chronic lyme

Chronic Lyme

Chronic neurologic manifestations of Lyme disease.

Logigian EL, Kaplan RF, Steere AC.
Department of Neurology, Tufts University School of Medicine, Boston, MA 02111.

http://www.ncbi.nlm.nih.gov/pubmed/2172819?dopt=Abstract

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.
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Published studies do show that chronic Lyme improves with long term antibiotic therapy.

http://lymemd.blogspot.com/2010/02/eye-of-beholder-specialist.html

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
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Author’s response to comments by Sigal and Hassett, Phillips et al., and Shapiro et al.

http://ije.oxfordjournals.org/cgi/content/full/34/6/1440

Victoria Cairns

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:

http://ije.oxfordjournals.org/cgi/content/full/34/6/1340

KEY MESSAGES

* 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.
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Some useful links on the persistence of Lyme

Why are we still sick?
http://www.bhia.org/lyme/still_sick.htm

Lyme Disease Action & persistence of Lyme:
http://www.lymediseaseaction.org.uk/articles/persistence.htm

Persistence of Lyme – peer reviewed articles:
http://www.lymeinfo.net/lymefiles.html
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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):
http://www.lymeinfo.net/medical/LDCysts.pdf

Cystic Forms – Advanced (30 pages):
http://www.lymeinfo.net/medical/LDAdverseConditions.pdf

Cystic Forms – Complete Bibliography 1905 to present (250 studies, 49 pages):
http://www.lymeinfo.net/medical/LDBibliography.pdf
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Sam Donta, MD writes about the challenges of Chronic/Late Lyme Disease at:

http://www.canlyme.com/donta.html
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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.

Interdisciplinary Perspectives on Infectious Diseases
Volume 2010 (2010), Article ID 876450, 4 pages
doi:10.1155/2010/876450

Research Article

Proof That Chronic Lyme Disease Exists
Daniel J. Cameron

Department of Medicine, Northern Westchester Hospital, Mt. Kisco, NY 10549, USA

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.

Abstract

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.

Abstract above. Following link contains a more detailed review:

http://www.hindawi.com/journals/ipid/2010/876450.html
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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.

http://www.lymeneteurope.org/forum/viewtopic.php?f=5&t=2776
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Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome & Fibromyalgia

May 15, 2002

By Sam Donta,M.D.

http://www.prohealth.com/library/showarticle.cfm?libid=8441
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NEWS: Major series on chronic Lyme from Maine TV station
07 July, 2010

http://www.lymedisease.org/news/lyme_disease_views/496.html

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.
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‘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!

http://ticktalkireland.wordpress.com/2010/07/28/persistence-seronegativity/
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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.”

http://www.waisbrenclinic.com/treatment-lyme-disease.html

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.

http://www.waisbrenclinic.com/aboutdr.html
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The Case For Chronic Infection:

Evidential persistence of Borrelia species post antibiotic exposure in vivo and in vitro.

Michael D. Parent & Erica Falkingham

Introduction Summary:

(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]

Introductory Conclusion:

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

https://acrobat.com/#d=sbb-EmpQrQTgrPoezLGreg

“Skepticism is the heart of science. Cynicism is the death of reason.”
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Long Term Inflammation in Lyme Borreliosis

Many, many articles on the persistence of infection leading to chronic Lyme disease:

http://www.lymenet.de/literatur/niches.htm
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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!

http://www.angelfire.com/me2/StarShar/Herx1.html
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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.

http://www.ncbi.nlm.nih.gov/pubmed/9233667?dopt=Abstract

Abstract

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]
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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)

DOI: 10.1111/j.1469-0691.2004.00895.x

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:
http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2004.00895.x/pdf
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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. judithmiklossy@bluewin.ch

Abstract

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:

http://www.ncbi.nlm.nih.gov/pubmed/18817547
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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.

http://www.prohealth.com/library/showarticle.cfm?libid=15689

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.
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Persister cells, dormancy and infectious disease

Kim Lewis

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?”

http://www.northeastern.edu/adc/publications/KL2007Pers.pdf

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.
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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:
http://www.springerlink.com/content/ntyjnvgkyjnukb9a/fulltext.pdf

Case report

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.
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US Army warns of LD & chronic LD in North Africa

http://www.afpmb.org/pubs/dveps/nort_afr.pdf

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.
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TIME FOR LYME RESEARCHER KAREN NEWELL EXPLORES CHRONIC INFLAMMATION

Research published in the October 2010 issue of the Journal of Leukocyte Biology

http://www.timeforlyme.org/TFL_newsletter_nov_2010_newell.htm

“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.
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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.

http://ezinearticles.com/?Chronic-Lyme-Disease-and-CCSVI&id=5399537
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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.

Abstract

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]

http://www.ncbi.nlm.nih.gov/pubmed/8240439
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80 page slideshow on chronic & seronegative Lyme – showing evidence that the IDSA choose to ignore..

http://www.ilads.org/lyme_research/chronic_lyme.html

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.
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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.

Abstract

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]

http://www.ncbi.nlm.nih.gov/pubmed/2138431
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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.

http://www.dovepress.com/articles.php?article_id=6013

Full article in PDF format available in above link!
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Discusses seronegative Lyme, prophylaxis & persistence of infection..

http://www.borelioza.org/materialy_lyme/volkman_review.pdf

• 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.”

http://www.prohealth.com/library/showarticle.cfm?libid=15675
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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.

http://www.dancingviolets.com/media/pdf/LymeDisease.pdf
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Biofilms & Clinical Implications for Chronic Borreliosis by Alan MacDonald MD, Uni New Haven

http://www.molecularalzheimer.org/files/Biofilm_New_Haven_ppt_Read-Only_.pdf
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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–
113.

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.

http://www.aaem.pl/pdf/aaem0217.pdf
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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.[42][43][44]

Various survival strategies of ”B. burgdorferi” have been posited to explain this phenomenon,[45] including the following:

★ Physical sequestration of ”B. burgdorferi” in sites that are inaccessible to the immune system and antibiotics, such as the brain[46] and central nervous system. New evidence suggests that ”B. burgdorferi” may use the host’s fibrinolytic system to penetrate the blood-brain barrier.[47]

★ Intracellular invasion.

”B. burgdorferi” has been shown to invade a variety of cells, including endothelium,[48] fibroblasts,[49] lymphocytes,[50] macrophages,[51] keratinocytes,[52] synovium,[53][54] and most recently neuronal and glial cells. [55] By ‘hiding’ inside these cells, ”B. burgdorferi” is able to evade the immune system and is protected to varying degrees against antibiotics,[56][57] 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,[58][59][60][61] in vivo,5459[62] and in an ex vivo model.[63] 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.[64][65]

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, [66] tinidazole, [67] and hydroxychloroquine, [68] 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[69] 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.[70]

★ 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.[71]

http://tripatlas.com/Lyme%20disease%20microbiology
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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 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 [5], causing confusion in the diagnosis and treatment of the late persistent phase in Lyme Disease patients.

http://www.immed.org/treatment%20considerations/NicolsonLYMEdiseaseACAM_06.rtf
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The expanding Lyme Borrelia complex – Clinical significance of genomic species?

1. G. Stanek,
2. M. Reiter

DOI: 10.1111/j.1469-0691.2011.03492.x

Copyright © 2011 European Society of Clinical Microbiology and Infectious Diseases

B. afzelii, B. burgdorferi and B. garinii are the confirmed agents of localised, disseminated and chronic manifestations of Lyme borreliosis…

http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2011.03492.x/abstract
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Human Side of Lyme

http://www.thehumansideoflyme.net/
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.”
http://www.ucihs.uci.edu/microbio/
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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
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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.

http://www.ncbi.nlm.nih.gov/pubmed?term=The+expanding+Lyme+Borrelia+complex-clinical+significance+of+genomic+species%3F

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.
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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.

Key issues:

• 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

http://www.grin.com/e-book/166179/prolonged-antibiotic-therapy-in-pcr-confirmed-persistent-lyme-disease#inside

20 page ebook available for download at above link..
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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.
Abstract

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.

http://www.ncbi.nlm.nih.gov/pubmed/9861561

PMID: 9861561 [PubMed - indexed for MEDLINE]
For full paper go to: http://www.angelfire.com/biz/romarkaraoke/Infect.html
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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).[10]

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.

http://campother.blogspot.com/2011/05/report-lyme-disease-antibiotics-more.html
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Evidential persistence of Borrelia species post antibiotic exposure in vivo and in vitro

Contains 83 pages of evidence of persistence of infection

http://www.lymekick.com/chroniclyme.pdf
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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

http://www.jci.org/articles/view/112683/files/pdf

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.
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Pathology of late or chronic Lyme neuroborreliosis compared to neurosyphilis
Judith Miklossy

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.

http://www.borreliose-gesellschaft.de/TagungenFortbildung/2011Wuppertal/Abstracts/Miklossy
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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.

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=568
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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
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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

http://www.ilads.org/lyme_research/lyme_articles11.html
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Antibodies linked to long-term Lyme symptoms
Researchers find molecules that might mark elusive syndrome.
Amy Maxmen

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
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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:
http://www.ilads.org/lyme_disease/written_testimony/15%20Liegner-Chronic%20Persistent%20Infection.pdf
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Persistent Infection/Tissue Culture research

A Selection of articles from A-Z on persistence of infection:

http://www.canlyme.com/persinfect.html
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Evaluation of Antibiotic Treatment in Patients with Persistent Symptoms of Lyme Disease

http://www.ilads.org/about_ILADS/position_papers2.html

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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.

Abstract:
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.

http://www2.lymenet.org/domino/abstract.nsf/8c703fae46ce57c28525670a0009ab7e/825c220b70bc345c8525650300058ba5?OpenDocument
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Chronic LD symptoms

http://www.livestrong.com/article/81278-chronic-lyme-disease-symptoms/