A Short History of Lyme

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
User avatar
inmacdonald
Posts: 973
Joined: Fri 13 Jan 2012 22:32

A Short History of Lyme

Post by inmacdonald » Sat 17 Nov 2012 15:56

A Short History of Lyme Borreliosis
By Alan B. MacDonald MD

For the history of Lyme borreliosis I divide the history into the pre-spirochetal era
( The years prior to 1982 when Willy discovered
the Bb)
and the Post Spirochetal Era ( 1982 to present).

In the pre-spirochetal era, there were no blood tests,
but there were clinical descriptions of joint, skin, Meningeal,
Facial palsy and heart rhythm disorders. Somewhere in that era
[ a time which was controlled by the Rheumatologist
Steere] there arose a dispute about the best practice therapy.
Steere insisted on the use of Steroids to reduce inflammation.
In Groton Connecticut, Physicians elected to treat Lyme with
antibiotics, and they published their positive results, and
were ridiculed by Steere.{Hospital Practice 1979}

After 1982 came the blood testing, the animal models of
experimental infection, the use of short term antibiotics by Steere,
and more publications. Also, more physicians and researchers
became involved in the study of Lyme. Differences in the views of
theory and practice for Lyme developed. Political camps developed
- some of the camp of Steere versus others with different views concerning
a widening clinical spectrum of Lyme organs system involvements and
with different views on types and duration of antibiotic therapy.

Chronic Lyme entered the picture. The Political divide widened between
the Camps. Steere declared that Chronic Lyme was psychosomatic while the
opposing camp declared that Chronic Lyme was due to persistence of infection
despite antibiotic therapy.

The divide between camps also widened because the Steere camp continued to believe
that the spiral motile form of Bb was the only legitimate form of the microbe inhuman
tissue. The opposing camp came to embrace alternate shape shifted forms of
borrelia such as Cystic, Granular, Cell wall deficient forms as equally virulent in disease
production and in maintenance of infection in the human host.

We now have entered a third era in Lyme Borreliosis - namely the Biofilm Era.

Biofilms of borrelia burgdorferi were undreamed of until year 2006 and proven to exist in vitro and recently In ViVO in human skin biopsies of Erythema Migrans and in living Ixodid Tick midguts.
Biofilm science is radically different from Planktonic microbiology. Biofilms are part of the
repertoire of over 99.9% of microbes. Biofilms form from planktonic microbial forms, but
biofilms provide mechanisms for microbial survival under adverse conditions which would eliminate
planktonic microbes. Biofilms explain Chronic antibiotic resistance. Biofilms are the mechanism
for Chronic Infections of many organ systems. The diagnostic names - infected artificial medical
device, bacterial endocarditis, Helicobacter pylori chronic gastritis, Dental root canal infections,
and may more- have the concept that these infections are solely due to biofilmsand the persistence of
biofilms in humans despite administration of antibiotics/

In biofilms the microbes {planktonic forms} undergo specialization and are no longer
identical to Planktonic [single free living microbes]. Biofilm microbes are biochemically specializing
(ie have a different biochemistry, different cell wall structure, have cell to cell intercommunications
[nanowires and nanotubes] which enable cell to cell communication between the cytoplasmic compartments, and form water channels to facilitate the flux of nutrients and the removal of waste
from the biofilm community. An envelope of Extracellular matrix invests biofilm communites. This matrix is derived from once living --now dead members of the biofilm community. For Borrelia biofilms
the matrix investment includes Sloughed Outer Surface Membrane {slime layer} of Bb, Extruded
DNA [eDNA], alginate-like material, and liposomes {micro vesicles} [blebs].

Biofilm communities may be and often are POLYMICROBIAL.

Biofilm communities spread from their sessile site of naissance to the body sites by
two mechanisms:
1. pieces of the Sessile community [Matrix invested specialized microbes] actually break apart
from the parent community and METASTASIZE to other sites.
2. Planktonic Showers rain from the sessile community from time to time and these
planktonic showers re-establish new communities in the mammalian host.

So in the year 2102, we have now entered into the 3rd era of Borrelia pathobiology;
namely the Biofilm Era.

Implicit in the biofilm concept is the ability of DNA transfer/exchange
[lateral DNA Transfer/ horizontal DNA transfer] among specialized members of the biofilm.
With DNa exchange, there is a mechanism for transfer of new virulence factors and new
modalities in antibiotic resistance. Persistence of biofilm infection in mammalian hosts
is in part due to PERSISTER microbes, which may reside within biofilm communities or which may reside intracellularly, or which may reside in so called "Sanctuary Sites"

The clinical spectrum of Lyme borreliosis continues to expand into areas of medicine
in which NAMED diseases of unknown cause [idiopathic diseases] are now incorporated within
the Lyme borreliosis disease complex. The number of skin conditions which are now Lyme disease
cutaneous manifestations has increased, thanks to the work of Dr Klaus Eisendle and Dr Bernhard Zelger to include many new entities, [ and more to be added with the use of FFM techniques]
I summarize these in my lecture on the International Cutaneous and Molecular Dermatopathology
of Lyme Borreliosis [attached , Boston Mass , Date November 4,2012]

In parallel with the expansion of cutaneous Borreliosis conditions, is the expansion of lymphoid
neoplasias linked to chronic Borrelia infections [ analogy with Helicobacter pylori induced
Malignant Lymphomas], Sarcoidosis in China as a borreliosis infection, Idiopathic lethal fibrosing
illnesses [Retroperitoneal Fibrosis, and Mediastinal fibrosis], borrelia to human Tranfections
mimicking human spontaneous gene mutations, Cardiomyopathies secondary to chronic Lyme borreliosis, giant cell arteritis [temporal arteritis] due to borrelia infection, Abdominal aortic aneurysms due to borrelia aortitis, and various intra-ocular inflammations {uveitis, optic neuritis},
Demyelination syndromes secondary to borrelia infections, and transplacental transmission of borrelia with possible lethal outcomes in the fetus in untreated conditions. The list above is only partial and will be added
to as future medical research utilizing molecular Tools such as DNA probes fleshes out the full spectrum of
Lyme borreliosis and related co-infections.

It is truly a great time to be alive.

With all good wishes,
Alan

Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: A Short History of Lyme

Post by Lorima » Sun 18 Nov 2012 15:56

Dear Dr. M,

I'm boning up on current technology, looking for the spot at which I can best enter. Thanks for your inspirational as well as informative words - you're right, it is a great time to be alive!

Best regards,
Lorima
"I have to understand the world, you see."
Richard Feynman

Camp Other
Posts: 996
Joined: Wed 2 Mar 2011 4:32
Contact:

Re: A Short History of Lyme

Post by Camp Other » Sun 18 Nov 2012 19:47

Lorima wrote:Dear Dr. M,

I'm boning up on current technology, looking for the spot at which I can best enter. Thanks for your inspirational as well as informative words - you're right, it is a great time to be alive!

Best regards,
Lorima
From a technology perspective, I agree it's a great time to be alive.

But this?
In parallel with the expansion of cutaneous Borreliosis conditions, is the expansion of lymphoid
neoplasias linked to chronic Borrelia infections [ analogy with Helicobacter pylori induced
Malignant Lymphomas], Sarcoidosis in China as a borreliosis infection, Idiopathic lethal fibrosing
illnesses [Retroperitoneal Fibrosis, and Mediastinal fibrosis], borrelia to human Tranfections
mimicking human spontaneous gene mutations, Cardiomyopathies secondary to chronic Lyme borreliosis, giant cell arteritis [temporal arteritis] due to borrelia infection, Abdominal aortic aneurysms due to borrelia aortitis, and various intra-ocular inflammations {uveitis, optic neuritis},
Demyelination syndromes secondary to borrelia infections, and transplacental transmission of borrelia with possible lethal outcomes in the fetus in untreated conditions. The list above is only partial and will be added [...]
All I can think of is damn, what the hell else is wrong with me next? I'm sure many patients would ask how likely is it that I am going to develop one of these complications?

Camp Other
Posts: 996
Joined: Wed 2 Mar 2011 4:32
Contact:

Re: A Short History of Lyme

Post by Camp Other » Sun 18 Nov 2012 22:13

inmacdonald wrote:A Short History of Lyme Borreliosis
By Alan B. MacDonald MD

For the history of Lyme borreliosis I divide the history into the pre-spirochetal era
( The years prior to 1982 when Willy discovered
the Bb)
and the Post Spirochetal Era ( 1982 to present).

In the pre-spirochetal era, there were no blood tests,
but there were clinical descriptions of joint, skin, Meningeal,
Facial palsy and heart rhythm disorders. Somewhere in that era
[ a time which was controlled by the Rheumatologist
Steere] there arose a dispute about the best practice therapy.
Steere insisted on the use of Steroids to reduce inflammation.
In Groton Connecticut, Physicians elected to treat Lyme with
antibiotics, and they published their positive results, and
were ridiculed by Steere.{Hospital Practice 1979}

After 1982 came the blood testing, the animal models of
experimental infection, the use of short term antibiotics by Steere,
and more publications. Also, more physicians and researchers
became involved in the study of Lyme. Differences in the views of
theory and practice for Lyme developed. Political camps developed
- some of the camp of Steere versus others with different views concerning
a widening clinical spectrum of Lyme organs system involvements and
with different views on types and duration of antibiotic therapy.

Chronic Lyme entered the picture. The Political divide widened between
the Camps. Steere declared that Chronic Lyme was psychosomatic while the
opposing camp declared that Chronic Lyme was due to persistence of infection
despite antibiotic therapy.

The divide between camps also widened because the Steere camp continued to believe
that the spiral motile form of Bb was the only legitimate form of the microbe inhuman
tissue. The opposing camp came to embrace alternate shape shifted forms of
borrelia such as Cystic, Granular, Cell wall deficient forms as equally virulent in disease
production and in maintenance of infection in the human host.
Dr. MacDonald, this is what I've pieced together of the two camps' history:

http://campother.blogspot.com/2011/03/w ... -lyme.html

I've just wondered what else has happened that helped shape those two camps and why there continues to be so much contentious debate.

Joanne60
Posts: 110
Joined: Mon 13 Feb 2012 15:49
Location: Guildford Surrey UK

Re: A Short History of Lyme

Post by Joanne60 » Sun 18 Nov 2012 22:26

Thank you Dr MacDonald for another excellent lesson in Lyme.

User avatar
inmacdonald
Posts: 973
Joined: Fri 13 Jan 2012 22:32

Re: A Short History of Lyme

Post by inmacdonald » Mon 19 Nov 2012 15:07

Dear Camp,

I can only guess why Steere's unchallenged authority on "Definer in Chief"
was challenged when the microbial etiologic agent [now agents]
was announced in 1982.

Having been there, I was impressed by the leadership of Dr. Jorge Benach, at the
State University of New York at Stony Brook, School of Medicine in Long Island, New York.
Dr Benach is an EIS graduate, but his training was heavily influenced by his years at
Rocky Mountain Laboratories, NIAID, NIH, Hamilton Montana. Dr. Benach was personally trained
Dr. Willly Burgdorfer at Rocky Mountain Labs. Dr. Benach is a PhD with many skills in bench
research, particularly in molecular Biology.


So it is not unexpected that in the Post spirochetal Era, that Dr Allen Steere would have
huge gaps in his personal knowledge about the bacteriology of a spirochete
which was unmasked as THE CAUSE of a Disease which was formerly HIS disease.

We know that Steere is parsimonious in his admissions concerning the contributions of
other scientists and other physicians to the ever expanding database on Lyme Disease [Lyme Borreliosis].

The first "alternate universes" to spring up in the post spirochetal Era were :
1. Dr Jorge Benach's Lyme Disease research laboratory at the School of Medicine, SUNY, Stony Brook
2. Southampton Hospital Lyme Disease research group { bench laboratory [MacDonald] and consortium of all members of specialists in clinical medicine of the Clinical Medical Staff} at Southampton Hospital, Southampton, New York.
3. Dr Willy Burgdorfer , Dr Alan Barbour, and Dr Tom Schwan's Lyme Disease Research Laboratories
at the Rocky Mountain laboratory,in Hamilton,Montana.
These post spirochetal arenas devoted to the Study of Lyme Disease, were the first to
challenge the "Territorial Imperatives" of Steere.

It became clear in the earliest Post spirochetal years, that Steere's Connecticut and Rheumatology preponderant clinical views, were in need of augmentation.

Dr. Bernard Berger, a brilliant and board certified dermatologist of the Staff of Southampton
Hospital [still inactive practice and research leadership], authored the manuscript, "Lyme Disease is a spirochetosis.". In that landmark paper which appeared in the American Journal of Dermatopathology in 1983, Dr Berger succeeded where Steere's group had fallen short, namely the microscopic identification of the pathogenic borrelia burgdorferi spirochete in the Erythema Migrans lesions, [Rheumatology has always found the search for the Bb spirochete in Joint and in synovial tissues fail to visualize the pathogen in diseased tissues]

Dr. Benach and his colleagues Dr Edward Bosler and Dr. Gail Habicht, wrote landmark bench research
manuscripts on the pathobiology of Bb in the tissues of Laboratory animals in laboratory induced
BB infections. Dr. Benach was among the first scientist in the world to compile a cohort of patients
presenting with simultaneous Babesiosis and Borreliosis , thereby opening up the entire study area
of Lyme Co-Infections.

The Harvard Medical School group commenced a Lyme Diseases Study research activity,including the late
Dr Gustave Damin, Dr. Andrew Spielman,and Dr Sam Telford.

The Boston University Medical School commenced a Lyme Disease Study group lead by Dr Samuel Donta.
As an expert in Infectious Disease Medicine, Dr Donta defined new antibiotic treatment protocols,
which were quite effective and which were at variance with the treatment protocols of Rheumatologist Dr Allen Steere.

European Research Groups brought their considerable skills to the study of European forms of Lyme borreliosis under the leadership of such distinguished physicians and scientists as De Gerold Stanek , Dr Bettina Wilske, Dr Vera Preac Mursic, Dr Eva Asbrink and her husband Dr Anders Hovmark, Dr Sven Bergstrom, and their postdoctoral research fellows, who went on to establish their own research centers.

Dr. Russell C. Johnson, Professor of Microbiology, University of Minnesota Medical School, performed extensive studies of the bench microbiology of borrelia burgdorferi.

The Combined Intelligence from all of these early research groups functioning autonomously and often
at variance with the dogmas of Dr. Allen Steere, advanced the knowledge of the pathobiology of
Lyme disease [Lyme Borreliosis]

So COMBINED INTELLIGENCE from many dedicated and talented individuals has advanced the knowledge
about Lyme borreliosis in the Post spirochetal era.

Lyme in the Pre - spirochetal times May have been Steere's.
Lyme in the Post-spirochetal time has become OURS.

Best,
Alan B.MacDonald MD
November 19, 2012

Joanne60
Posts: 110
Joined: Mon 13 Feb 2012 15:49
Location: Guildford Surrey UK

Re: A Short History of Lyme

Post by Joanne60 » Mon 19 Nov 2012 16:23

Thank you once again Dr MacDonald.

I note you mention Wilske, it is some time since I read some of her research articles but from memory her early work refers to persistent difficult to treat infections and difficulties with unreliable tests. It appeared that about 1982 she seemed to change her view and reported that in late Lyme Disease tests were 98%? accurate. I could find no reference to why she changed her view or any reference for that change of view at the time I wondered if she was referring to the published work of Bacon et al ( I know the criticism of this) but she seemed to change her view before Bacon et al was published.

Sorry I am a little vague in details but if anyone can shed any light on why Wilske changes her tune I would appreciate hearing particularly as her later paper is sighted by HPA in UK as why chronic lyme testing is so reliable.

Camp Other
Posts: 996
Joined: Wed 2 Mar 2011 4:32
Contact:

Re: A Short History of Lyme

Post by Camp Other » Mon 19 Nov 2012 20:03

Joanne60 wrote:Thank you once again Dr MacDonald.

I note you mention Wilske, it is some time since I read some of her research articles but from memory her early work refers to persistent difficult to treat infections and difficulties with unreliable tests. It appeared that about 1982 she seemed to change her view and reported that in late Lyme Disease tests were 98%? accurate. I could find no reference to why she changed her view or any reference for that change of view at the time I wondered if she was referring to the published work of Bacon et al ( I know the criticism of this) but she seemed to change her view before Bacon et al was published.

Sorry I am a little vague in details but if anyone can shed any light on why Wilske changes her tune I would appreciate hearing particularly as her later paper is sighted by HPA in UK as why chronic lyme testing is so reliable.
I've noticed the same thing with Wilske as well, and she is not the only one.

I would like to know why some researchers changed their tune regarding B. burgdorferi in general...

Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: A Short History of Lyme

Post by Lorima » Tue 20 Nov 2012 0:21

Regarding Bettina Wilske:

In 1999, Wilske published this paper, suggesting a criterion for two bands in IgG and one in IgM Western blot. In this paper, she and her group are clearly relying upon their own data and analysis:
http://www.ncbi.nlm.nih.gov/pmc/article ... 002241.pdf 
J Clin Microbiol. 1999 Jul;37(7):2241-7.
Validity of interpretation criteria for standardized Western blots (immunoblots) for serodiagnosis of Lyme borreliosis based on sera collected throughout Europe.
Hauser U, Lehnert G, Wilske B.
Source
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie der Ludwig-Maximilians-Universität München, D-80336 Munich, Germany.
Abstract
Western blotting (WB; immunoblotting) is a widely used tool for the serodiagnosis of Lyme borreliosis (LB), but so far, no generally accepted criteria for performance and interpretation have been established in Europe. The current study was preceeded by a detailed analysis of WB with whole-cell lysates of three species of Borrelia burgdorferi sensu lato (U. Hauser, G. Lehnert, R. Lobentanzer, and B. Wilske, J. Clin. Microbiol. 35:1433-1444, 1997). In that study, interpretation criteria for a positive WB result were developed with the data for 330 serum samples (from patients with LB in different stages [n = 189] and from a control group [n = 141]) originating mostly from southern Germany. In the present work, the interpretation criteria for strains PKo (Borrelia afzelii) and PBi (Borrelia garinii) developed in the previous study were reevaluated with 224 serum samples (from patients with LB in different stages [n = 97] and from a control group [n = 127]) originating from throughout Europe that were provided by the European Union Concerted Action on Lyme Borreliosis (EUCALB). De novo criteria were developed on the basis of the reactivities of the EUCALB sera and were evaluated with the data for the samples from southern Germany. Comparison of all results led to the following recommendations: For WB for immunoglobulin G (IgG), at least two bands among p83/100, p58, p43, p39, p30, OspC, p21, p17, and p14 for PKo and at least one band among p83/100, p39, p30, OspC, p21, and p17b for PBi; for WB for IgM, at least one band among p39, OspC, and p17 or a strong p41 band for PKo and at least one band among p39 and OspC or a strong p41 band for PBi. WB with PKo was the most sensitive, and this strain is recommended for use in WB for the serodiagnosis of LB throughout Europe.
PMID: 10364592 [PubMed - indexed for MEDLINE] PMCID: PMC85128 Free PMC Article

snip

Table 3 shows the results of an evaluation of various interpretation criteria for positive WB results. Separate calculations of sensitivities and specificities on the basis of reactivities of the sera provided by EUCALB as well as the sera included in our previous study were performed, and the results were compared. The results for the interpretation criteria (band combinations) that we considered most favorable for the respective serum panels are boxed. For WB for IgG with strain PKo, all interpretation rules resulting in optimal discriminatory abilities encompassed at least two reactive bands among p83/100, p58, p43, p39, p30, OspC, p21, and p14 plus one or two additional bands. In the previous study, p17 was included in this combination; however, for the EUCALB serum panel, omission of p17 and inclusion of p60 resulted in slightly superior results. Four samples (3%) in the EUCALB control group had shown IgG reactivity to p17 as well. For WB for IgG with strain PBi, the best criterion found in the preceding study was at least one reactive band among p83/100, p39, OspC, p21, and p17b. According to the results obtained with the EUCALB sera, inclusion of p30 in this combination would be favorable. However, three samples (2%) from the control group in the previous study with sera from patients in southern Germany were also reactive to p30 of PBi. If at least two reactive bands were required for a positive WB result, all of the band combinations resulting in optimal discriminatory abilities showed specificities of at least 99%, but this strict criterion resulted in a significant loss of sensitivity, primarily if the sera from patients in southern Germany were considered (56 versus 42%; P < 0.01). Of this panel, 11 (13%) and 6 (7%) serum samples from patients with neuroborreliosis as well as 5 serum samples (8%) and 1 (2%) serum sample from patients with EM showed isolated reactivities to OspC and to p39, respectively.

snip

Since in Europe the immune response of patients with LB seems to be more restricted than that in North America (7), the interpretation criteria for positive WB results recommended by the Centers for Disease Control and Prevention (1, 8, 10) cannot be used. Interpretation rules must be referred to the borrelial strains for which they have been developed (15). Other European investigators (9, 21–23, 25) proposed the use of criteria that require more reactive bands than the number that we recommend from our results, but none of them systematically evaluated a series of different criteria. These proposals seem to be rather arbitrary. Direct comparison of studies by different investigators is not possible since a variety of strains and different WB protocols have been used. Furthermore, not all bands mentioned in different studies have been identified with monoclonal antibodies.

snip
In 2000, she joined with other European experts in this collaborative paper, in which many possible algorithms were considered, and no strong conclusions were reached: 
http://www.ncbi.nlm.nih.gov/pmc/article ... 002097.pdf
J Clin Microbiol. 2000 June; 38(6): 2097–2102.
PMCID: PMC86736
A European Multicenter Study of Immunoblotting in Serodiagnosis of Lyme Borreliosis

J. Robertson,1 E. Guy,2 N. Andrews,3 B. Wilske,4 P. Anda,5 M. Granström,6 U. Hauser,4 Y. Moosmann,7 V. Sambri,8 J. Schellekens,9 G. Stanek,10 and J. Gray11,*
Public Health Laboratory, Southampton General Hospital, Southampton,1 Public Health Laboratory, Singleton Hospital, Swansea,2 and Public Health Laboratory Service Statistics Unit, Colindale, London,3 United Kingdom; Pettenkofer Institute, University of Munich, Munich, Germany4; Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain5; Department of Clinical Microbiology, Karolinska Hospital, Stockholm, Sweden6; Diagnostic Parasitology, University of Neuchâtel, Neuchâtel, Switzerland7; Microbiology, St. Orsola Hospital, University of Bologna, Bologna, Italy8; Diagnostic Laboratory for Infectious Diseases, National Institute of Public Health, Bilthoven, The Netherlands9; Hygiene Institute, University of Vienna, Vienna, Austria10; and Department of Environmental Resource Management, University College Dublin, Dublin, Ireland11

ABSTRACT
A European multicenter study of immunoblotting for the serodiagnosis of Lyme borreliosis showed considerable variation in results obtained from tests with a panel of 227 serum samples. Six laboratories used different immunoblot methods, and a wide range of bands was detected in all the assays. Multivariable logistic regression analysis of data from individual laboratories was used to determine the most discriminatory bands for reliable detection of antibodies to Borrelia burgdorferi sensu lato. These bands were used to construct individual interpretation rules for the immunoblots used in the six laboratories. Further analysis identified a subset of eight bands, which were important in all the laboratories, although with variations in significance. Possible European rules, all closely related, were formulated from these bands, although there was no single rule that gave high levels of sensitivity and specificity for all the laboratories. This is a reflection of the wide range of methodologies used, especially the use of different species and strains of B. burgdorferi sensu lato. The panel of European rules provides a framework for immunoblot interpretation which may be adapted in relation to the characteristics of Lyme borreliosis in local areas.

The clinical diagnosis of Lyme borreliosis (LB) can be difficult because symptoms, other than a typical erythema migrans (EM) of early infection, may be of a nonspecific nature. In addition, the interpretation of laboratory diagnostic test results has been problematic because of wide variation in the sensitivities and specificities of the tests used.

Immunoblotting is both sensitive and specific, has been in wide use in diagnostic laboratories, and in the United States has been recommended as a confirmatory test for the serodiagnosis of Lyme disease (5). However, in Europe an extensive range of blotting methodologies is in use (antigens prepared from different genospecies of Borrelia burgdorferi sensu lato, different polyacrylamide gel electrophoresis [PAGE] and immunoblotting protocols), and although recommendations on the interpretation of band patterns have been published in Europe and the United States (5, 8, 10, 11, 15, 17, 18, 23, 25, 28, 34), no consensus exists.

As part of the European Union Concerted Action on Lyme Borreliosis (EUCALB) program from 1994 to 1996, clinicians and scientists in several European countries participated in a multicenter immunoblotting study. The aims of the study were to identify criteria for the interpretation of immunoblots for individual participating laboratories, to assess the sensitivity and specificity of European immunoblot methods for the diagnosis of LB, and to determine, if possible, a set of criteria for the interpretation of immunoblots which could be used in diagnostic laboratories across Europe.

(Preliminary accounts of this work were presented at the Fifth International Potsdam Symposium on Tick-Borne Diseases, Berlin, Germany, 26–27 February 1999, and at the Eighth International Conference on Lyme Borreliosis and Other Emerging Tick-Borne Diseases, Munich, Germany, 20–24 June 1999.)
I suspect that the lack of consensus on a set of universal criteria was seen as an intolerable situation by some, if not most, of the clinicians. The push for standardized and speedy medicine is as strong in Europe as in the US. Not having strict rules would violate the desire for "one right answer", and would make avoiding uncertainty and complexity impossible.

In 2003, Wilske published the following paper with Barbara J Johnson of the US CDC as an author. Johnson is an enthusiastic apologist for all of Steere's recommendations. However, merely being coauthors on one or a few papers doesn't necessarily imply that scientists are ideologically aligned. Just an interesting observation that may not mean much.
http://www.ncbi.nlm.nih.gov/pmc/article ... f/0677.pdf
J Clin Microbiol. 2003 March; 41(3): 1299–1303.
doi:  10.1128/JCM.41.3.1299-1303.2003
PMCID: PMC150259
Significant Improvement of the Recombinant Borrelia-Specific Immunoglobulin G Immunoblot Test by Addition of VlsE and a DbpA Homologue Derived from Borrelia garinii for Diagnosis of Early Neuroborreliosis

Ulrike Schulte-Spechtel,1 Gisela Lehnert,1 Gaby Liegl,1 Volker Fingerle,1 Christiane Heimerl,1 Barbara J. B. Johnson,2 and Bettina Wilske1,*
Max von Pettenkofer-Institut für Medizinische Mikrobiologie und Hygiene der Ludwig-Maximilians-Universität München, D-80336 Munich, Germany,1 Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, Colorado 805222
*Corresponding author. Mailing address: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität München, Pettenkoferstr. 9a, D-80336, Munich, Germany. Phone: 49 89-51605231. Fax: 49 89-51604757. E-mail: Bettina.Wilske@mvp-bak.med.uni-muenchen.de.
In 2004, these guidelines, were published, on which all the authors are European, and the later 2006 IDSA guideline authors (Stanek and Strle) are not present. Still, this paper recommends a two-tier approach, requiring a positive ELISA, and suggests that late (stage III), "especially" arthritic and ACA Lyme patients, have high IgG titers. It also says that late neuro cases additionally need to show intrathecal antibody synthesis (spinal tap), making it even more restrictive than US requirements.
(Does "especially" mean that late, predominantly neurologic cases are less likely to have high IgG titers? It would seem so.)
http://onlinelibrary.wiley.com/store/10 ... 7e4be787fe 
ESCMID STUDY GROUP REPORT 10.1111/j.1469-0691.2004.01019.x Guidelines for the diagnosis of tick-borne bacterial diseases in Europe
P. Brouqui, F. Bacellar, G. Baranton, R. J. Birtles, A. Bjoe ̈rsdorff, J. R. Blanco, G. Caruso*, M. Cinco, P. E. Fournier, E. Francavilla, M. Jensenius, J. Kazar, H. Laferl, A. Lakos, S. Lotric Furlan, M. Maurin, J. A. Oteo, P. Parola, C. Perez-Eid, O. Peter, D. Postic, D. Raoult, A. Tellez, Y. Tselentis and B. Wilske
Members of ESCAR (ESCMID Study Group on Coxiella, Anaplasma, Rickettsia and Bartonella) and the European Network for Surveillance of Tick-Borne Diseases (EC QLK2-CT-2002-01293)
ABSTRACT
Ticks are obligate haematophagous acarines that parasitise every class of vertebrate (including man) and have a worldwide distribution. An increasing awareness of tick-borne diseases among clinicians and scientific researchers has led to the recent description of a number of emerging tick-borne bacterial diseases. Since the identification of Borrelia burgdorferi as the agent of Lyme disease in 1982, 11 tick-borne human bacterial pathogens have been described in Europe. Aetiological diagnosis of tick-transmitted diseases is often difficult and relies on specialised laboratories using very specific tools. Interpretation of laboratory data is very important in order to establish the diagnosis. These guidelines aim to help clinicians and microbiologists in diagnosing infection transmitted by tick bites and to provide the scientific and medical community with a better understanding of these infectious diseases.
Keywords Borrelia, guidelines, Lyme disease, review, Rickettsia, tick-borne disease Clin Microbiol Infect 2004; 10: 1108–1132 

snip

There is no single optimum test for the serodiagnosis of Lyme borreliosis. The existing methods must therefore be combined logically in order to achieve the highest possible diagnostic efficiency. A stepwise diagnostic protocol is recommended in which a screening assay, as defined above, is used as the first step (Fig. 7). If the result of the screening assay is positive or borderline, a confirmatory Western blot should be used. A two-tier protocol has also been recommended in the USA by the Centers for Disease Control (CDC) [107]. Such an approach, the aim of which is to increase the pre-test probability, and thus the predictive value, of a positive result with each step, can only work if the tests are performed in succession. Following a positive screening assay, the possibility of cross-reactivity with Treponema pallidum must be considered, and this can be clarified by means of a T. pallidum haemagglutination assay.

Figure 7. Stepwise serodiagnosis of Lyme borelliosis [92]. IFA, immunofluorescent assay; IHA, immunohaemagglutination assay.
Meanwhile, other European experts were deepening their collaboration with the US establishment. 

I don't know the publication history of all the European experts, and there are many more that I am leaving out here, so the following is a rather sketchy first pass at narrowing down when the European experts capitulated to the American establishment, and who among them pushed for it. So take this with a grain of salt. 

Although Gerold Stanek, the current head of the EUCALB group, had published a paper early on (1993) with Steere and Benach, and other instances of collaboration occurred, there wasn't evidence of the mass merging of the two establishments until later. See below: Jeremy Gray of the UK, Franc Strle of Slovenia, and Gerold Stanek of Germany became enthusiastic endorsers of the Steere/CDC disease model, by the early 2000's. Susan O'Connell of the UK was also involved. By 2006, IDSA's influence over European Lyme was complete, evidenced by the presence of European experts in the authorship list for the 2006 IDSA guidelines, the appearance of copycat guidelines in the European literature, and the appearance of editorials in the European literature castigating patients and activists for protesting the Steere/CDC disease model. 
1.
Lyme borreliosis.
Stanek G, Wormser GP, Gray J, Strle F.
Lancet. 2012 Feb 4;379(9814):461-73. Epub 2011 Sep 6. Review.
PMID: 21903253 [PubMed - indexed for MEDLINE]
Related citations

2.
The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.
Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB.
Clin Infect Dis. 2006 Nov 1;43(9):1089-134. Epub 2006 Oct 2. Erratum in: Clin Infect Dis. 2007 Oct 1;45(7):941.
PMID: 17029130 [PubMed - indexed for MEDLINE] Free Article
Related citations

3.
Advances in the treatment and prevention of Lyme borreliosis.
Wormser GP, Stanek G, Strle F, Gray JS.
Wien Klin Wochenschr. 2005 Jun;117(11-12):381-4. Review. No abstract available.
PMID: 16053191 [PubMed - indexed for MEDLINE]
Related citations

4.
Lyme borreliosis.
Stanek G, Gray J, Strle F, Wormser G.
Lancet Infect Dis. 2004 Apr;4(4):197-8; discussion 198-9. No abstract available.
PMID: 15050933 [PubMed - indexed for MEDLINE]
Related citations
Wilske did not join in, or was not invited; perhaps her lack of enthusiastic endorsement of the Steere/Dearborn criteria, pushed by the US CDC as the diagnostic "gold standard", was responsible. 
Last edited by Lorima on Tue 20 Nov 2012 13:05, edited 1 time in total.
"I have to understand the world, you see."
Richard Feynman

Joanne60
Posts: 110
Joined: Mon 13 Feb 2012 15:49
Location: Guildford Surrey UK

Re: A Short History of Lyme

Post by Joanne60 » Tue 20 Nov 2012 10:56

Lorima

Thank you so much for such a detailed response. I will look forward to reading it in more detail shortly.

Joanne
ps not sure why I wrote 1982 it must clearly have been a later date but as my computer crashed some months ago I lost all the notes I had made on the matter.
Last edited by Joanne60 on Tue 20 Nov 2012 11:42, edited 1 time in total.

Post Reply