Politics and Medicine - Why Yale, McSweegan, Steere, et al are such LOSERS

Author

Why Yale, McSweegan, Steere, et al are such LOSERS

kathleen

2005-09-28, 9:42 am

The number one reason Steere,
Schoen, ALDF and Yale, et al are such losers
Date: Wed, 28 Sep 2005 04:13:27 +0000

If they hadn't insisted people with seronegative Lyme were crazy and
not sick,
we would have discovered things like why the tuberculosis vaccines
failed, oh,
maybe 20 years ago.

If they hadn't blown off the adverse LymeRIX events patients, they
would have
made some real medical advances 8-10 years previous to this:

TLR

J Immunol. 2001 Jul 15;167(2):910-8.

Toll-like receptor 2-dependent inhibition of macrophage class II MHC
expression
and antigen processing by 19-kDa lipoprotein of Mycobacterium
tuberculosis.

Noss EH, Pai RK, Sellati TJ, ***Radolf JD,*** Belisle J, Golenbock DT,
Boom WH,
Harding CV.

Department of Pathology, Case Western Reserve university and University

Hospitals of Cleveland, Cleveland, OH 44106, USA.

Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet
persists
inside macrophages, evading host immunity. MTB bacilli or lysate was
found to
inhibit macrophage expression of class II MHC (MHC-II) molecules and
MHC-II Ag
processing. This report characterizes and identifies a specific
component of MTB that mediates these inhibitory effects. The inhibitor
was extracted from MTB lysate with Triton X-114, isolated by gel
electroelution, and identified with Abs to be MTB 19-kDa lipoprotein.
Electroelution- or immunoaffinity-purified MTB 19-kDa lipoprotein
inhibited MHC-II expression and processing of both soluble Ags and Ag
85B from intact MTB bacilli. Inhibition of MHC-II Ag processing by
either MTB bacilli or purified MTB 19-kDa lipoprotein was dependent on
Toll-like receptor (TLR) 2 and independent of TLR 4. Synthetic analogs
of lipopeptides from Treponema pallidum also inhibited Ag processing.
Despite the ability of MTB 19-kDa lipoprotein to activate microbicidal
and innate immune functions early in infection, TLR 2-dependent
inhibition of MHC-II expression and Ag processing by MTB 19-kDa
lipoprotein during later phases of macrophage infection may prevent
presentation of MTB Ags and decrease recognition by T cells. This
mechanism may allow intracellular MTB to evade immune surveillance and
maintain chronic infection. PMID: 11441098 [PubMed - indexed for
MEDLINE]

That's what happens when arrogant fools run the show, and is trademark
Corrupticut.

http://actionlyme.org/
http://actionlyme.org/USDOJ_COMPLAINT_RICO.htm

Note that the famous, brilliant, "Astute Clinician," Allen Steere was
not
rewarded with a CDC Bio4 weapons lab.

In 2001, Jan, I said to the FDA:
http://www.fda.gov/ohrms/dockets/ac...s/3680s2_11.pdf

"We simply don't know all the variables, at present, that effect
systemic
illness from immune dysregulation caused by Bb infection, and
especially the
effect of a such a large dose of a known immune irritant, Osp A upon
this
system, the asymptomatic Lyme patient. "

================
"My name is Kathleen Dickson. I am an analytical chemist from
Southeastern
Connecticut. I would like to discuss the validity of the results of the
LYMErix
adult vaccine trial, specifically--
the validity of serological standard used, and how that standard
affected the
vaccine trial results.

THE PROBLEM IS THE DEARBORN/DRESSLER IgG STANDARD.

One of the testing procedures used in the trial, the Western blot,
looks for
antibodies to specific antigens expressed by B. burgorferi. The
limitation of
the Western blot, is that it qualifies the body's reaction to the
infection but
does not actually identify the infectious agent.

In Lyme disease, patients produce variable antibodies over time, most
likely a
result of antigenic variation - the organism changes its outer membrane

components, and even most of those identified antigens are variable
antigens.
Current diagnostic methods now target the invariable region of the
variable
antigens, for this reason.

[Slide-1]

According to Allen Steere, Chief of Rheumatology, Tufts: (2 reports)
1) 1986, Journal of Clinical Investigation, (Title: "Antigens of
Borrelia
burgdorferi recognized during Lyme disease. Appearance of a new
immunoglobulin M response and expansion of the immunoglobulin G
response late in the illness.")

"...The IgG response in these patients appeared in a characteristic
sequential pattern over months to years to as many as 11 spirochetal
antigens."
[Slide-2]

2) 1993, Dressler/Steere, (Title: "The Serodiagnosis of Lyme Disease",
which
came to be the CDC/Dearborn IgG criteria), Journal of Clinical
Infectious
Diseases, 1993 Feb;167(2):392-400.
"...The specific immune response in Lyme disease develops gradually
over a
period of months to years to greater than or equal to 10 spirochetal
polypeptides."
---------------------------------------

10 or 11 antibodies characteristically show up in Lyme. Some are more
specific than others. These 10 or 11 bands don't all show up at once,
however. They show up one or two or a few at a time. Persistent
infection is evidence by changing bands over time.

CDC decided to establish another serodiagnostic standard, based on
these
specific antigens and called for a Second Serodiagnostic Conference to
be held
in Dearborn Michigan, late October, 1994.

However, in May, 1994, immediately prior to the start of the LYMErix/
ImmuLyme
Lyme vaccine clinical trials, members of the CDC and others, privately
met in
Fort Collins and decided that the Dressler/Steere standard for IgG of 5
of 10
bands be the CDC standard, according to transcripts of the June 1994
FDA Lyme
vaccine meeting, presumedly to facilitate the vaccine trials.

[Slide 3, Table 1 of Dressler]

The problem with the Dressler IgG standard of 5 of 10 bands is that it
was

-calculated to be 99% specific, and was not empirically derived...

-It was generated from strain G 39/40, a strain Barbara Johnson of the
CDC,
later, at the Dearborn meeting, recommended NOT using,

-And represents an artificially compressed summary of what only the
arthritis-presenting patients showed over time.

And does not represent what's going on in neuroborreliosis, a much more
serious
and disabling disorder.

Table 1 reports the frequency of certain antigens, polypeptide and
lipoproteins.

>From the arthritis data set, were derived the bands for this case
definition.

Dressler/Steere report that individual *specific* bands, such as OspA,
B, C,
18-, 93-, and 28-kD, generated from Bb strain G39/40, are specific
markers of
infection.

Dresser/Steere report that 18, 28, 93 are the most specific, because
they never
showed in the controls. That they never showed in controls and are
specific,
would mean, in the presence of symptoms, that one of these bands
indicate that
Lyme is the source of the illness.
P93 and 23kD (OspC) seem to be the consensus on highest specificity, as
seen in
the literature.

That Steere came up with 28, instead of 23, could be a reflection of
the
potential of this odd strain, G39/40 to generate sufficient antigen of
diagnostic value.

Confoundingly, OspA and B were left out of Dressler/Dearborn IgG case
criteria.
We surmised that this was because it was intended that these be vaccine

immunogens.

Therefore, the Dearborn case standard criteria for IgG excluded, to
quote
Steere, "major", "immunogenic, outer surface proteins" from the case
criteria,
the Osps A and Osp B.

The exclusion of Osp A and B has resulted in, is, for example,
unvaccinated
people who have 3 IgG bands plus Osp A and Osp B, aren't diagnosed as
positive,
according to the CDC case definition, even though they have 5 bands.

So we really don't know what Dearborn IgG means.

[Slide 4- Imugen Report]
Further decreasing the potential for getting early and adequate
antibiotic
therapy is the practical misinterpretation of what the CDC criteria
for IgG of
5 of 10 bands means.

For example, Imugen, uses reporting forms which state: "Normal Range: <
5
bands".

[Slide 5- Zoom of Imugen Report, Bottom Right]

Normal is not "less than 5 bands" --If the patient has clinical signs
of Lyme
disease plus 2 specific antibody bands for B. burgdorferi, no honest
diagnostician would assert that the patient does not have Lyme disease.
This
kind of misinterpretation of CDC criteria further compound the problem.

"Normal" is no bands and no clinical symptoms of Lyme.

[Slide 6 - Zoom of Imugen Blots, Show Strain ID]

Note that this lab uses G39/40 and FRG, a strain from West Germany. We
question
how many people in the US will have been exposed to this bug, such that
they
will have antibodies to it.

Clearly, the Dearborn Conference also did not resolve the another
problem of
standardization, as demonstrated by this labs' use of odd strains and
reporting
concepts.

To miss patients by using this Dearborn case definition serodiagnosis
standard,
instead of weighting the specificity of an individual band, such as Osp
C or
P93, both highly specific alone, will result in the patient's lost
opportunity
for early and successful treatment.

THE PRE-DEARBORN DIAGNOSTIC STANDARD
[Slide 7 - page 29 Dearborn Conference Summary]
[Slide 8- Zoom]

Changing bands over time was formerly the criteria for determining
later stage
Lyme disease, in place before the Dearborn conference, as reported by
David
Dennis of the CDC:

"1) Isolation of Bb from Clinical specimens

2) Demonstration of diagnostic levels of IgM or IgG antibodies to the
spirochete
in the serum or the CSF, or

3) Significant change in IgM or IgG antibody response to Bb in paired
acute-phase and convalescent sera phase

Although potentially useful in confirming active Lyme disease, neither
cultural
isolation nor paired serum specimen testing has been much used for
validating
cases in routine Lyme testing, since the procedures are not often
performed in
the general medical setting."
--------------------------------------------------------------------------------
--------
The majority of the other recommendations made by the invited
researchers to the
Dearborn conference on IgG serology, were based on the frequency and
identity
of these known-to-be specific bands, but these 8-9 other
recommendations were
ignored.

The overall accuracy of this Dressler IgG standard never exceeded 28%
in actual
practice and these results were reported by the other invited
researchers at
Dearborn. In other words, most people with Lyme disease DON'T have a 5
of 10
band profile.

HOW DOES DEARBORN APPLY TO THE VACCINE TRIAL?

If few people have Lyme disease - and this Dressler/Dearborn criteria
will
exclude most Lyme patients - the vaccine will not be shown to be a
failure or
cause adverse events.

We believe this is exactly what happened in the trial.

[Slide 9 Table 2 of NEJM SKB Vaccine Results]

Only 22 people got Lyme disease the first year in the vaccine group,
while there
were 515 unconfirmed cases - compared to in the placebo group of 468.

There 10% more unconfirmed cases than in the placebo group in the
first year of
the trial.

There were ~1750 Unconfirmed Lyme disease cases reported during the SKB
trial of
~11,000 over two years.

The Western Blot serology from these unconfirmed Lyme cases will need
to be
reviewed for evidence of other Bb specific bands and compared to the
placebo
group by an independent group of analysts. If there are any other
specific
bands besides OspA, the case must be counted as a Lyme disease case, in
the
presence of symptoms.

Note that there were only 2 asymptomatic cases the first year in the
vaccine
group vs 13 in the placebo group. In the second year, there were 0
(zero) in
the vaccine group and 15 in the placebo group.

We believe these results do not show that the vaccine is effective at
preventing
asymptomatic Lyme, which SKB reports, but rather, that it is turning
asymptomatic Lyme cases into symptomatic ones.

As a support group leader in Southeastern CT, I have met ~10 people,
who found
my name on the internet, who had adverse events and were ill, looking
for help.
After learning more about these patients, I found that all but one of
these
cases had previous Lyme, and that one got the Erythema Migrans rash
during the
series of vaccination. NOT ONE SINGLE PERSON DID NOT HAVE OTHER BANDS
ON FOLLOW
UP WESTERN BLOT.

It is because I have gotten so many calls from patients looking for
help because
of their illness, that I am here today.

Continued follow up on these Unconfirmed patients should have been
with further
Western blotting from one of the CDC recommended strains (B31, 297,
2591) and
the original case definition, to look for changing bands, and/or one of
the
newer antigen-decomplexing methods, like that of Len Sigal's of RWJ or
Steven
Schutzer's, for IgM or IgG.

In the re-tabulated results, which we insist be performed, cases where
active
infection is not found by these follow up methods, should be
resummarized as the
"Uncomfirmed Lyme/Possible Seronegative Lyme".

VACCINE FAILURE AND ADVERSE EVENT

[Slide 10 Persing's Patent]
Dr. David Persing, formerly of Mayo, now with CORIXA recorded in his US
patent
6,045,804:
"Additional uncertainty may arise if the vaccines are not completely
protective; vaccinated patients with multisystem complaints
characteristic of
later presentations of Lyme disease may be difficult to distinguish
from
patients with vaccine failure. Vaccine failures have been occasionally
noted in
animal models (E. Fikrig et al., Science, 250, 553-6 (1990)),..."

Vaccine failure and vaccine adverse event cannot be distinguished from
each
other. An asymptomatic Bb infected adverse LYMErix event case may
never be
detected until the patient is vaccinated and symptoms occur, which we
think
explains the majority of the adverse events reported to FDA re:
LYMErix. Many
previously infected Lyme cases report systemic symptoms after
vaccination. Many
find out they had Lyme after being vaccinated, becoming ill, being
tested for
Lyme and finding other specific antibodies.

FDA should therefore not be looking for only arthritis as a potential
adverse
event, to the exclusion of systemic illness.

FREQUENCY OF ASYMPTOMATIC INFECTION [Slide - 10]

According to Allen Steere's 1986 report, it is possible that, for
every one
Bb-infected person with symptoms, there is one walking around without
symptoms.

SUMMARY

Vaccine failure and exacerbation of asymptomatic infection are
identical,
according to the patient data collected, and on the online VAERS
database.
Dearborn/Dressler is not a valid criteria for assessing Lyme, the
former CDC
criteria of changing bands is valid.

Until there is an independent review of the WB data from the trial, we
have no
idea how safe this OspA vaccine is.

[Slide- SBK Results Table]

OUTLOOK

By what mechanism vaccination of the asymptomatic Bb infected patients
is
causing the Lyme like illness, we do not know exactly.

Previous infection could be "priming" the immune system, as Denise
Huber of
Tufts has suggested, in "Identification of LFA-1 as a Candidate
Autoantigen in
Treatment-Resistent Lyme Arthritis" July 31, 1998, Science, Vol 281, p
703. or
the vaccine is activating a dormant infection by the immune
dysregulation it
causes, as demonstrated by the effect of Bb infection and Osp A alone,
on NK
cells population, T cells, neutrophils, and the effects on the various
inflammatory regulating biomoleclues, such as IL-10.

We simply don't know all the variables, at present, that effect
systemic illness
from immune dysregulation caused by Bb infection, and especially the
effect of a
such a large dose of a known immune irritant, Osp A upon this system,
the
asymptomatic Lyme patient.

The vaccine should be taken off the market immediately, until the true
data, the acknowledgement of the presence of other bands besides Osp A
in all 4 groups of uncomfirmed Lyme is published and re-presented to
the FDA.

Certainly this vaccine should not be approved for use in children,
until we know the true results of the adult vaccine trial. "

Kathleen

--
"We must instill a sense of duty in our children"; "every right implies
a
responsibility; every opportunity, an obligation; every possession, a
duty"-
John D.Rockefeller Jr

mockingbird

2005-09-28, 9:42 am

steere didn't get an NLB grant, but klempner did...and harvard got an
RCE grant, also tulane and barbour at irvine...