teh text, and one, of
the two, noted
above, met the authors' criteria for
"complete" vaccination.
One might also note that 3 or 5 cases (the text is
contradictory)
occurred in employees who had different numbers of
vaccine doses, and 15
cases occurred in placebo vaccinees.
Meryl Nass, MD