GLOBAL LYME ALLIANCE: TREATMENT FOR PERSISTING LYME INFECTIONS

Prolonged symptoms following treatment of Lyme disease – Should patients with persistent symptoms following standard treatment of Lyme disease receive additional antibiotics?, pages 62-63, lines 1445-1449 and 1464-1468: Four randomized, controlled trials are cited as evidence against repeated antibiotic treatment (references #317, 321, 319).

careful statistical analysis of the trials and their design calls into question the conclusion that repeated antibiotic treatment has no benefit. DeLong et al. showed that two trials conducted by Klempner (reference #317) had sample sizes too small to detect true minimum clinically important differences, particularly in SF-36 scores.

The guidelines state that in study by Fallon et al. (reference #321) “A cognitive index score at week 24 did not differ between treatment and control groups.” While true that objective measures such as cognitive test results did not show differences between PTLDS patients and controls, it is important to note that PTLDS patients in the study had to invest considerably more effort to achieve the same test scores. This would argue against the notion “that this phenomenon, in whole or in part, represents anchoring bias…”. Additionally, the authors did note a positive effect on fatigue, similar to that observed in the Krupp trial (reference #319), and Fallon and co-authors highlighted the need for further study.

In reviewing these clinical studies, DeLong et al. concluded that “primary outcomes originally reported as statistically insignificant were likely underpowered.” At the very least, DeLong’s analysis should be cited in the IDSA guidelines as evidence that further study of repeated antibiotic use should be very carefully designed, executed, and interpreted.

Regarding continued or repeated antibiotic treatment for persistent symptoms, the guidelines state that “A body of literature conducted in animal models has raised hypotheses of microbiological persistence”. While correct, this statement is wholly disingenuous as it fails to reference any of the studies and, worse, neglects to acknowledge that experimental results are presented that support the hypotheses put forward. It also is stated that “Moreover, animal models cannot reproduce the human experiences of fatigue and pain, and it is unlikely that any animal study can give reliable insight into the biology of humans experiencing such symptoms following treatment of Lyme disease.” Again, this statement neglects a significant body of literature describing animal models of human fatigue and chronic pain.  Such studies have been instrumental in advancing our understanding of the pathogenesis of these human conditions and have spurred the development of novel treatments. This statement also fundamentally misrepresents the intent of the diverse animal studies conducted that provide evidence of persistence of spirochetes post-antibiotic treatment of infected animals. The purpose of using animal models as articulated by Monica Embers, Ph.D. (Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center) is “to understand the etiology of post-treatment Lyme disease syndrome (PTLDS), namely whether or not the spirochetes persist post-treatment and could thus contribute to chronic symptoms.” Symptoms experienced by PTLDS patients are not restricted to fatigue and pain, so one cannot reasonably discount the results of animal findings supporting spirochetal persistence because they are purported not to recapitulate all the symptoms experienced by humans.

Recent human evidence that continued bacterial presence may contribute to long-term symptoms was published by Jutras et al. in a 2019 PNAS article. They found that B. burgdorferi peptidoglycan, a component of the cell wall, was recovered from 94% of synovial fluid samples from Lyme arthritis patients, with specific IgG responses. Many of these patients had previously been treated with antibiotics. As peptidoglycan is shed from actively growing live bacteria, it’s at least plausible and worth further inquiry to study whether bacteria persist in these patients. If not, one is left with a less plausible explanation that foreign bacterial antigens must remain in inflamed tissues for weeks, months, or even years after (presumed) effective antibiotic-mediated killing of B. burgdorferi. With such intriguing findings at least hinting at the possibility of persistent organisms in Lyme disease patients, the authors of the revised guidelines should consider specifically referencing these animal and human studies rather than covering the entire topic by citing one publication (reference #320) and summarily discounting the results presented in so many other peer-reviewed scientific journals.

Comments from “The Patient -Centered Care Advocacy Group”

Inadequacy of tick- bite prophylaxis recommendations:

The IDSA recommendation for prophylaxis of Lyme disease are based on a study published in the New England Journal of Medicine in 2001.[i]

The study evaluated the efficacy of a single dose of doxycycline for preventing Lyme disease after a tick bite. Endpoints in the study included erythema migrans (EM), isolation of Borrelia burgdorferi in culture, or seroconversion. The study design was randomized, double-blind, and involved over 450 subjects. The end points used to determine if subjects were infected with B. burgdorferi and developed Lyme disease are shown below:

“The primary end point was the development of erythema migrans at the site of the tick bite. Erythema migrans occurring at a different site from that of the identified tick bite and laboratory evidence of B. burgdorferi infection in the absence of erythema migrans were analyzed as secondary end points. Seroconversion was defined as a change from a negative result on ELISA to an equivocal or positive result in association with the presence of IgM bands on immunoblotting that met the recommended criteria for seropositivity.”

The conclusion of this study that the prophylaxis “prevented Lyme disease” is inadequately supported by the data presented in the paper. The study design is based on “end points” for Lyme disease which rule out subjects who did not develop an EM rash or seroconvert during the 6-week study period. As noted in the HHS Tick-Borne Disease Working Group 2018 report to Congress[ii], the clinical observations of acute viral-like illness without EM, disseminated EMs, asymptomatic seroconversion, and febrile episodes are, in fact, symptoms associated with Borrelia burgdorferi infection (Lyme disease), and in some cases these symptoms may not occur for weeks to months after infection.

CDC surveillance data from 1992-2006 documented that 31% of surveillance cases lacked an EM rash.[iii] Patient-derived data from the MyLymeData patient registry (a project by LymeDisease.org)[iv] noted that only 34% of 3,903 patients recalled having an EM rash. More commonly reported early symptoms were flu-like symptoms (64%) and severe headache or stiff neck (44%).

In a comprehensive study of the pathobiology of infection with B. burgdorferi in outbred non-human primates (NHPs), the rate of EM in NHPs infected by nymph tick bite and confirmed to be infected by culture or PCR, was only 10%. It is noted by the NHP researchers that more than half of infected NHPs do not develop any erythematous rash (personal communication with the study authors) following infection. NHP studies convincingly demonstrate that the macaque model most closely resembles human borreliosis and provides the best experimental model to study Lyme disease.[v] In this animal model, the rate of association between EM and B. burgdorferi infection is low.

Since the association between EM and B. burgdorferi infection (Lyme disease) is quite low (40-70%), the number of subjects who developed Lyme disease cannot be determined from the data. The data shows only that there was a statistical difference in the rate of EM, but not Lyme disease, between the prophylaxis and placebo groups.

In a study which evaluated existing diagnostic tests for a “definitive diagnosis” of Lyme disease, the sensitivity of ELISA during the acute phase of infection is less than 50%.[vi]  Subjects in the single dose prophylaxis study were therefore equally likely to have Lyme disease, whether the ELISA was positive or negative.

As noted in the HHS Tick Borne Disease Working Group report to Congress, seroconversion, defined by the study authors as “a change from a negative result on ELISA to an equivocal or positive result in association with the presence of IgM bands on immunoblotting,” may not occur during the first 4-6 weeks of infection. It was also noted that treatment of B. burgdorferi infection with an antibiotic, prophylactic or otherwise, is shown to prevent seroconversion, and that a proportion of people infected with B. burgdorferi do not seroconvert at all. As this study ended at 6 weeks, subjects who were infected but did not seroconvert or develop symptoms for weeks to months post infection, would not have been considered to have Lyme disease.

In Table 3 of the NEJM article, three subjects—one in the treatment group and two in the placebo group—had nonspecific symptoms and evidence of B. burgdorferi infection (secondary endpoints of the study). It should be noted for these characteristics – nonspecific symptoms and seroconversion – there appears to be no statistical difference between the treatment and placebo groups, which indicates that the prophylaxis does not prevent Lyme disease.

Since neither the primary or secondary end points used in this study will identify subjects with Lyme disease, the conclusion that the single dose prophylaxis prevents Lyme disease is invalid.

As detailed in Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease, published by the International Lyme and Associated Diseases Society (ILADS) in 2014,[vii] the quality of the evidence supporting the use of a single 200 mg dose of doxycycline following a tick bite is very low, implying that the true effectiveness of this prophylaxis is likely to be substantially different from the effectiveness rate reported in the NEJM article.

Instead, ILADS makes the following recommendation: “Clinicians should promptly offer antibiotic prophylaxis for known Ixodes tick bites in which there is evidence of tick feeding, regardless of the degree of tick engorgement or the infection rate in the local tick population. The preferred regimen is 100–200 mg of doxycycline, twice daily for 20 days.” 

Finally, in the Discussion section of the NEJM article that is used to support the recommendation that a single dose doxycycline prophylaxis prevents Lyme disease, the authors note, “The efficacy rate found in our study should be interpreted cautiously, however, because of the relatively small number of subjects in whom Lyme disease developed and the resultant wide 95 percent confidence interval (25 to 98 percent).” They also concluded that “Our results contrast with those of previous studies,6-8 which showed no clear protection attributable to antimicrobial prophylaxis given after a tick bite.

Since there is contrasting evidence showing that antimicrobial prophylaxis does not prevent Lyme disease, the recommendation should be removed until such time that an unbiased study on tick bite prophylaxis can be completed.

Nadelman R, Nowakowski J, Fish D et al. Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite. New England Journal of Medicine. 2001;345(2):79-84. doi:10.1056/nejm200107123450201 https://www.ncbi.nlm.nih.gov/pubmed/11450675

[ii] 2018 Report to Congress by the Tick Borne Disease Working Group.
www.hhs.gov/ash/advisory-committees/tickbornedisease/reports/index.html

[iii] Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease–United States, 1992-2006. MMWR SurveillSumm. 2008;57(10):1–9.  www.ncbi.nlm.nih.gov/pubmed/18830214

[iv]MyLymeData  https://www.lymedisease.org/mylymedata-lyme-disease-research

[v] Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC, Doyle-Meyers LA, Philipp MT, et al. Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding. PLoS ONE 12(12): e0189071. https://doi.org/10.1371/journal.pone.0189071

[vi] Coulter P, Lema C, Flayhart D, et al. Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease. J Clin Microbiol. 2005;43(10):5080–5084. doi:10.1128/JCM.43.10.5080-5084.2005 https://www.ncbi.nlm.nih.gov/pubmed/16207966

[vii] Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103–1135. doi:10.1586/14787210.2014.940900 https://www.ncbi.nlm.nih.gov/pubmed/25077519

[i] Nadelman R, Nowakowski J, Fish D et al. Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite. New England Journal of Medicine. 2001;345(2):79-84. doi:10.1056/nejm200107123450201 https://www.ncbi.nlm.nih.gov/pubmed/11450675

[ii] 2018 Report to Congress by the Tick Borne Disease Working Group.
www.hhs.gov/ash/advisory-committees/tickbornedisease/reports/index.html

[iii] Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease–United States, 1992-2006. MMWR SurveillSumm. 2008;57(10):1–9.  www.ncbi.nlm.nih.gov/pubmed/18830214

[iv]MyLymeData  https://www.lymedisease.org/mylymedata-lyme-disease-research

[v] Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC, Doyle-Meyers LA, Philipp MT, et al. Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding. PLoS ONE 12(12): e0189071. https://doi.org/10.1371/journal.pone.0189071

[vi] Coulter P, Lema C, Flayhart D, et al. Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease. J Clin Microbiol. 2005;43(10):5080–5084. doi:10.1128/JCM.43.10.5080-5084.2005 https://www.ncbi.nlm.nih.gov/pubmed/16207966

[vii] Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103–1135. doi:10.1586/14787210.2014.940900 https://www.ncbi.nlm.nih.gov/pubmed/25077519

[i] Nadelman R, Nowakowski J, Fish D et al. Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite. New England Journal of Medicine. 2001;345(2):79-84. doi:10.1056/nejm200107123450201 https://www.ncbi.nlm.nih.gov/pubmed/11450675

[ii] 2018 Report to Congress by the Tick Borne Disease Working Group.
www.hhs.gov/ash/advisory-committees/tickbornedisease/reports/index.html

[iii] Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease–United States, 1992-2006. MMWR SurveillSumm. 2008;57(10):1–9.  www.ncbi.nlm.nih.gov/pubmed/18830214

[iv]MyLymeData  https://www.lymedisease.org/mylymedata-lyme-disease-research

[v] Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC, Doyle-Meyers LA, Philipp MT, et al. Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding. PLoS ONE 12(12): e0189071. https://doi.org/10.1371/journal.pone.0189071

[vi] Coulter P, Lema C, Flayhart D, et al. Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease. J Clin Microbiol. 2005;43(10):5080–5084. doi:10.1128/JCM.43.10.5080-5084.2005 https://www.ncbi.nlm.nih.gov/pubmed/16207966

[vii] Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103–1135. doi:10.1586/14787210.2014.940900 https://www.ncbi.nlm.nih.gov/pubmed/25077519

Bruce Alan Fries, President

 

Ad Hoc Patient Physician Coalition Comments to IDSA Proposed Guidelines

The following organizations have endorsed the Ad Hoc Patient and Physician Coalition Comments of the IDSA Proposed Lyme Guidelines, August 8, 2019

Bay Area Lyme Foundation

Brookfield/Wolfeboro New Hampshire support group

Central Massachusetts Lyme Foundation

Charles E. Holman Morgellons Disease Foundation

Colorado Tick-Borne Disease Awareness Association

Florida Lyme Disease Association

International Lyme and Associated Diseases Society

Kentucky Lyme Disease Association

Litchfield County Lyme Network (Connecticut)

LivLyme Foundation

Lyme Action Network

Lyme Alliance of the Berkshires

LymeDisease.org

Lyme Disease Association

Lyme Disease Association of Southeastern Pennsylvania

Lyme Disease Association, Rhode Island Chapter

Lyme Disease Education & Support Groups of Maryland

Lyme Stats

LymeConnection.org

Madison Lyme Support Group

Memphis Tennessee Lyme Network

Midcoast Lyme Disease Support & Education

New Jersey Lyme Resource

New York City Lyme Disease Support Group

Ontario Lyme Alliance (Canada)

PA Lyme Resource Network (Statewide)

PA Lyme Resource Network, Bucks County

PA Lyme Resource Network, Columbia County

PA Lyme Resource Network, Lehigh Valley

Patient Centered Care Advocacy Group

Pennsylvania Lyme Disease Awareness Committee of Chester-Delaware County Farm Bureau (PLDAC)

Sam’s Spoons Foundation for Lyme Support& Education

Southern Arizona Lyme Disease Association

The Dean Center for Tick Borne Illness, Massachusetts

The Massachusetts Lyme Legislative Task Force

Wisconsin Lyme Network

York North Lyme (Canada)

How long should a patient with EM be treated?

How long should a patient with EM be treated?

IDSA Draft Guideline Recommendation:

“We recommend that patients with EM be treated with either a 10-day course of doxycycline or a 14-day course of amoxicillin, cefuroxime axetil or phenoxymethylpenicillin rather than longer treatment courses (strong recommendation, moderate quality of evidence).”

IDSA guidelines recommending a 14-day course of antibiotics rely heavily upon research by Dr. Wormser, andcolleagues, (1) and (2)

In the more recent Wormser study, the authors concluded that a 12-day course of antibiotics was highly effective, even though 4 of 24 subjects had PTLDS.  As pointed out by Rosalie Greenberg, (5) this translates into roughly 70,000 cases annually.The actual rate of treatment failure in this study is greater than the 16.7% with PTLDS:  4 patients developed “PTLDS” and 2 more having had recurrent EM. That means 6/22 or 27% failed treatment.

Symptoms of PTLDS are generally considered “subjective” and not included in studies of Lyme Disease.  They include disabling headache, fatigue, brain fog, paresthesia, and dizziness.  But behind these subjective symptoms are small fiber peripheral neuropathy and dysautonomia.  Recent studies show evidence of biological causes: glial activation and cerebral hypoperfusion:  Novak has postulated that the low blood pressure and hypoperfusion of the brain may be responsible for the brain fog. (3,4)

Another referenced study by Wormser, (7) studied 120 patients with EM rash with a varying length of time of Doxycycline treatment, up to 20 days.  Outcome measures were “objective” findings at up to 30 months.  PTLDS or “subjective” findings was defined as “partial response.”  Two patients in the 20-day treatment developed Bell’s palsy but was considered a success at 30 months.  One patient in the 10-day treatment group was considered a complete failure, with development of meningitis.  Thirteen patients divided between all groups developed recurrence of EM rash., which was attributed to a second illness rather than recurrence. These patients alone may be considered a 13% failure rate.  But additionally, there was a 17% rate of PTLDS.  A reasonable conclusion is that 30% of patients failed all treatment interventions.

The conclusion was that “More than 83% of the evaluable patients in each treatment group had a complete response at 30 months” which means that 17% of patients developed PTLDS

Because we do not have studies at this time which show any effective treatment which does not result in a failure rate approaching 30%, a recommendation for 14 days of antibiotics cannot be made.

References

1Wormser et al., 2019

G.P. Wormser, K.C. Brady, M.S. Cho, C.A. Scavanda, D. McKenna.Efficacy of a 14-day course of amoxicillin for patients with erythema migrans.

Diagn Microbiol Infect Dis (2019), 10.1016/j.diagmicrobio.2019.01.003

(2)  Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2003; 138(9): 697- 704.

  1. Novak et al., 2019
  2. Novak, D. Felsenstein, C. Mao, N.R. Octavien, N. ZubcevikAssociation of small fiber neuropathy and post treatment Lyme disease syndrome

PLoS One, 14 (2) (2019), Article e0212222, 10.1371/journal.pone.0212222

  1. Coughlin et al., 2018

J.M. Coughlin, T. Yang, A.W. Rebman, K.T. Bechtold, Y. Du, W.B.Mathews, et al.Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [11C]DPA-713 PET

J Neuroinflammation, 15 (346) (2018), 10.1186/s12974-018-1381-4

(5)        Rosalie Greenberg, comment: https://doi.org/10.1016/j.diagmicrobio.2019.03.008

Jane Marke, MD

Lyme And Psychiatric Symptoms

Letter regarding the IDSA/AAN/ACR 2019 Draft Lyme Disease Guidelines

Lyme and Psychiatric Illness 7/28/2019

As a psychiatrist specializing in infection-associated psychiatric illness I have some concerns about the proposed 2019 draft of Lyme disease guidelines.

1.On the question of should all adult patients with psychiatric illness be tested for Lyme disease the guideline authors recommend against this testing.  It is interesting how the guideline authors selectively chose only literature to cite that supports their view of psychiatric symptoms being an independent factor, as if unconnected in an individual with Lyme disease. The literature supports there being an association between many bacterial infections and psychiatric symptoms even streptococcal pharyngitis, (PANDAS)   The draft states that  there is no systematic evidence supporting a causal relationship.   This is untrue.

I agree with the authors that routinely testing psychiatric patients is a questionable practice but that is only because the present recommended two-tier testing is so poor and only identifies a little over 50% of the cases (Stricker and Johnson BMJ 2007).  Dennis Parenti MD, a past group director of adult vaccines for SmithKline Beecham in a presentation of results from the Lyme Vaccine Trial that occurred between  Jan 1995-Nov 1996 and included over 11,000 patients found that the  rate of seroconversion (positive testing for BB) in the closely monitored study population was 90/142 or 64%  He concluded that “In this study had we relied only on seroconversion we would have missed one third of the cases.”  This flaw alone makes the reliance of serologic testing questionable (especially with the high number of false negatives) limiting the utility of routine testing for BB in psychiatric patients.

2.The authors appear to have overlooked multiple articles in the literature supporting the link between Lyme disease and psychiatric illness, including increased rates of depression and anxiety as well as suicidal and homicidal behavior.  This is a significant error that has major effects on patient’s diagnosis, treatment and prognosis.

Examples of relevant literature include:

  1. Fallon BA, Nields JA,Parsons B,Liebowitz MR,Klein DF. Psychiatric manifestations of Lyme borreliosis; J Clin Psychiatry. 1993 Jul;54(7):263-8.
  2. Fallon BA, Nields JA. Lyme disease:  a neuropsychiatric illness.; Am J Psycho Nov 1994.
  3. Bransfield RC. Lyme disease, comorbid tick-borne diseases, and neuropsychiatric disorders. Psychiatric Times. 2007;24(14):59–6
  4. Bransfield RC. Neuropsychiatric Lyme Borreliosis: An Overview with a Focus on a Specialty Psychiatrist’s Clinical Practice
  5. Healthcare 2018, 6(3), 104;https://doi.org/10.3390/healthcare6030104
  6. Greenberg R. Infections and Childhood Psychiatric Disorders: Tick-Borne

Illness and Bipolar Disorder in Youth. Bipolar Disorder 3:113. December

2016.DOI: 10.4172/2472-1077.1000113

3.Even though LD testing is of limited accuracy, it would be reasonable to recommend it be done in cases of psychiatric mood disorders, psychosis, and/or behavioral disturbances that appear treatment resistant to standard psychotropic medication. In these difficult atypical cases, it is important to keep neurologic, autoimmune and infectious diseases on the diagnostician’s radar.  In these situations, testing for

Borrelia species, just like testing for treponema pallidum infections is warranted.

I sincerely hope that the guideline authors will be receptive to this input.

Rosalie Greenberg MD FAPA DFAACAP

Board Certified in Child, Adolescent and Adult Psychiatry

Numerous Flaws in the Guidelines

Tick borne diseases offers unique health care challenges. Well-written guidelines can offer a unique opportunity to address them. Numbers of tick borne disease cases continue to increase along with missed or late diagnoses and unacceptable levels of treatment failure. By employing root cause analysis, some of these problems can be defined and corrected through guidelines that are clear and easy to use.

Numerous organizations agree that healthcare guidelines meet the following requirements: 1.)improving quality of care 2.) Improving process of care 3.) Improving patient outcomes.

To address root cause failures, it is important to ask: What actually happens to patients as they move through the health care system? What can be done differently? How do the guidelines remove barriers to rapid and accurate diagnosis?

Barriers to meeting requirements within these guidelines include:

• The guidelines are complex

• The guidelines are difficult to apply

• The guidelines do not translate naturally in simple, clear corrective action recommendations.

• The guidelines are often subjective because of a lack of data or data that fits an existing narrative.

• Treatment options are confusing with multiple options and uncertainty about outcomes.

• Patients are not easily diagnosed because of the complexity involved in administering the standard test. If testing is done too soon or after antimicrobials are given, the lab tests are frequently negative with hazards transferred to the patient when no treatment is provided.

• If patients wait several weeks before testing, the delay causes the disease to advance making complete recovery more difficult, again presenting a hazard to the patient.

• Solutions to prevent or treat long term or permanent disability caused by missed diagnosis or late diagnosis is not addressed.

Carefully considered guidelines are critical to preventing health, financial and social burdens from being borne by the patient and health care system, and eventually by taxpayers in the form of unemployment, disability payments, welfare, Medicaid and Medicare when patients are not properly diagnosed and treated.

I hope this is useful and offers constructive direction for revision.

Clinical Diagnosis and treatment is an Inexact and Evolving Art and Science: IDSA Guidelines are not evolving

Medicine has never been an exact science and is dependent on research and new discoveries and the incorporation of new and updated clinical and evidence-based information and innovative approaches to treatment for illnesses. (For example we no longer use blood-letting as a form of treatment for “consumption.”) Guidelines written in 2006 for a disease that is constantly evolving because of the modes of infection (including sexual transmission and via placenta from mother to baby before childbirth,) the increasing incidence of ticks and their expanding territories due to climate change, the inadequacy of testing and the lack of a vaccine for prevention of Lyme and related Tick-Borne diseases are an abomination because they are more than a decade old and obsolete yet staunchly defended by infectious disease doctors who stubbornly adhere to obsolete information and treatment and eschew any new information informed by clinical practice. New information also identifies co-infective agents (in addition to Lyme) carried by ticks and includes other vectors carrying the disease and the extraordinary survival strategies of the infecting agent (spirochetes) which can morph into a variety of forms to avoid detection.

Historically, medications and treatments for certain maladies have evolved as new information is discovered or comes forward. The IDSA Guidelines are outdated and instead of being studied and validated per clinical evidence, research and peer review, they were grandfathered in to treat a disease that keeps evolving. Standards of care must necessarily change as discoveries and new avenues of treatment evolve, necessitating updated guidelines. And guidelines certainly should not be a test to take legal action against practitioners who choose to diagnose based on clinical signs and symptoms especially since standard tests available for Lyme are inaccurate almost half the time.

The current climate of friction between societies, treatment guidelines, and the scarcity of resources for those unfortunate enough to be afflicted with Lyme that went undiagnosed and untreated and has now overwhelmed the physical body, makes it nearly impossible to get the expertise and treatment needed. Doctors who claim something does not exist simply because it is inconvenient to their standard theories do a disservice to patients who struggle with a serious illness affecting all quality of life issues. The stubborn refusal of societies to evolve, cooperate, share resources result in patients being harmed as many have opted for suicide rather than live one more day in frustration and depression because they must suffer in the background while so-called “professionals” argue over minutiae.

Doctors who are actively engaged in the clinical diagnoses and treatment of Lyme patients forgotten or dismissed by others clinging tenaciously to obsolete information, must be given a voice in the quest for controlling an illness whose incidence is growing and that left unaddressed as it is now, threatens to become a serious epidemic while overwhelming the healthcare system.

Neurodegenerative Diseases

These guidelines are terribly flawed and I hope that you reconsider. Patients with ALS, MS, dementia, Parkinson’s and sudden seizures may also have Lyme and TBDs and should be tested and treated if the test is positive.

A month of abx. has been in the guidelines for years. One doxycycline pill will have no effect at all. There is absolutely no other illness that is treated with only one antibiotic pill.

Please avoid bringing this major epidemic into the legal system.

Robert Morgenstern

Flawed Literature Base for Guidelines

To the IDSA, AAN and ACR regarding the proposed Lyme disease guidelines I’ve reviewed the draft of the new Lyme disease guidelines. I am struck by a few things On page 6 the draft states “Abstracts and conference proceedings, letters to the editor, editorials, review articles, and unpublished data were excluded. The panel made an a priori decision to only include sufficiently peer-reviewed articles to avoid serious risk of bias associated with a lack of editorial oversight.”

My concerns are as follows:

1. The choice not to include letters to the editor in the literature reviewed for guideline creation makes it easier to make studies cited as definitive, even though they may contain crucial flaws in design, content or conclusions
revealed by letters to the editor.
2. The decision to omit Review Articles in the literature surveyed is also a way to bias information. A good review article will provide different viewpoints, or conflicting findings, by a variety of authors. A commentary
on the quality of the different studies should then be noted, but at least discordant findings would be acknowledged and provide a more complete and fair review.
3. The decision to review only literature from standard peer review journals can also be a way to limit results presented to the guideline creators. It is well known that controversy exists regarding the diagnosis and treatment of
Lyme disease. Often, an article or commentary that expresses doubt in the official IDSA doctrine that Lyme disease is easy to both diagnose and treat, has a very difficult time getting published in mainstream top tier journals.

Many editors as well as reviewers are strongly involved in supporting the stated Lyme guidelines (not uncommonly having been involved in their creation). This in effect results in omitting studies that challenge the status
quo. Unfortunately, guidelines based on review of selective literature cannot be expected to halt the dramatic increase in the number of individuals affected by this potentially devastating disorder. They have been quite
ineffective so far. Doing the same thing and expecting a different outcome is fraught with problems from the start, even if it is advertised to be a new start.

Rosalie Greenberg, MD, FAPA, DFAACAP

Summit, New Jersey

medicalartspsychotherapy@verizon.net