Dearborn_Who_Approved
"DEARBORN"
The term
"Dearborn" refers to this conference, in
which this standard was accepted for
serodiagnosis, when it will miss about
80% of those infected with the Lyme
infections.
http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00038469.htm
The
following is an exerpt of the
datapackage delivered to the January 31,
2001, FDA Vaccine Meeting Committee
members by K. M. Dickson, regarding the
validity of the Dressler/Steere CDC
IgG
standard used to qualify the LYMErix
vaccine:
http://www.fda.gov/ohrms/dockets/ac/01/slides/3680s2.htm
http://www.fda.gov/ohrms/dockets/ac/01/slides/3680s2_11.pdf
The
CDC's Dressler/Steere IgG antibody
criteria are not valid. In
Dressler and Steere's prospective study,
the IgG accuracy was 72% for
arthritis-presenters, who represent 30
to 35% of the general population in HLA
haplotypes. 72% of 33% is about
22%, which was nearly the exact
percentage of vaccine failures in the
LYMErix trial. And the vaccine was
claimed to be ~78% safe and effective.
(If the Dressler/Steere standard was 10%
accurate, the vaccine may be been
declared 90% safe and effective.)
Dressler/Steere also left out OspA and
B, although Steere first reported OspB
(34 kilodaltons) and flagellin were the
first antibodies to appear, and later
published, that indeed, he did see early
OspA antibodies. These are among
Tufts Funny Lab Tricks.
============
Contributions:
From the
1994 Dearborn Conference booklet--page
29
"Standardization of Lyme Disease
Serologic Testing for Epidemiologic
Purposes" by David T Dennis, MD, MPH
(This was the former criteria for
serodiagnosis; before Dearborn)
"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."
Prior to
May, 1994, it was recognized that
changing bands was serodiagnostic.
From an
invitation from the CDC/NIH/NCID printed
October 1994
"DON'T MISS
AN OPPORTUNITY TO CONTRIBUTE TO THE
DISCUSSIONS!" [in bold print]
page 2
"The goal
of the second national conference if to
create a forum in which all individuals
and groups interested in Ld
serodiagnosis may contribute and express
their opinion. Specific topics for
discussion include developing a set of
recommendations that will establish
standards for interpretive criteria;
setting the criteria appropriate for the
development and evaluation of new
diagnostic tests; sharing information on
establishment of standard laboratory
methods; and discussing the FDA criteria
that Ld kit manufacturers must meet to
certify their tests."
This gives
the appearance that researchers were
invited to Dearborn to contribute to a
consensus on serology.
However,
CDC and SKB already had a standard for
IgG that they were sticking with, by the
start of the SKB, vaccine trial,
June 1994. Whoever was in charge
at Dearbon, ignored the other
recommendations. Arthur Weinstein
was in charge of the Workgroup on IgG
and IgM recommendations, Henry
Feder agreed also with Dressler, but
added that IgM was not necessary and
that some other bands were diagnostic in
children because they were not likely to
have been treponemal bands and children
have different immune systems than big
people. For instance 50kD was
related to Ld in children.
Who else
was there:
1) MarDx
Labs- included 31 and 34. IgG
sensitivity of 12 bands in late disease
was 100% That means this 5 of 12
criteria was only seen in Ld.
SKB Vaccine trial was already underway
using this lab.
They were
sent positive CDC blood. It
appears everyone else tried out CDC IgG
criteria in the field.
2) Imugen-
said using CDC method for IgG only
detected Lyme in 14% of the time.
3) New York
Medical College, Vahalla- 36% for EM
7-14 days, 20% in <7 days EM
(it is not
common practice to Western Blot patients
with EM, so we don’t know what these
resulst mean. Western blotting is
normally used in the absense of a rash.)
4) Lutheran
Hospital, La Crosse Wisconsin -
22% for were positive by this IgG
criteria.
They
report: "Highly significant
decrease in sensitivity when the
proposed CDC criteria were applied for
interpretation"
5) Zemel,
UCONN - did not reportt give %
positive by Dressler IgG their results.
Only discussed how many bands they
found in the JRA patients, etc.
Recommended 5 bands.
6) Roche
Biomedical Labs, 28% were positive
for every possible IgG band,
Others were positive for IgM and IgG
were equivocal. It’s possible from
the notes that this lab was not certain
of how their observations were to be
reported
7)
Wadsworth- had some different scoring
system, did not report % frequency in
which they found 5 bands.
8) CDC
Atlanda, Hofmeister and Childs --talked
about mice. Their criteria was 2
out of three of OspC, 16 kD, 17.9 kD for
IgG, for the mice.
9) Canada,
Ontario, Ontario Ministry of Health. Did
not report how they performed their
survey. 66% of the positive ELISAs
were WB positive was the only data
related to this.
10) Igenex--
Concurrent positive serology with
greater than 3 symptoms: 8%
11)
Wisconsin State Laboratory of Hygiene
and the College of American
Pathologists: CDC criteria for IgG
had a sensitivity of 15%. They
reported the frequency that they found
the various specific bands.
The
Wisconsin State Laboratory gave probably
the best objective summary of what
happens in serology. They
recommended standardization of the
method should preceed the establishment
of the interpretive criteria.
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