ACTIONLYME PRE-HISTORY- all about me and my famous
self!!! (NOT)
1993,
Joe Burrascano, Congressional
Oversight Hearing Lyme disease- MD Harassment
1998
New London Day Article May
by
KMDickson
After dealing with the abuse
and neglect by the State of Connecticut,
ACTIONLYME founded Sep 1999
1999, e-Petitions, First ActionLyme, anti-Conflicts of
Interest Campaign/Report/Summary to "authorities," by K. M. Dickson:
http://groups.google.com/groups?hl=en&lr=&ie=ISO-8859-1&q=Petition+Dattwyler+Kathleen+group%
http://groups.google.com/groups?q=Pataki+Rowland+Kathleen+group:sci.med.diseases
1999, ActionLyme Reporting Adverse
Events Reporting Campaign Begins, Summer
Allen Steere, the "Astute Clinician"
http://groups.google.com/groups?q=kathleen+Parenti+group:sci.med.diseases.lyme+group:sci.med.diseases.lyme
1999, Vikay Sikand, East
Lyme, CT ("Ha, Ha, Aren't we all
getting old and forgetful"), reporting
Sikand to the FDA
LDF and Lymerix,
April 2001
Vijay's LYMErix
Blow-Off and Lewis Bull
1999, Fall: The Poughkeepsie
Lyme Initiative. The Bard Conference nearly
was caved due to pressure from New York Medical College (source of
NY DOH’s OPMC “Experts”) THE SPIN, >>>
http://www.lymenet.de/aktive/pli.htm
compiled by K.M. Dickson (Medical Detectives>>
Xxxxxx- who wishes to remain anonymous,
Vanderhoof-Forschner, Dickson)
Mass. Lyme's
ActionItem: REPORTING Allen Steere
for Medical Misconduct: Steere,
Report
----
Edward McSweegan DCF-like stalking and harassment
2000, NOVEMBER, First ActionLyme Website, "The Lyme Disease
Dilemma"
http://www.geocities.com/kmdickson0308/lyme-dilemma.html,
by K.M. Dickson
===
2001, January 31,
FDA LYMErix Vaccine Meeting, KMDickson, and
ActionLyme, the sum of complaints brought about FDA's
call for a hearing- OspA
associated with activation of something
like Lyme disease and the lack of Asymptomatically infected
in the Vaccine (rOspA) group. We
ratted out VIJAY
SIKAND (above, documented mistreatment of a trial
participant in East Lyme, CT)
http://www.fda.gov/ohrms/dockets/ac/01/slides/3680s2_11.pdf
Edward McSweegan attended this FDA Meeting and was FURIOUS at what I told
the FDA
LOL
because the bogus Lyme vaccine was
all his idea
(see the Barry Goldwater Letter)
Pam Weintraub:
http://www.whale.to/m/lymerix8.html
"The
Bitter Feud over LYMErix
Big Pharma Takes on the
Wrong Little Osp"
OTHER FDA TESTIMONY, at the
Jan 31, 2001 Vaccine Meeting, See
Lobet's and TRLA as persisting infection
http://www.fda.gov/ohrms/dockets/ac/01/slides/3680s2.htm
TRANSCRIPT of Jan 2001 FDA Vaccine
Meeting:
http://www.fda.gov/ohrms/dockets/ac/cber01.htm#Vaccines%20&%20Related%20Biological
Choose:
3680t2.rtf at the very bottom,
center of the page.
LYME FOUNDATION
Lyme Foundation.
Vaccine withdrawn 2/27/02
LYME ASSOCIATION:
http://www.lymediseaseassociation.org/Vaccine.html
BELOW, Submission
to the OPMC, November 2001, Albany, NY
Medical Licensing Board (OPMC) Abuse of
Lyme-Treating Physicians Hearings
(submitted by K.M. Dickson, below--
Includes Bransfield/Brand's Rebuttal to Klempner, July 12, 2001,
NEJM and "The Chronic Lyme Study" which
was anything butt...)***
From/For the Albany
OPMC Hearing: Spirochetes, their
Nature More below
OPMC Hearing Testimony, Kenneth B.
Liegner, MD, and “social pathology”:
http://www.aapsonline.org/testimony/liegtest.htm
Other Testimony at
Albany, November 27, 2001
http://www.lymeinfo.net/part1.html
ActionLyme.50megs
(second homepage—see especially, the
“Planet CDC” Explainer.)
http://www.actionlyme.50megs.com
by K.M. Dickson
Trouble in Rhode
Island, the R.I. Tick Borne Diseases
Management Plan-- by K.M.
Dickson
(link, see partial report in
Pathologies.)
ILADS Position Paper on
Klempner (authors:
RC Bransfield, VT Sherr, Se Phillips, KM
Dickson, RB Stricker, HA Smith, S Brand)
REPORTING Lenny
Sigal for Medical Misconduct :
SIGAL
=============================
*** ALBANY,
November, 2001
ASSEMBLY
COMMITTEE ON HEALTH
CORRECTED VERSION 7/14/02 Replaced
Phylum with Order (see Lynn Margulis’
work)
Richard
N. Gottfried Chair
Lara
Kassel
Legislative Associate
Assembly
Member Gottfried's office
822
Legislative Office Building
Albany,
NY 12248
From:
ActionLyme, International Patient
Advocacy Group, by K. M. Dickson
ActionLyme Mission: To influence
planning and policy in Vector Borne
Diseases founded upon a complete
presentation of the dynamic and
extensive evidence of both spirochetal
diseases, in general, and Borreliosis,
more specifically, in humans.
Introduction:
"Lyme
disease" is infectious arthritis in a
joint, with a high antibody response (i.e,
5 of 10 bands on a Western Blot),
according to the CDC. It is
culturable Borrelia burgdorferi
organisms from joint fluid.
Neuroborreliosis, or Lyme borreliosis is
the chronic neurologic illness that is
more commonly, and historically, (i.e.,
before Lyme, CT's Polly Murray
discovered a cluster of juvenile
arthritis) associated with spirochetal
infections of mammals. The
simplest analogy is tertiary syphilis, a
late neurologic spirochetal illness.
It is
extremely uncommon for there to be a
spirochetal infection that results in
joint inflammation alone. "Lyme
disease" may be unique among spirochetal
infections, in that respect.
Part I.
VALIDATION OF THE SCIENCE
In
answer to the question, “Do the NY OMPC
investigated Lyme treating physicians
have valid reason to believe Lyme
borreliosis is a persisting infection,
such that they treat and retreat Lyme
Borreliosis according to methods that
match the extensive evidence of how
spirochetal microbes in general, and
Borrelia burgdorferi, in particular,
behave,” ActionLyme has provided a summary of
scientific articles which support not
only the Borreliae as persisting
organisms, but support the ruggedness
and persistence of the representatives
of the entire Order
Spirochaetales against environmental
extremes, including chemical or
antibiotics.
Part I
of this ActionLyme response, examples of
persistence from Nature, are only
part of the picture of persistence
across the Order. The greater bulk of
confirming scientific publications are
available to be read on the ActionLyme
website:
http://actionlyme.50megs.com/OPMC.htm
In
summary, Spirochetes are capable of:
-Morphological changes- spheroplast or
"cyst" form, which is
infectious/regenerates to intact form
-Dessication
or near-Dessication
-Antimicrobial resistance-gene sharing,
via plasmid
-Lateral
gene transfer
-Intracellular persistence resulting
in immune and antibiotic evasion (Klempner)
-Antigenic variation resulting in immune
evasion
-Freezing. Lyme patients
cannot donate blood, per the Red Cross
Spirochetes do not behave like other
bacteria. They are their own Order, the
next degree of taxonomic classification
under the Animal Kingdom is Class
considerable uniqueness from other
bacteria (Linnaean System: Kingdom,
Phylum, Class, Order, Family Genus,
Species)..
Part II
is a summary of publications and
testimony on "Autoimmunity" in
Neuroborreliosis. The argument
that treatment-resistant Lyme arthritis
is an autoimmune disorder is commonly
known, although still a hypothesis;
there is a known association to T cell
haplotypes, or the genetic code for
Major Histocompatibility Complex class
II "antigens", or antigen-presenting
molecules in autoimmune disease and in
autoimmune Lyme arthritis. Simply
put, people with HLA-DR4 or -DR2, the
arthritis-prone individuals, tend to
have a high antibody response and
prolonged and extensive joint
inflammation from B. burgdorferi,
or, they have "Lyme disease".
There
are now 2 known associations with
persistent Neuroborreliosis as an
autoimmune disorder, HLA-DR1*1501 and
HLA-DQB1*0602, which are the two primary
class II haplotypes associated with
Multiple Sclerosis. Klempner
found that Chronic Lyme patients tend to
have this *0602 haplotype much more than
would be expected, and therefore,
believes may be a correlate in this
illness. This discovery was
not reported in the New England Journal
last summer. It is still a
hypothesis, that these
antigen-presenting molecules have
"molecular mimicry" or similarity to,
and attack self, but there is an
increased prevalence of at least one of
these two haplotypes expressed in
Multiple Sclerosis/Lyme and is
therefore, now a current area of
discovery.
Multiple
Sclerosis is a Central Nervous System
disease. Lyme borreliosis patients
have been accused of exhibiting behavior
that is not rational (Steere), neurotic (Weld), may be
Munchausen and Munchausen-by-Proxy
(Sigal), paranoid (Schoen), anxious
(Shapiro), ignorant (Benach), neuropsychiatric illness without
objective evidence (Klempner),
etc.,…
Rather than publicly
stating that Lyme borreliosis patients
have a CNS disorder, rather than
providing the evidence of the
association in MS haplotypes, rather
than providing the evidence in the
pathophysiology that these researchers
have found, this data is withheld,
and instead, it is publicly
suggested that Neuroborreliosis patients
exhibit severely psychopathology.
It is
said, by these researchers, that
Neuroborreliosis symptoms are "vague",
but actually, they are only "vague" when
the physician doesn't look at symptoms
with the available objective tools.
"Lyme
disease" is not vague. A swollen,
red knee does not require anything more
than human eyes to detect. It is
Lyme borreliosis, that requires
more sophisticated perceptive abilities
and analytical equipment.
The
medical and social respect, care, and
deference given to MS, Lupus,
Narcolepsy, HIV and other neurological
patients are being denied Lyme
borreliosis patients. Instead,
these researchers invoke the stigma of
mental illness as a deliberate means to
deny the validity of our complaints and
our access to treatment for a medical
condition. This denial of 1) our
basic human dignity and 2) access to
medical care for a medical condition,
are Human Rights Abuses.
Whether
Lyme borreliosis becomes a form of
Multiple Sclerosis, or Lyme borreliosis
is a cause of multiple sclerosis in the
absence of persisting organism, or that
any infectious cause of Multiple
Sclerosis is either persisting infection
or is true autoimmunity, are subjects of
current scientific debate.
The
evidence in Neuroborreliosis is that
spirochetes persist past antibiotic
treatment. The
evidence is that patients have one of
three outcomes: 1) Lyme arthritis
and high antibody response, 2) signs of
infection resolve and the patient
becomes asymptomatic, 3) patients
develop a chronic neurologic syndrome
clinically indistinguishable from
Multiple Sclerosis.
It is
scenario 3 that Lyme treating physicians
treat, primarily; the chronic fatigue/
chronic musculoskeletal/ chronic
neurocognitive disorder. That they treat
with longer antimicrobial therapies than
would meet with the intentions of
Managed Care bottom line, is because the
evidence from the Order is that
spirochetes do not behave like other
bacteria- they undergo physical changes
which protect them from enviromental
extremes.
We have
no data that says spirochetal infections
are not persistent.
There is no specific antibiotic cure for
Borreliosis, nor are there any specific
antibiotic cures for Syphilis,
Leptospirosis, or Brachyspirosis. That is the state of the science:
There is no specific, targeted,
antibiotic known to kill all these
organisms in any mammal.
ActionLyme will provide evidence from
the scientific research that, indeed,
Neuroborreliosis results in a CNS
disease with similarities to Multiple
Sclerosis, and is the presence of real
pathology, rather than is a psychogenic/hypochondriacal
syndrome.
Table of
Contents: (HARD COPY of these will
be hand-delivered Tuesday Nov 27 to
Assembly)
Part I.
THE CAUSE OF CHRONIC NEUROBORRELIOSIS,
Evidence from Nature. The Order, on
persistence.
1)
"Composite, large spirochetes from
microbial mats: spirochete structure
review."
Morphological changes may be responsible
for relapsing, persisting illness.
http://www.pnas.org/cgi/reprint/90/15/6966.pdf
2)
"Conversion of Borrelia garinii cystic
forms to motile spirochetes in vivo."
Transfer
of the spheroplast results in infection.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11478686&dopt=Abstract
3)
“Effects of Penicillin, Ceftriaxone, and
Doxycycline on Morphology of Borrelia
burgdroferi”
Conversion to spheroplast may not be the
end stage.
http://aac.asm.org/cgi/reprint/39/5/1127.pdf
4) -
"The Complexity of Vector-borne
Spirochetes (Borrelia spp)"
Willy
Burgdorfer 12th
International Conference on Lyme Disease
and Other Spirochetal and Tick-Borne
Disorders April 9, 1999 Keynote
Address
Dr.
Burgdorferi recognizes the older data on
morphological variants.
http://www.medscape.com/medscape/cno/1999/lyme/Story.cfm?story_id=534
5)
"Detection of Borrelia burgdorferi
DNA by polymerase chain reaction in
synovial fluid from patients with Lyme
arthritis."- Steere
Standard
antimicrobial therapy does not kill all
spirochetes. The longer the
therapy, the lower the DNA concentration
in Lyme arthritis.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8272083&dopt=Abstract
6)
"Fibroblasts protect the Lyme disease
spirochete, Borrelia burgdorferi,
from Ceftriaxone in vitro."-- Klempner
14 days
exposure to ceftriaxone does not kill
all B. burgdorferi due to
intracellularity of the organism.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1634816&dopt=Abstract
7)
“Relapsing Fever—Treatment and Control”
Chapter by Jay P. Sanford, from Biology
of Parasitic Spirochetes, Academic
Press, 1976, edited by Russell C.
Johnson Jay P. Sanford, Uniformed
Services University School of Medicine,
Bethesda, Maryland p. 390
"There are aspects
of the treatment of relapsing fever,
syphilis, leptospirosis that illustrate
similarities and from which therapeutic
principles may be developed. The ability of borrelia, especially
tick-borne strains, to persist in the
brain and in the eye during remission
after treatment with arsenic or with
penicillin or even after apparent cure
is well known (1). The
persistence of treponemes after
treatment of syphilis is a major area
which currently requires additional
study (3,5,10,11)."
8)
"Central nervous system manifestations
of Lyme disease." -Duray, Steere,
Pachner
Brain
biopsy from patient with subacute Lyme
encephalitis produced an organism
morphologically compatible with B.
burgdorferi. It appears
spirochetes infect human brain tissue.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2742551&dopt=Abstract
9) "In
vivo activities of Ceftriaxone and
Vancomycin against Borrelia spp. in the
mouse brain and other sites." – Barbour
After 7
days delay, vancomycin treatment failed
to eradicate Borrelia from the brains of
immune compromised mice.
http://aac.asm.org/cgi/reprint/40/11/2632.pdf
Part II.
THE EFFECT OF NEUROBORRELIOSIS
Multiple
Sclerosis and Persisting
Infection? Evidence from the laboratory.
(More,
again, on the ActionLyme website.)
1)
Martin (NIH) and T cells and
HLA-DR1*1501:
"Identification of candidate T-cell
epitopes and molecular mimics in chronic
Lyme disease"
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v5/n12/full/nm1299_1375.html
2)
Klempner (Tufts) quoting Martin (NIH),
"Is it thee or me?-autoimmunity in Lyme
disease"
Autoreactive T
cells to human nerves.
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v5/n12/full/nm1299_1346.html
3)
Klempner to Rhode Island Doctors and
HLA-DQB1*0602
South
County Hospital, "Diseases of Summer
Conference", July, 2001
What was
discovered, but not published in NEJM
The
validity of the Fibromyalgia Impact
Questionnaire or SF-36 as assessment
tools for outcomes of standard
treatment, over re-examining and
re-reporting cerebrospinal fluid Matrix-
Metalloproteinases- enzymes seen in the
pathophysiology of Multiple Sclerosis,
and previously reported by Klempner in
Neuroborreliosis patients.
See
separate pages ___;Bransfield/Brand
Rebuttal to Klempner, July 12, NEJM.
4)
"Matrix metalloproteinases in the
cerebrospinal fluid of patients with
Lyme neuroborreliosis."
Klempner
reports MMPs- enzymes found in the CSF
of Multiple Sclerosis patients, as well
as Borreliosis patients.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9466528&dopt=Abstract
5) "Clonal
expansion is a characteristic feature of
the B-cell repertoire of patients with
rheumatoid arthritis”
B cells and
"Autoimmunity"- The picture
involves more than T cells. It
could be there is continually presented
antigen- from somewhere.
http://arthritis-research.com/content/2/1/50
6) "Lyme
Disease and the Clinical Spectrum of
Antibiotic Responsive Chronic
Meningoencephalomyelitides"
Ken
Liegner's autopsy results. Many
sad stories. Probably not
psychogenic.
http://www.medscape.com/SLACK/JSTD/1997/v04.n03/jst0403.04.lieg/jst0403.04.lieg-01.html
7) THE
EARLY HISTORY OF LYME TREATMENT:
At one
time, all of the Authors of the IDSA
Guidelines, except Durland Fish who is
an entomologist, believed there was
evidence to provide longer treatment.
See “Early Treatment History Data” set.
Page___
8) So
where are we? Some
researchers are still dedicated, despite
the harassment by the OPMC and similar
controlling entities elsewhere in the
US, and the frustrations of dealing with
Managed Care, to figuring out how
to help patients with borreliosis.
There were two studies completed in the
United States that have shown
improvement with longer term therapy;
outside imaginary, and as yet,
un-validated, standards of care.
One is an ongoing study by Dr. Brian
Fallon of Columbia, See:
http://www.columbia-lyme.org/
a)
"Repeated Antibiotic Treatment in
Chronic Lyme Disease"- Fallon, et al.
http://www.medscape.com/SLACK/JSTD/1999/v06.n04/std0604.02.fall/std0604.02.fall-01.html
b) "Tetracycline
therapy for chronic Lyme disease."
Sam T. Donta, Boston University School
of Medicine, Infectious Diseases
Faculty.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9233665&dopt=Abstract
Mark Klempner, Tufts, to
Rhode Island Doctors: South County
Hospital, "Diseases of Summer
Conference", July, 2001
What was
discovered, but not published in NEJM.
An audio transcript.
"Um,
There, these patients obviously, are
very, very much interested in that
question, as we are, and I just want to
highlight a preliminary piece of data of
where we think we're going from here,
unpublished*, and not for large, uh,
dissemination, but here is the
preliminary data.
And,
that is, that when you look for the
possibility of an autoimmune disease,
the best way to look is to see if there
is any genetic clustering in HLA
haplotypes. The reason for that is the
way antigens get presented in the
context of who you are, that is, your
HLA haplotype. And we can talk in
some detail about that. Those
diseases that I think everybody would
agree are so called Autoimmune: lupus,
rheumatoid arthritis, type 1 diabetes,
and perhaps MS, have some clear genetic
clustering that leads us to believe that
these are indeed autoimmune diseases,
although we do not satisfy so-called
co-postulates of autoimmune disease that
we've written about. And the odds
ratio for your having that particular
HLA type, in the case of Rheumatoid
arthritis, a DR4. Or a DQB0602 to
protect you from type 1 diabetes, are on
the order of 3 to 6. One of
the ones that is probably highest,
of course, is B27, in patients
with alkyloiding spondolytis and the
like. It turns out that if you
look at the first 51 patients with post-
treatment chronic Lyme disease, the
patient population that participated in
our study, there was a very high
incidence of DQB0602 with an odds ratio
of 770%. So it may well be that
exposure to THAT organism with THAT
background of HLA haplotype may lead you
to develop chronic symptoms. That
is a hypothesis that needs to be tested.
It would obviously lead to an entirely
new form and approach to therapy."
"There
were also many outcomes that were done
in the laboratory. I won't focus
that much on them. They are still
a focus of great interest for us. And
that is these serial plasma samples for
PCR, at the dates that I mentioned here
to try to determine if we could pick up
sequestered infectious organisms.
Urine samples on multiple days for
antigen testing and I'll comment on
perhaps at the end of there's time,
about the Lyme Urine Antigen Test- what
we found in that regard. Um, a new
test that we're still working on,
looking in the spinal fluid for a
particular matrix-metalloproteinase, a
CSF gelatinase, which I won't have time
to comment on. We published on
this before, we're still looking at it,
and it may be an interesting marker in
these patients."
Early Treatment
History Data set
TITLE:
Treatment of Lyme disease., Schoen
RT, Conn Med 1989 Jun;53(6):335-7
ABSTRACT: Lyme disease, a
tick-transmitted spirochetal infection,
can be divided into three stages that
can overlap or occur alone. The goals of
antibiotic therapy in stage one are to
shorten the duration of early disease
and to prevent the development of later
stages of the illness. This can usually
be accomplished with oral antibiotic
therapy. Later stages of the
illness are frequently more difficult to
treat, requiring prolonged oral or
intravenous antibiotic therapy.
Dattwyler and Luft
TITLE: A
perspective on the treatment of Lyme
borreliosis., Luft BJ; Gorevic PD;
Halperin JJ; Volkman DJ; Dattwyler RJ,
Department of Medicine, University of
New York, Stony Brook 11794-8153.
SOURCE: Rev Infect Dis 1989
Sep-Oct;11 Suppl 6:S1518-25
ABSTRACT: Lyme borreliosis has
become the most common tick-borne
infection in the United States.
Although both beta-lactam and
tetracycline antibiotics have been shown
to be effective in the treatment of this
spirochetosis, the development of
optimal therapeutic modalities has been
hampered by the lack of reliable
microbiologic or immunologic criteria
for the diagnosis or cure of this
infection. In vitro sensitivity studies
have been performed by several
laboratories, but there has been no
standardization of the methodology for
measuring either inhibitory or
bactericidal levels. Clinical studies
have documented the efficacy of
antibiotics, but therapy has failed
in as many as 50% of cases of chronic
infection. Although new antibiotic
regimens appear promising, the optimal
treatment of this infectious disease
remains to be determined. In this report
we review the clinical and experimental
rationale for the antibiotic regimens
that we currently use and the need for a
more standardized approach to treatment
trials.
CONTRAST
quote to New York Times by Dattwyler:
“In
contrast, antibiotics have been shown to
work extraordinarily well when, for
instance, the Lyme organism has
demonstrably infected the brain, Dr.
Dattwyler said.”
Coyle
TITLE:
Seronegative chronic relapsing
neuroborreliosis [see comments],
Lawrence C; Lipton RB; Lowy FD; Coyle PK,
Department of Medicine, Albert Einstein
College of Medicine, New
York, N.Y., USA. Eur Neurol
1995;35(2):113-7
ABSTRACT: We report an unusual patient
with evidence of Borrelia burgdorferi
infection who experienced repeated
neurologic relapses despite aggressive
antibiotic therapy. Each course of
therapy was associated with a
Jarisch-Herxheimer-like reaction.
Although the patient never had
detectable free antibodies to B.
burgdorferi in serum or spinal fluid,
the CSF was positive on multiple
occasions for complexed anti-B.
burgdorferi antibodies, B. burgdorferi
nucleic acids and free antigen.
Coyle on
long term effects
TITLE:
Cognitive functioning in late Lyme
borreliosis [see comments], Krupp LB;
Masur D; Schwartz J; Coyle PK;
Langenbach LJ; Fernquist SK; Jandorf L;
Halperin JJ, Department of Neurology,
State University of New York, Stony
Brook 11794., Arch Neurol 1991
Nov;48(11):1125-9
ABSTRACT: Lyme borreliosis, a tick-borne
multisystem disease, may cause a variety
of neurologic complications, including
meningoencephalitis and encephalopathy.
To evaluate neurobehavioral function
following treated Lyme borreliosis, 15
patients with Lyme disease and
complaints of persistent cognitive
difficulty a mean of 6.7 months
following antibiotic treatment underwent
neuropsychological evaluation and were
compared with 10 healthy controls,
matched in aggregate for age and
education, who underwent the identical
neuropsychological assessment. Compared
with controls, patients with Lyme
disease exhibited marked impairment on
memory tests and particularly on
selective reminding measures of memory
retrieval. The memory impairment did
not correlate with serum or
cerebrospinal fluid anti-Borrelia
burgdorferi antibody titers and was not
explained by magnetic resonance imaging
findings or depression. The
cause of this encephalopathy is
currently unknown; however, indirect
effects of systemic infection or other
toxic-metabolic factors may be partly
responsible.
Wormser
and Nadelman
TITLE:
Isolation of Borrelia burgdorferi from
the blood of seven patients with Lyme
disease., Nadelman RB; Pavia CS;
Magnarelli LA; Wormser GP: Department of
Medicine, New York Medical College,
Valhalia., Am J Med 1990
Jan;88(1):21-6
ABSTRACT: PURPOSE: Borrelia burgdorferi,
the etiologic agent of Lyme disease, has
rarely been successfully cultured from
blood. We report on seven patients from
Westchester County, New York, with B.
burgdorferi bacteremia diagnosed between
April 1987 and August 1987. PATIENTS AND
METHODS: One hundred thirty-two attempts
to isolate spirochetes were made on
blood specimens obtained from 104
patients. Twenty-two of these specimens
were obtained from nine patients who had
recently been bitten by Ixodes ticks but
who were asymptomatic. Heparinized blood
or serum specimens (0.2 to 0.4 mL) were
inoculated onto 6 mL of modified
Barbour-Stoenner-Kelly medium. Lyme
serology was performed by enzyme-linked
immunosorbent polyvalent, IgM, and IgG
assays, fluorescent immunoassay, and
microhemagglutination. RESULTS:
Four of the seven patients had erythema
migrans, two had facial nerve palsy, and
one had a flu-like syndrome without
rash. These patients represented 21%
(four of 19) of all patients with the
characteristic skin lesion who had blood
cultures for B. burgdorferi, and 40%
(two of five) of all those with facial
nerve palsy. Serologic testing was
frequently nonreactive; two patients had
no detectable antibody on multiple sera
by five different assays. All patients
improved with antibiotic treatment, and
had negative subsequent blood cultures, but five of seven had persistent
complaints after completion of therapy.
CONCLUSION: Culturing blood for B.
burgdorferi may be useful in confirming
the diagnosis of Lyme disease in
selected patients. Use of spirochete
blood cultures may facilitate a better
understanding of the pathogenesis and
natural history of Lyme disease.
Wormser
and Nadelman
TITLE: A
clinical approach to Lyme disease.,
Nadelman RB; Wormser GP, Department of
Medicine, New York Medical College,
Valhalla., Mt Sinai J Med 1990
May;57(3):144-56
ABSTRACT: Lyme disease (also known as
Lyme borreliosis) is an emerging, newly
described infectious disease with
diverse clinical manifestations.
The disease is caused by the spirochetal
agent Borrelia burgdorferi, which is
transmitted to humans by the bite of
certain species of Ixodes ticks
harboring the organism. The most readily
identifiable clinical feature is the
distinctive skin lesion, erythema
migrans. If recently infected
patients go untreated, approximately 15%
will develop neurologic conditions (most
commonly facial nerve palsy), 8% will
develop myocarditis (typically with
heart block), and 60% will develop
migratory mono- or pauci-articular
arthritis. Diagnosis depends on
clinical suspicion, recognition of the
characteristic signs and symptoms, and
appropriate testing for antibody to B.
burgdorferi. Serology for Lyme
disease, although in need of better
standardization, is most useful in
diagnosing patients with manifestations
of Lyme disease other than erythema
migrans. All manifestations of Lyme
disease are potentially treatable with
either a beta-lactam antibiotic (for
instance penicillin, amoxicillin, or
ceftriaxone) or a tetracycline
preparation. However, the optimal
antimicrobial regimen, including choice
of drug, drug dose, route of
administration, and length of
therapy, is unknown. Other important
areas for future research include Ixodes
biology and control, improved laboratory
tests for diagnosis and for assessing
response to therapy, and vaccine
development.
Rush
This
study was about the treatment results of
acute disseminated Lyme disease, which
is within the first month of infection
AND NOT DISSEMINATED INTO THE CNS. This
is not a treatment study about Chronic
Lyme disease. There are no other
publications by this scientist other
than the Guidelines and possibly one on
AIDS.
TITLE:
Ceftriaxone compared with doxycycline
for the treatment of acute
disseminated Lyme disease., Dattwyler
RJ; Luft BJ; Kunkel MJ; Finkel MF;
Wormser GP; Rush TJ; Grunwaldt E; Agger
WA; Franklin M; Oswald D; Cockey L;
Maladorno D, Department of
Medicine, State University of New York,
Stony Brook, 11794-8161, USA., N Engl J
Med 1997 Jul 31;337(5):289-94
ABSTRACT:
BACKGROUND: Localized Lyme disease,
manifested by erythema migrans, is
Usually
treated with oral doxycycline or
amoxicillin. Whether acute disseminated
Borrelia
burgdorferi infection should be treated
differently from localized infection is
unknown. METHODS: We conducted a
prospective, open-label, randomized,
multicenter study comparing parenteral
ceftriaxone (2 g once daily for 14 days)
with oral doxycycline (100 mg twice
daily for 21 days) in patients with
acute disseminated B. burgdorferi
infection but without meningitis.
The erythema migrans skin lesion was
required for study entry, and
disseminated disease had to be indicated
by either multiple erythema migrans
lesions or objective evidence of organ
involvement. RESULTS: Of 140
patients enrolled, 133 had multiple
erythema migrans lesions. Both
treatments were highly effective. Rates
of clinical cure at the last evaluation
were similar among the patients treated
with ceftriaxone (85 percent) and those
treated with doxycycline (88 percent);
treatment was considered to have failed
in only one patient in each group. Among
patients whose infections were cured, 18
of 67 patients in the ceftriaxone group
(27 percent) reported one or more
residual symptoms at the last follow-up
visit, as did 10 of 71 patients in the
doxycycline group (14 percent, P > or =
0.05). Mild arthralgia was the most
common persistent symptom. Both regimens
were well tolerated; only four patients
(6 percent) in each group withdrew
because of adverse events. CONCLUSIONS:
In patients with acute disseminated Lyme
disease but without meningitis, oral
doxycycline and parenterally
administered ceftriaxone were equally
effective in preventing the late
manifestations of disease.
Rahn
TITLE:
Treatment of Lyme disease., Steere
AC; Green J; Hutchinson GJ; Rahn DW;
Pachner AR; Schoen RT; Sigal LH; Taylor
E; Malawista SE, Zentralbl
Bakteriol Mikrobiol Hyg [A] 1987
Feb;263(3):352-6
ABSTRACT: We compared phenoxymethyl
penicillin, erythromycin, and
tetracycline, in each instance 250 mg
four times a day for 10 days, for the
treatment of early Lyme disease
(stage 1). None of 39 patients given
tetracycline developed major late
complications compared with 3 of 40
penicillin-treated patients and 4 of 29
given erythromycin (p = 0.07). However, with all three antibiotic
agents, nearly half of patients had
minor late symptoms. For neurologic
abnormalities (stage 2), 12 patients
were treated with high-dose intravenous
penicillin, 20 million U a day for 10
days. Pain usually subsided during
therapy, but a mean of 7 to 8 weeks was
required for complete recovery of motor
deficits. For the treatment of
established arthritis (stage 3), 20
patients were assigned treatment with
intramuscular benzathine penicillin (7.2
million U) and 20 patients received
saline. Seven of the 20
penicillin-treated patients (35%) were
apparently cured, but all 20 patients
given placebo continued to have attacks
of arthritis (P less than 0.02). Of 20
arthritis patients treated with
intravenous penicillin G, 20 million U a
day for 10 days, 11 (55%) were
apparently cured. Thus, all 3 stages of
Lyme disease can be treated with
antibiotic therapy, but some patients
with late disease may not respond.
Rahn,
Steere, Schoen
TITLE:
Treatment of refractory chronic Lyme
arthritis with arthroscopic
synovectomy. Schoen RT; Aversa JM;
Rahn DW; Steere AC, Department of
Medicine, Yale University School of
Medicine, NewHaven,Connecticut 06510.,
Arthritis Rheum 1991 Aug;34(8):1056-60
ABSTRACT: Of 20 patients who underwent
arthroscopic synovectomy for refractory
chronic Lyme arthritis of the knee, 16
(80%) had resolution of joint
inflammation during the first month
after surgery or soon thereafter, and
they have remained well during the
3-8-year followup period. Three of these
16 patients who were more disabled
preoperatively, still had mild
functional limitation at long-term
followup. The remaining 4 patients
(20%) had persistent or recurrent
synovitis. We conclude that
arthroscopic synovectomy is effective in
treating chronic Lyme arthritis in
patients in whom the disease does not
respond to antibiotic therapy.
----Kathleen M. Dickson
The
Klempner Article
Bransfield and Brand
The
recent article in the NEJM, "Two
Controlled Trials of Antibiotic
Treatment in Patients with Persistent
Symptoms and a History of Lyme Disease,"
by Klempner, et. al. provides some
interesting data, but the proper
interpretation of this data is of little
relevance to both clinical practice and
guidelines related to chronic Lyme
disease. It does, however, provide some
interesting insight about the
significance of PCR and IgG testing in
Lyme disease, it demonstrates a poor
quality of life is associated with a
history of Lyme disease and it is an
excellent example of the failure of
objectivity in a peer reviewed article
in a prestigious medical journal
followed by misperceptions of the
significance of this article by the
media, resulting in the improper use of
this article by the insurance industry.
An objective review of this article is
one issue, while the role of this
article towards perpetuating false
beliefs about Lyme disease is an
additional and more significant issue.
Medicine
today, is much like law. Both have
adversarial qualities. Information is
presented a manner that is most
effective in arguing a point of view.
When this technique is effective, guilt
is proven to be innocence; black is
proven to be white, etc. The technique
is always the same. There are a series
of statements and conclusions. Each
statement is a 10-degree twist on the
truth, so small that it can go below the
radar of our ability to detect
deception. After a series of complicated
and related statements, there is a
180-degree twist to the truth.
The
twists to this article began many years
ago when a few rheumatologists involved
in Lyme disease incorrectly attempted to
apply their observations of acute Lyme
arthritis to explain late stage Lyme
disease and Lyme neuroborreliosis. The
problem was compounded when Lyme disease
was conceptualized from the perspective
of an acute infection rather than
recognizing the persistent relapsing
nature of this microbe. These and many
other similar twists set the stage to
bias the researchers to confirm their
prior views on the subject. A failure to
recognize and comprehend that tick-borne
diseases were often complex interactive
infections involving multiple stealth
and persistent pathogens, and an
excessive reliance upon molecular
mimicry hypotheses further added to the
problem. As a result of these and other
errors, a twenty-first century problem
is approached with a nineteenth century
view of infectious disease. The bias was
further solidified as patent issues,
competing diagnostic systems, research
grants, reputations, lawsuits, and a
need to defend prior consultant
decisions that were provided to
insurance companies as high paid
consultants further clouded scientific
objectivity. Anyone coming from this
perspective would be highly motivated to
design a study that would argue that
persistent infection was not a
significant issue in Lyme disease, and
this is exactly what happened.
The
study design guaranteed the study would
fail. The design of the research
protocol is the most critical step in
the project. This study had a very
restrictive inclusionary and
exclusionary criteria. The vast majority
of patients with chronic Lyme disease do
not meet the criteria for inclusion into
the study, therefore the findings and
stated conclusions have no relevance to
most patients with CLD. The other two
NIH sponsored trials had much better
study designs. I recall sitting in a
meeting several years ago at NIH when
the study design of the NIH intramural
study was discussed. A pyramid was used
as an analogy. At the bottom of the
pyramid were the patients who had some
of the features of Lyme disease with
disagreement about whether or not these
patients truly had Lyme disease. The
intent was to select the patients at the
tip of the pyramid who clearly had Lyme
disease. This strategy was NOT used in
the Klempner study. Patients who
demonstrated DNA evidence of the
presence of Borrelia burgdorferi by PCR
testing were excluded from the study.
There was only one short sentence in the
journal article that discussed this, and
this was the most significant sentence
in the entire article. PCR testing
has been considered absolute proof in
the legal system, why would a PCR
positive patient ever be excluded? It
was stated that it would have been
unethical to give a placebo, rather than
the antibiotic treatment to a PCR
positive patient. This is a clear
endorsement that positive PCR testing is
considered confirmation of persistent
infection with Bb. Depression, a
major symptom of the neuropsychiatric
manifestations of Lyme disease, was also
an exclusionary criterion. Even though
both PCR and depression were
exclusionary criteria, the status of the
study participants was measured by PCR
testing on the spinal fluid and the Beck
Depression Scale. Other means of
evaluating the status of the patients
were the SF-36 and other testing.
Basically, the wrong tests and tests
that lacked objectivity were used to
evaluate the status of the patients.
Although there were 12 authors, none
were psychiatrists. Why?
Neuropsychiatric symptoms are a major
part of
the later manifestations of Lyme
disease. How can a study, which is
supposed to study late stage disease,
not have the input of a psychiatrist
with experience on working
with
Lyme disease? The neuropsychological
scales that were implemented in the
study were notably insufficient to
adequately assess the psychiatric
symptoms and the executive functioning
impairments, which are associated with
persistent Lyme disease infections. The
SF-36 scale was used. The scores were
quite low, reflecting a poor quality of
life for these patients. In addition,
the SF-36 is only a subjective scale
based solely upon patient opinion, and
contains no objective criteria for the
assessment of patients' status.
Rather
than PCR, a positive IgG Western Blot
test based upon five bands at only one
laboratory was used as a reference
point. No studies have ever demonstrated
whether the absence of IgG reactivity
had diagnostic significance in late
stage disease.
The study was
designed to provide patients with
"intensive antibiotics." Although
one month of ceftriaxone and two months
of doxycycline would be considered
intensive for the treatment of many
acute infectious diseases, few
physicians who shoulder the
responsibility of treating chronic Lyme
disease would consider this to be an
adequate retreatment for a patient with
late stage Lyme disease who had failed
prior courses of significant treatment.
Results, from recent scientific studies
on dog models by Straubinger of chronic
Lyme disease, indicate persistent
infection even after 6 months of
antibiotic treatment. Furthermore,
experience in the treatment of human
infections caused by other persistent
bacteria, such as Treponema pallidum,
Mycobacterium tuberculum and
Helicobacter pylori demonstrates that
prolonged antibiotic therapy and/or
different combinations of antibiotics
would result in greater improvement than
was observed in this study.
Additionally, while the study tested
patients for tick-borne coinfections,
like babesiosis or ehrlichiosis, it
failed to offer any treatment
strategies.
The
placebo and treatment groups appeared to
start with significantly different
scores on the primary outcome measures.
In the group of seropositive patients,
those in the placebo group had
significantly better scores on the MOS
Cognitive measures, and exhibited fewer
neurocognitive symptoms at base-line,
than the patients in the antibiotic
group. In addition, within the
seronegative group, patients in the
placebo group had significantly poorer
scores on the SF-36 Mental Component,
the MOS Pain scale, and the Fibromyalgia
Impact Questionnaire. The categorization
of patients into Improved, Unchanged and
Worse on each of the outcome components
seems to lose a certain amount of
information about the magnitude of
change in functioning from base-line
until post-treatment, and to be lacking
in statistical power compared with other
procedures for analyzing these data. In
view of these two points, it would seem
advisable to utilize Analysis of
Covariance procedures to measure the
impact of treatment on the outcome
measures, after adjusting for patients'
baseline scores on the measures of
functioning. This procedure would take
into consideration the baseline
differences between groups,
would
treat change in the outcome measures as
a continuous rather than a categorical
variable, and would afford more
statistical power in testing differences
between the placebo and antibiotic
groups. Since the symptoms of chronic
Lyme disease are different in different
patients, some patients presented
impairments primarily in specific areas
of functioning, and change from
treatment would be expected in the
specific areas that were problematic for
each patient. An analysis of change in
the most problematic items on each of
these scales would provide a more
sensitive assessment of potential
treatment effects. In addition, the
small sample size raises concerns about
statistical power, and further
undermines the validity of the study.
The 35%
improvement threshold, when combined
with the other study design constraints
would predict a failure, even before
initiating the study. It should have
been necessary to adjust the status
assessment to make allowances for the
Jarish-Herxheimer rection, but this was
not a part of the study design. It would
be important to know more details of the
NIH NIAID Data Safety and Monitoring
Board's termination of the study.
Since
the patients with seronegative Lyme
disease showed better improvement on
antibiotics than their seropositive
counterparts, it appears that negative
IgG reactivity is not a useful criterion
to deny the presence of persistent
infection. If the investigators feel
persistent infection was not a cause of
the patient's current symptoms, then
what else is a truly more plausible
explanation?
A
disclaimer reviewing the potential
conflicts of interests of the authors
was absent from the article, and would
have been most appropriate in light of
the significant political, financial,
and ethical controversies surrounding
chronic Lyme disease. This should have
included disclosures of the authors'
Lyme disease-related insurance
consultations, roles as defendants in
Lyme related law suits and their roles
as paid expert witnesses, as well as
their ownership of Lyme disease related
patents, commercial diagnostic systems
and their financial vaccine interests.
Along
with three other related articles, the
Klempner article was distributed on the
Internet a month before the date of
publication. The reason for the early
release is a subject of considerable
speculation. When the article was
released, there was a well-orchestrated
flood of articles in the media, which
mostly interpreted the significance of
the article out of context. Since the
release, insurance companies have
already used the article as proof to
deny coverage for the treatment of Lyme
disease.
In
summary, the design of the research and
the manner in which the article was
written and promoted in the media even
before it was published reflects many of
the biases that have obstructed
scientific objectivity and medical
progress surrounding Lyme disease for
decades. The study demonstrates that
patients with a history of exposure to
Lyme disease in the past, who probably
do not have active infection at the time
of the study as demonstrated by negative
PCR's and a history of significant
antibiotic treatment in the past, do not
respond to inadequate antibiotic
treatments as measured by incorrect and
highly subjective criteria that are not
representative of symptoms associated
with CLD administered by physicians who
appear to not know how to treat Lyme
disease, some of whom have strong
conflicts of interest to the contrary in
a study that was never completed. In
short, the study proves very little. It
does, however demonstrate, that it is
very easy to waste large amounts of
Federal money for something of little
benefit to taxpayers. In a backhanded
way, it validates PCR testing as proof
of persistent infection. It
suggests that IgG testing by Dearborn
criteria is not a valid criterion to
either confirm or refute the presence or
absence of active infection. Most
importantly it demonstrates that false
beliefs can be self-perpetuating,
information in the peer reviewed medical
literature can be highly inaccurate and
deceptive and it is very easy for
medical information to be improperly
interpreted by the media, insurance
industry and potentially by the legal
system.
Robert C
Bransfield, MD
Private
Practice of Psychiatry
Red
Bank, NJ
Stephen
Brand, Ph.D.
Assistant Professor (Research)
National
Center on Public Education
University of Rhode Island
===