Strains and Research
page in process
Lyme strains and closely related spirochetes
Life phases and morphology of spirochetes
California studies of tick and human positivity
**Killing of lymphocytes (human and mouse) Observations
Neurological / physical aspects
Chronicity/Persistance see Cheryl's Lyme info site excellent web site.
Lyme and Syphilis pathogenic shifting comparisons
(stealth, NIAIDS report)
General multisystem
Heart
Bones Joints and Cartilage
Digestive System
Vectors robert (?) bransfield
Links other sites with study/article collections
Strains and closely related spirochetes
http://archderm.ama-assn.org/issues/v135n11/abs/dst9024.html Infection With Multiple Strains of Borrelia burgdorferi Sensu Stricto in Patients With Lyme Disease
Borrelia geonome site list of strains. (home page) This list is not complete or updated. Notice several california species with the prefixes of HUM, MEN, LAKE and NY. These stand for Humbolt, Mendocino & Lake co.s in California, and NY where these strains were found. There are over 150 strains in the US and still counting. You could probably write to these people & they should verify that. The strains can vary a great deal in their effects on the human body.
Examples of the many strains and families
http://jcm.asm.org/cgi/content/full/36/12/3497#F3
(Journal of Clinical Microbiology, December 1998, p. 3497-3504, Vol. 36,
No. 12)
"Up to now, the only species in the complex Borrelia burgdorferi sensu lato known to cause Lyme borreliosis in the United States has been B. burgdorferi sensu stricto. However, some atypical strains closely related to the previously designated genomic group DN127 have been isolated in the United States, mostly in California. [...] we analyzed the nucleotide sequences of the rrf-rrl intergenic spacer regions from 19 atypical strains (18 from California and one from New York) and 13 North American B. burgdorferi sensu stricto strains (6 from California). [...] A heterogeneous group comprising strains belonging to the previously designated group DN127 clustered separately from B. burgdorferi sensu stricto. Within this cluster, the deep branches expressing the distances between the rrf-rrl sequences reflect a high level of divergence. This unexpected diversity contrasts with the monomorphism exhibited by B. burgdorferi sensu stricto. [...] We conclude that the taxonomy and phylogeny of North American B. burgdorferi sensu lato should be reevaluated. For now, we propose that the genomic group DN127 should be referred to as a new species, B. bissettii sp. nov., and that other related but distinct strains, which require further characterization, be referred to as Borrelia spp. "
Discussion in plainer English;
http://www.dis.strath.ac.uk/vie/LymeEU/biology_spiro-borrelia-strains.html
Caledonia
strains renamed ;
Expanded Diversity among Californian Borrelia Isolates and Description
of Borrelia bissettii sp. nov. (Formerly Borrelia Group DN127) D.
Postic,1,* N. Marti Ras,1 R. S. Lane,2 M. Hendson,2 and G. Baranton1 Unité
de Bactériologie Moléculaire et Médicale, Institut
Pasteur, 75724 Paris Cedex 15, France,1 and Department of Environmental
Science, Policy and Management, Division of Insect Biology, University
of California, Berkeley, Berkeley, California 947202
"The results show that these strains significantly diverge at a level that is compatible with several distinct genomic groups. We conclude that the taxonomy and phylogeny of North American B. burgdorferi sensu lato should be reevaluated. For now, we propose that the genomic group DN127 should be referred to as a new species, B. bissettii sp. nov., and that other related but distinct strains, which require further characterization, be referred to as Borrelia spp. [...] The latter strains cannot be assigned to specific genomic groups until more isolates representative of each group are available for further characterization. "
Goes on to say that they don't know if this species can be acquired by humans because none have been found in humans. Of course they may be very hard to find if you are not looking for them in humans... Points out that a similar strain of B. bissettii has been found to cause human disease in Eurasia.
" It might be presumed that B. andersonii does not infect humans because its vector tick, I. dentatus, does not usually bite humans, but a recent paper reports that I. dentatus ticks attached to three humans in three different counties in North Carolina [...] Novel strains of borreliae occur in ticks feeding on humans, and therefore, at least some humans in that area are likely exposed to strains of borreliae other than the classic B31 type strains. [...] Moreover, strains genetically similar to those of B. bissettii from New York, California, South Carolina, and Florida have been isolated from several humans in Slovenia. Those patients had clinical presentations ranging from relatively benign illness to some severe afflictions. Some of the patients had variable and unpredictable serologic responses, including a lack of antibody response despite disseminated disease (29). Interestingly, some of the Lyme disease patients in the southern United States also lacked a serologic response to antigens derived from B. burgdorferi sensu stricto (9). More isolates of B. bissettii from humans and especially isolates from the United States need to be studied to allow a better understanding of its frequency and pathogenicity in humans."
Examples of related spirochetes
Borrelia lonestari, Alabama etc. CDC- http://www.cdc.gov/ncidod/EID/vol7no3/burkot.htm Vol. 6, No. 2 March-April 2000
[...] Serum samples from these patients did not recognize B. burgdorferi antigens [...] Hence, these cases have been diagnosed as STARI. Recently, novel DNA sequences [...] have identified a new spirochete in A. americanum and B. lonestari . This page last reviewed March 14, 2000 (CDC)
Fatal spirochetosis due to a relapsing
fever-like Borrelia sp. in a northern
spotted owl.
Thomas NJ, Bunikis J, Barbour AG, Wolcott MJ
J Wildl Dis 2002 Jan 38:187-93 , .TXT ABSTRACT
http://www.yale.edu/opa/v29.n29/story8.html Unnamed spirochete found in the US. closely resembles Borrelia miyamotoi which causes human disease in Japan.
"...the organism, as yet unnamed, closely resembles a spirochete found in ticks in Japan, Borrelia miyamotoi, and is a close cousin to Borrelia burgdorferi, the spirochete that causes Lyme disease"[...] said the new organism has been found in about 2% of the nymphs tested in four states [...] findings show that up to 20% of the infected ticks are carrying this new organism instead. "It is completely cryptic, which means there is no way to diagnose it..." [...] If it does [infect humans], it's likely that the same treatment for
Lyme disease would be effective against this organism."
This study describes the
identification of 2 new Borrelia parkeri spirochetes in
Colorado
Life phases and morphology of spirochetes
Morphology Simplified- The words "cyst" and "bleb" are interchangeable in regards to lyme spirochetes. Same thing. In some of the older literature in particular, cysts are also called "granular" forms. Same thing. People in the Marshal Protocol camp also tend to call them "granular" forms. All this tends to confuse everyone, not just you and I.
Although the terms "egg" and "larvae" are not used in describing bacteria, these commonly used biology terms are appropriate. These terms may not be correct here to some microbiologists but thinking of them is useful in understanding what the heck these studies are talking about. Young spirochetes have been observed and documented as emerging from cyst forms. I call the cyst forms "eggs" when describing them to someone. You can call cyst forms whatever you like, but that's what at least some of them are. Reproductive forms serving the function of eggs. Eggs! Yep, that's right. Eggs. ""L" form variants" or "Young Spirochetes" have been observed and documented emerging from cyst forms. You can see a great family picture of well formed little spirochete babies safe and snug inside their cozy transparent egg on the homepage of this website, along with a picture of a parent carrying it's slimey little egg cases around. I wouldn't go so far as to use the term "Larvae" for "L" forms though. They might not be very different from the adults. I don't think anyone knows yet.
Also I wonder if it is possible if some of the cysts serve the function of hibernation-like chambers for adults. I haven't seen any direct observational statements that spell that out specifically, that adults not hatchlings sometimes emerge from the eggs. There are references to "adult spiral forms" emerging, but it's not clear to me at least, that the person observing this is differentiating "L" forms from adult Spiral forms. Some observers see them as the same. Or maybe the adults don't use cyst forms to hibernate in, maybe when adults die off the eggs all just delay "hatching" until conditions are right and it's as simple as that. I hope so.
Cyst (egg) forms require different antibiotics than do adult forms. Not considering this is one of the reasons for some current failures of antibiotic treatment in tertiary and in disseminated lyme. Please see Brorson's studies below. Protocols are evolving that address the life phases and behaviors of these bacteria in disseminated cases. For instance a cyst buster like flagyl or tinidazole is now being added to rocephin by some doctors from both the ID and ILADS schools of thought. It may also be that an additional beginning week or 2 of rocephin heals the bbb enough that flagyl is better tolerated.
Morphology, or changing form, is not unusual in nature. Think of the life stages of butterflies or frogs. The lyme bacteria (a spirochete bacteria) has a simpler life cycle than either of those; Cyst (egg) to "L" form (just emerged or "hatched"), then to Spiral form (adult). Not too complex. For an example of real complexity, do a google for the life cycle of Babesia!
B.b. bacteria also "exchange genetic material". In other words- they mate. Don't ask me how- I've never watched it myself. Are they male and female or hermaphrodites? I don't know. I don't know if anyone knows. But they don't just reproduce by splitting in two. Nope, they mate and lay all their eggs in you, the little buggers...
quick sampler of studies & pictures of cyst phases.
Association between
multiple sclerosis and cystic structures in cerebrospinal fluid.
Brorson O, Brorson SH, Henriksen TH, Skogen PR, Schoyen R.
Dept. of Microbiology, Vestfold Sentralsykehus, Tonsberg, Norway. VERY
INTERESTING STUDY. FULL TEXT
more studies by the Brorson's . Excellent and solid researchers, this is a collection of studies with very useful information.
http://www.lymenet.de/literatur/cystsl.htm "Historical Observations of Spirochetal Cysts and L-Forms". A list of summaries and abstracts of some of the best historical observations of Lyme and Syphilis spirochetal behavior and morphism. Spirochetes may reproduce both by fission and eggs (cysts). They have also been observed covering themselves with particles from a hosts cells like a cloak and entering and hiding directly inside host cells. They are highly mobile.
pdf file 172k, good samples (abstracts) of cyst phase studies with pictures. "Studies on the Cystic Form of Borrelia burgdorferi Mechanisms of Persistence" Within this file is a US study which confirms the existence of cyst phases. I guess people in the US have to have a US study... Serum Starvation-Induced Cyst Formation in Borrelia burgdorferi Under Defined Conditions; Paper confirming the Brorsons’ work on cystic forms of Borrelia burgdorferi. Alban PS; Nelson DR. University of Rhode Island, Kingston, RI 02181 Presented at the 1999 International Conference on Lyme Disease in Munich, Germany. Subsequently published in Microbiology, Jan 2000;146 (Pt 1):119-27.
Effects of penicillin, ceftriaxone,
and doxycycline on morphology of Borrelia burgdorferi.
AUTHORS: Kersten A; Poitschek C; Rauch S; Aberer E
AUTHOR AFFILIATION: Department of Dermatology, University of Vienna, Austria.
Please read Brorsons'
for information on antibiotic susceptibilities of the cyst form
Chronicity
California studies of tick and human positivity
Ukiah area study pdf file 187k.
collections of links and info
**Killing of lymphocytes (human and mouse) Observations
Invasion and Cytopathic
Killing of Human Lymphocytes by Spirochetes Causing Lyme Disease pdf
file FULL TEXT David W. Dorward, Elizabeth R. Fischer,and
Diane M. Brooks. From the National Institute of Allergy and Infectious
Diseases, Rocky Mountain Laboratories, Hamilton, Montana
Large file; 810 kilibites and well worth it. In vitro. Is this
learned behavior? look closely at the images. This is frightening but
it is also a strange study. Lymphocytes were grown with a "100 fold
excess" of spirochetes in vitro (outside of a body- test tube or
petri dish sort of thing.) "...Killing was reduced at infection ratios
of 10:1 and 1:1 and was insignificant at lower ratios..." FULL TEXT
here is a link to a few pictures
from the above study in html format. ***NOTE: varies with strains.
quote from text;
"Lyme disease is a persistent low-density spirochetosis caused by Borrelia burgdorferi sensu lato. Although spirochetes causing Lyme disease are highly immunogenic in experimental models, the onset of specific antibody responses to infection is often delayed or undetectable in some patients. The properties and mechanisms mediating such immune avoidance remain obscure. To examine the nature and consequences of interactions between Lyme disease spirochetes and immune effector cells, we coincubated B. burgdorferi with primary and cultured human leukocytes. We found that B. burgdorferi actively attaches to, invades, and kills human B and T lymphocytes. Significant killing began within 1 hour of mixing. Cytopathic effects varied with respect to host cell lineage and the species, viability, and degree of attenuation of the spirochetes. Both spirochetal virulence and lymphocytic susceptibility could be phenotypically selected, thus indicating that both bacterial and host cell factors contribute to such interactions. These results suggest that invasion and lysis of lymphocytes may constitute previously unrecognized factors in Lyme disease and bacterial pathogenesis."
***NOTE: varies with strains.
Murine
Model for Lymphocytic Tropism by Borrelia burgdorferi
David W. Dorward* and Ralph S. Larson
Rocky Mountain Laboratories, National Institute of Allergy and Infectious
Diseases, Hamilton, Montana . Follow up study to the one above. FULL
TEXT "...To assess whether spirochetes interact directly with
lymphocytes in mammals, we developed a mouse model for lymphotropism..."
***NOTE: varies with strains.
General
Neurological
Controversies in Neuroborreliosis
by Audrey Stein Goldings, M.D. Updated October, 2002
Neurological / physical aspects
How
does one distinguish between Multiple Sclerosis and neurologic Lyme Disease?
University of Coloumbia article. UC is now the leading United States research
facility for nuerological aspects of lyme. (The US is behind in recognizing
cyst phases.)
& does it matter? Association
between multiple sclerosis and cystic structures in cerebrospinal fluid.
Brorson O, Brorson SH, Henriksen TH, Skogen PR, Schoyen R.
Dept. of Microbiology, Vestfold Sentralsykehus, Tonsberg, Norway.
Functional Brain Imaging and Neuropsychological
Testing in Lyme Disease
Brian A. Fallon, Sam Das, Jeffrey J. Plutchok, Felice Tager,
Kenneth Liegner, and Ronald Van Heertum
From The New York State Psychiatric Institute, the Department of
Psychiatry of Columbia University and Columbia-Presbyterian Medical
Center, and the Department of Nuclear Medicine of Columbia-
Presbyterian Medical Center, New York, New York; and private practice
in Armonk, New York FULL TEXT, PDF file 400k (LARGE
FILE)
"Differentiating neuropsychiatric Lyme disease from a primary psychiatric disorder can be a daunting task. This article describes how functional brain imaging and neuropsychological testing can be particularly valuable in helping to make diagnostic distinctions."
Of interest in spirochetosis of MS patients; http://www.lymenet.de/mattms.htm "Spirochaeta Myelophthora in Multiple Sclerosis" A short loose collection of references to studies related to this subject. Also http://www.sanytel.com/consuAest0001.htm is an essay on the history of spirochete research concerning MS & arguments for spirochetosis as a cause of MS. The Brorson's work includes a modern study confirming the presence of spirochetes. Bb has also been found in brain tissue on autopsy of patients diagnosed with MS and Altimers.
Concurrent Neocortical
Borreliosis and Alzheimer's Disease
Demonstration of a Spirochetal Cyst Form Date of Publication:
1988
Source: Annals of the New York Academy of Sciences, 468-470
Author: Alan B. MacDonald
Institution: Southampton Hospital, Southampton, NY 11968
Bb spirochetes found in brain at autopsy.
PDF file (page 15)
University of Columbia; Fallon has and is doing research on this aspect. There is some information on other aspects. Overview of Neuropsychiatric Lyme Disease
The
Neuropsychiatric Manifestations of Lyme Borreliosis Brian
A. Fallon, M.D. Department of Psychiatry, College of Physicians and Surgeons
of Columbia
University, and Division of Therapeutics, New York State Psychiatric Institute,
New York, New York., Jenifer A. Nields, M.D., Joseph J. Burrascano, M.D.
Southampton Hospital, Southampton, New York., Kenneth Liegner, M.D. Northern
Westchester Hospital Center, Mt. Kisco, New York. Donato DelBene, B.A.
Department of Psychiatry, College of Physicians and Surgeons of Columbia
University, and Division of Therapeutics, New York State Psychiatric Institute,
New York, New York., Michael R. Liebowitz, M.D. Department of Psychiatry,
College of Physicians and Surgeons of Columbia University, and Division
of Therapeutics, New York State Psychiatric Institute, New York, New York.
Reprinted from: Psychiatric Quarterly, Vol63, No 1, Spring 1992
Higher
Prevalence of Antibodies to Borrelia Burgdorferi in Psychiatric Patients
Than in Healthy Subjects FULL TEXT Am J Psychiatry 159:297-301, February
2002
A
Controlled Study of Cognitive Deficits in Children With Chronic Lyme Disease
J Neuropsychiatry Clin Neurosci 13:500-507, November 2001
Tager, Fallon, Keilp, Rissenberg, Jones, Liebowitz Click
on the link on this page. Pdf file, 80k. FULL TEXT
Essays by Dr Fallon
Neurologic Lyme Disease excellent overview of neurological lyme. FULL TEXT
Differential Diagnosis in Lyme Disease presented at the 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders. Similarities between Fibromyalgia, CFIDs and Lyme diagnosis. FULL TEXT
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15665404 Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer Disease. Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ. University Institute of Pathology, Division of Neuropathology, University Medical School (CHUV), 1011, Lausanne, Switzerland. and University of British Columbia, Department of Psychiatry, Kinsmen Laboratory of Neurological Research, Vancouver, B.C. V6T 1Z3, Canada.
"The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD. "
Lyme and Syphilis pathogenic shifting comparisons
http://www.jci.org/cgi/content/full/107/6/651
Borrelia burgdorferi and Treponema pallidum: a comparison
of functional genomics, environmental adaptations, and pathogenic mechanisms
Stephen F. Porcella and Tom G. Schwan Laboratory of Human Bacterial Pathogenesis,
Rocky Mountain Laboratories, National Institute of Allergy and Infectious
Diseases, NIH, Hamilton, Montana, USA
Very technical, but even without understanding the language or many of the concepts, there are interesting bits and pieces from this article.
"B. burgdorferi has 15 silent vls genes adjacent to an expression site (vlsE), which is found near the telomere of a 28 kb plasmid (21) (Figure 2). Recombination of vls genes occurs early during mammalian infection and involves a gene conversion event in which a silent vls cassette replaces a corresponding region in the vls gene residing in the vlsE expression site. The vls system has the potential to produce millions of antigenic variants during infection of the mammalian host (21), and it has been speculated that Vls variation contributes to persistence of the organism in vivo. "
[Italics mine. Check out the diagram]
Is this saying what I think it's saying? Could it be possible for B.b. to change our ability not only to detect antigens but also it's genes/DNA? As in current PCR tests? Could this account for non-detection of cyst forms? If anyone understands this please e-mail me?
[Syphilis. Italics mine.]
"[...] Although tpr genes lack a consensus lipoprotein sequence, three members (TprF, TprI, and TprK) are predicted to be associated with the outer membrane of T. pallidum (22). The presence of multiple tprK alleles within the same isolate of T. pallidum and heterogeneity of the tprK gene among isolates (23) suggests that multiple subpopulations or genetic variants exist. The presence of a complex tpr gene family with multiple tprK gene alleles also suggests that tprK has the capacity to undergo recombination with the generation of new alleles or gene variants within an isolate. Because the tprK genes are not restricted to a single locus with one promoter, the mechanism for generating gene variation must be different from that used in borreliae at the vmp and vls loci. However this diversity is generated, tprK gene(s) or other members of the tpr gene family apparently helps explain the lack of cross-immunity in animals challenged with nonhomologous strains."
results of the reliability of 2 tests for lyme; http://www.niaid.nih.gov/dmid/lyme/luat.htm Best test is around 2/3 reliable. Unpublished study. Considering the variations of over 100 subspecies now known, the morphism of the spirochetes, the qualifications of Lyme in studies on these tests, and the tests that are used to compare other tests for accuracy, these tests are likely to be much less accurate than stated here. Lyme is a clinical dx. Tests for Erlichosis and Babesiosis are not very good either. Babeosis has over 12 species. There are tests for only 2 species of Babeosis, which is a common co-infection of Lyme.
The Elisa test is possibly the least sensitive.
*** Explanation of the bands in Western blot test Igg and Igm band results;
http://www.geocities.com/HotSprings/Oasis/6455/western-blot.txt
Complete listed explanation of bands.
NOT all labs can or will do a full report on all bands, That is not a
complete test. Many tests are based on CDC surveillance strain b32 only.
Some strains test differently which is one of the reasons why all Lyme
tests so far are highly inaccurate. Lyme is categorized as a clinical
dx by the CDC. And CDC's diagnostic guidelines are set up for research
purposes only, not for practical diagnosis.
IgeneX is an experienced and reliable lab for this test. IgeneX; http://www.igenex.com/index.shtml http://www.igenex.com/formset1.htm Tel. 650.424.1191 / 800.832.3200 Fax. 650.424.1196
These are links to a few possible vectors other than ticks.
Eukaryotic Cell Multijournal search engine
Google ...the Elmer Fudd version. This interface is fully functional and makes searching a little less dry. Coups to whoever did this!
Lymenet search archives
LINKS to other sites with study collections
Cheryl's Lyme Info & her page Lyme Files One of the best places online to find info on studies.
Lots Of Links On Lyme Disease Art Dohertie's site (very extensive- some links outdated). Over 12,000 Categorized Links on Lyme Disease.