Updated 4th April 2016
Researchers investigate four promising new treatments for Lyme disease
March 29, 2016 by Thea Singer
When Northeastern researchers reported last May how the bacterium that causes the disease evades antibiotics, suggesting new treatments, the media and the general public took notice.
University Distinguished Professor Kim Lewis, who leads the Lyme disease research team, is now expanding that therapeutic reach with the help of a $1.5 million grant from the Steven and Alexandra Cohen Foundation.
The team is pursuing four arms of treatment-related research at Northeastern’s Antimicrobial Discovery Center, which Lewis directs.
More on the article available at:
Lyme Disease May Linger for 1 in 5 Because of “Persisters”
A new theory about long-lasting Lyme disease symptoms suggests treatment option By Melinda Wenner Moyer on September 1, 2015
These ideas stem from the observation of a few rogue bacterial cells. Kim Lewis, director of the antimicrobial discovery center at Northeastern University, and his colleagues grew B. burgdorferi in the laboratory, treated them with various antibiotics and found that whereas most of the bacteria died within the first day, a small percentage—called persister cells—managed to survive the drug onslaught. Scientists first discovered persister cells in 1944 in Staphylococcus aureus, the agent of staph infections, and Lewis and others have observed them in other species of bacteria, too—but the observations that B. burgdorferi also form persisters is new.
PS: other studies on persisters available further down this page (search for Lewis or Zhang)
Utah drug research company, Curza, takes aim at Lyme disease
By Chris Miller Wednesday, August 26th 2015
(KUTV) Curza, a Provo-based pharmaceutical research company, is on the cusp of a medical breakthrough that could treat victims of chronic Lyme disease.
The company is entering phase two of clinical research on their newly designed antibiotic called CZ-99. They’ll soon be testing the drug on infected mice at the University of California, Davis.
An initial clinical trial at the University of New Haven in Connecticut, found CZ-99 to be 60 percent more effective in treating Lyme disease than the traditional antibiotics used to treat the illness.
Curza CEO Ryan Davies says they have a patent on a technology used to penetrate bacteria’s protective outer layer, or biofilm, making its new antibiotic more effective than outdated medications.
Lyme Borreliosis: Is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains?
Bosn J Basic Med Sci. 2015 Jul 8;15(3):1-13. doi: 10.17305/bjbms.2015.594. Hodzic E
Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous subpopulation of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, with B. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues. A number of host cytokines were up- or down-regulated in tissues of both shame- and antibiotic-treated mice in the absence of histopathology, indicating a lack of host response to the presence of antimicrobial tolerant/resistant spirochetes.
Severity of chronic Lyme disease compared to other chronic conditions:
PeerJ 2:e322; DOI 10.7717/peerj.32 Johnson et al. (2014)
Comparison study of chronic Lyme compared to IBS, Lupus, MS, Diabetes, Heart Disease & more (21 page PDF) https://peerj.com/articles/322.pdf
Updated 26th June 2015
Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection
Emerging Microbes & Infections (2015) 4, e31; doi:10.1038/emi.2015.31
Published online 3 June 2015
Jie Feng, Wanliang Shi, Shuo Zhang and Ying Zhang
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Part of intro:
Consistent with the difficulty to eradicate B. burgdorferi in animal models, B. burgdorferi develops various morphological variant forms, such as round bodies and microcolonies, that are refractory or resistant to antibiotics and stresses. For example, it has been demonstrated that whereas the frontline drugs, such as doxycycline and amoxicillin, kill or inhibit the growing spirochetal form of B. burgdorferi effectively, they have little activity in killing non-growing persisters that are enriched in the stationary phase or microcolonies or as biofilm-like aggregates of B. burgdorferi. There is significant interest in the identification of drugs that target B. burgdorferi persisters.
To identify drugs that can more effectively kill B. burgdorferi persisters, we recently developed a new viability assay using SYBR Green I/propidium iodide (PI) dyes, which allowed us to screen an Food and Drug Administration (FDA)-approved drug library against stationary phase B. burgdorferi persisters. Using this high-throughput assay, we identified a number of drug candidates, such as daptomycin, clofazimine, cefoperazone, and carbomycin that have excellent activity against in vitro B. burgdorferi persisters. In our previous study, we found that daptomycin had the highest activity against B. burgdorferi persisters among all of the candidate drugs. Although daptomycin could almost eradicate B. burgdorferi persisters at 50 μM, this drug concentration is too high for clinical use, and daptomcyin has to be used intravenously, which is not convenient to administer.
Part of abstract:
We took advantage of our recently developed high-throughput viability assay and screened the National Cancer Institute compound library collection consisting of 2526 compounds against stationary phase B. burgdorferi. We identified the top 30 new active hits, including the top six anthracycline antibiotics daunomycin 3-oxime, dimethyldaunomycin, daunomycin, NSC299187, NSC363998 and nogalamycin, along with other compounds, including prodigiosin, mitomycin, nanaomycin and dactinomycin, as having excellent activity against B. burgdorferi stationary phase culture. The anthracycline or anthraquinone compounds, which are known to have both anti-cancer and antibacterial activities, also had high activity against growing B. burgdorferi with low minimum inhibitory concentration. Future studies on the structure–activity relationship and mechanisms of action of anthracyclines/anthraquinones are warranted. In addition, drug combination studies with the anthracycline class of compounds and the current Lyme antibiotics to eradicate B. burgdorferi persisters in vitro and in animal models are needed to determine if they improve the treatment of Lyme disease.
Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells.
American Soc Microbiology 26 May 2015, doi: 10.1128/AAC.00864-15
Bijaya Sharma1, Autumn V. Brown1, Nicole E. Matluck1, Linden T. Hu2 and Kim Lewis1*
1Department of Biology, Northeastern University, Boston, Massachusetts, USA
2Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, USA.
In this study, we examined the ability of B. burgdorferi to form persisters. Killing of growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary phase cells, but not persisters. [This study by Feng et al showed that although daptomycin had the highest activity against non-growing persisters, it had relatively poor activity or a high minimal inhibitory concentration (MIC) against growing/replicating B. burgdorferi]. Mitomycin C, an anti-cancer agent that forms adducts with DNA, killed persisters and eradicated both growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse-dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and antibiotic was added again. Four pulse-doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.
Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline
Jie Feng, Paul G. Auwaerter, Ying Zhang
PLOS Published: March 25, 2015 / DOI: 10.1371/journal.pone.0117207
Although most Lyme disease patients can be cured with antibiotics doxycycline or amoxicillin using 2-4 week treatment durations, some patients suffer from persistent arthritis or post-treatment Lyme disease syndrome. Why these phenomena occur is unclear, but possibilities include host responses, antigenic debris, or B. burgdorferi organisms remaining despite antibiotic therapy. In vitro, B. burgdorferi developed increasing antibiotic tolerance as morphology changed from typical spirochetal form in log phase growth to variant round body and microcolony forms in stationary phase. B. burgdorferi appeared to have higher persister frequencies than E. coli as a control as measured by SYBR Green I/propidium iodide (PI) viability stain and microscope counting.
To more effectively eradicate the different persister forms tolerant to doxycycline or amoxicillin, drug combinations were studied using previously identified drugs from an FDA-approved drug library with high activity against such persisters. Using a SYBR Green/PI viability assay, daptomycin-containing drug combinations were the most effective. Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefoperazone or carbenicillin) or an energy inhibitor (clofazimine). Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations.
These findings may have implications for improved treatment of Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human infection.
Chronic Lyme Disease: Persistent Clinical Symptoms Related to Immune Evasion, Antibiotic Resistance and Various Defense Mechanisms of Borrelia burgdorferi
Aaron J. Smith, John Oertle, Dino Prato, Envita, Scottsdale, AZ, USA
Open Journal of Medical Microbiology
Vol.04 No.04(2014), Article ID:52890,8 pages, 10.4236/ojmm.2014.44029
There are several factors involved in the ability of Borrelia burgdorferi to retain a persistent infection within a mammalian host. These factors of immune evasion include regulation of membrane proteins, variable epitopes of surface proteins, protection against the immune system through tick saliva, the ability to migrate to regions where it is not exposed to the immune system or antibiotics, invagination or invasion within various cells, pleomorphic forms, and the potential to produce biofilms. The window of conventional treatment for Lyme disease is short and has the potential to display different symptoms depending on the strain of Borrelia bugdorferi. These symptoms are dependent on the localization of Borrelia burgdorferi which correlates to the significance of diagnosing Lyme disease early to prevent such a spread throughout the body. Such complications of Borrelia burgdorferi may demand new clinical treatment discoveries for patient fighting the chronic form.
Covers the following topics:
1. Introduction 2. Outer Surface Proteins 3. Variable major protein like sequence 4. Complement Regulatory-Acquiring Surface Proteins 5. Tick Saliva 6. Motility 7. Survival and Immune Escape of B. Burgdorferi by Tissue Localization 8. Intracellular Localization in Nerve Cells 9. Pleomorphism 10. Persistent Symptoms of Chronic Lyme Arthritis 11. Biofilms 12. Discussion
Persisters, persistent infections and the Yin–Yang model
Emerging Microbes & Infections (2014) 3, e3; doi:10.1038/emi.2014.3
Published online 8 January 2014
1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
2Key Laboratory of Medical Molecular Virology of MOE/MOH, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
Snippets from paper:
Persisters pose significant challenges for the treatment of many chronic and persistent bacterial infections such as TB,8 Lyme disease47 and urinary tract infections (Table 2). Persisters underlie latent infections, chronic and recurrent infections, biofilm infections and lengthy therapy of certain bacterial infections, such as TB, and post-treatment persistence and relapse…
..More recently, Borrelia burgdorferi has been demonstrated to have a persistence problem despite antibiotic treatment using mouse and monkey models,53,54 which may provide some explanation for persisting chronic Lyme disease observed in some patients.47 In addition to bacterial factors that vary in persistence, the host susceptibilities that vary among individuals play a role in the degree of persistence during infection as well. These variations at the levels of bacterial persistence and host defense mechanisms can have implications in treatment of bacterial infections and might explain why some individuals develop chronic disease and relapse after treatment, whereas others seem to have a stable cure.
Full review at: http://www.nature.com/emi/journal/v3/n1/full/emi20143a.html
Lyme disease: an infectious and postinfectious syndrome.
Asch ES1, Bujak DI, Weiss M, Peterson MG, Weinstein A.
J Rheumatol. 1994 Mar;21(3):454-61.
To determine chronic morbidity and the variables that influence recovery in patients who had been treated for Lyme disease.
Retrospective evaluation of 215 patients from Westchester County, NY, who fulfilled Centers for Disease Control case definition for Lyme disease, were anti-Borrelia antibody positive and were diagnosed and treated at least one year before our examination.
Erythema migrans had occurred in 70% of patients, neurological involvement in 29%, objective cardiac problems in 6%, arthralgia in 78% and arthritis in 41%. Patients were seen at a mean of 3.2 years after initial treatment. A history of relapse with major organ involvement had occurred in 28% and a history of reinfection in 18%. Anti-Borrelia antibodies, initially present in all patients, were still positive in 32%. At followup, 82 (38%) patients were asymptomatic and clinically active Lyme disease was found in 19 (9%). Persistent symptoms of arthralgia, arthritis, cardiac or neurologic involvement with or without fatigue were present in 114 (53%) patients. Persistent symptoms correlated with a history of major organ involvement or relapse but not the continued presence of anti-Borrelial antibodies. Thirty-five of the 114 (31%) patients with persistent symptoms had predominantly arthralgia and fatigue. Antibiotic treatment within 4 weeks of disease onset was more likely to result in complete recovery. Children did not significantly differ from adults in disease manifestations or in the frequency of relapse, reinfection or complete recovery.
Despite recognition and treatment, Lyme disease is associated with significant infectious and postinfectious sequelae.
Added 22nd December 2014
Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library
Emerging Microbes & Infections (2014) 3, e49; doi:10.1038/emi.2014.53
Published online 2 July 2014
Jie Feng1, Ting Wang1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul G Auwaerter2 and Ying Zhang1
1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Part of Abstract..To identify drug candidates that can eliminate B. burgdorferi persisters more effectively, we screened an Food and Drug Administration (FDA)-approved drug library consisting of 1524 compounds against stationary-phase B. burgdorferi by using a newly developed high throughput SYBR Green I/propidium iodide (PI) assay. We identified 165 agents approved for use in other disease conditions that had more activity than doxycycline and amoxicillin against B. burgdorferi persisters. The top 27 drug candidates from the 165 hits were confirmed to have higher anti-persister activity than the current frontline antibiotics. Among the top 27 confirmed drug candidates from the 165 hits, daptomycin, clofazimine, carbomycin, sulfa drugs (e.g., sulfamethoxazole), and certain cephalosporins (e.g. cefoperazone) had the highest anti-persister activity. In addition, some drug candidates, such as daptomycin and clofazimine (which had the highest activity against non-growing persisters), had relatively poor activity or a high minimal inhibitory concentration (MIC) against growing B. burgdorferi. Our findings may have implications for the development of a more effective treatment for Lyme disease and for the relief of long-term symptoms that afflict some Lyme disease patients.
DNA Sequencing Diagnosis of Off-Season Spirochetemia with Low Bacterial Density in Borrelia burgdorferi and Borrelia miyamotoi Infections
Part of text.. Full-blown spirochetemia in Lyme borreliosis is a transient phenomenon and occurs within the first 30 days of the disease . Since the spirochetemia detected in these 14 patients was unlikely to be the result of a recent infection and some of the patients had received multiple courses of antibiotics for the treatment of the disease up to the date of blood testing, we interpret these 14 patients as cases of undiagnosed Lyme or related borrelioses, or as cases of “Lyme disease” not completely cured by the standard courses of antibiotic treatment.
Chronic Lyme Proven in Recent Medical Research
April 7, 2012 by Jenna Smith:
Persistence of Borrelia burgdorferi in mice after antibiotic therapy
A copy of one of the studies mentioned in link above can be found at (PDF): http://archive.poughkeepsiejournal.com/assets/pdf/BK193588818.pdf
Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review
International Journal of Family Medicine
Volume 2014 (2014), Article ID 138016, 10 pages
Liesbeth Borgermans,1 Geert Goderis,2 Jan Vandevoorde,1 and Dirk Devroey1
1Department of Family Medicine & Chronic Care, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium
2Department of General Practice and University Hospitals Leuven, Katholieke Universiteit Leuven (KUL), Kapucijnenvoer 33, 3000 Leuven, Belgium
Published 24 November 2014 / Academic Editor: Christos D. Lionis
Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.
Added 21 Nov 2014
SPECT Brain Imaging in Chronic Lyme Disease
Donta, Sam T. MD*; Noto, Richard B. MD†; Vento, John A. MD‡
From the *Department of Medicine (Infectious Diseases), Boston University Medical Center, Boston, MA; †Department of Diagnostic Imaging (Nuclear Medicine), Rhode Island Hospital, and The Warren Alpert Medical School of Brown University, Providence, RI; and ‡Department of Diagnostic Imaging and Therapeutics (Nuclear Medicine), University of Connecticut School of Medicine, Farmington, CT.
Received for publication January 25, 2011; and revision accepted April 23, 2012.
Methods: A total of 183 individuals who met the clinical definition of chronic Lyme disease underwent SPECT scanning of the brain using 99mTc and standard nuclear imagine techniques. Abnormalities of perfusion to affected areas of the brain were defined as mild, moderate, or severe.
Results: Of all patients, 75% demonstrated abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes. Patients considered to be seropositive and those considered seronegative had similar rates, types, and severity of perfusion defects. Abnormalities of MRI of the brain were seen in 14% of patients. Treatment with antibiotics, especially those with intracellular-penetrating activity, resulted in resolution or improvement of abnormalities in 70% of patients over a 1- to 2-year period.
Conclusions: Brain SPECT scans are abnormal in most patients with chronic Lyme disease, and these scans can be used to provide objective evidence in support of the clinical diagnosis. The use of certain antibiotic regimens seems to provide improvement in both clinical status and SPECT scans.
Dark field microscopy can expose spirochetes:
Samples used are from 4 people, all with chronic illness longer than 15 years and with wide-ranging symptoms and severe disability. All have been diagnosed at some time with M.E. 3 have had negative ELISA/WB tests for Lyme disease (1 not tested). 3 have had more than 3 years antibiotic treatment; 2 of these include treatment specifically for borrelia. (Images of spirochetes & video available in the link below)
The experiment above showed blood from 11 patients: 6 women and 5 men donated samples. All donors have had long-term health problems with 8 of 11 being ill for 19 years or longer. 8 donors have at some time been diagnosed with M.E. 10 of 11 donors had been tested for Lyme borreliosis through the NHS and the result was negative (1 not tested). 9 of 11 had private tests that were positive; (2 not tested privately). 7 of 11 had taken antibiotics within one week of preparing their culture sample. (Images of spirochetes & video available in the link above)
Granulomatous hepatitis associated with chronic Borrelia burgdorferi infection: a case report
Marianne J Middelveen1, Steve A McClain2, 3, Cheryl Bandoski4, Joel R Israel3, Jennie Burke5, Alan B MacDonald1, Arun Timmaraju3, Eva Sapi4, Yean Wang5, Agustin Franco5, Peter J Mayne1, Raphael B Stricker1 (rstricker at usmamed dot com) #
1 International Lyme and Associated Diseases Society, Bethesda, MD, USA. 2 Departments of Dermatology and Emergency Medicine, State University of New York, Stony Brook, NY, USA. 3 McClain Laboratories LLC, Smithtown, NY, USA. 4 Department of Biology and Environmental Science, University of New Haven, West Haven, CT, USA. 5 Australian Biologics, Sydney, NSW, AustraliaDOI
In summary, we describe a case of granulomatous hepatitis associated with chronic Lyme disease. The findings of motile spirochetes in blood culture and various morphological forms of Bb within the liver despite antibiotic therapy provide evidence that Lyme disease may be a chronic infection that affects different organs at different times and in different ways. Improved antibiotic treatment for chronic Lyme disease should become a priority for future investigation.
New insights into stages of lyme disease symptoms from a novel hospital-based registry.
J Prim Care Community Health. 2014 Oct;5(4):284-7. doi: 10.1177/2150131914540693. Epub 2014 Jun 25.
Lobraico J1, Butler A2, Petrini J2, Ahmadi R2.
BACKGROUND: Western Connecticut Health Network created the Lyme Disease Registry in response to the community’s request and clinical need for more Lyme disease research. The registry includes acute, recovered, and persistently symptomatic patients to better define the different stages of the disease. The design of the registry was guided by community and clinician input through a community-based participatory research process.
METHODS: Registry participants are asked questions regarding their diagnosis, symptoms, treatments, recovery, and satisfaction with the Registry. A blood specimen is also collected and stored at the initial appointment.
RESULTS: The Lyme Disease Registry has enrolled 256 participants, 24% are acute cases, 45% are persistently symptomatic cases, and 31% are recovered cases. The symptoms experienced by the group of patients with persistent symptoms had unexpectedly strong overlap with those experienced by acutely infected patients.
CONCLUSION: The difference between symptoms in the acutely infected patients and those experiencing persistent symptoms is not as large as initially thought.
Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi.
A Kersten, C Poitschek, S Rauch, and E Abere
Antimicrob Agents Chemother. May 1995; 39(5): 1127–1133.
Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survival in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated the different modes of degeneration of Borrelia burgdorferi suspensions during a 96-h exposure to various antibiotics. By dark-field microscopy and ultrastructural investigations, increasing blebbing and the gradual formation of granular and cystic structures could be followed during the exposure time. Although antibiotic concentrations at the MIC at which 90% of organisms are inhibited after 72 h were 80% or even greater, motile organisms were still present after incubation with penicillin and doxycycline but not after incubation with ceftriaxone. By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested. According to experiences from studies with other spirochetes it is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme borreliosis.
Clinical implications of delayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi.
MacDonald AB1, Berger BW, Schwan TG.
Acta Trop. 1990 Dec;48(2):89-94.
Lyme borreliosis, a spirochetal infection caused by Borrelia burgdorferi, may become clinically active after a period of latency in the host. Active cases of Lyme disease may show clinical relapse following antibiotic therapy. The latency and relapse phenomena suggest that the Lyme disease spirochete is capable of survival in the host for prolonged periods of time. We studied 63 patients with erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and examined in vitro cultures of biopsies from the active edge of the erythematous patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to 10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in certain situations. Some patients with Lyme borreliosis may require more than the currently recommended two to three week course of antibiotic therapy to eradicate strains of the spirochete which grow slowly.
PMID: 1980573 [PubMed – indexed for MEDLINE
Is there a place for xenodiagnosis in the clinic?
Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist after antibiotic therapy is an area of ongoing controversy. In animal models, B. burgdorferi DNA can be detected in tissues after antibiotic therapy as well as by using the natural tick vector to acquire the organism through feeding (xenodiagnosis). Vector arthropods have been successfully used in xenodiagnosis to describe the etiology of infections such as malaria, typhus and Chagas disease. Our recent safety trial of xenodiagnosis demonstrates that ticks may be successfully fed on patients and may help determine the biological basis for post-treatment Lyme disease syndrome.
In the absence of treatment, the agent of Lyme disease can establish long-term, persistent infections in multiple animal species, including humans. B. burgdorferi s.l. has been recovered from the skin lesions of acrodermatitis chronicum atrophicans (a late manifestation of Lyme disease) patients as long as 10 years after the original infection . The first evidence that B. burgdorferi or its remnants may persist following administration of antibiotics was described for dogs [17,18], although it is possible that their treatment regimen was not sufficient . Xenodiagnosis using subadult deer ticks (Ixodes dammini or Ixodes scapularis) demonstrated the persistence of B. burgdorferi or its remnants after antibiotic treatment in mice [20–23] and non-human primates [24,25]. However, B. burgdorferi could not be reliably cultured from antibiotic-treated animals…
..Although it was not a main endpoint of this study, we analyzed most of the ticks that we collected by multiple methods, and found two patients whom we considered positive by xenodiagnosis (DNA detection), a patient with erythema migrans who initiated antibiotic therapy at the same time that the ticks were placed and a PTLDS [post lyme treatment disease] patient. Now that xenodiagnosis using SPF larval I. dammini ticks has been demonstrated to be safe and well tolerated, a larger trial is needed to determine whether a positive xenodiagnosis correlates with persistence of symptoms.
TREATMENT OF LYME DISEASE WITH HYPERBARIC OXYGEN THERAPY
Author: Fife, WP; Freeman, DM
BACKGROUND: It has been shown that the spirochete, Borrelia burgdorferi is a facultative anaerobic organism which can survive in an oxygen partial pressure of 35 mm Hg, but not in an oxygen partial pressure of 160 mm Hg. When Lyme disease becomes chronic and the spirochete is sequestered in cells, the cells may protect the spirochete against the antibiotic which then is not fully effective. Spirochete survival after more than 15 years of antibiotic therapy is known. METHOD: Subjects were exposed to an ambient pressure of 2.36 ata (45fw) for a period of 60 minutes per treatment in a multiplace chamber. Treatments usually were administered twice each day for a total of from 10 to 125 exposures resulting in an oxygen partial pressure at the tissue level of approximately 200 mm Hg. RESULTS: The study included 90 subjects, all of whom had failed IV antibiotics some for as long as 5 years and who were continuing to deteriorate. All presented with Jarisch-Herxheimer’s reaction within 4 days of beginning HBO. All except 4 subjects showed significant improvement after termination of the treatment regimens. Aproximately 70percent continued to feel well after recovery while other had some relapse but showed further improvement with re-treatment. CONCLUSIONS: No cure is claimed by this treatment even though many who have completed the regimen remain essentially well or are much improved. It is clear that this treatment improves the quility of life after all other treatments have failed.
* US Charity Publish Survey Results on Chronic Lyme Disease:
Added 10 Jun 2014
Seronegative chronic relapsing neuroborreliosis.
Lawrence C1, Lipton RB, Lowy FD, Coyle PK. – Eur Neurol. 1995;35(2):113-7.
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.
Relapsing neuroborreliosis. [Eur Neurol. 1996]
Resurgence of Persisting Non-Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice
Emir Hodzic, Denise Imai, Sunlian Feng, Stephen W. Barthold
Published: January 23, 2014 DOI: 10.1371/journal.pone.0086907
The agent of Lyme borreliosis, Borrelia burgdorferi, evades host immunity and establishes persistent infections in its varied mammalian hosts. This persistent biology may pose challenges to effective antibiotic treatment. Experimental studies in dogs, mice, and non-human primates have found persistence of B. burgdorferi DNA following treatment with a variety of antibiotics, but persisting spirochetes are non-cultivable. Persistence of B. burgdorferi DNA has been documented in humans following treatment, but the significance remains unknown.
The present study utilized a ceftriaxone treatment regimen in the C3H mouse model that resulted in persistence of non-cultivable B. burgdorferi in order to determine their long-term fate, and to examine their effects on the host. Results confirmed previous studies, in which B. burgdorferi could not be cultured from tissues, but low copy numbers of B. burgdorferi flaB DNA were detectable in tissues at 2, 4 and 8 months after completion of treatment, and the rate of PCR-positive tissues appeared to progressively decline over time. However, there was resurgence of spirochete flaB DNA in multiple tissues at 12 months, with flaB DNA copy levels nearly equivalent to those found in saline-treated mice.
Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, flaB DNA was acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues by immunofluorescence and immunohistochemistry, respectively. A number of host cytokines were up- or down-regulated in tissues of both saline- and antibiotic-treated mice in the absence of histopathology, indicating host response to the presence of non-cultivable, despite the lack of inflammation in tissues.
Added 09 Jun 2014
Lyme and associated tick-borne diseases: global challenges in the context of a public health threat
Christian Perronne* Front. Cell. Infect. Microbiol., 03 June 2014 | doi: 10.3389/fcimb.2014.00074
Infectious Diseases Unit, Hôpitaux Universitaires Paris-Ile de France-Ouest, Assistance Publique – Hôpitaux de Paris, University of Versailles – Saint Quentin en Yvelines, Garches, France
Covers the following topics:
Diagnostic Pitfalls in Routine Practice
Occult Infections and Their Role in the Pathophysiology of Some Diseases of Unclear Etiology
Serology, the Current Main Diagnostic Method
Calibration of Serology
Clinical and Epidemiological Consequences of Negative Serology
Possible Causes of Seronegativity
Conclusion and Perspectives
Full paper available at: http://journal.frontiersin.org/Journal/10.3389/fcimb.2014.00074/full
Abstract Title: Persister Formation in Borrelia burgdorferi
Author Block: B. Sharma, A. Brown, K. Lewis;
Northeastern Univ., Boston, MA
American Soc for Micro Biology May 2014 Presentation….
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne infection in North America and Europe. In 10-20% of cases, patients develop chronic Lyme disease after completing antibiotic treatment. The cause of these chronic symptoms is, however, poorly understood. We have previously shown that high-persister mutants are selected for over the course of relapsing chronic infections of Pseudomonas aeruginosa in cystic fibrosis patients and Candida albicans in oral thrush patients. It seems likely that these high persister mutants may contribute to the recalcitrance of the infection. Persister cells are drug-tolerant phenotypic variants of normal cells and may cause recurrent bacterial infections by resuming growth once antibiotic treatment has ceased. We hypothesize that persister cells play a role in the treatment failure that leads to chronic Lyme disease. Here, using time-dependent and dose dependent survival assays, we show that B. burgdorferi forms persister cells to the antibiotics commonly used for treatment of Lyme disease. Our results indicate that in a B.burgdorferi population, 0.001% to 1% of the cells can survive lethal doses of various antibiotics in vitro. These persister cells may contribute to treatment failure in chronic Lyme patients. Future experiments are aimed at screening for a better antimicrobial therapy to eradicate persisters in B. burgdorferi.
Macrolide therapy of chronic Lyme Disease.
Donta ST.- Med Sci Monit. 2003 Nov;9(11):PI136-42.
Macrolide antibiotics are highly active in vitro against B.burgdorferi, but have limited efficacy in the treatment of patients with Lyme Disease. As macrolides are less active at a low pH, their poor clinical activity might be due to localization of borrelia to an acidic endosome, and their activity improved by alkalinization of that compartment with hydroxychloroquine.
235 patients with a multi-symptom complex typical of chronic Lyme disease, ie fatigue, musculoskeletal pain, and neurocognitive dysfunction and with serologic reactivity against B.burgdorferi were treated with a macrolide antibiotic (eg clarithromycin) and hydroxychloroquine.
Eighty % of patients had self-reported improvement of 50% or more at the end of 3 months. After 2 months of treatment, 20% of patients felt markedly improved (75-100% of normal); after 3 months of treatment, 45% were markedly improved. Improvement frequently did not begin until after several weeks of therapy. There were no differences among the three macrolide antibiotics used. Patients who had been on hydroxychloroquine or macrolide antibiotic alone had experienced little or no improvement. Compared to patients ill for less than 3 years, the onset of improvement was slower, and the failure rate higher in patients who were ill for longer time periods.
These results support the hypothesis that the Lyme borrelia reside in an acidic endosome and that the use of a lysosomotropic agent augments the clinical activity of macrolide antibiotics in the treatment of patients with chronic Lyme Disease. In contrast, the efficacy of tetracycline in such patients is not affected by hydroxychloroquine.
PMID: 14586290 [PubMed – indexed for MEDLINE]
A Controlled Study of Cognitive Deﬁcits in Children With Chronic Lyme Disease
Felice A. Tager, Ph.D., Brian A. Fallon, M.D., John Keilp, Ph.D., Marian Rissenberg, Ph.D., Charles Ray Jones, M.D., Michael R. Liebowitz, M.D
Received August 7, 2000; revised January 3, 2001; accepted January 10, 2001. From the Columbia University Department of Psychiatry, Division of Behavioral Medicine, New York, New York.
Copyright 2001 American Psychiatric Publishing, Inc.
J Neuropsychiatry Clin Neurosci 13:4, Fall 2001
A snippet below but lots more info in full report..
All of the (20) children had received oral antibiotics (mean=23.21 +/- 21.99 weeks), and 11 had received intravenous antibiotics (8.79 +/- 16.10 weeks). All initially beneﬁted from antibiotic therapy, but improvement was sustained in only 10% (2 /20) after oral antibiotics and in 36% (4 /11) after IV antibiotics. At the time of testing, 7 children (35%) were being treated with oral antibiotics and 2 (10%) were being treated with IV antibiotics.
Based on physician assessment, the most common symptoms during LD were marked fatigue (100%), arthralgias (100%), frequent and severe headaches (100%), irritability /depression (94%), short-term memory problems (94%), schoolwork deterioration (94%), myalgias (88%), brain fog (88%), neck pain (88%), insomnia (82%), distractibility (82%), word-ﬁnding problems (82%), and severe ﬂu (80%). Arthritis was noted in only 38% of the sample. On the more extensive parent-rated questionnaire, children were rated as having moderate to severe sensory hyperacusis to sound (58%) and /or light (74%); insomnia (77%); word-ﬁnding problems (79%); and radicular pains (56%).
Full report available at: http://neuro.psychiatryonline.org/doi/abs/10.1176/jnp.13.4.500
Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi.
R A Kalish, J M Leong and A C Steere – Infect. Immun. July 1993 vol. 61 no. 7 2774-2779
Of 15 patients monitored for 4 to 12 years, 11 (73%) developed strong immunoglobulin G responses to both OspA and OspB near the beginning of prolonged episodes of arthritis, from 5 months to 7 years after disease onset. When single serum samples from 80 patients with Lyme arthritis, were tested, 57 (71%) showed antibody reactivity to recombinant Osp proteins; in contrast, none of 43 patients who had erythema migrans or Lyme meningitis (P < 0.00001) and 1 of 5 patients who had chronic neuroborreliosis but who never had arthritis (P = 0.03) showed antibody reactivity to these proteins.
Among the 60 antibiotic-treated patients with Lyme arthritis, those with the HLA-DR4 specificity and Osp reactivity had arthritis for a significantly longer time after treatment than those who lacked Osp reactivity (median duration, 9.5 versus 4 months; P = 0.009); a similar trend was found for the HLA-DR2 specificity. For other HLA-DR specificities, arthritis resolved within a median duration of 2 months in both Osp-reactive and nonreactive patients.
We conclude that the combination of the HLA-DR4 specificity and OspA or OspB reactivity is associated with chronic arthritis and the lack of a response to antibiotic therapy.
Added 09 May 2013
Immune Evasion & Persistence of Infection by Keith Berndtson (PDF hit back button to return to page!)
Also check out Keith Berndtson’s slide show at: http://lookingatlyme.blogspot.co.uk/2013/05/review-of-evidence-for-immune-evasion.html
See article on Persistence of Infection https://ticktalkireland.wordpress.com/2010/07/28/persistence-seronegativity/
Added 05 Jul 2012
European neuroborreliosis: quality of life 30 months after treatment
1. R. Eikeland1,
2. Å. Mygland2,3,4,
3. K. Herlofson1,
4. U. Ljøstad2
Article first published online: 9 FEB 2011
Objectives– The prognosis after Lyme neuroborreliosis (LNB) is debated. The aim of this study was to assess health-related Quality of Life (QoL) and neurological symptoms 30 months after treatment in European patients with LNB.
Materials and methods– In a prospective case–control designed study, we investigated 50 well-characterized patients with LNB who had participated in a treatment trial for LNB 30 months earlier and 50 matched control persons with the health QoL questionnaire Short-Form 36 (SF-36), the Fatigue Severity Scale (FSS), the Montgomery and Åsberg Depression Rating Scale (MADRS), the Starkstein Apathy Scale (SAS), and the Mini Mental State (MMS). Clinical and demographic data were collected by semi-structured interviews and clinical neurological examination.
Results– Lyme neuroborreliosis-treated patients scored lower than control persons in the SF-36 domains physical component summary (PCS) (44 vs 51 P < 0.001) and mental component summary (MCS) (49 vs 54 P = 0.010). They also scored lower than control persons in all the SF-36 subscales, except for bodily pain, and on FSS (3.5 vs 2.1 P < 0.001), but not on MMS (28 vs 29 P = 0.106). There was a difference in MADRS (3.1 vs 0. 8 P = 0.003) and SAS (13 vs 11 P = 0.016), but the scores were low in both groups. Fatigue was the most frequently reported symptom among LNB-treated patients (50%). Patients who reported complete recovery (56%) after LNB had similar QoL scores as the controls.
Conclusion– European persons treated for LNB have poorer health-related QoL and have more fatigue than persons without LNB.
Chronic neurologic manifestations of Lyme disease.
Logigian EL, Kaplan RF, Steere AC.
Department of Neurology, Tufts University School of Medicine, Boston, MA 02111.
BACKGROUND AND METHODS. Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is associated with a wide variety of neurologic manifestations. To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients (age range, 25 to 72 years) with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection.
RESULTS. Of the 27 patients, 24 (89 percent) had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients (70 percent) had polyneuropathy with radicular pain or distal paresthesias; all but two of these patients also had encephalopathy. In 16 patients electrophysiologic testing showed an axonal polyneuropathy. One patient had leukoencephalitis with asymmetric spastic diplegia, periventricular white-matter lesions, and intrathecal production of antibody to B. burgdorferi. Among the 27 patients, associated symptoms included fatigue (74 percent), headache (48 percent), arthritis (37 percent), and hearing loss (15 percent). At the time of examination, chronic neurologic abnormalities had been present from 3 months to 14 years, usually with little progression. Six months after a two-week course of intravenous ceftriaxone (2 g daily), 17 patients (63 percent) had improvement, 6 (22 percent) had improvement but then relapsed, and 4 (15 percent) had no change in their condition.
CONCLUSIONS. Months to years after the initial infection with B. burgdorferi, patients with Lyme disease may have chronic encephalopathy, polyneuropathy, or less commonly, leukoencephalitis. These chronic neurologic abnormalities usually improve with antibiotic therapy.
N Engl J Med. 1990 Nov 22;323(21):1438-44.
Published studies do show that chronic Lyme improves with long term antibiotic therapy.
Sunday, February 21, 2010
The eye of the beholder: a specialist
Donta, 1997, Boston University published a study of 277 patients with chronic Lyme disease.
He reported that patients frequently did not improve for several weeks. After 2 months 33% of patients had improved, after 5 months, 61% had improved. He claimed 20% of patients were cured, 10% did not improve, and 70% showed some improvement. The duration of the study was for 1 to 11 months. He concluded: CONTROLLED STUDIES NEED TO BE CONDUCTED TO VALIDATE THESE OBSERVATIONS.
In 2003, Donta published a study on the use of Biaxin, Biaxin with Plaquenil and Plaquenil alone.
The effective therapy was Biaxin and Plaquenil. Conclusion: THESE RESULTS SUPPORT THEHYPOTHESISIS THAT lYME BORRELIA RESIDE IN AN ACID ENDOSOME…. .
Cameron, 2008, published a double-blind placebo controlled clinical trial.
He replaced the term chronic Lyme disease with Lyme disease with persistent symptoms (LDPS). He found a 46% improvement of subjective quality of life in treated patients and vs 18% in non treated patients. He concluded: WORTHY OF FURTHER STUDY.
Clarrisou et al, 2009, Med Mal Infect, published: Efficacy of long-term antibiotics in patients with a chronic Tick Associated Poly-organic Syndrome (TAPOS Investigators keep inventing new terminology for the same disease. Why?
A cohort of 100 patients was followed. The study showed favorable results in subjective symptoms. The authors point out flaws and limitations of their study but recommend: RANDOMIZED, DOUBLE BLIND STUDY.
The number of patients studied in all of these studies was significantly higher than the number of patients studied in the 3 NIH sponsored studies. This has mostly to do with study design and patient selection limitations.
Hopkins-Harvard- Yale-IDSA- CDC: Where are you?
Those folks are sticking with the “Best science.”
Problem: best science supports these conclusions (fatigue, qualitly of life) if you take another look at the Krupp and Fallon outcomes. A patient suffering with Lyme and chronic fatigue recently told me: ” Hell, I would gladly go on 3 months of IV Rocephin if it only helped with fatigue.”
I asked an esteemed professor(infectiou s disease) from Hopkins about his success with severe neruo-syphilis He told me with pride that he has treated it, (it is rare these days)–the penultimate expert. I asked him about patients with severe brain damage. “When the squash is gone there is no squash.” Good answer. Even patients with persistent vegetative states have been shown to frequently have significant neurological and cognitive activity.
Patients with neuroborreliosis have recovered. SPECT scans, PET scans have improved. Patients with neuro-syphilis- dementia (general paresis) have been treated with only penicllin. These patients pathologically have blebs and cysts in their brains, similar to those seen in patients with neuroborrelosis. As stated, there are not many of these patients around anymore. There have been no studies since TUSKEGEE. How would neuro-syphilis patients do if they were treated with other therapies, including IV Flagyl? Not studied
How about this:
Why don’t we let psychologists and psychiatrists evaluate cognitive functioning, radiologists evaluate objective, radigrophic signs of improvement and neurologist evaluate for evidence of neurological improvements. How about listening to our patients as well? I know–a novel concept.
Why does a professor of of infectious disease medicine, with little or no knowledge of these other fields, tell us about squash, a “fancy” designation for brain?– what are his qualifications to tell us that chronic Lyme disease–including neuroborreliosis does not exist?
I went to medical school, internship and residency. We made round, sometimes with esteemed attendings: we were intimidated: they knew everything, we were abysmally ignorant. We were ready to be chastised; we were swine waiting for pearls to be cast to our feet. I remember, Super-star attendings– Power, honor, prestige: with it comes a sense of infallibility- -after all, you are the last word, the highest authority. You have to be self assured. Perfectly understandable. That is why I became a generalist, not a specialist. It is understandable. Nonetheless: sometimes you are wrong, dead wrong.
Posted by Lyme report: Montgomery County, MD
Author’s response to comments by Sigal and Hassett, Phillips et al., and Shapiro et al.
In 1995, Sigal1 wrote ‘We must be aware of the mythology surrounding Lyme disease in our communities and counter with facts and the results of scientific studies’. To do this, we pooled the data from all scientific studies on random selections of patients who had had a diagnosis of Lyme borreliosis (LB) a few years earlier and, for comparison, random selections of subjects without LB from the general population. The prevalence of symptoms in LB patients was over and above the underlying prevalence of symptoms from other diseases such as fibromyalgia in the general population. Our meta-analysis2 shows clearly that a small percentage of patients with LB have symptoms persisting for years. No other data have been provided that contradict this.
Inevitably, diagnoses based on subjective patient reports are prone to error, particularly of post-LB syndrome where the original diagnosis of LB may be in doubt. Steere et al.3 concluded that a large proportion (57%) of patients referred to their Lyme Disease Clinic had not had LB, but these patients would not be representative if many were selected for referral because their diagnosis was uncertain. Fatigue, musculoskeletal problems and neurocognitive difficulties are relatively common in the general population, and, as pointed out by Shapiro et al.,4 some LB patients with symptoms due to other disorders may misattribute them to post-LB syndrome. In their commentary Sigal and Hassett5 report that many of the patients referred to their centre had fibromyalgia, and not post-LB syndrome. The pain following LB seems to be mostly roving, asymmetrical pain in the limbs, which is unlike the pain required for a diagnosis of fibromyalgia.6 So, although fibromyalgia is often accompanied by fatigue and forgetfulness, it should usually be distinguishable from post-LB syndrome. Uncertainty and misdiagnosis in some patients does not mean that these two disorders are not distinct entities. There is clearly a potential for misdiagnosis of post-LB syndrome, and that is an important issue, but it was not the topic of our meta-analysis.
Sigal and Hassett report that many of the patients with post-LB syndrome referred to their centre had positive scores on depression and anxiety scales. Depression and anxiety scales often include symptoms such as fatigue, listlessness, slowed speech, difficulties in working, concentration and memory problems, muscle aches and pain, increased sweating, and weight changes, all of which may be symptoms of post-LB syndrome. And with the distress that often arises from such a chronic illness, it is not surprising if some patients have positive scores on these scales. They also state that this disorder is seen predominantly in women implying this is evidence that it has a psychological basis. Fibromyalgia and many autoimmune diseases are also seen more often in women. It cannot therefore be concluded from their observations that the persistent symptoms following LB are simply due to psychological disturbances.
Shapiro et al. state that the usual course after treatment for LB is a slow resolution of symptoms over weeks to months, and cite three studies. Actually, the results of those three studies are consistent with the results of our meta-analysis. In the first study on patients with early LB,7 20% of patients had not completely responded 12 months after treatment, and 13% had not completely responded after 30 months. In the second study on patients treated for late LB,8 the investigators rated 15% of the patients not cured 12 months after treatment. In the third study on Lyme encephalopathy,9 61% of the patients stated they had not completely recovered after 12–24 months. However, in all three studies, almost all the patients with persistent symptoms had improved.
More from this author on chronic Lyme ‘meta-analysis’ can be found at:
* This meta-analysis provides strong evidence that some patients with Lyme borreliosis have fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years.
* The higher prevalence seen in these patients of certain neurocognitive symptoms but not others, in the same pattern as reported in the literature, is further confirmation of the syndrome.
* The pattern of persistent symptoms appears to be different from that seen in fibromyalgia, depression, and chronic fatigue syndrome.
Some useful links on the persistence of Lyme
Why are we still sick?
Lyme Disease Action & persistence of Lyme:
Persistence of Lyme – peer reviewed articles:
A reason why Lyme is said to persist is the existence of cyst formations in Lyme. The spirochaete has the ability to transform into a cyst form when attacked by antibiotics. The drug of choice in targetting these resistant forms is flagyl. For more details on cyst formations / peer reviewed article please refer to:
Cystic Forms – An Introduction (17 pages):
Cystic Forms – Advanced (30 pages):
Cystic Forms – Complete Bibliography 1905 to present (250 studies, 49 pages):
Sam Donta, MD writes about the challenges of Chronic/Late Lyme Disease at:
Proof That Chronic Lyme Disease Exists
Daniel J. Cameron
Department of Medicine, Northern Westchester Hospital, Mt. Kisco, NY 10549, USA
Interdisciplinary Perspectives on Infectious Diseases
Volume 2010 (2010), Article ID 876450, 4 pages
Received 11 December 2009; Accepted 26 March 2010
Academic Editor: Guey Chuen Perng
Copyright © 2010 Daniel J. Cameron. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The evidence continues to mount that Chronic Lyme Disease (CLD) exists and must be addressed by the medical community if solutions are to be found. Four National Institutes of Health (NIH) trials validated the existence and severity of CLD. Despite the evidence, there are physicians who continue to deny the existence and severity of CLD, which can hinder efforts to find a solution. Recognizing CLD could facilitate efforts to avoid diagnostic delays of two years and durations of illness of 4.7 to 9 years described in the NIH trials. The risk to society of emerging antibiotic-resistant organisms should be weighed against the societal risks associated with failing to treat an emerging population saddled with CLD. The mixed long-term outcome in children could also be examined. Once we accept the evidence that CLD exists, the medical community should be able to find solutions. Medical professionals should be encouraged to examine whether: (1) innovative treatments for early LD might prevent CLD, (2) early diagnosis of CLD might result in better treatment outcomes, and (3) more effective treatment regimens can be developed for CLD patients who have had prolonged illness and an associated poor quality of life.
Following link contains a more detailed review:
An in vitro evaluation of antibiotic susceptibility of different morphological forms of Borrelia burgdorferi
Kaur Navroop MS, Datar Ak****a BS, Luecke David BS, Bien-Aim H. Lubraine BS, Mpoy Cedric BS, Pabbati Namrata MS, Sapi Eva Ph.D
Lyme and Tick-borne Diseases Research Group, Department of Biology and Environmental Sciences, University of New Haven, West Haven, CT 06516 USA
A tick borne, multisystemic disease, Lyme borreliosis caused by the spirochete Borrelia burgdorferi has grown into a major public health problem during last ten years. The primary treatment for chronic Lyme disease is administration of various antibiotics. However, relapse of the disease often occurs when antibiotic treatment is discontinued. It is suggested that this resistance and reoccurrence of Lyme disease might be due to formation of different morphological forms of Borrelia burgdorferi. The two major known resistant morphologies are cyst and biofilm, which forms in response to stress conditions such as exposure to antibiotics.
To be able to provide novel and effective therapeutic approaches for physicians to explore the treatment options for chronically ill Lyme disease patients, we need to better understand the direct effect of antibiotics on the different morphological forms of Borrelia burgdorferi. In this study, we tested an in vitro susceptibility of several morphological forms of Borrelia burgdorferi to different antibacterial agents such as tetracyclines, hydroxycholoroquine and 5- nitroimidazoles. Cell viability assays have been performed before and after the administration of the different drugs to cultures of Borrelia burgdorferi and different microscopic techniques such as dark field and fluorescent have been used to monitor those morphological forms of Borrelia burgdorferi.
Our study suggested that exposure of Borrelia burgdorferi cultures to concentrations greater than minimum bactericidal concentration (MBC) of doxycycline (>25µg/ml) and hydroxychloroquine (Plaquenil) (>50µg/ml) significantly reduced the spirochete population but unfortunately also increased the number of cystic forms. However, similar treatment of 5- nitroimidazoles such as metronidazole (greater than MBC as >35µg/ml) and tinidazole (greater than MBC as >32µg/ml) led to reduction of cystic forms in the culture. Furthermore, when combinations of most effective concentrations of 5- nitroimidazoles and tetracycline were tested in vitro, both cystic and spirochete forms of Borrelia burgdorferi were significantly eliminated Our study suggests that Borrelia burgdorferi specific combination therapy for Lyme disease patients might provide treatment option with a better outcome.
Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome & Fibromyalgia
May 15, 2002
By Sam Donta,M.D.
NEWS: Major series on chronic Lyme from Maine TV station
07 July, 2010
Anchor/reporter Sharon Rose, of WCSH TV station in Portland, Maine, has produced a four-part series on chronic Lyme disease. In addition to her televised reports, the TV station’s website has a lot of information about Lyme disease, as well as an invitation for Lyme patients to tell their own stories in the comments section. (This listing’s links will be updated as more information is added to WCSH’s website.)
On the morning of July 6, reporter Sharon Rose blogged about her upcoming series on chronic Lyme, calling it the most challenging assignment in her 20-year career.
‘there is no convincing biologic evidence to support a diagnosis of chronic Lyme disease after completion of the recommended treatment’
Are the IDSA correct in saying chronic Lyme doesn’t exist? Click here to find out!
UPDATE OF AN APPROACH TO THE TREATMENT OF CHRONIC LYME DISEASE
(A detailed review on treating chronic Lyme)
Burton Waisbren MD GFACP and a founding member and fellow of the IDSA
“It is my hope that the experiences mentioned here may result in some patients receiving more aggressive treatment for chronic Lyme disease and will perhaps raise the understanding of some in the “establishment” regarding how some physicians try to operate by thinking “outside the box” in their attempts to help problem patients.”
About Dr. Waisbren
Burton A. Waisbren, Sr., M.D. is a native Milwaukean who received his B.S. and M.D. degrees from the University of Wisconsin Medical School in Madison, Wisconsin. He served his internship at the Harvard Service at Boston City Hospital. His military service was at the Navy Medical Research Institute, Bethesda, Maryland and the Biological Warfare Center, Camp Dietrick, Maryland. His residency and fellowship was served at the University of Minnesota Hospitals where he was an instructor in the medical school. He received a master’s degree in bacterial genetics from the University of Minnesota in 1951. He moved to Milwaukee, his hometown, in 1951 and established a private practice in internal medicine, infectious disease and immunology. At that time, he also headed the infectious disease control unit at the Milwaukee County Hospital. From 1951 to 1969, he was the director of the infectious disease division of first the Marquette Medical School and then the Medical College of Wisconsin. During that time, he was appointed associate clinical professor of medicine. He was the medical director of the St. Mary’s Hospital Burn Center from 1962 to 1982. He has directed a cancer immunotherapy clinic in Milwaukee since 1973. He has published numerous articles in the peer reviewed medical literature and has authored books on systematic methods of critical care and on medical emergencies.
Dr. Waisbren is board certified by the American Board of Internal Medicine and also is a fellow of the American College of Physicians and the Infectious Disease Society of America. He is a founding member of the Infectious Disease Society of America, the American Burn Association, and the Critical Care Society of America.
The Case For Chronic Infection
Contains 83 pages of evidence of persistence of infection
Evidential persistence of Borrelia species post antibiotic exposure in vivo and in vitro.
Michael D. Parent & Erica Falkingham
(Relevant studies and cross references within the link below)
There is an abundance of evidence demonstrating that Borrelia Burgdorferi, the causative agent of Lyme Disease, and related pathogenic species, can persist within specific body tissues and cells of various mammals despite adequate antibiotic therapy: ponies,[93.5, 111.5]non-human primates, [50, 86]dogs,[65.5, 70, 80, 81, 82, 84] mice, [44, 62, 88, 100, 107, 108, 110, 114] and humans. [all others] There is also abundant evidence that Borrelia Burgdorferi has evolved in a manner similar to other bacteria that evade the immune system via pleomorphic modification, in other words, the bacteria can change its shape beyond the conventional spirochetal form. [45, 55, 61, 64, 90, 105, 109, 113] L-forms, and cystic Borrelia have been identified in a number of studies. [45, 68, 77, 87, 105, 109, 112, 113] When these “forms” are exposed to the typical antibiotics — such as Penicillin family antibiotics or Doxycycline, they are unaffected. When the antibiotic is removed from the environment, the bacterium will alter its form once more morphing back into a spiral form, allowing ongoing mobility. [45, 68, 87, 90, 105, 109]
I have taken the time to “bold” the conclusions and various other aspects that clearly indicate a deviation from the point of view given by a number of physicians and researchers who deny the possibility of ongoing chronic infection within the human host. The current guidelines issued by the Infectious Disease Society Of America are consistently used to dismiss further discussion regarding the subject of persistence.
“The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis” Clinical Infectious Diseases 2006; 43:1089–134″
Patients who receive a diagnosis of Lyme Disease, either based on clinical observation, and or objective indicators often improve with antibiotic therapy, [1, 4, 18, 19, 26, 33, 66] however if they have been undiagnosed and untreated for a long period of time, it often takes longer to see progress in symptom reduction [15, 66, 73, 93, 105] that “double blind placebo controlled” trials have not allowed for. Most of the NIH studies were under 3 months.
Patients with documented medical records indicating Chronic Lyme Disease or a Lyme-Like Illness who have been untreated often do not see improvement until 4-6 months of treatment, and even still, the improvements are modest initially in many patients and may require an ongoing open ended treatment regimen with antibiotics. [66, 93]
It is well understood and agreed upon universally that the more time Borrelia Burdorferi has had to disseminate into various ligaments, bones, collagen, muscles, and other tissues, the higher the probability of ongoing complications or symptoms post-antibiotic therapy. Presently studies indicate that antibiotics can not access many of the areas that Borrelia Burgdorferi disseminates to unless the bacterium itself leaves the safe haven of a Fibroblast skin cell [11, 22, 23, 24, 25, 29, 35, 52, 64, 70, 72, 80, 81, 84, 94], or synovial tissue cells and fluid. [1, 7, 9, 31, 34, 37, 42, 60, 61, 69, 70, 71, 102]
Therefore, we have studies demonstrating abundant persistence. We have National Institute Of Health funded studies that do not treat patients long enough to confirm whether the treatment really is effective or not. The short term studies we do have contradict other studies as well as those based on clinical reports from health care providers treating these patients with antibiotics beyond the currently accepted time frame. It is unwise to claim that long term antibiotic therapy doesn’t work when you’ve only performed a study for 3 months, when the vast majority of the patients in the study have had the infection for many years and require at least 3-6 months of oral antibiotic before clinical improvements are seen. IV antibiotics may demonstrate minor to moderate symptomatic improvement after 1- 3 months, but if that treatment is only given for 3 months and then discontinued, then it will be equally ineffective and the symptoms will return to pre-treatment levels. Coincidentally, that’s exactly what happened in Dr. Brian Fallon’s study. Some symptoms improved, but then returned upon discontinuing therapy.
I have discussed merely one specific possibility for the failure of patients to thrive and improve during the currently available randomized double-blind placebo-controlled clinical trials (RCT). Dr. Daniel J. Cameron writes in the Journal Of Medical Hypothesis that a number of limitations exist within the currently structured (RCTs), that strongly support the position I’ve laid forth. Med Hypotheses. 2009 Jun;72(6):688-91. Epub 2009 Mar 5. Insufficient evidence to deny antibiotic treatment to chronic Lyme disease patients. First Medical Associates, Medicine, 175 Main Street, Mount Kisco, NY 10549, USA. Cameron@LymeProject.com
“Evidence for the hypothesis: There are eight limitations that support the hypothesis: (1) the power of the evidence is inadequate to draw definite conclusions, (2) the evidence is too heterogeneous to make strong recommendations, (3) the risk to an individual of facing a long-term debilitating illness has not been considered, (4) the risk to society of a growing chronically ill population has not been considered, (5) treatment delay has not been considered as a confounder, (6) co-infections have not been considered as a confounder, (7) the design of RCTs did not address the range of treatment options in an actual practice, and (8) the findings cannot be generalized to actual practice. Implications of the hypothesis: This hypothesis suggests that physicians should consider the limitations of the evidence before denying antibiotic treatment for Chronic Lyme Disease (CLD). Physicians who deny antibiotic treatment to CLD patients might inform their patients that there are some clinicians who disagree with that position, and then offer to refer them for a second opinion to a doctor who could potentially present a different point of view. The hypothesis also suggests that health care insurers should consider the limitations of the evidence before adopting policies that routinely deny antibiotic treatment for CLD patients and should expand coverage of CLD to include clinical discretion for specific clinical situations.”
There is more than enough information to justify at least a neutral position in respect to whether Borrelia Burgdorferi and related infectious species persist in human beings despite the Infectious Disease Society Of America’s recommendations. Due to this uncertainty, treating physicians can not conclusively deny that persistence in human beings may be more problematic than assumed.
The scientific studies available on Lyme Disease contradict each other to a significant degree. Many study authors state in no uncertain terms that the discussion of Lyme Disease is a closed case. I disagree. The evidence disagrees. The Chief Medical Officer in the United Kingdom echoed the sentiments of the IDSA in 2009 stating: “There is no biological evidence of symptomatic chronic Lyme disease amongst those who have received the recommended treatment regimen.” – CMO, Autum 2009, Issue 49, pg. 4. The IDSA states: “To date, there is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease.” – Clin Infect Dis 2006 Nov 1;43(9):1089-134
“Skepticism is the heart of science. Cynicism is the death of reason.”
Long Term Inflammation in Lyme Borreliosis
Many, many articles on the persistence of infection leading to chronic Lyme disease:
Late Stage Lyme Disease, Patient Information
‘Can’t lie to ya. Rough road ahead. In fact, getting well may be about the
hardest and most difficult thing you’ll ever do. But it’s worth it! Stick with
it! Never give up hope!
The first thing you should know is that it gets worse before it gets better.
It can in fact get a lot worse before it gets better. It depends on how long
you’ve had it, how much of the bacteria has built up, what strain you have, and
many other factors as well.’
For a very comprehensive list of tips, how different antibiotics work & why it takes so long to get better follow the link below – HIGHLY recommended reading!
Why is chronic Lyme borreliosis chronic?
Clin Infect Dis. 1997 Jul;25 Suppl 1:S64-70.
Aberer E, Koszik F, Silberer M.
Department of Dermatology, University of Graz Medical School, Austria.
Chronic Lyme borreliosis (CLB) can present not only in different organs but also in different patterns. Although many theories exist about the mechanisms leading to CLB, it is known that viable Borrelia burgdorferi can persist for decades and cause late skin manifestations of acrodermatitis chronica atrophicans (ACA). Thus, the immunopathogenetic findings in ACA can serve as a model for studying the chronic course of Lyme borreliosis. Recent findings indicate that the most important cell for antigen presentation, the epidermal Langerhans cell (LC), is invaded by B. burgdorferi in early Lyme borreliosis. Therefore, LCs were stained immunohistochemically with different markers to investigate their functional activity. Numbers of CD1a+ LCs were reduced in erythema migrans but normal or slightly elevated in ACA. In both diseases there was also a marked downregulation of major histocompatibility complex class II molecules on LCs, as measured by staining of human leukocyte antigen DR. This phenomenon might be a mechanism that protects against the presentation of autoantigens and may be the cause of the impaired capacity of LCs to eliminate B. burgdorferi antigens, thus explaining why CLB is chronic.
PMID: 9233667 [PubMed – indexed for MEDLINE]
Lyme borreliosis: from infection to autoimmunity
1. S. K. Singh,
2. H. J. Girschick
Article first published online: 4 JUN 2004 (Clinical Microbiology and Infection)
It has been suggested that chronic persistence of B. burgdorferi in affected tissues is of pathogenic relevance. Long-term exposure of the host immune system to spirochaetes and/or borrelial compounds may induce chronic autoimmune disease. The study of bacterium–host interactions has revealed a variety of proinflammatory and also immunomodulatory–immunosuppressive features caused by the pathogen. Therapeutic strategies using antibiotics are generally successful, but chronic disease may require immunosuppressive treatment.
For full article go to:
Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis.
J Neuroinflammation. 2008 Sep 25;5:40.
Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL.
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada. email@example.com
BACKGROUND: The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis.
METHOD: Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes.
RESULTS: Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex.
CONCLUSION: The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form.
PMID: 18817547 [PubMed – indexed for MEDLINE]
Some great pictures of cyst forms can be found at the following site:
The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis –
The experience from one year of a university hospital’s Lyme neuroborreliosis outpatients clinic – Source: European Journal of Neurology, Oct 27, 2010
by M Djukic, et al.
Background and purpose: Studies addressing the diagnostic relevance of anti-Borrelia burgdorferi (BB) serum antibodies in patients with non-specific symptoms and suspected chronic Lyme neuroborreliosis (LNB) are scarce. [Note: LNB involves chronic symptoms involving the central nervous system/brain, such as mental problems, headache, sleep disturbance, effects of increased intracranial pressure, meningitis, or, rarely, effects on the eyes or spinal cord.]
Methods: In this study, we enrolled within 1 year 122 patients with suspected chronic LNB.
• 114 patients had previously tested positive for BB.
• All patients had previously received antibiotic treatment.
Each patient received a clinical examination and measurement of BB-specific antibodies. The diagnosis of neuroborreliosis was made according to the national guidelines of the German Society of Neurology.
• Nine patients had acute borreliosis. One of the nine met the criteria of acute LNB.
• Of the remaining 113 patients, 85 patients underwent a lumbar puncture.
• Ten seronegative subjects without lumbar puncture were also considered.
In 61.8% of these 95 patients the quality of life, of sleep, mood, and anxiety were assessed.
Results: Of 95 patients:
• 25.3% had symptoms without a somatic cause or evidence of borreliosis,
• 38.9% had a well-defined illness unrelated to BB infection,
• And 29.5% suffered from symptoms without a detectable somatic cause, displaying antibodies against BB.
• Six patients were grouped as post-LNB syndrome.
Most common symptoms in all categories were arthralgia [joint pain], myalgia [muscle pain], dysaesthesia [nerve pain, e.g., burning sensation], depressive mood and chronic fatigue.
Conclusion: Patients with persistent symptoms with elevated serum antibodies against BB but without signs of cerebrospinal fluid inflammation require further diagnostic examinations to exclude ongoing infection and to avoid co-infections and other treatable conditions (e.g., autoimmune diseases).
One patient with acute LNB, who was treated with ceftriaxone for 3 weeks suffered from LNB with new headaches and persistent symptoms 6 months later.
These data should encourage further studies with new experimental parameters.
Source: European Journal of Neurology, Oct 27, 2010. DOI: 10.1111/j.1468-1331.2010.03229.x, by Djukic M, Schmidt-Samoa C, Nau R, Von Steinbüchel N, Eiffert H, Schmidt H. Department of Neurology, University of Goettingen Department of Geriatrics; Evangelisches Krankenhaus Weende Medical Psychology and Medical Sociology, University of Goettingen Department of Neuropathology; University of Goettingen Medical Microbiology, Goettingen, Germany.
Persister cells, dormancy and infectious disease
Abstract | Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.
“Persistent infections. Several infections, such as syphilis, lyme disease and tuberculosis (TB), persist for years in the body in an apparently benign form. In most chronic (persistent) infections it seems that the pathogen is at least partially shielded from the immune system — Treponema pallidum (syphilis) and Borrelia burgdorferi (Lyme disease) migrate into the CNS, whereas M. tuberculosis (TB) is hidden in macrophages or granulomas61. Are dormant persister cells responsible for the latent, asymptomatic stages of disease?”
Concluding remarks: (page 7 & 8)
The entrance of cells into a dormant, persistent state is largely responsible for the multidrug tolerance of infections. The presence of dormant persisters in biofilms accounts for their tolerance to all known antimicrobials. Persisters are likely to be responsible for latent (chronic) diseases, such as TB, which can be suppressed, but not eradicated, with existing antimicrobials. The need to develop novel therapeutics capable of killing persister cells and eradicating infections is acute. Finding genes responsible for persister formation and maintenance should lead to drugs that disable persisters and might allow conventional antibiotics to eradicate an infection.
Nerve paralysis in Lyme disease.
R. Savas × A.Sommer × F.Gueckel × M.Georgi
Department of Diagnostic Radiology, Sta¨ dtisches Klinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, D-68167 Mannheim/Germany
Extract below – full report can be found at:
A 12-year-old girl was referred for cranial MRI because of chronic,
recurrent borreliosis. Since the age of 7 she had suffered from recurrent
oculomotor nerve paralysis. She presented with right ptosis,
double vision and headache when she was 5 years old. Examination
revealed an incomplete oculomotor nerve paralysis and meningism.
She had a history of tick bites. The history led to the suspicion of
borreliosis, confirmed by the laboratory findings of an elevated serum
and spinal fluid IgG level and a pleocytosis in the spinal fluid.
The patient was treated with antibiotics, and the symptomsresolved.
Two years after the first admission, she again suffered acute attacks
of headache, fever, and oculomotor nerve palsy; laboratory testing
showed positive borrelia serology in serum and cerebrospinal fluid.
The diagnosis was second-stage Lyme disease, with mononeuritis.
However, treatment did not relieve the oculomotor palsy.
From that time until admission to our hospital there was no
further treatment or follow-up examination. She was admitted
again with headache that had slowly increased in severity over
some days and a persistent oculomotor nerve palsy. Routine blood
examination, CT and EEG were normal. MRI revealed a 4-mm,
rounded mass of low intensity in the right side of the interpeduncular
fossa (Fig. 1). Contrast-enhanced images showed a well-defined
lesion with sharp margins directly at the base of the oculomotor
nerve (Fig. 2). On T2-weighted images, this segment of the
nerve gave higher signal than its fellow. The other cranial nerves
and brain parenchyma were normal. The patient underwent conventional
panangiography, which was completely normal.
The lesion was therefore considered a manifestation of chronic,
recurrent borreliosis with oculomotor neuritis.
US Army warns of LD & chronic LD in North Africa
http://www.afpmb.org/pubs/dveps/nort_afr.pdf NB: link now broken but have kept for reference purposes…
D. Lyme Disease. (page 103)
Lyme disease is also called Lyme borreliosis, tick-borne meningopolyneuritis, erythema
chronicum migrans, Lyme arthritis, and Barnwart’s syndrome. The causative agent is the spirochete bacterium Borrelia burgdorferi. Like syphilis, the clinical disease manifests itself in acute and chronic stages. Initially there is a highly characteristic expanding skin lesion (erythema migrans) that develops in about 60% of cases. Flu-like symptoms usually occur about the same time. Weeks to months after initial infection, cardiac,neurological or arthritic symptoms and other joint abnormalities may occur and persist for years. Treatment in the late stages of the disease can be difficult.
*Chronic Lyme disease can be very debilitating. Early recognition and treatment are critical.
TIME FOR LYME RESEARCHER KAREN NEWELL EXPLORES CHRONIC INFLAMMATION
Research published in the October 2010 issue of the Journal of Leukocyte Biology
“We are excited to learn about a mechanism that has the potential to offer new therapeutic interventions to chronic inflammatory diseases,” Newell stated. “This “auto-immune” reaction of sorts may be partly responsible for symptoms of chronic Lyme disease,” adds Dr. Kotsoris, Medical Director at TFL.
Chronic Lyme Disease and CCSVI
By Jenna Smith
Part of text as follows:
Chronic Cerebrospinal Venous Insufficiency (CCSVI) is a chronic condition in which blood from the brain has difficulty returning to the heart. It is caused by a narrowing in neck veins (and potentially others as well) that drain the central nervous system.
In some cases, there is a development of alternate veins in an attempt to facilitate additional drainage. The research suggests that because these compensatory blood vessels do not have the same wall integrity as larger veins, they leak cellular waste into the adjacent tissue, resulting in an accumulation of toxins.
The discovery, and more importantly the surgical repair for CCSVI, has miraculous application to MS, but also to other diseases that has a vascular aspect that is a significant factor in the neurological component of the disease, such as neurological Lyme disease.
Arthritis Rheum. 1993 Nov;36(11):1621-6.
Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis.
Häupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schönherr U, Kalden JR, Burmester GR.
Department of Medicine III, University of Erlangen-Nuremberg, Germany.
OBJECTIVE: To document the persistence of Borrelia burgdorferi in ligamentous tissue samples obtained from a woman with chronic Lyme borreliosis.
METHODS: Spirochetes were isolated from samples of ligamentous tissue, and the spirochetes were characterized antigenetically and by molecular biology techniques. The ligamentous tissue was examined by electron microscopy. Humoral and cellular immune responses were analyzed.
RESULTS: Choroiditis was the first recognized manifestation of Lyme disease in this patient. Despite antibiotic therapy, there was progression to a chronic stage, with multisystem manifestations. The initially significant immune system activation was followed by a loss of the specific humoral immune response and a decrease in the cellular immune response to B burgdorferi over the course of the disease. “Trigger finger” developed, and a portion of the flexor retinaculum obtained at surgery was cultured. Viable spirochetes were identified. Ultramorphologically, the spirochetes were situated between collagen fibers and along fibroblasts, some of which were deeply invaginated by these organisms. The cultured bacteria were identified as B burgdorferi by reactions with specific immune sera and monoclonal antibodies, and by polymerase chain reaction amplification and Southern blot hybridization techniques.
CONCLUSION: To our knowledge, this is the first report of the isolation of B burgdorferi from ligamentous tissue. This suggests that tendon tissues serve as a specific site of spirochete residence in human hosts.
PMID: 8240439 [PubMed – indexed for MEDLINE]
80 page slideshow on chronic & seronegative Lyme – showing evidence that the IDSA choose to ignore..
Page 71: Is Dr Steere’s testing better? Mother gave birth to still born child. Child was positive via CDC & New York State Dept of Health but negative via Steer’s lab in Yale. Fetal autopsy showed borrelia (Lyme bacteria) in placenta, liver, adrenals, brain & heart.
NB The above link is now broken – have kept here whilst we look for an alternative..
Experimental chronic Lyme borreliosis in Lewis rats.
Am J Trop Med Hyg. 1990 Feb;42(2):165-74.
Moody KD, Barthold SW, Terwilliger GA, Beck DS, Hansen GM, Jacoby RO.
Yale University School of Medicine, New Haven, Connecticut.
The course of Lyme borreliosis in LEW/N rats inoculated intraperitoneally as infants with 10(6) Borrelia burgdorferi was followed for 360 days. Spirochetes were detected in the blood through 30 days, in the brain through 60 days, and persisted in the spleen, liver, kidneys and articular tissue through 360 days. Acute exudative arthritis, tendonitis, and bursitis were evident in multiple joints by day 30. Arthritis regressed thereafter but capsular fibrosis and lymphoplasmacytic infiltrates persisted throughout the study. Several rats developed exacerbations of acute arthritis within days 180-360, a pattern similar to that encountered in human Lyme disease. Rats had a high prevalence of nonsuppurative myocarditis and vasculitis during days 90-360. Spirochetes were visualized by microscopy in joints and other tissues during the first month of infection, but were seen only sporadically thereafter. All rats seroconverted to B. burgdorferi by day 30. IgM titers persisted and IgG titers rose progressively through day 360. Immunoblots revealed IgM reactivity to a single 41 kDa protein until 360 days, when reactivity to a 60 kDa protein emerged. IgG reactivity occurred against progressively more proteins with time, indicating continued antigenic stimulation. Chronic and recurrent arthritic lesions and myocardial involvement suggest that the rat is a reliable model for further investigation.
PMID: 2138431 [PubMed – indexed for MEDLINE]
Lyme disease: the next decade
Published Date January 2011 , Volume 2011:4 Pages 1 – 9 DOI 10.2147/IDR.S15653
Raphael B Stricker, Lorraine Johnson
International Lyme and Associated Diseases Society, Bethesda, MD, USA
Abstract: Although Lyme disease remains a controversial illness, recent events have created an unprecedented opportunity to make progress against this serious tick-borne infection. Evidence presented during the legally mandated review of the restrictive Lyme guidelines of the Infectious Diseases Society of America (IDSA) has confirmed the potential for persistent infection with the Lyme spirochete, Borrelia burgdorferi, as well as the complicating role of tick-borne coinfections such as Babesia, Anaplasma, Ehrlichia, and Bartonella species associated with failure of short-course antibiotic therapy. Furthermore, renewed interest in the role of cell wall-deficient (CWD) forms in chronic bacterial infection and progress in understanding the molecular mechanisms of biofilms has focused attention on these processes in chronic Lyme disease. Recognition of the importance of CWD forms and biofilms in persistent B. burgdorferi infection should stimulate pharmaceutical research into new antimicrobial agents that target these mechanisms of chronic infection with the Lyme spirochete. Concurrent clinical implementation of proteomic screening offers a chance to correct significant deficiencies in Lyme testing. Advances in these areas have the potential to revolutionize the diagnosis and treatment of Lyme disease in the coming decade.
Full article in PDF format available in above link!
Discusses seronegative Lyme, prophylaxis & persistence of infection..
• This interview highlights key points in Dr. Nicolson’s presentation to the ILADS group – “Reversing Mitochondrial Damage and Increasing Cellular Energy in Chronic Lyme and Lyme-Associated Infections.”
Chronic Lyme Disease and Co-infections: Clinical Overview
Rebecca Snow, MS, RH (AHG), CNS, LDN
This paper summarizes the major clinical issues surrounding chronic Lyme disease and the underlying pathophysiology of the disease. This information will serve as a foundation for the herbal practitioner’s clinical approach to chronic Lyme disease.
Biofilms & Clinical Implications for Chronic Borreliosis by Alan MacDonald MD, Uni New Haven
LONGTERM DECREASE IN THE CD57 LYMPHOCYTE SUBSET IN A PATIENT WITH CHRONIC LYME DISEASE
Stricker RB, Burrascano JJ, Winger EE: Longterm decrease in the CD57 lymphocyte
subset in a patient with chronic Lyme Disease. Ann Agric Environ Med 2002, 9, 111–
Abstract: Lyme disease is a tickborne illness caused by the spirochete Borrelia
burgdorferi. In a previous report we described a decrease in the CD57 lymphocyte
subset in patients with chronic Lyme disease. We have now identified a patient with
chronic relapsing and remitting symptoms of Lyme disease who had decreased levels of CD57 lymphocytes over 10 years. This observation represents the longest duration of an immunologic abnormality ever documented in chronic Lyme disease.
The CD57 lymphocyte subset appears to be a useful marker of longterm infection with the Lyme disease spirochete.
Mechanisms of persistence
While ”B. burgdorferi” is susceptible to a number of antibiotics in vitro, there are contradictory reports as to the efficacy of antibiotics in vivo. ”B. burgdorferi” may persist in humans and animals for months or years despite a robust immune response and standard antibiotic treatment, particularly when treatment is delayed and dissemination widespread. Numerous studies have demonstrated persistence of infection despite antibiotic therapy.
Various survival strategies of ”B. burgdorferi” have been posited to explain this phenomenon, including the following:
★ Physical sequestration of ”B. burgdorferi” in sites that are inaccessible to the immune system and antibiotics, such as the brain and central nervous system. New evidence suggests that ”B. burgdorferi” may use the host’s fibrinolytic system to penetrate the blood-brain barrier.
★ Intracellular invasion.
”B. burgdorferi” has been shown to invade a variety of cells, including endothelium, fibroblasts, lymphocytes, macrophages, keratinocytes, synovium, and most recently neuronal and glial cells.  By ‘hiding’ inside these cells, ”B. burgdorferi” is able to evade the immune system and is protected to varying degrees against antibiotics, allowing the infection to persist in a chronic state.
★ Altered morphological forms, i.e. spheroplasts (cysts, granules).
The existence of ”B. burgdorferi” spheroplasts, which lack a cell wall, has been documented in vitro, in vivo,5459 and in an ex vivo model. The fact that energy is required for the spiral bacterium to convert to the cystic form58 suggests that these altered forms have a survival function, and are not merely end stage degeneration products. The spheroplasts are indeed virulent and infectious, able to survive under adverse environmental conditions, and have been shown to revert back to the spiral form in vitro, once conditions are more favorable.
A number of other factors make ”B. burgdorferi” spheroplasts a key factor in the relapsing, chronic nature of Lyme disease. Compared to the spiral form, spheroplasts have dramatically reduced surface area for immune surveillance. They also express different surface proteins – another reason for seronegative disease (i.e. false-negative antibody tests), as current tests only look for antibodies to surface proteins of the ”spiral” form. In addition, ”B. burgdorferi” spheroplasts are generally not susceptible to the antibiotics traditionally used for Lyme disease. They have instead shown sensitivity in vitro to antiparasitic drugs such as metronidazole,  tinidazole,  and hydroxychloroquine,  to which the spiral form of ”B. burgdorferi” is not sensitive.
★ Antigenic variation and gene expression.
Like the Borrelia that cause relapsing fever, ”B. burgdorferi” has the ability to vary its surface proteins in response to immune attack.45 This ability is related to the genomic complexity of ”B. burgdorferi”, and is another way ”B. burgdorferi” evades the immune system to establish a chronic infection.
★ Immune system suppression.
Complement inhibition, induction of anti-inflammatory cytokines such as IL-10, and the formation of immune complexes have all been documented in ”B. burgdorferi” infection.45 Furthermore, the existence of immune complexes provides another explanation for seronegative disease (i.e. false-negative antibody tests of blood and cerebrospinal fluid), as studies have shown that substantial numbers of seronegative Lyme patients have antibodies bound up in these complexes.
DIAGNOSIS AND THERAPY OF CHRONIC SYSTEMIC CO-INFECTIONS IN LYME DISEASE AND OTHER TICK-BORNE INFECTIOUS DISEASES
Prof. Garth L. Nicolson
The Institute for Molecular Medicine (Website http://www.immed.org)
16371 Gothard Street H, Huntington Beach, CA 92647
About Lyme: This disseminated disease can become persistent or chronic and involve the central and peripheral nervous systems as well as ophthlamic, cardiac, musculoskeletal and internal organ invasion. At this late persistent phase chronic arthritis, neurologic impairment with memory and cognitive loss, cardiac problems (mycocarditis, endocarditis causing palpitations, pain, bradycardia, etc.) and severe fatigue are often apparent [2-4]. Unfortunately, the signs and symptoms in the late persistent phase of the disease usually overlap with other chronic conditions, such as Chronic Fatigue Syndrome, Fibromyalgia Syndrome, Rheumatoid Arthritis, among others , causing confusion in the diagnosis and treatment of the late persistent phase in Lyme Disease patients.
Human Side of Lyme
By Virginia T. Sherr 7-31-05
Lyme borreliosis is a brain disease as well as a multisystemic disease caused by spirochetal bacteria.* Quite frankly, it is an infection that has been burdened with a thousand inaccurate medical diagnoses. The manner in which the current pandemic of tertiary Lyme disease, neuroborreliosis, has usually been handled— either angrily dismissed or strangely misdiagnosed–throughout the 30 years following its “discovery,” has blemished the historic excellence of modern American Medicine.
After all the years, neuroborreliosis is still actually considered rare by a majority of physicians, most of whom are spirochetally naïve. Officially tallied patients (the numbers showing a dip down to 19,804 cases in 2004 after flawed reporting styles were instituted), when combined with uncounted cases may approach upward of an annual quarter million new borreliosis infections in the USA alone. And Lyme infections have been verified as present on all but one continent, globally. The disease is more often than not accompanied by several of a half-dozen or so of the other serious tick-borne co-infections that currently have been identified.
Losses of acuity in the human brain’s visual cortex have been observed as early as 6 hours following the toxic bite of an infected tick. Lyme may persist after too brief a period of treatment or if there has been no treatment, and may result in chronic infections whereupon Lyme borreliosis becomes a potential cause of every symptom in medical and psychiatric lexicons. It is the “Great Imitator” of this Millennium, spirochetal paresis (neuro-syphilis) having been its precursor and its model.
Chronic or persistent Lyme disease–neuroborreliosis–seldom is identified by the symptoms of its most frequent form—subacute encephalitis–an infected/inflamed brain as well as an infected nervous system. However, this is the form in which it most commonly exists. Unfortunately, the syndrome that is falsely considered typical–a bull’s eye rash, fever, positive Elisa test, and/or a swollen large joint–occurs in fewer then half of proven cases. Instead, Lyme borreliosis confirms itself in subtle to profound neuro-psychiatric symptoms, such as overriding confusion, loss of organizational skills, decreased concentration, memory loss, mood disorders, irritability, and unprovoked rages–to mention just a few. These symptoms can be very obvious to an experienced professional practicing in a Lyme-endemic area. However, cerebral-behavioral symptoms of neuro-Lyme remain invisible to those whose diagnoses are solely based on old-fashioned concepts limited only to the aforesaid doctor-viewed rashes, swollen knees with positive Elisa blood tests.
Blood tests completed by local labs most frequently show false negatives due to general laboratories’ inadequate understanding of proper diagnostic technique and choices of poor quality spirochetal samples on which to base tests. Of course, insurance companies prefer their negative tests. As mentioned, Lyme can rapidly go from Stage One (Early borreliosis) to Late (Tertiary) Stage disease following attachment of an infected deer tick’s or other vector’s bite so that quick and competent treatment are of the greatest importance. Later, accurate findings by sophisticated laboratories may be helpful, especially if Late Stage symptoms appear many years after the infection.
Over the years, I have been asked to create a compendium of my published and unpublished works on the subject of Borrelia’s neuropsychiatric epidemic. These literary contributions advocate for correction of medical neglect–the usually inadequate, sometimes cruel, diagnostic and treatment neglect experienced by victims of chronic Lyme borreliosis and its co-infections. I also have had articles published in an effort to attract attention from Organized Medicine—attention badly needed on behalf of a nearly invisible but serious epidemic that is more significant by far than anything this country has experienced since the Spanish Flu of 1918, the causative spirochete being less immediately deadly than was the virus of that epidemic, but deadly, nonetheless, cerebrally.
Sadly, Organized Medicine has mostly ignored or deserted the field of neuro-Lyme’s immense proportions. The American public rapidly is becoming jaundiced toward doctors’ lack of up-dated knowledge of spirochetal science and, having read the latest (indeed copious) peer-reviewed recent literature for themselves, are turning to other disciplines—even to veterinarians for accurate medical advice on the subject of Lyme disease and its co-infections. Veterinarians are more up to date on the diagnosis and treatment of human Lyme than the “Diagnose-and-treat-by-the-old-Guidelines” types of powerful but passé Academic physicians who cling to outdated medical dogma.
I have written about the rampant epidemiology of neuro-Lyme disease and its potent co-infections (especially the red cell parasite that causes babesiosis) and the fact that these are being systematically ignored, minimized, or distorted by this Nation’s overseeing Healthcare Agencies. Astoundingly, there are Agencies that, in ignorance or arrogance, may actively persecute the victims of such borrelial, pan-systematic illness, traumatizing parents and children as well as their treating physicians. There are those in authority who sponsor the official separation of children from parents whose only sin is that they persist in seeking help for their ailing children. Tragically, those authorities are empowered to permanently remove sick or partially healed young ones from their devoted families.
To their everlasting shame, medical authorities have stood by while innocent mothers have been sent to jail for insisting that their children were ill and again have stood by while the parent’s belief was verified by the death of their sick child while under State “care.” The rights of patients and their treating physicians have been trampled by governmental and insurance agencies in ways reminiscent of the era when AIDs was trivialized and its victims spurned as “psychosomatic.” Today’s infected millions worldwide show how wrong they were. The phenomenon of that epidemic is being repeated with the spread of Lyme borreliosis. My writing is an effort to illuminate this dark and now vast expanse of Medicine and to inspire activism and compassion for those patients who are suffering in agony while having to hear caretakers say, “I don’t know what you are worried about–you look just fine–maybe you are just depressed.” Or as one unknowing, dismissive and flippant doctor joked to a frightened patient who came to him for treatment and reassurance, “Well, we all have to die of something, sometime.”
*Alan G. Barbour, MD: “These tick-borne infections are notable for multiphasic antigenic variation through DNA recombinations in the case of relapsing fever, the occurrence of chronic arthritis in the case of Lyme disease, and invasion of and persistence in the brain in the case of both diseases.”
(link no longer working but left for reference!)
The Emperor’s New Clothes, Chronic Lyme Disease, and the Infectious Disease Society of America
Burton A Waisbren Sr. M.D. FACP
Founding Member and Fellow of the Infectious Disease Society of America
This essay will start with a definition of Chronic Lyme disease: Chronic Lyme disease is a syndrome that results when individuals who have been inoculated with multiple microorganisms by infected ticks and who have not responded to an initial course of doxycycline develop extreme fatigue, intermittent fever, joint pain, muscle pain, brain fog, concentration difficulties, skin rashes, and in many instances symptoms of autoimmune disease to the extent that they impinge upon their quality of life.
When one comes face to face with patients of this type in whom other diseases are ruled out, it is obvious that something serious is amiss.
It’s a conundrum why a group of respected physicians who are members of the Infectious Disease Society of America have not recognized this and have, instead, written a guideline that essentially denies that the syndrome exists. This guideline has resulted in literally hundreds of patients unable to be treated for Chronic Lyme disease.
Conclusions regarding this conundrum may be:
1) The physicians who wrote and signed the guidelines of the Infectious Disease Society of America may have seen what they expected to see in the manner of the populace described in the Hans Christian Anderson’s perceptive fairy tale, “The Emperor’s New Clothes.”
2) Perhaps the authors of the guidelines had too much respect for authority and decided to sign the guidelines based on the opinion of some of the members of the society without having personal involvement in the treatment of the syndrome.
3) Perhaps they were unduly influenced by the expenses incurred in the many factors concerned in the empirical treatment of Chronic Lyme Disease.
4) Most probably they were influenced by controlled studies in the medical literature, which were based on Deductive conclusions rather than Inductive conclusions as described by Francis Bacon in 1622. Have they forgotten the well accepted statistical dictum – absence of proof does not equal proof of absence.
More info at: http://www.waisbrenclinic.com/chronic-lyme-disease-idsa.html
The expanding Lyme Borrelia complex-clinical significance of genomic species?
Clin Microbiol Infect. 2011 Apr;17(4):487-93. doi: 10.1111/j.1469-0691.2011.03492.x.
Stanek G, Reiter M.
Institute for Hygiene and Applied Immunology, Medical University of Vienna, Vienna, Austria.Of these 18 genomic species B. afzelii, B. burgdorferi and B. garinii are the confirmed agents of localized, disseminated and chronic manifestations of Lyme borreliosis, whereas B. spielmanii has been detected in early skin disease, and B. bissettii and B. valaisiana have been detected in specimens from single cases of Lyme borreliosis. The clinical role of B. lusitaniae remains to be substantiated.
Prolonged antibiotic therapy in PCR confirmed persistent Lyme disease
Wolfgang Klemann, MD, PhD
Bernt-Dieter Huismans, MD, PhD
Stephan Heyl, MD, PhD
Previous studies usually included patients that were diagnosed with Lyme
borreliosis based on clinical and serologic findings most of which were in an early
stage of the disease [5,6]. These serological criteria were introduced primarily for
epidemiologic purposes reasons and lack sensitivity [4,7] for clinical use. It is
doubtful whether results obtained from these studies can be generalized and
applied to other cases of lyme disease. Articles that document cases diagnosed by
detection of borrelial DNA have, to our knowledge, been limited to case reports
and case series [8,9]. For this article we have gathered a large number of patients
that were diagnosed with late stage lyme disease based on clinical and
serological findings as well as direct evidence of the causative microorganism by
using polymerase chain reaction (PCR). We provide long term follow up on the
clinical course and treatment of these patients and evaluate the efficacy of
prolonged courses (range 6-60 months) of antibiotics in these patients.
Serologic testing by ELISA and Western blot was performed on all patients.
Surprisingly, only 57% of patients had a positive Borrelia serology, even though
all had PCR confirmed disease. The serologic findings of our sample are shown in
figure 3. The IgG western blot exhibited the highest degree of sensitivity (58%).
Only 43,52% (37/85) of patients had both a positive ELISA test and a positive
Western blot, while in 10,85% (9/85) the positive ELISA result was not confirmed
by the Western blot. In 24,70% (21/85) of cases the ELISA test remained negative
despite a positive Western blot, even though, to be useful as a screening tool, the
ELISA test should theoretically exhibit higher sensitivity. These results question
the often recommended two- tiered testing approach [3, 4, 7], since some patients
with a negative ELISA test will still have a strongly positive Western blot.
• All study patients were Borrelia- DNA positive
• Commonly reported symptoms included fatigue, muscolo- sceletal and neuro-psychiatric complaints
• Only about 42% of patients had a history of an erythema migrans
• Serologic testing is fairly insensitive in late disseminated lyme disease
• Antibiotic treatment must be tailored to the individual clinical response in late disseminated lyme disease
• The majority of patients benefited from long term antibiotic treatment
• Recurrence of symptoms was common during treatment
• Long term antibiotic therapy was generally well tolerated
20 page ebook available for download at above link..
A proposal for the reliable culture of Borrelia burgdorferi from patients with chronic Lyme disease, even from those previously aggressively treated.
Infection. 1998 Nov-Dec;26(6):364-7.
Phillips SE, Mattman LH, Hulínská D, Moayad H.
Greenwich Hospital, CT 06830, USA.
Since culture of Borrelia burgdorferi from patients with chronic Lyme disease has been an extraordinarily rare event, clarification of the nature of the illness and proving its etiology as infectious have been difficult. A method for reliably and reproducibly culturing B. burgdorferi from the blood of patients with chronic Lyme disease was therefore sought by making a controlled blood culture trial studying 47 patients with chronic Lyme disease. All had relapsed after long-term oral and intravenous antibiotics. 23 patients with other chronic illness formed the control group. Positive cultures were confirmed by fluorescent antibody immuno-electron microscopy using monoclonal antibody directed against Osp A, and Osp A PCR. 43/47 patients (91%) cultured positive. 23/23 controls (100%) cultured negative. Although persistent infection has been, to date, strongly suggested in chronic Lyme disease by positive PCR and antigen capture, there are major problems with these tests. This new method for culturing B. burgdorferi from patients with chronic Lyme disease certainly defines the nature of the illness and establishes that it is of chronic infectious etiology. This discovery should help to reestablish the gold standard in laboratory diagnosis of Lyme disease.
PMID: 9861561 [PubMed – indexed for MEDLINE]
For full paper go to: http://www.angelfire.com/biz/romarkaraoke/Infect.html
A look at long term antibiotics for other infection so why not Lyme?
“A central controversy in treating people who have persisting symptoms of Lyme disease is whether or not they should receive more than three weeks of antibiotics to treat their condition.
And my question about this is why not treat them with longer courses of antibiotics if that is what is needed? Why is this such a big deal?
There are plenty of situations for which long term treatment with antibiotics is warranted. The most well known are tuberculosis (often treated for 9-12 months, sometimes longer) and Hansen’s disease (leprosy, often treated for two years).”
In the transcript of an educational course on acne treatment, “Long-term Oral Antibiotics for Acne”, dermatologists stated they have no problem giving their acne patients another 2 or 3 months worth of antibiotics to treat their acne if it isn’t cleared up after the first 2-3 months of treatment.
The Mayo Clinic states this about rosacea: “The duration of your treatment depends on the type and severity of your symptoms, but typically you’ll notice an improvement within one to two months. Because symptoms may recur if you stop taking medications, long-term regular treatment is often necessary.
Antibiotics have been used to treat Crohn’s disease, and a meta analysis concluded that long-term treatment with nitroimodazoles or clofazimine is effective in patients with Crohn’s disease (median treatment length was 6 months; duration ranged from 3-24 months).
Researchers from the University of South Florida College of Medicine found a combination of antibiotics can be an effective treatment for reactive arthritis caused by Chlamydia bacteria. Reactive arthritis symptoms usually last 3-12 months, although symptoms can return and develop into a long-term disease.
Antigens of Borrella burgdorferi Recognized during Lyme Disease
Appearance of a New Immunoglobulin M Response and Expansion of the Immunoglobulin G Response Late in the Illness
Joseph E. Craft, Duncan K. Fischer, Grant T. Shimamoto, and Allen C. Steere
Implications regarding pathogenesis. Among immune-mediated diseases, it is of central importance whether a persistent infectious agent is necessary for continued disease activity or whether such an agent triggers disease, which is then followed by autoimmunity. Recent evidence-the demonstration of spirochetes by silver staining in the synovium of two of nine patients (38) and the response of approximately half of patients with arthritis to parenteral penicillin therapy (39)-suggest that the Lyme spirochete is alive in the joint during arthritis. Although the current study did not implicate a particular spirochetal antigen as important in the pathogenesis of the arthritis, the appearance of a new IgM response and the expansion of the IgG response late in the disease and the lack of such responses in patients with ECM alone further suggest that B. burgdorferi remains alive throughout the illness.
Pathology of late or chronic Lyme neuroborreliosis compared to neurosyphilis
International Alzheimer Research Center
Alzheimer Prevention Foundation, 1921 Martigny-Combe, Switzerland
Whether spirochetes persist in the affected host tissues and are responsible for the chronic or late manifestations of neurosyphilis was also the subject of strong debate in the history of medicine. The early and late clinical and pathological manifestations of neurosyphilis are distinct. It was Noguchi and Moor (1913), who, by detecting Treponema pallidum in brains of patients suffering from general paresis, established a direct pathogenic link between spirochetal infection and dementia. Today it is generally accepted that Treponema pallidum can persist in the brain even decades following the primary syphilitic infection and cause various chronic neuropsychiatric symptoms, including stroke and dementia. The terms chronic or late neurosyphilis were both used to define tertiary neurosyphilis.
Today, the same question is in the center of debate with respect to Lyme neuroborreliosis. As in neurosyphilis the neuropsychiatric and neuropathological manifestations of early and late neuro-borreliosis are distinct. The secondary manifestations are mostly confined to the leptomeninges, leptomeningeal arteries, cranial and peripheral nerves and are clinically reflected as meningitis, vasculitis and neuritis. In contrast, brain parenchymal involvement defines late or chronic Lyme neuroborreliosis. The existence of both, the meningovascular and meningoencephalitic forms of late or chronic Lyme neuroborreliosis were clinically and pathologically confirmed. In these cases, Borrelia spirochetes were detected in the affected tissues and/or were cultivated from the brain or cerebrospinal fluid. The existence of these late forms of Lyme neuroborreliosis indicates that Borrelia burgdorferi in an analogous way to Treponema pallidum can evade from destruction by the host immune system, persist in the host tissues and cause chronic inflammation and slowly progressive tissue damage.
The confirmation of late or chronic Lyme neuroborreliosis should be based on the characteristic clinical symptoms and pathological changes, on the positive serology of Borrelia burgdorferi and on the cultivation or detection of spirochetes or their specific antigens or DNA in the affected tissues.
The existence of late Lyme disease is approved by all guidelines established in the U.S.A. and Europe. The use of chronic Lyme neuroborreliosis as a different entity is not justified as, in analogy to syphilis, both determine tertiary Lyme neuroborreliosis.
Further research, exchange of knowledge and open discussions at an international level are important.
NB the above link appears to be broken but for a similar piece go to:
Chronic or Late Lyme Neuroborreliosis: Analysis of Evidence Compared to Chronic or Late Neurosyphilis
Open Neurol J. 2012; 6: 146–157.
Published online Dec 28, 2012
Disseminated and chronic Lyme borreliosis in Norway, 1995 – 2004
Eurosurveillance, Volume 10, Issue 10, 01 October 2005
K Nygård, A Broch Brantsæter, R Mehl
Norwegian Institute of Public Health, Division of Infectious Disease Control, Oslo, Norway
In this article, we review surveillance data for disseminated and chronic Lyme borreliosis in Norway during the ten year period 1995-2004 in order to examine trends over time, geographical distribution, characteristics of patients and their clinical presentation.
LYME DISEASE – OFTEN MISSED AS A CAUSE OF CHRONIC ILLNESS
Dr. Holtorf on Lyme Disease Diagnosis and Treatment – A Culmination of the
LiteratureProHealth .com by Kent Holtorf, MD*
June 1, 2011
“To adequately detect and treat chronic Lyme disease, physicians must understand
that standard testing will miss the majority of these patients and standard
treatment will fail the majority of the time.”
More follows at: http://www.prohealth.com/library/showArticle.cfm?libid=16301&B1=EG060111
Outcomes in Cases of Chronic Disseminated Lyme Disease for Three Infected Physicians
Described in Their Own Essays, Published in Peer Reviewed Journals by Virginia T. Sherr, MD
Antibodies linked to long-term Lyme symptoms
Researchers find molecules that might mark elusive syndrome.
Some patients with Lyme disease still show symptoms long after their treatment has finished. Now proteins have been discovered that set these people apart from those who are easily cured.
People who experience the symptoms of Lyme disease, which include fatigue, soreness and memory or concentration loss, after treatment for the disorder are sometimes diagnosed as having chronic Lyme disease or post-Lyme disease syndrome. But these diagnoses are difficult to make, because the individuals no longer seem to harbour the bacteria that cause Lyme disease. And the symptoms could instead be indicative of chronic fatigue syndrome or depression.
Now Armin Alaedini at Weill Cornell Medical College in New York and his colleagues have found that patients diagnosed with post-Lyme disease syndrome have antibodies that suggest they carried the infection for an unusually long time. The finding, published in Clinical Immunology1, might help the syndrome to be better understood, diagnosed and treated.
More at: http://www.nature.com/news/2011/110805/full/news.2011.463.html
Chronic Persistent Infection in Lyme Neuroborreliosis Despite Prior Intensive Antibiotic Treatment – Challenge to Duration of Treatment for Late Neurologic Lyme Disease and Post-Lyme Syndromes.
Kenneth B. Liegner, M.D., P.C.
Internal & Critical Care Medicine
Lyme Borreliosis & Related Disorders
8 Barnard Road
Armonk, New York 10504
Ph: (914) 273-2121
FAX: (914) 273-4801
April 16, 2009
Challenge to IDSA guidelines:
Persistent Infection/Tissue Culture research
A Selection of articles from A-Z on persistence of infection:
Evaluation of Antibiotic Treatment in Patients with Persistent Symptoms of Lyme Disease
http://www.ilads.org/about_ILADS/position_papers2.html (This link is currently broken & have left until we can find an alternative. Meanwhile this paper may be of interest..)
Antibiotic retreatment of Lyme disease in patients with persistent symptoms: a biostatistical review of randomized, placebo-controlled, clinical trials.
Delong AK1, Blossom B, Maloney EL, Phillips SE.
Contemp Clin Trials. 2012 Nov;33(6):1132-42. doi: 10.1016/j.cct.2012.08.009. Epub 2012 Aug 19.
Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases.
Authors: Bayer ME, Zhang L, Bayer MH
Source: Infection 1996 Sep-Oct;24(5):347-53
Organization: Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
The presence of Borrelia burgdorferi DNA was established by PCR from urine samples of 97 patients clinically diagnosed as presenting with symptoms of chronic Lyme disease. All patients had shown erythema chronica migrans following a deer tick bite. Most of the patients had been antibiotic-treated for extended periods of time. We used three sets of primer pairs with DNA sequences for the gene coding of outer surface protein A (OspA) and of a genomic sequence of B. burgdorferi to study samples of physician-referred patients from the mideastern USA. Controls from 62 healthy volunteers of the same geographic areas were routinely carried through the procedures in parallel with patients’ samples. Of the 97 patients, 72 (74.2%) were found with positive PCR and the rest with negative PCR. The 62 healthy volunteers were PCR negative. It is proposed that a sizeable group of patients diagnosed on clinical grounds as having chronic Lyme disease may still excrete Borrelia DNA, and may do so in spite of intensive antibiotic treatment.
Chronic LD symptoms