2 2009 Final Report's Proposed Changes to IDSA Lyme Disease Guidelines

I decided to take a break from discussing The Lancet antiscience letter and highlight a few items of note about proposed upcoming changes to the Infectious Disease Society of America's 2006 guidelines for the treatment of Lyme disease.

Below is a list of some Lyme disease guideline items and recommendations for their revision taken from the 2009 Final Report [.pdf] that the Infectious Disease Society of America (IDSA) review panel wrote in response to Senator Blumenthal's antitrust investigation of the IDSA a few years ago.

In this report, an independent review panel came to the conclusion that several changes needed to be made to the 2006 guidelines which would be included in the next version of the guidelines (which has yet to be published).

I have provided a table from the original final report which outlines what the quality of the evidence is which supports each recommendation and the strength of each recommendation, based on the IDSA review panel's judgment.

Following that table, I have provided a more detailed table which takes portions of the original 2006 Lyme disease diagnosis and treatment guidelines (which are more or less identical to the IDSA's 2000 treatment guidelines for Lyme disease with few exceptions) alongside the recommendations of the 2009 panel for the next version of the IDSA guidelines.

I provide this information, along with a few questions for readers:

1. The state of the science in Lyme disease has been moving along at a fair clip, and with more cases, more doctors are also getting a fair amount of clinical experience in treating Lyme disease (as well as other tickborne infections which are on the rise). Why is it that now, in 2013, doctors are referring to guidelines based on data from 2000 and not recommendations made from 2009? Is it the view of most doctors that they won't change their practice concerning Lyme disease until the IDSA's official guidelines are updated to include the changes in this 2009 report? Why wait?
   
   
2. A number of proposed changes which the panel highlighted - such as measuring elevated liver enzymes and looking for signs of disseminated disease - are old news to patients who were treated by LLMDs during the past decade. If LLMDs found these tests and diagnoses of value in helping patients earlier, couldn't their clinical experience have been incorporated into changes to guidelines sooner? Or, is the case that because there are some LLMDs who are viewed with suspicion by mainstream medical professionals that all of their experience is of no value and cannot be validated - therefore their clinical approach would not be considered in new guidelines? Or, is it the case that LLMDs were doing something some infectious disease doctors already had been doing - but none of their clinical ideas were being integrated into new guidelines anyway? What happened?
   
   
3. If one were to write out a table such as the one below with the strength of the recommendation and quality of evidence for each of the ILADS'guidelines, how would they compare to the revised guidelines with the included changes below?
   
   

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Table 1 - Infectious Diseases Society of America-US Public Health Service Grading System for ranking recommendations in clinical guidelines:

Category, grade
Strength of Recommendation:

A - Strongly in favor
B - Moderately in favor
C - Optional
D - Moderately against
E - Strongly against

Ranking of Quality of the Evidence:

I - Evidence from >1 properly randomized, controlled trial
II - Evidence from >1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from >1 center); from multiple time series studies; or from dramatic results from uncontrolled experiments
III - Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

Please take note of the category AND quality of the evidence ranking for each item below. In particular, note items marked with a Level III evidence ranking, and those of Level I ranking which were considered by panel members to be too high.

Table 2 - Old 2006 Guidelines Versus Recommended Changes For New Guidelines:

Item - Tick Bite Prophylaxis Judgment	Recommendation
(p. 6) A single dose of doxycycline may be offered to adult patients (200 mg dose) and to children >8 years of age (4 mg/kg up to a maximum dose of 200 mg) (B-I) when all of the following circumstances exist: (a) the attached tick can be reliably identified as an adult or nymphal I. scapularis tick that is estimated to have been attached for >36 h on the basis of the degree of engorgement of the tick with blood or of certainty about the time of exposure to the tick; (b) prophylaxis can be started within 72 h of the time that the tick was removed; (c) ecologic information indicates that the local rate of infection of these ticks with B. burgdorferi is >20%; and (d) doxycycline treatment is not contraindicated. The time limit of 72 h is suggested because of the absence of data on the efficacy of chemoprophylaxis for tick bites following tick removal after longer time intervals. Infection of  >20% of ticks with B. burgdorferi generally occurs in parts of New England, in parts of the mid-Atlantic States, and in parts of Minnesota and Wisconsin, but not in most other locations in the United States. Whether use of antibiotic prophylaxis after a tick bite will reduce the incidence of HGA or babesiosis is unknown.	When the 2006 Lyme Guidelines are next updated, the Review Panel recommends the careful consideration of the grading for quality of evidence. One panel member thought the quality of evidence assigned to the recommendation (I) might be too high.
Item - Doxycycline Use, Pregnant Women and Young Children	Recommendation
(p. 7) Doxycycline is relatively contraindicated in pregnant women and children less than 8 years old. The panel does not believe that amoxicillin should be substituted for doxycycline in persons for whom doxycycline prophylaxis is contraindicated because of the absence of data on an effective short-course regimen for prophylaxis, the likely need for a multiday regimen (and its associated adverse effects), the excellent efficacy of antibiotic treatment of Lyme disease if infection were to develop, and the extremely low risk that a person with a recognized bite will develop a serious complication of Lyme disease (D-III).	When the 2006 Lyme Guidelines are next updated, the Review Panel recommends removal of the modifiers “relatively” contraindicated and “excellent” efficacy.
Item - Need For Doctors To Identify Tick & Engorgement Degree	Recommendation
(p. 7) To prescribe antibiotic prophylaxis selectively to prevent Lyme disease, health care practitioners in areas of endemicity should learn to identify I. scapularis ticks, including its stages (figure 1), and to differentiate ticks that are at least partially engorged with blood (figure 2A and 2B) (A-III).	When the 2006 Lyme Guidelines are next updated, the Review Panel recommends the careful consideration of the strength of recommendation. Although a subjective measure, two Review Panel members thought that the strength assigned to this recommendation (A) might be too high.
Item - Specifics On Monitoring Tickborne Coinfections & Disseminated Lyme Disease	Recommendation
(p. 8) Health care practitioners, particularly those in areas of endemicity, should become familiar with the clinical manifestations and recommended practices for diagnosing and treating Lyme disease, HGA, and babesiosis (A-III). Persons who have removed attached ticks from themselves (including those who have received antibiotic prophylaxis) should be monitored closely for signs and symptoms of tickborne diseases for up to 30 days; in particular, they should be monitored for the development of an expanding skin lesion at the site of the tick bite (erythema migrans) that may suggest Lyme disease. Persons who develop a skin lesion or viral infection–like illness within 1 month after removing an attached tick should promptly seek medical attention to assess the possibility of having acquired a tickborne infection.	The Review Panel determined that this recommendation is medically/scientifically justified in light of all of the evidence and information provided (8-0). When the 2006 Lyme Guidelines are next updated, the Review Panel recommends that consideration be given to specifying what constitutes “monitoring” and to providing anticipatory guidance for patients about possible manifestations of disseminated Lyme disease (e.g., arthritis, meningitis).
Item - Treatment of Early Lyme Disease	Recommendation
(p. 9) Doxycycline (100 mg twice per day), amoxicillin (500 mg 3 times per day), or cefuroxime axetil (500 mg twice per day) for 14 days (range, 10–21 days for doxycycline and 14–21 days for amoxicillin or cefuroxime axetil) is recommended for the treatment of adult patients with early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic manifestations (see Lyme meningitis, below) or advanced atrioventricular heart block (A-I). Ten days of therapy is sufficient if doxycycline is used; however, given the much shorter half-life of ß-lactam drugs, such as amoxicillin or cefuroxime axetil, it is unclear whether a 10-day course of these drugs would be as effective. Therefore, for uniformity, a 14-day course of therapy is recommended for all of the first-line oral agents. Each of these antimicrobial agents has been shown to be highly effective for the treatment of erythema migrans and associated symptoms in prospective studies. Doxycycline has the advantage of being effective for treatment of HGA (but not for babesiosis), which may occur simultaneously with early Lyme disease. Doxycycline is relatively contraindicated during pregnancy or lactation and in children less than 8 years of age.	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests removal of the modifiers “highly” and “relatively.”
Item - Choice of Treatment Modality	Recommendation
(p. 10) Because of a lack of biologic plausibility, lack of efficacy, absence of supporting data, or the potential for harm to the patient, the following are not recommended for treatment of patients with any manifestation of Lyme disease: first-generation cephalosporins, fluoroquinolones, carbapenems, vancomycin, metronidazole, tinidazole, amantadine, ketolides, isoniazid, trimethoprim- sulfamethoxazole, fluconazole, benzathine penicillin G, combinations of antimicrobials, pulsed- dosing (i.e., dosing on some days but not others), long-term antibiotic therapy, anti-Bartonella therapies, hyperbaric oxygen, ozone, fever therapy, intravenous immunoglobulin, cholestyramine, intravenous hydrogen peroxide, specific nutritional supplements, and others (see table 4) (E-III).	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that “lack of biological plausibility, lack of efficacy” be replaced with “lack of demonstrated efficacy in controlled studies.” There are data demonstrating that the following are ineffective in the treatment of Lyme disease: first-generation cephalosporins, fluoroquinolones, carbapenems, vancomycin, metronidazole, tinidazole, ketolides, isoniazid, trimethoprim-sulfamethoxazole, fluconazole, benzathine penicillin G and combinations of antimicrobials. There are also data demonstrating that the following are potentially harmful: combinations of antimicrobials, pulsed-dosing (i.e., dosing on some days but not others), and long-term antibiotic therapy (e.g., more than 4 weeks). There is a paucity of data regarding the safety and effectiveness of the use of the following in the treatments for Lyme disease: hyperbaric oxygen, ozone, fever therapy, intravenous immunoglobulin, cholestyramine, intravenous hydrogen peroxide, and specific nutritional supplements, but some of these are likely to be harmful to the patient. Many of these examples, such as fever therapy and hydrogen peroxide, carry considerable risk of harm to the patient.
Item - Diagnosing Tickborne Coinfections	Recommendation
Coinfection with B. microti or A. phagocytophilum or both may occur in patients with early Lyme disease (usually in patients with erythema migrans) in geographic areas where these pathogens are endemic. Coinfection should be considered in patients who present with more- severe initial symptoms than are commonly observed with Lyme disease alone, especially in those who have high-grade fever for >48 h, despite receiving antibiotic therapy appropriate for Lyme disease, or who have unexplained leukopenia, thrombocytopenia, or anemia (A-III).	When the 2006 Lyme Guidelines are next updated, the Review Panel recommends that abnormal hepatic transaminases (AST and ALT), lactate dehydrogenase, or bilirubin should also prompt evaluation for coinfection with B. microti or A. phagocytophilum.
(p. 11) Coinfection might also be considered in the situation in which there has been resolution of the erythema migrans skin lesion, but either no improvement or worsening of viral infection like symptoms (B-III).	When the 2006 Lyme Guidelines are next updated, the Review Panel recommends that consideration be given to changing “might” to “should.”
Item - Early Acute Neuroborreliosis Treatment	Recommendation
For adult patients with early Lyme disease and the acute neurologic manifestations of meningitis or radiculopathy, the use of ceftriaxone (2 g once per day intravenously for 14 days; range, 10–28 days) in early Lyme disease is recommended for adult patients with acute neurologic disease manifested by meningitis or radiculopathy (B-I).	When the 2006 Lyme Guidelines are next updated, the Review Panel recommends that consideration be given to the emerging data supporting the use of oral doxycyline as first line therapy in selected patients with neurologic manifestations of Lyme disease, such as those with hypersensitivity to beta lactam antibiotics.
Item - Lyme Arthritis Without Neurological Disease	Recommendation
(p. 14) Lyme arthritis can usually be treated successfully with antimicrobial agents administered orally. Doxycycline (100 mg twice per day) (B-I), amoxicillin (500 mg 3 times per day) (B-I), or cefuroxime axetil (500 mg twice per day) (B-III) for 28 days is recommended for adult patients without clinical evidence of neurologic disease.	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that careful consideration be given to the current quality of evidence for amoxicillin. Two Review Panel members thought that the quality of evidence assigned to doxycycline in this recommendation (I) might be too high based on the available evidence.
Item - Lyme Arthritis in Children	Recommendation
For children amoxicillin (50 mg/kg per day in 3 divided doses [maximum of 500 mg per dose]) (B-I), cefuroxime axetil (30 mg/kg per day in 2 divided doses [maximum of 500 mg per dose]) (B-III), or, if the patient is >8 years of age, doxycycline (4 mg/kg per day in 2 divided doses [maximum of 100 mg per dose]) (B-I) is recommended. Oral antibiotics are easier to administer than intravenous antibiotics, are associated with fewer serious complications, and are considerably less expensive. However, it is important to recognize that a small number of patients treated with oral agents have subsequently manifested overt neuroborreliosis, which may require intravenous therapy with a ß-lactam antibiotic for successful resolution. Further controlled trials are needed to compare the safety and efficacy of oral versus intravenous therapy for Lyme arthritis.	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that careful consideration be given to the current quality of evidence for amoxicillin. Two Review Panel members thought that the quality of evidence assigned to this recommendation (I) might be too high based on the available evidence.
Item - Diagnosis and Treatment of Neurological Disease	Recommendation
Neurologic evaluation that may include lumbar puncture should be performed for patients in whom there is a clinical suspicion of neurologic involvement. Adult patients with arthritis and objective evidence of neurologic disease should receive: parenteral therapy with ceftriaxone (A-II) for 2-4 weeks. Cefotaxime or penicillin G administered parenterally is an acceptable alternative (B-II).	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests consideration of specifying neurological issues that should be included/excluded. In addition, the Review Panel suggests that “evidence of neurologic disease” be defined and that the adjective “objective” be deleted. Clarifying the language to indicate that penicillin is inferior to cefotaxime in this clinical setting should also be considered when the guideline is next updated.
For children intravenous ceftriaxone or intravenous cefotaxime is recommended (B-III); penicillin G administered intravenously is an alternative (B-III).	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that consideration be given to clarifying the language to indicate that penicillin is inferior to cefotaxime.
Adult patients with late neurologic disease affecting the central or peripheral nervous system should be treated with intravenous ceftriaxone for 2 to 4 weeks (B-II). Cefotaxime or penicillin G administered intravenously is an alternative (B-II). Response to treatment is usually slow and may be incomplete. Re-treatment is not recommended unless relapse is shown by reliable objective measures.	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that consideration be given to adding a rating for strength of recommendation and level of evidence to the last part of this recommendation. Consideration should also be given to providing examples of reliable “objective measures.”
Item - Post (-Treatment) Lyme Disease Syndrome	Recommendation
There is no well-accepted definition of post–Lyme disease syndrome. This has contributed to confusion and controversy and to a lack of firm data on its incidence, prevalence, and pathogenesis. In an attempt to provide a framework for future research on this subject and to reduce diagnostic ambiguity in study populations, a definition for post–Lyme disease syndrome is proposed in these guidelines. Whatever definition is eventually adopted, having once had objective evidence of B. burgdorferi infection must be a condition sine qua non. Furthermore, when laboratory testing is done to support the original diagnosis of Lyme disease, it is essential that it be performed by well-qualified and reputable laboratories that use recommended and appropriately validated testing methods and interpretive criteria. Unvalidated test methods (such as urine antigen tests or blood microscopy for Borrelia species) should not be used.	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that the sentence that begins with “Whatever definition” be modified as follows: “Whatever definition is eventually adopted, having once had objective clinical or laboratory evidence of B. burgdorferi infection must be a condition sine qua non until a syndrome is formally defined.”
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.	When the 2006 Lyme Guidelines are next updated, the Review Panel suggests that consideration be given to changing the phrase “no convincing biologic evidence” to something more specific, such as “Reports purporting to show the persistence of viable B. burgdorferi organisms after treatment with recommended regimens for Lyme disease have not been conclusive or corroborated by controlled studies.” It has been proposed by some that there are hardy, drug-tolerant reservoirs of B. burgdorferi, including intracellular cystic forms. To date, this has not been shown to correlate with symptom persistence, nor has eradication of these forms been shown to correlate with symptom improvement.
Antibiotic therapy has not proven to be useful and is not recommended for patients with chronic (>6 months) subjective symptoms after recommended treatment regimens for Lyme disease (E-I).	Panel determination summary: [...] in the case of Lyme disease, there has yet to be a single high quality clinical study that demonstrates comparable benefit to prolonging antibiotic therapy beyond one month. Therefore, the Review Panel concluded that in the case of Lyme disease inherent risks of long-term antibiotic therapy were not justified by clinical benefit. [...] This conclusion was reached despite the large volume of case reports, case series, anecdotes, and patient testimonials reviewed that attested to perceived clinical improvement during antibiotic therapy. In the end, such sources of evidence were felt to be fertile material for hypothesis- generation, but intrinsically incapable of hypothesis-testing. By contrast, the prospective, randomized, controlled trials were formal hypothesis tests with strict recruitment criteria, prospectively defined outcome measures, and independent oversight. The Panel’s conclusions, which are consistent with those reached by guidelines panels from the IDSA as well as other societies, represent the state of medical science at the time of writing. Only high-quality, prospective, controlled clinical trial data demonstrating both benefit and safety will be sufficient to change the current recommendations.

These proposed changes to some of the guidelines look like a case of updating them to reflect a reality those of us who have been ill already knew years ago based on testing and experience. In particular:

• It appears antibiotics used to treat Lyme disease in its early acute stage are not as effective as they were originally thought to be. 
• It appears that objective evidence of neurological involvement isn't the only reason to consider more intense antibiotic treatment - subjective neurological symptoms may be considered, too - provided they are well-characterized and defined.
• Abnormal liver panels can be used to indicate the presence of coinfections.
• Coinfections should always be considered when symptoms are severe and/or persist after initial antibiotic treatment for Lyme disease.
• A single 200 mg dose of doxycycline as prophylaxis may not have the originally stated quality of evidence to back its use. 

The IDSA has stated repeatedly that its current 2006 guidelines are evidence-based and are the best science has to offer. But it seems that the current guidelines are already outdated and have been, and do not reflect the state of the science nor clinical experience. They need to be updated, even within the most conservative perspective of how Lyme disease should be viewed and treated.

It should be noted that in a number of cases, items with Level I evidence ratings were considered to be rated too high according to some members of the review panel.

One thing I question is what the state of the science is and level of transparency on any recommendation which is labeled with an evidence level of "III". Those who wrote the guidelines used their expertise and unpublished information to determine that recommendation, with no external validation as to which data they relied upon and how they drew their conclusions about that recommendation based on that data. Level III recommendations are about opinion - not double blind, random controlled trials or observational studies on patients, which are a higher level of evidence.

If anyone is an investigative reporter or researcher on Lyme disease - let alone a patient suffering from it - wouldn't you like to know more about how the experts came to their conclusions about such recommendations in the first place?

While the debate rages on about chronic Lyme disease or Post-treatment Lyme Disease Syndrome, and the reviewers of these guidelines stated that there isn't evidence to support the use of long term antibiotics for patients with persisting symptoms - the reviewers do not offer any alternative treatment methods or recommendations, either. This is a long outstanding issue which strongly needs to be addressed.

Either doctors who are using long term treatments and having success with their patients will be asked to produce evidence of that success outside of testimonials and case studies - or longer clinical trials using antibiotic regimens other than those already used in double blind clinical trials will need to be conducted.

But even before one gets there, one has to ask this question: How adequately have early stage Lyme disease cases been treated based on some of the above proposed changes to the guidelines? 

And whether patients agree or not with the proposed changes to guideline recommendations, why is anyone still waiting for these proposed changes to be included and published 3 YEARS after the 2009 report?

Has any research been completed in the past 3 years which challenges the content in these guidelines?

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0 WBUR Series: Living With Lyme

On June 26, 2012, WBUR, Boston's NPR (National Public Radio) station, 90.9, began publishing a series, "Living With Lyme", on their website.

The series of articles are accompanied by free downloadable podcasts and sometimes photos and slideshows. In addition to these articles, a live streaming video discussion on Lyme disease was broadcast on June 28 and is available online in its archives.

Additional Lyme disease related articles continue to be published on WBUR after the initial series was posted.

Here is a comprehensive list of all the articles published in the "Living With Lyme" series, from the oldest to the newest post:

Resource List - Lyme Disease:
http://www.wbur.org/2012/06/25/lyme-disease-resources

In Lincoln, It's Town Vs. Ticks:
http://www.wbur.org/2012/06/25/lyme-disease-lincoln

Map: Lyme Disease Cases In Mass., By Town:
http://www.wbur.org/2012/06/25/massachusetts-lyme-disease-map

A Long, Painful Battle With Lyme Disease:
http://www.wbur.org/2012/06/26/barbara-macleod-lyme-disease

The Debate Over 'Chronic' Lyme Disease:
http://www.wbur.org/2012/06/26/chronic-lyme-disease

What To Do If You Think You've Been Exposed To Lyme Disease:
http://www.wbur.org/2012/06/26/lyme-what-to-do

Why Your Dog Can Get Vaccinated For Lyme Disease And You Can't:
http://www.wbur.org/2012/06/27/lyme-vaccine

Some Cape Residents Worry Tourists Aren’t Taking Precautions To Prevent Lyme:
http://www.wbur.org/2012/06/27/cape-cod-lyme

How Much Lyme Disease Are We Living With?:
http://www.wbur.org/2012/06/28/lyme-prevalence

Lyme Disease Complicates Doctor-Patient Relationship:
http://www.wbur.org/2012/06/29/lyme-science-controversy

The Complexities Of Diagnosing Lyme Disease:
http://www.wbur.org/2012/06/29/diagnosing-lyme-disease

Emerging Tick-Borne Diseases Causing Concern In Mass.:
http://www.wbur.org/2012/06/29/tick-borne-diseases

For a series on Lyme disease, it is surprising how few patients have left comments on a number of these posts to date. It's been my observation that most of the time, patients participate in commenting on articles about Lyme disease and ticks far more frequently than this series has been responded to so far.

There are a few exceptions, such as the vaccine thread, which I commented on some days ago and which is still receiving more new comments. Sometimes the comments are more informative than the article itself, so they are worth a look. (Other times, they are educational only as a magnifying lens under which one can view other people's psychology... use your judgment, do your own research, and weigh the evidence linked to what people have to state.)

Here is the link to the Special Lyme Disease Panel Discussion (online streaming video):
http://www.wbur.org/2012/06/28/lyme-disease-panel

Panelists include:

• Dr. Thomas N. Mather, a.k.a. the TickGuy, conducts public education programs on tick-borne illnesses
• Rep. David Linsky, sponsored the bill that created a state commission on Lyme disease
• Dr. Sheila Statlender, a clinical psychologist and advocate for Lyme disease patients

And just today, an additional article was posted about tracking Lyme disease:

http://onpoint.wbur.org/2012/07/03/tracking-lyme-disease

A lot of thought-provoking articles to read at WBUR, with some thought-provoking comments in response. Check it out...

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2 Viral Genetics Update On Chronic Lyme Drug, VGV-L

Today Viral Genetics posted a letter to shareholders with the following information which relates to their experimental chronic Lyme disease candidate, VGV-L.

The letter stated:

"We are still finalizing scheduling a meeting with the FDA and our team to discuss our Lyme disease pre-IND submission from earlier this spring. Scheduling has been difficult with the number of people involved and the looming summer season. Following this meeting we expect to have a clear road map to follow towards clinical trials"

I am looking forward to hearing more about this meeting. It seems there have been a number of delays on the pre-IND road for VGV-L so far, though, and I can't predict when one is going to see progress on getting this treatment to trial stage.

Now might be the time to contact Viral Genetics and begin asking them questions about what sort of ideas they are coming up with in terms of clinical trial design. As a chronic Lyme disease patient reading along, your input may be informative and useful for researchers.

Stay tuned for more updates on VGV-L as I get them.

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3 "Time For Lyme" Becomes "Lyme Research Alliance"

Just recently, the Lyme disease advocacy group, Time For Lyme - which is credited with creating a partnership with Columbia University Medical Center and the national Lyme Disease Association to establish and endow a Lyme and Tick-borne Disease Research Center in New York City at Columbia - changed its name to the "Lyme Research Alliance".

The name change came about as an effort to reflect the organization's growing emphasis on supporting more research into chronic Lyme disease and how to improve serological testing and treatment.

See this page to view a list of their currently funded research projects:

http://www.lymeresearchalliance.org/research_projects.html

Camp Other blog has written about a few Lyme Research Alliance funded projects such as:

Dr. Karen Newell Rogers' proposed chronic Lyme disease
treatment, VGV-L:
Viral Genetics' VGV-L Candidate For Treating Chronic Lyme Disease
Notes Posted On VGV-L 

Dr. Armin Alaedini's research on antibody response in chronic Lyme disease/PLDS patients:
Antibodies linked to long-term Lyme symptoms 

Dr. Steven Schutzer's research on biomarkers for late stage Lyme disease/PLDS:
Spinal Fluid Proteins Distinguish Lyme Disease From Chronic Fatigue Syndrome

I've checked out the Lyme Disease Alliance's new web site, and I approve of their overall mission and think it was fantastic they gave $3 million to fund the Columbia Lyme and Tick-borne Disease Research Center.

One thing I'm hoping to see with the change in name and greater commitment to research is a shift in the kind of accomplishments they had in the past, where videos, education packets, and legislation has been a focus - to a focus in assessing what kind of research projects would settle the Lyme disease controversy as well as focus on backing research on more novel treatment methods, such as they have done with VGV-L.

It is my dream that someday all the different Lyme disease organizations will unite for a single effort and come up with one large scale, fully funded Lyme disease research project that will help thousands of patients. I'd like to see focus on that project alone for a solid two or three years and see how far we can get in our understanding of Lyme disease.

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10 Commentary On Chronic Lyme Disease and Skepticism

When I began writing this blog, I originally wrote it to give a point-by-point analysis of how one article in the Chicago Tribune, "Chronic Lyme: A dubious diagnosis", did not address the issue of whether or not Lyme disease could be a chronic and persistent infection after initial or delayed antibiotic treatment. I wrote the analysis using Carl Sagan's Baloney Detection Kit, because I thought it was a good framework for deconstruction of the article.

I thought this analysis would attract the attention of a number of skeptics, and from there, we'd engage in a lively discussion about how the article skirted the issue of whether or not chronic Lyme disease is possible and dive into the evidence for and against chronic Lyme disease being a persistent - if only subclinical - infection.

It never happened. 

Over a year later, and it still didn't happen.

And, to this day, only one person has ever left me a comment which directly challenged what I was writing about and judged the content of this blog - at least as far as the idea of persistent infection is involved.

That comment was this:

You error in giving any credit to the "chronic lyme disease" movement.

I recommend this paper in the current issue of The Lancet (Sep 2011;11:713-719) :

Antiscience and ethical concerns associated with advocacy of Lyme disease

Abstract: Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health.

And pertinent to this blog, the authors conclude, in part:

"This situation is not likely to end anytime soon. As with other antiscience groups, many Lyme disease activists are well funded and often connected to influential political and media sources. Treatment of Lyme disease with long-term antibiotics is profitable for LLMDs and can be falsely reassuring to patients, who believe that they have a debilitating chronic infection and thus do not seek diagnosis and treatment for other disorders. There is no deficiency of either new patients or activists. The medical anthropologist Sharon Kaufman wrote that “Information technology has transformed the way trust and knowledge are produced”.67 Most people now find medical information on the internet, and the websites of LLMDs and activists are often viewed as legitimate and reliable sources of information, which they may not be."

         - LindaRosaRN


I responded to her, asked her a few questions, and she never responded in return. A drive by. 

She obviously wanted to be heard but did not want to engage. Her comment was on a post about the Huffington Post and Under Our Skin; it wasn't even related to the antiscience letter to which she referred.

And since then, it's been crickets all around when it comes to skeptics  - even though I get visits from Spirochetes Unwound (of Research Blogging), and other web sites which are science and skeptic-oriented on a number of levels.

It's almost as if someone gets to the front door of this site and decides it's not for them just because it mentions the words, "chronic Lyme disease".

I'm guessing the skeptical person who stumbles upon this page with that first glance thinks, "Oh, well, it's another one of those chronic Lyme activists. Why are they ignoring all the evidence that after antibiotic treatment, those with persisting symptoms develop an autoimmune disorder? I'm getting out of here. I'm not wasting my time on this..."

If they're thinking that, then perhaps an overhaul is in order for this blog because I'm not trying to ignore the evidence about autoimmunity or immune dysregulation related to persisting symptoms.

I'm trying to look at a number of different hypotheses - including chronic infection - because these topics are of interest to other patients and I think they all deserve discussion. And there are other hypotheses outside of chronic infection and autoimmunity which are being researched such as chronic Lyme disease as a metabolic disorder, and I give them exposure.

Because I enjoy science, I look at research and science news related to tickborne infections and their reservoir hosts in general, without any particular goal in mind other than to say, "Hey, look at this - isn't this weird/interesting/informative?" I want to inspire the curiosity of the world I have in others.

At first glance, this blog has been primarily written for other patients with persisting symptoms related to Lyme disease infection. But it has also been written to open the floor to anyone for discussion about different causes for persisting symptoms.

This includes skeptics. They are welcome to comment here and share their perspective, as long as they aren't rude and can state their position while providing supporting evidence.

After all - I have a history of being a skeptic myself, and at times don't just want the cheering section behind me saying they support me as a fellow patient. I also want someone to occasionally shake me out of my complacency if I've been stuck in it. I occasionally want someone to present me with a different point of view or new evidence if they have it so I can consider other lines of inquiry in trying to understand my condition.

I have to wonder sometimes if I need a colorful banner or animated message on the top left corner of the homepage which states, "I am a skeptic and a patient with persisting symptoms related to Lyme disease".

Or maybe I need a paragraph at the top of one of my sidebars in order to say more about who I am.

Something like this:

Side note to all scientists and skeptics, in case you missed it: 

This blog is written from the perspective of one person who has been in the unfortunate position of being a skeptic who is suffering from persisting symptoms after receiving an infected tick bite.  

I want answers to questions such as, "What on earth does someone in my position do?" and "What kind of pragmatic approach can I have to dealing with my illness when I am a skeptic and want evidence to support my position and the decisions I make?" and "What research is out there which supports one or another position as to the cause for my condition?"

This has to be done carefully, though, for the sake of my audience.

While I want skeptics to feel welcome here,  I don't want to scare other patients away who are dealing with the same struggles. And I want everyone to feel welcome here and not like they have to constantly defend their illness to others who may not only be skeptical - but who have the potential to engage in less than civil behavior online.

My concern here is not unwarranted. I have read skeptic sites for a number of years, and while I can read sites where issues concerning chronic Lyme disease are debated by infectious disease specialists, researchers, doctors, and patients - such as this BMJ series of Rapid Responses - I practically choke on some of the comments on this chronic Lyme disease post on Respectful Insolence blog, because some of the exchanges are insulting and do little to advance serious discussion about Lyme disease. (Some of them are thoughtful and intelligent, too, though, so I don't avoid reading the thread entirely just because there are insults.)

And I have to remind myself that any blog on the internet has the potential for ill-informed comments, regardless of the original content.

One response on the above linked blog betrays a certain basic ignorance about Lyme disease:

"Yikes, always knew Chronic Lyme disease was complete woo. It's called an anxiety disorder, get your meds. Even acute Lyme disease is looking to be a bit far fetched, now I am far from an expert but it seems a little bit out of a sci fi novel for a tick to harbor some strange virus, who proved this and what experimental data did they have? What were the experiments that prove that some tick borned virus is the cause of a human disease in the first place?"

What the... 

Acute Lyme disease looks far fetched and it must be sci fi that a tick harbors a strange virus?

Far from expert?

Indeed. 


And some comments are thoughtful and the response is respectfully delivered even if the content is something a number of patients would find disagreeable:

"...I don't doubt your story, but given how common tick bites are, it seems likely that an association could be found regardless of whether or not the tick bite actually caused the condition. Thus, anecdotes are not that useful in understanding the disease. Anecdotes don't tell us cause and effect. They show us why we should care, and they are important for that reason, but they do not tell us what is true. It takes a lot of carefully collected data to do that. 

How do you know the antibiotics are really responsible for your improved state of health? Remember, coincidences do happen -- during the summers I take Pulmicort, but is it really making my asthma better, or is the variable course of my asthma just being kind to me right now? I have anecdotes galore, but it's the clinical trial data that convinces me the Pulmicort really is working and it's not just my own desire for it to work making it seem as though it is.

Indeed, one day the truth may come out. But it'll have a hard time coming out when the science of Lyme disease is decided by politicians, and when those most invested in chronic Lyme disease would rather spend their effort treating patients than finding out whether or not they're actually doing the right thing for their patients. Too many of the positive studies I have seen have been enterprises in proving a point rather than testing an hypothesis; science can't be fair or unbiased or *truthful* if it does not entertain equally the possibility of being wrong."

They have a valid point. I can see that.

The problem is, when is this "one day where the truth may come out"?

I have to make decisions about what to do about my health TODAY.

That's the one truth which few of these exchanges seem to address:

How does one make an informed decision as to how to approach and treat one's condition when there is a medical controversy over how to treat it where one of the two options is not to treat it at all - and doing nothing leads to more suffering?

While the author takes the time to explain that anecdotes are not data (with which I agree) and that tick bites in and of themselves are common, there is plenty of medical research and documentation which provides evidence that a subset of infected Lyme disease patients go on to have persisting symptoms after initial treatment. For some of these patients, these symptoms are severe. For a number of them, symptoms persist not for months but for years.

The IDSA and other medical institutions and researchers acknowledge this condition. It's not well understood - but this phenomenon has been documented and is not the creation of a handful of woo charlatans looking to cash in on me.

And I am, for whatever unfortunate reason, the poor bastard who has this condition. And I:
- had a documented tick bite,
- developed an EM rash,
- received a positive blood test later on,
- developed all these symptoms which were clinically diagnosed as Lyme disease.

Unlike the claim made by Ms. Rosa above, no one has tried to con me into this diagnosis. I had a textbook case of Lyme disease. The evidence was there.

If anything, when I first contracted Lyme disease, I thought I was getting it taken care of early enough and would not have to touch the "Lyme controversy" with a twenty foot pole.

Unfortunately, life had other plans for me.

I ended up not being able to work, got sicker than I'd ever been in my life for months on end, then finally got better and off antibiotics and return to work... only to relapse, have to leave my job, and try to figure out what to do next.


Why me? I didn't ask for this. As someone who reads Free Inquiry on occasion, worked as a researcher, lived in a dorm full of physics and chemistry geeks, and thought Carl Sagan was one of the most brilliant and compassionate minds on Earth, I really did ask "Why me?".

But you know, the answer to a pathetic "Why me?" really is "Why not me?". No one asks for this. No one asks to be hit by a car, abused as a child, diagnosed with breast cancer, or to watch a parent die. We are all subject to things which happen beyond our control. It was just the random luck of the draw that someone who happened to be a skeptic would get a condition of which others are skeptical.

Ticks don't care if you like Sagan or vote for Romney. They just want lunch.

For better or worse, here I am. Now, how can I make the best of this? What can I make of this situation now that I'm smack in the middle of it?

I've thought that all I can do is write, research, and encourage others to do research. Learn and encourage others to learn more about tickborne illnesses. Encourage those who are out there who are working in microbiology and biology to engage in education and outreach which helps patients and sidesteps the politics. Educate one doctor at a time that someone with my condition exists, and that a tickborne infection can lead to chronic symptoms. Warn others and tell them to protect themselves when they go hiking and camping so they can avoid my fate.

Mainly what I want to do is get better and get back to living life as I was before - but this time, perhaps a little humbler, a little wiser, and with more compassion for others and more gratitude for myself.

In meantime, I keep hoping I'll meet others here who came from a similar background.

So far, in terms of scientists, I have had a few other Lyme disease patients with science degrees and research positions (or friends and partners of patients with science backgrounds) comment on this blog. Outside of these patients, researchers have commented less often and anonymously.

And I keep hoping someone who is a skeptic and also struggling with chronic Lyme disease or perhaps CFS/ME will come forward and we can review research together and try to make sense of it and figure out what the best course of action is. Even better? I keep hoping to see a microbiologist who researches Borrelia burgdorferi and has had persisting symptoms from Lyme disease take up blogging on their own and publish more insights of which are but a faint glimmer in my own head.

But so far? Crickets.

Surely we can do better than this. Surely one can light more candles against the darkness?

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1 Three Notable NIAID 2012 Research Projects On Lyme Disease

The National Institute of Allergy and Infectious Disease (NIAID) is conducting some Lyme disease related research which I think readers should know about. There are a number of projects to be found on the Project Reporter web site which may be fascinating, but I took the time to select and highlight a few projects which would be of greater interest to patients suffering with Lyme disease and/or its coinfections.

Project: AN INTRACELLULAR NICHE FOR BORRELIA BURGDORFERI
Institution: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
PI: Skare, Jonathan

Description (by applicant):

Lyme disease, caused by the spirochetal bacterium Borrelia burgdorferi, is the leading arthropodborne infection in the United States and causes significant morbidity in endemic areas. If untreated B. burgdorferi can persistently infect individuals even though the host mounts a potent adaptive immune response such that antibodies obtained from infected patients or experimentally infected animals effectively kills in vitro cultivated B. burgdorferi. In addition, a robust cell-mediated proinflammatory response is observed that induces IL-6, IL-12 and IFN- and inhibits IL-10. Furthermore, the spirochete can resist complement killing demonstrating that this important component of the innate immune response is not sufficient to eliminate B. burgdorferi infection.

The observation that B. burgdorferi persists in such a hostile environment indicates that the spirochete is adept at evading the host immune response via mechanisms that have not been completely elucidated. One possibility is that B. burgdorferi invades host cells and survives at low levels. Recently we have determined that B. burgdorferi invade both immortalized and, more importantly, primary cells (both fibroblasts and endothelial cells) and persist as viable cells in o-culture. In addition we have preliminary data suggesting that the ability to invade host cells involves both integrin binding and Src kinase activity.

In this application we propose to further characterize the internalization of B. burgdorferi and track the fate of B. burgdorferi within thes infected cells to determine how they affect the localized host response following infection. To accomplish this we will use both in vitro correlates of invasion and intracellular survival as well as in vivo imaging of experimentally infected mice as readouts for our studies.

Specifically, we propose to:

(1) Characterize the invasion of Borrelia burgdorferi into primary fibroblasts. The working hypothesis here is that B. burgdorferi exploits invasion as an additional mechanism to avoid host clearance. Our preliminary studies demonstrate that B. burgdorferi invasion is not dependent on host fibronectin, but does involve B1 integrins other than a5B1. In this Aim we will identify the subunit that pairs with B1 to promote invasion and will also evaluate how B. burgdorferi traffics within these cells; and

(2) Determine if invasion is required for B. burgdorferi persistence in vivo. Our working hypothesis is that invasion contributes to persistence by providing an immunoprotected niche for B. burgdorferi. Since Src kinases are required for borrelial internalization in vitro, we will determine whether Src kinase inhibitors alter the infectivity potential of B. burgdorferi in vivo. In addition to standard cultivation and molecuar approaches, novel in vivo imaging will be employed to assess how the inhibitor affects colonization.

The overall goal of these studies is to determine the extent in which an intracellular locale contributes to borrelial persistence.

PUBLIC HEALTH RELEVANCE: Borrelia burgdorferi, the etiologic agent of Lyme disease, is the most common arthropod-borne infectious agent in the United States, and, as such, represents an important Public Health issue. The studies described in this application are designed to address how B. burgdorferi is able to persist effectively in infected mammals despite effective innate immune killing mechanisms and a potent adaptive immune response directed against this pathogen. The hypothesis being tested herein is that B. burgdorferi is capable of low-level intracellular survival in non-immune cells as an additional strategy to prevent borrelial host clearance.

Link: http://projectreporter.nih.gov/project_info_description.cfm?aid=8300386&icde=12284856

Comment: This really begins fulfilling my wishlist, and I look forward to the imaging study videos that I hope will be made and posted online. If there is some sort of confirmation of intracellular Bb in vivo this may explain why some patients need additional antibiotics and why existing treatments may be inadequate as a matter of timing.

This next project is bound to generate discussion, as it involves the potential role of toxins in Borrelia burgdorferi. In this case, the researcher is looking for gene clusters in Borrelia burgdorferi which may create cytolysins similar to the toxins which are found in Staphylococcus aureus, Listeria monocytogenes, and Clostridium botulinum.

Project: A COMMON DENOMINATOR OF PATHOGENESIS; A RARE OPPORTUNITY FOR NOVEL THERAPEUTIC DE(VELOPMENT)
Institution: UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN
PI: Mitchell, Douglas

Description (by applicant):

Abstract: The 20th century witnessed several major advances in medicine. Perhaps most important were the discovery of antibiotics for bacterial infections and effective vaccines for several major viruses. Unfortunately, the creation of effective vaccines for bacteria has lagged behind analogous anti-viral strategies. Compounded with the rise in antibiotic resistance and a lack of interest from the pharmaceutical industry in pursuing novel antibiotics, we risk losing the fight against bacterial pathogens.

Described herein is an unconventional strategy to exploit bacterial toxins as both novel targets for antibacterial agents and antigens for vaccine development. To intelligently address the increasing threat posed by bacterial pathogens, more effort is needed to uncover the molecular underpinnings of virulence. Our group specializes in the use of bioinformatics, in vitro reconstitution, and genetic manipulation to identify and characterize gene clusters that are responsible for the biosynthesis of virulence-promoting cytolysins. The best-known toxin in this family is the highly modified peptide, streptolysin S (SLS, produced by Streptococcus pyogenes).

SLS production is required for the infective process, but not essential life processes. Our work has uncovered SLS-like toxins are synthesized by at least three other notorious human pathogens, including Staphylococcus aureus, Listeria monocytogenes, and Clostridium botulinum. We aim to study the potential role of the SLS-like toxin in an additional organism, Borrelia burgdorferi (Bb), which causes Lyme disease.

Although widely known, the Bb molecular mechanism of pathogenesis is inadequately defined. If the SLS-like toxin was indeed employed during Bb infections, this would represent the first demonstration of toxin utilization in this family of organisms and would prompt a major revision of borrelioses.

Because bacteria typically employ disparate pathogenic mechanisms, the conserved, SLS-like pathway provides a rare opportunity to develop more broadly applicable, yet targeted countermeasures. From our perspective, new antimicrobial strategies should directly target the pathogenic mechanism, rather than DNA replication, protein synthesis, or the cell wall. This approach holds enormous potential, as these drugs will theoretically be resistant to resistance.

This project will identify inhibitors of SLS toxin biosynthesis for the specific purpose of developing novel antibacterials. Moreover, SLS is non-immunogenic, rendering it an unfeasible candidate for vaccine development.

We have succeeded in generating attenuated variants with the anticipation that these can be used for raising toxin-neutralizing antibodies. The notion of immunizing against a bacterial toxin represents a potentially general strategy for future vaccine development.

With this proposal, we aim to not only fundamentally shift the accepted view of Bb pathogenesis, but also to challenge the paradigm that antibiotics must kill bacteria and non-immunogenic toxins are intractable vaccine candidates. These seemingly unrelated goals are actually quite intertwined. Our approach rests on the philosophy that a more complete understanding of toxin biosynthetic pathways and chemical structure can be rationally exploited to design novel therapeutics.

Public Health Relevance: Bacterial pathogens employ numerous mechanisms to evade the human immune system. We have discovered a novel strategy within the organism that causes Lyme Disease, who's pathogenesis remains largely enigmatic. A greater understanding of these processes will lay the foundation for developing the next generation of antimicrobial drugs.

Link: http://projectreporter.nih.gov/project_info_description.cfm?aid=8145943&icde=12284856

Comment:

Wait... I thought Radolf & co. said Borrelia burgdorferi does not produce a toxin? I know Donta patented some genes in Bb he saw as being analogous to a toxin.

Is there now evidence of newly researched genes which create a toxin in Bb? Or is this an old hypothesis which is being revisited?

Project: ASSESSMENT OF PATIENTS WITH BORRELIA INFECTION
Institution: NIAID
PI: Marques, Adriana

Description (by applicant):

Lyme disease is a multisystem illness caused by infection with the spirochete Borrelia burgdorferi and it is the leading vector-borne disease in the United States. Our current work addresses the following areas in Lyme disease: development of new tests and biomarkers for infection, investigation of persistence of infection with B. burgdorferi in humans, search for the cause of Southern Tick-associated Rash Illness (STARI), and investigation of the role of immune response in Lyme disease and PLDS.

One of the main problems in Lyme diagnosis has been the lack of highly specific and sensitive assays for B. burgdorferi and the lack of a test that could be used to assess response to therapy. Such assays should greatly facilitate the accurate diagnosis of Lyme disease and assessment of response to therapy in individual patients. Currently, no such test is available.

We have developed a new test using the luciferase immunoprecipitation systems (LIPSs) for profiling of the antibody responses to a panel of B. burgdorferi proteins for the diagnosis of Lyme disease. A synthetic protein consisting of a repeated antigenic peptide sequence, named VOVO, had the best diagnostic performance, similar to the C6 test (a diagnostic test using a peptide ELISA that we have helped develop and is highly sensitive and specific). The VOVO LIPS test displays a wide dynamic range of antibody detection spanning over 10,000-fold without the need for serum dilution; and offers an efficient quantitative approach for evaluation of the antibody responses in patients with Lyme disease.

Recent studies have shown that B. burgdorferi may persist in animals after antibiotic therapy and can be detected by using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding. Whether this occurs in humans is unknown.

We have implemented a new clinical protocol to investigate the utility of this approach for identifying persistence of B. burgdorferi in treated human Lyme disease.

STARI is a rash similar to the rash of Lyme disease that occurs in persons residing in southeastern and south-central states and is associated with the bite of the lone star tick, Amblyomma americanum. The cause of the rash is unknown, as it is the natural course of the disease.

We have a clinical protocol to investigate the cause of STARI, and we are applying new genomic tools that identify bacteria based on species-specific sequences in the 16S rRNA ribosomal genes to the skin biopsies from patients with STARI.

Inflammatory innate immune responses are critical in the control of early disseminated infection, while adaptive immune responses are vitally important, particularly the humoral immune response, in controlling spirochete levels in tissues and resolution of Lyme arthritis in animal models. We are examining the antibody response to immunogenically dominant antigens of B. burgdorferi in PLDS patients and controls.

Further investigation of the anti-borrelia immune response may help in elucidating the pathogenic mechanism of PLDS and yield important information for future approaches to diagnosis and treatment. We have a clinical protocol in which we use DNA microarrays to characterize gene expression patterns in skin biopsies from individuals with EM, with the aim of capturing the human host response to pathogen exposure.

We are also investigating the differences in immunological response between predominantly lymphocytic meningitis and predominantly neutrophilic meningitis. Results from these studies will serve as a window into the fundamental biology of the infection.

Link: http://projectreporter.nih.gov/project_info_description.cfm?aid=8336099&icde=12284856

Comment:

The existence of the VOVO LIPS test is nothing new - reports on the development of this test have been around since 2010. Also, there is already information about a chronic Lyme disease xenodiagnosis study out there.

It seems like this project has a large scope - or consists of more than one project under the same umbrella. So far, no project end date has been posted for this entry.

What would be of most interest to me would be finding differences in immunological response between patients with acute Lyme disease and those with assumed PLDS - something Alaedini has already been studying.

(Side note: I thought that it was already determined that Borrelia lonestari, a relapsing fever spirochete, was the cause of STARI or Masters disease - did I miss something?)

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6 Health Matters Magazine And Lancet Anti-Science Lyme Disease Rebuttals

I wanted to point out two noteworthy online venues which are discussing Lyme disease as well as chronic Lyme disease - one article and a series of rebuttal letters which have been circulating around the Lyme disease patient community recently.

The first venue is Health Matters, an online magazine in the UK which is edited by Steve Iliffe, a professor at the University College of London, and Paul Walker,  an independent health consultant who worked for the NHS for many years.

This month, Health Matters published part one of an article by Kate Bloor on Lyme disease, "Falling Through The Gap?: Part One: Lyme Disease Prevention In The UK."

The article does not focus on the controversy around chronic Lyme disease but instead goes straight to the roots of Lyme disease by asking about which agencies and institutions in the UK are responsible for educating the public on prevention of tickborne illnesses and how well this job has been done to date.

Quoting Kate:

"Approaches that only target those in traditional high risk groups, may not reach far enough. New research shows that one in five people diagnosed with Lyme became infected either in an allotment, park or garden and one in five patients was infected abroad. These are not normally considered high risk areas or high risk activities."

Any program for prevention should be designed to reach all those groups who are found to be at risk and not some fraction of them, and should include prevention where substantial minority groups are at risk.

Kate also included this useful bit of statistical information:

"A survey of GP’s showed that 72% reported using the wrong method of tick removal, of the surveyed councils, only 7% provided information to staff, and only 7% claimed to have information for the public on their website."

From the research I've read from Russia, one of the major causes of infection from tick bites stems from improper removal of the tick. Every effort should be made to carefully remove the entire tick including the head and mandibles, without placing pressure on the tick's abdomen/gut. This will lessen the odds of contracting an infection greatly. Here, citing that 72% of doctors removed ticks incorrectly is very concerning; doctors are the front line for treatment and should be removing ticks properly nearly 100% of the time.

That regional councils would not have their own staff education and education for the public in place is also important to note, and I have to wonder how much those who have been bitten by ticks in these areas have informed the councils on their experience and requested more warnings to the public on tickborne illnesses. To me, it seems like it would require a small amount of effort and money invested in education to help prevent more people from being bitten.

The rest of the article outlines how prevention is being managed (or not) by various organizations, the educational strides being made by patient advocacy organizations such as Borreliosis and Associated Diseases Awareness UK (BADA-UK), and the need for national and local government health agencies to make tickborne illness a priority.

More here, at the link: http://www.healthmatters.org.uk/?p=1203

The second venue I want to mention is The Lancet, which has recently published a series of rebuttal letters in response to an opinion piece posted last year, "Antiscience and ethical concerns associated with advocacy of Lyme disease" (abstract only).

• Stella Huyshe-Shires, chairperson of Lyme Disease Action, writes about how the situation Auwaerter and his coauthors outline in the US is different from that which is experienced in the UK in regards to Lyme disease prevention, education, and treatment. She focuses on patient advocacy group's drive for awareness and evidence-based medicine to treat patients, and she mentions that the British Infection Association is now collaborating with LDA (UK) and a Department of Health funded body, the James Lind Alliance, on documentation of the uncertainties in treatment and diagnosis of Lyme disease.
  
  
• Christian Perronne, of the Infectious Diseases Department of the University of Versailles-St Quentin, France, points out the high variability and sensitivity of serological tests for Lyme disease, how tests do not account for strain varieties, and that other microbial infections may mimic that of Lyme disease. He points out that syndromes of an unknown cause should no longer be referred to as being chronic Lyme disease, and should be investigated for other microbial and non-microbial causes using an open-minded scientific approach.

• Carl Tuttle, of Hudson, New Hampshire, USA, wrote about how his experience of Lyme disease did not seem to match that of Auwaerter's experience, given how many people he knows have suffered serious symptoms with Lyme disease that was not diagnosed early - whereas Auwaerter indicated Lyme disease is easily diagnosed and treated. He mentions the inadequacy of serological testing and how it can lead to late stage cases which went undiagnosed and untreated, and how legislation has been passed in several states which protect doctors who treat Lyme disease patients with long-term antibiotics. He asks if the IDSA is correct in its position, then why is there so much legislation being passed which protects doctors who offer long-term antibiotic treatment?
  
  
• And lastly, Auwaerter et al offers a response to these rebuttals here:
  http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(12)70056-7/fulltext.
  
  Auwaerter et al state that a huge percentage of patients are being improperly diagnosed with chronic Lyme disease by alternative practitioners when these patients have another condition. They point out that serological testing is reliable, and evidence that testing is unreliable would be needed by Mr. Perronne and Mr. Tuttle in order to support their position. Auwaerter et al point out that the current guidelines stand based on independent scientific review and that "Vague symptoms such as chronic pain, fatigue, and neurocognitive complaints are poorly understood by modern medicine but are the focus of this debate." (Ed: The last full paragraph of this response is as long as the previous two put together and is comprised of nothing but a list of stated possible conflicts of interest.)

Comments:

While I agree with a lot of what Ms. Huyshe-Shires had to say, I would like to step away from the argument that "Lyme disease in ______ is different because it's different here".

I've heard this before, and this argument has been made to try to distance European patients from those in the US, with an underlying belief that since European strains are different, that diagnosis and treatment should be determined using European scientists and research - not that of American based IDSA. Fine, but then I will argue that since Europeans also contract Borrelia burgdorferi that they should come up with diagnostic and treatment methods for the US as well!

Scientific research to date has shown that Borreliosis is Borreliosis, whether it is caused by Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, and a number of other strains. The symptoms produced by these organisms may differ somewhat from one locale to the next, but many have the potential to cause neuroborreliosis, and indeed, even those with a most conservative view of the Lyme disease controversy have stated that there has been too much emphasis on Europe having more neuroborreliosis and different symptoms when the situation is that clinical presentations in the US have been very similar to those in the UK. 

Receiving an early diagnosis and treatment matters regardless of where one is in the world and which strain they have.

I can relate to Mr. Perronne's position, to some degree. I don't think this is a heterogeneous condition - nor was it from the start even if just basing it on those who have had tick bites - since a number of ticks are coinfected with pathogens other than Borrelia burgdorferi/afzelii/garinii. I think it's possible some patients have a different infection which they contracted through a tick bite or perhaps even a tick bite made them more susceptible to a new, undefined infection. More research is needed to determine why this group is heterogeneous, and to study those with a definite history of a tick bite and persisting symptoms very closely (regardless of serological test results) as their own separate group.

Mr. Tuttle's remarks reflect the fact that regardless of what side of the Lyme disease controversy you stand on, people are suffering a lot and heated debates on the state level end up weighing in on the side of the patient. Access to extended treatment is winning - whether the IDSA approves or not.

Auwaerter et al's response, to me, is predictable and to be expected. It would be appreciated if one day they were to focus more on the content of Mr. Perronne's position and join him in it by finding a way to initiate research which directly helps patients who are suffering with persisting symptoms and to stop spending an inordinate amount of time focusing on whether or not certain doctors and patients promote pseudoscientific practices and beliefs. They've already made it quite clear to The Lancet and the public what their position is.

One has to face reality here: If some alternative to current treatment practices is discovered which is safe and effective, patients will use it. In the meantime, patients who are suffering greatly will try any of a number of drugs, antibiotics, herbs, and supplements which are available in order to get well regardless of the IDSA's position on their condition and its treatment.

Whether these attempts to relieve symptoms are scientifically backed or not is irrelevant to someone who is seeking relieve pain and is nearly (if not completely) on the verge of suicide with pain. It is this human element of suffering which Auwaerter et al do not seem to want to contend with and address in a compassionate way - nor in a clinical, scientific way by either engaging in research which directly resolves the controversy or by finding the treatment of all treatments based on their own hypothesis of what causes persisting symptoms.

Patients with persisting post treatment Lyme disease symptoms have often tried mainstream approaches to treating their conditions when they were diagnosed with something other than chronic Lyme disease - only to either experience no improvement or even experience a significant worsening of their condition. The use of steroid-based drugs used for treating rheumatic conditions has been one such example of where patients with chronic Lyme disease have tried them based on an apparent diagnosis of a rheumatic condition - only to get sicker and become more symptomatic. Why is that? Someone needs to research this, too.

At some point I need to write a detailed scientifically cited response to Auwaerter et al's original letter to the Lancet instead of the rant I wrote in response to the abstract alone last year. At the time, I was too personally offended that I and my condition were equated with pseudoscience and my offense led to ranting rather than a rational, objective calling out of each point in the full text with a substantiated counterpoint of my own. 

It's difficult to be without bias. As a person suffering with the fallout from Lyme disease and Babesiosis, I cannot be completely without bias no matter how hard I try. But I can try to read the scientific arguments and research that different parties put forward and weigh them independently of how rotten I feel. It is possible, even if at times difficult. 

In the end, I genuinely want someone to just figure out what has brought me to the level of suffering I've experienced over the past several years - even if in some of that figuring out the cause turns out to differ from that which I've suspected. Fine. Just find it, and find a treatment that gets me back to my old self. 

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1 The Phenomenon Of ‘Chronic Lyme’; An Observational Study

Recently, the results of an observational study on chronic Lyme disease in Norway were published in the European Journal of Neurology. (The full text of the study is behind a pay wall on Wiley - but otherwise you can read the abstract online.) According to the National Institute of Health (NIH) clinical trials database, the purpose of the study was:

"... to chart clinical and laboratory findings in Norwegian patients with symptoms attributed by themselves or their doctor to ongoing chronic Bb infection. Objectives are to assess laboratory findings in relation to established diagnostic criteria and to form a picture of the burden of symptoms and illness perception in this group of patients. The study is essentially exploratory, and is supposed to raise rather than to test hypotheses."

Based on this, it sounds like the authors' original expectations for this study were that the researchers would find out in a given population that among those who either suspect they have chronic Lyme disease and have it - and those who suspect they have chronic Lyme disease and don't have it - that it would be discovered what clinical differences and diagnostic markers would set them apart.

But the abstract doesn't indicate what the criteria are for a case definition of chronic Lyme disease if the researchers had one in mind. Rather, it indicates that of the patients enrolled in the study, there was no evidence that any patient had an existing infection with Borrelia burgdorferi.

The following comments are strictly preliminary and based on the content of the abstract only - a more detailed review is in order once the full text has been read:

First, I was disappointed to find out that the total enrollment expected for this study was a mere 30 participants - and in the actual study, there were only 29 enrollees. This is a very small pool of applicants, and I don't think the data can be extrapolated to fit a large group of people - or even more so, a large group of people from an area which is highly endemic for Lyme disease.

Second, this study in no way set out to solve the problem of whether or not chronic Lyme disease is a real condition - I don't think that was the researchers' goal. Their goal was to characterize those people who either self-reported that they thought they had chronic Lyme disease based on their symptoms or their doctors suspected they had chronic Lyme disease based on their symptoms. Nothing less, nothing more.

It would have been more productive for patients had the researchers taken additional steps to determine what exactly the cause of these symptoms were. But the study was not designed to take those additional steps and just left us with these basic data points:

• Twenty patients (72%) had symptoms of an unknown cause; of them six met the criteria for Post Lyme disease syndrome (PLDS).

• Fourteen patients (48%) had the presence of anti-Borrelia burgdorferi antibodies.

• Eight patients (28%) had other well-defined illnesses.

The researchers stated, "None had evidences of persistent Bb infection, but whether current diagnostic criteria are functional in patients with longstanding complaints is controversial."

Looking at all of this, I'm not sure how to even interpret the initial data shared in the abstract... When those 72% are discussed - of which six patients met the criteria for Post Lyme disease syndrome - are those six patients exclusive of the fourteen patients with anti-Borrelia burgdorferi antibodies or are they inclusive?

If it's exclusive, then twenty of the twenty nine patients have evidence of some relationship to a Borrelia burgdorferi infection. If it's inclusive, then it's only fourteen patients who have evidence of this relationship.

But let's assume they are inclusive, and only fourteen had evidence of anti-Borrelia burgdoferi antibodies. Even if only 48% of the patients studied already have a history of exposure to Borrelia burgdorferi and continue to have persisting symptoms, I think that counts as evidence towards a relationship between Lyme disease and persisting symptoms. Either as a trigger or present causative agent. The researchers themselves state that this is at least partly the case, by reporting that, "sequelae from earlier Lyme disease were probable as main explanatory factor in some cases."

That said, a whopping 72% of patients had symptoms of an unknown cause. So what did they have? It is unknown to me if the issue of seronegativity was considered in patients' reports, whether or not patients with positive antibodies were tested for other conditions with cross reactive antibodies, or whether or not patients were studied for evidence of other tick-borne illnesses.

What is known, however, without having access to the full text is that patients had their blood tested and their CSF studied for any abnormalities and the presence of intrathecal antibodies, as shown in Table 1 of the Supporting Information section. And what is found there leaves me questioning the results - at least in part.

For example, the first patient mentioned in the "unknown causes" category is a 43 year old male who is both IgM and IgG positive for Borrelia burgdorferi antibodies, had 78 weeks of IV antibiotic treatment, and yet is not considered by their definition to have Post Lyme disease syndrome because there was "no documented episode of Lyme disease". This is puzzling - if someone has serological evidence of Lyme disease and they continue to have symptoms - wouldn't this indicate by the most conservative view that the patient at least has Post Lyme disease syndrome (regardless of the controversy over persistent infection)?

That there was no earlier documented acute case of Lyme disease seems to be at the heart of determining whether or not a patient is at least meeting the criteria for Post Lyme disease syndrome. According to this study, it seems that if there was no earlier record of an EM rash and evidence of a tick bite by a doctor, then the patient is disqualified from a Post Lyme disease syndrome diagnosis. Why this is the case when there is evidence patients do not always recall a tick bite, a rash is not always present (and this is even more likely in Europe based on some research), and there are documented cases of patients who are asymptomatic in the early stage - only to be profoundly disabled by symptoms later - is unknown. It doesn't make sense to me.

It would have been interesting had the researchers ran epitope and proteomic analysis of patients' CSF and confirmed earlier research completed by Chandra/Alaedini and Schutzer - so far, I see no evidence this was done; I would expect such an analysis would be included in the abstract. I would also like to know what - if any - immunological factors were examined in each of these patients.

After reading this abstract, what one is left with is are more questions about the nature of chronic Lyme disease than answers.

What is a good starting point for more research of this nature?

What is the relationship between persisting symptoms and infection with Borrelia burgdorferi?

The abstract for this study and its supporting information do not answer these questions. All this study does is begin to examine what relationship there is between Borrelia burgdorferi and persisting symptoms in a small group of people.

References:
http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2012.03691.x/abstract
http://clinicaltrials.gov/ct2/show/NCT01151150
http://www.sciencedirect.com/science/article/pii/S1521661611001914
http://www.plosone.org/article/metrics/info%3Adoi%2F10.1371%2Fjournal.pone.0017287

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