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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4 Commentary: Slate's Article On Romney & Lyme Disease

It seems like over the past two weeks, every time I turned around, there's a new article about Mitt Romney and chronic Lyme disease. How much mileage from one topic can the media get? You would think by now they would have moved on, but today The Day decided it was going to post yet another rehashing about this subject.

Well, if they get to rehash, then so do I. I have some things to say in response to the Slate's article, "Why Is Romney Campaigning on Medical Quackery?", even though it's not the most recent in this set of offerings.

And again, I'd like to make one request of the media at large:

Can you please investigate more deeply the issue of people with persisting symptoms after delayed or initial antibiotic treatment for Lyme disease?

And not just spout out the same tired phrase that clinical trials to date have not shown that the use of long term antibiotics has been effective for the treatment of chronic Lyme disease (or what the CDC and other organizations call "Post Lyme Disease Syndrome")?

But I digress...

On to eviscerating the Slate...

"Let’s play doctor. A patient comes to you with joint pain, difficulty concentrating, anxiety, poor attention, and mood swings. You might run a series of tests to rule out a persistent infection or other disorder. If your patient lives in a tick- and Lyme-disease-infested area, you would be wise to test for the bacterium Borrelia burgdorferi and, if detected, prescribe a course of antibiotics. But suppose the tests come back negative and there is little evidence that your patient was bitten by a tick or was infected with the Lyme disease bacterium. If you are a good doctor, and you are, you might explore a diagnosis of depression, a disease that afflicts almost 10 percent of the population at any given time."

Okay, I'm going to respond to this with, "let's NOT play doctor", because it's not within our training and expertise to give medical advice if we are blogging or writing for online magazines and we are not doctors - or even if we are doctors, and have not actually seen the patient in question before making a diagnosis.

But as we are talking about some hypothetical case here - patient X - and not a real person, then I'm going to use patient X to discuss hypotheticals.

First, joint pain, difficulty concentrating, anxiety, poor attention, and mood swings can be indicative of any of a number of disorders. The doctor is correct to consider different diagnoses, and rule out or rule in anything which may be causing these symptoms. They can be related to some rheumatoid or autoimmune disorder, exposure to certain toxic substances, stress, immunological problems, and other conditions. Patient X may even have more than one condition which is producing these symptoms and need proper diagnosis and treatment.

I would not automatically leap to the conclusion that depression is the disease that is happening - and even so, depression can be a symptom of another underlying condition such as hypothyroidism, hormonal imbalance, or serious vitamin deficiency.

Let's reexamine this portion, and part of the succeeding paragraph:

"But suppose the tests come back negative and there is little evidence that your patient was bitten by a tick or was infected with the Lyme disease bacterium. [...] If you are a doctor who believes that the CDC and NIH have misrepresented carefully vetted clinical trial data about the diagnosis and treatment of Lyme disease, however, you might diagnose your patient with chronic Lyme disease and prescribe an intensive, long-term, side-effect-laden, mega-dose of antibiotics."

First of all, is clinical trial data about the diagnosis and treatment of Lyme disease the only data on which a medical practitioner should base their diagnosis and treatment of tickborne diseases in a particular individual patient?

The problem is this soundbite doesn't even begin to offer an overview of why a medical practitioner would think that maybe - just maybe - someone with a negative test for Lyme disease might still have Lyme disease. Or how it is that diagnosing Lyme disease can be a difficult task at times for any doctor.

The words chosen that follow - "prescribe an intensive, long-term, side-effect-laden, mega-dose of antibiotics" - reflect the judgment of the writer on how people with Lyme disease are treated without the writer actually investigating which antibiotics are used at which dosage for how long, nor how long-term antibiotic treatment for Lyme disease compares with long-term antibiotic treatment for other conditions, nor even what happens to those who have Lyme disease who do not receive long-term antibiotic treatment.

The costs and benefits of antibiotic treatment in general are not weighed and shared, so all it can be is a negative description of this treatment without investigating the long term outcomes of case-by-case studies of those patients who are either receiving it or where such treatment has been withheld.

On to another part of the article...

"As a Slate story pointed out years ago, chronic Lyme disease—not the persistent effects of a long-term bacterial infection but a collection of mysterious symptoms—has powerful supporters. Advocates for the diagnosis tend to blame the medical establishment for not taking them seriously enough."

Here I have a problem with this description of the condition, because it's not reflecting reality.

No one seems to really understand entirely what chronic Lyme disease is and what causes it. No one.

The CDC and IDSA have said that Lyme disease cannot become a chronic and persisting infection after a certain minimum allotment of antibiotic treatment, and offer up the hypothesis that any symptoms beyond this treatment are a (potentially autoimmune) condition known as Post Lyme Disease Syndrome (PLDS). However, this is a hypothesis, and thus far there are no treatment trials which put this hypothesis to the test.

If this hypothesis is so strongly supported, then why are federally funded treatment trials currently being conducted which are about providing evidence for Lyme disease as a persisting infection? Why is there a study currently recruiting which is entitled, "Searching For Persistence In Infection In Lyme Disease"? And why has another study been conducted in Europe, known as the "Persistent Lyme Empiric Antibiotic Study Europe (PLEASE)"?

This doesn't sound like the issue of what causes chronic Lyme disease's persisting symptoms is settled. If so, treatment trials which address this devastating autoimmune condition would outweigh clinical trials on Lyme disease. If one searches for clinical trials for treating Post Lyme Disease Syndrome, the total sum is zero.

To add to this, why is it that the researchers who completed the most recent research on persisting Lyme disease infection in non-human primates concluded this at the end of their recent publication, "Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection"?:

"Our studies do however offer proof of the principle that intact spirochetes can persist in an incidental host comparable to humans, following antibiotic therapy. Additionally, our experiments uncover residual antigen associated with inflammatory foci. Whether persistent spirochetes or spirochetal antigen can cause PTLDS remains unanswered."

That chronic Lyme disease is a mystery is true. That one can readily come to the conclusion that it is not a persistent infection under any circumstances, in any situation, has yet to be established - just as these symptoms being caused an autoimmune condition has yet to be established.

But the content of Slate's article and that of others is very negative about the hypothesis of persisting infection without any specific evidence to strongly back an alternative explanation - or refute the evidence provided in a study such as Embers et al, above.

To continue...

"In 2008, the attorney general of Connecticut investigated the Infectious Diseases Society of America, a 50-year-old organization with more than 9,000 physician and scientist members, for misrepresenting the science of Lyme disease. Not to be outdone, Virginia Gov. Bob McDonnell assembled a governor’s task force on Lyme disease. He appointed Michael Farris as its chair. Farris is a lawyer and the chancellor of Patrick Henry College, aka God’s Harvard, whose motto is “For Christ and for Liberty” and whose “Statement of Faith” holds that the “Bible in its entirety” is “inerrant.” The school isn’t known for its biology department"

You know, we can argue this one until the cows come home. I honestly am not too keen that politicians are getting involved with medical debates - even though I as a patient want more recognition for my condition and more research for it.

What I want is more recognition from the medical profession, and for there to be programs put in place to help those of us with chronic Lyme disease. And what I really want is for someone with an understanding of the disease who has researched it extensively - and has suffered with it long term themselves - to come forward and represent me and other patients; to work from a desire to find the truth about what is causing our symptoms.

I do not need to see another advisory board, appointed chair, or politician try to defend my condition without a more intimate and thorough understanding of it. And I definitely do not need to see my condition being used in a political free-for-all from any side, from any party or special interest group, in order to try to gain more votes.

I find Slate's use of pulling out an appointed chair who is not big on science and who oversees a college with a statement of faith which holds the Bible as being infallible as being a diversion from the issue at hand: the issue of whether or not Borrelia burgdorferi can be a persistent infection.

All we see is an obvious character to take issue with if one is on the side of science and skepticism and wants an easy target to use to rail against the chronic Lyme disease issue... Of course those who are scientifically minded and skeptics are not going to take the word of an evangelical young earth creationist as being one educated about Lyme disease.

On the other hand, if we take one governor and one evangelical chair out of the picture, who do we have left that could have been interviewed instead? How about some scientists, for example? What about Dr. John Aucott of John Hopkins University, Dr. Stephen Barthold of UC Davis, Dr. Monica Embers of Tulane University, Dr. Straubinger, Dr. Brian Fallon of Columbia University, and others who have been studying Borrelia burgdorferi? They have nothing to lose by being asked for their opinion, being neither in politics, nor making money directly off treating patients, or nor working directly for the IDSA. Why doesn't Slate ask them about their scientific opinion on the cause of chronic Lyme disease?

But Slate doesn't do this. Slate goes for low-hanging fruit to support its diatribe against chronic Lyme disease - with the primary goal of denigrating Romney's attempts to appeal to voter subgroups and to support their characterization of Romney as being anti-science.

The mistake Slate makes is in conflating Romney's anti-science leanings with chronic Lyme disease as a condition which does not have enough evidence to support it. The two topics are issues which deserve independent examination.

Onward and upward...

"But the task force seems to have bought into the conspiracy theory that the infectious disease establishment is maliciously interfering with proper treatment. It states: “There is no scientific basis for concluding that 30 days or less of antibiotics is sufficient treatment for every case of Lyme disease.” Again, tell it to the Centers for Disease Control and Prevention."

I am not one of those people who will sit here and spout conspiracy theories. Refer to my page, What To Expect Here, if you have any questions. But there is the issue of oversimplifying and dumbing down the issues involved with properly treating Lyme disease - which is exactly what this article is doing.

It is not true that every case of Lyme disease is sufficiently treated with 30 days or less of antibiotics. Most acute cases are sufficiently treated with 30 days or less, but even when looking at the IDSA's guidelines themselves, they state that up to 10% of all acute Lyme disease patients experience treatment failures. These patients must be retreated and investigated for presence of tickborne coinfections. Also, a certain percentage of patients will have Lyme arthritis, which even Allen Steere treats with two months of oral antibiotics - and if symptoms are still present, a third month of IV antibiotics as well.

I can offer a number of cases where IDSA infectious disease doctors themselves have given individual patients with Lyme disease more than 30 days of antibiotics without thinking too hard, but cannot do so in detail because it would violate HIPAA practices. But these patients are out there, and have been helped by more than 30 days of antibiotics by patients treated by the IDSA's own specialists.

To add to this, there are those outliers with late stage Lyme disease and chronic Lyme disease who do not respond as well to treatment as early acute cases do. These patients have not been studied anywhere nearly enough, in part because fewer cases in these categories are diagnosed - but also because these patients' conditions are not as well understood or always as easily diagnosed to begin with because the obvious, early acute symptoms like a bull's eye rash are missing.

The Slate article continues...

"Another treatment point is telling: “We received substantial testimony from lay witnesses that they had been successfully treated with long-term antibiotics.” Pro tip: the plural of anecdote is not data. Just because someone signed up to address a public portion of the task force meeting does not mean their understanding or explanation of their own medical care is accurate or relevant."

I've said before that I know that the plural of anecdote is not data. And I understand that someone's own experience of their own medical care is not admissible as treatment for everyone.

But then, I've never made the claim that it was, anywhere... I've only made the statement that I think it is possible some people might need longer courses of antibiotics than the guidelines suggest are needed. How long, I think depends on the patient and their condition (genetics, underlying conditions, coinfections, etc).

But that is not for me to judge. I'm not a doctor, and we're talking about individual cases here... If IDSA doctors have the clinical leeway to make decisions to treat individual patients with more than 30 days worth of antibiotics and have it be covered by insurance, well, so then do other doctors - including my own primary care physician and someone who calls themselves an LLMD. The keyword in the document they published, after all, is guidelines.

If that's not happening and insurers are not covering additional treatment for patients when doctors authorize it, then that's an issue that Slate and other publications should be investigating.

To continue...

"I don’t mean to make fun of people who are suffering from what they think is chronic Lyme disease. Their symptoms are real, and they deserve help. But giving them a phantom diagnosis and making them part of a crusade to bring truth to medicine just perpetuates the idea that the symptoms they describe must be part of a complex, classic disease."

Look, this is all fine and good to hold this opinion. However, consider that I don't see enough evidence supporting an alternative diagnosis. The CDC, as you've cited, mentions Post Lyme Disease Syndrome. And yet, this is just a hypothesis and it has yet to graduate to being theory.

Just because the outcome of three clinical trials for long term antibiotic treatment on some patients with chronic Lyme disease showed that continued treatment did not permanently alleviate symptoms once treatment stopped does not mean that there isn't a persistent infection present.

And if Post Lyme Disease Syndrome is a genuine condition, with what may very well be its own genuine biomarkers for it - then as its own separate disease complex, it requires its own research arm and treatment for it.

Now Slate, are you saying PLDS doesn't exist, either, and you're going to flake on this illness which has scientific evidence to back its existence and call it depression?

Of course - because the next thing out of Slate's mouth is this:

"It’s much more likely to be depression, and depression is treatable."

Here we go with the depression, again.

Funny you should say this. Because I have had episodic depression. And I will tell you: Episodic depression was a fucking walk in the park compared to Lyme disease.

There simply is no comparison between the two, other than, well, having Lyme disease has made me feel depressed because it totally changed my life and not for the better.

Why would someone who could work full time at a high paying salary who had lots of friends and opportunity to travel the world a lot give that up to stay at home on the sofa with constant headaches and fatigue and hardly see anyone or go anywhere? To be seriously broke and give up on one's dream of owning a home?

The Lyme disease made me depressed. I don't have depression here as a separate clinical entity all on its own.

And depression, in my experience, never gave me a tick bite, an EM rash, high fevers, swollen lymph nodes, visible joint swelling, paresthesias, and a stocking and glove pattern of neuropathy on my feet.

I challenge you to ask any therapist if they think these symptoms are signs of depression. They'll tell you what they told me: "Your illness is not in your head; you have a genuine physical illness. See a doctor, but see me to deal with the depression that being ill can bring on if you need it."

And seriously... While taking antidepressants can help people with depression, if there is an organic cause for one's depression, such as infection, that needs to be treated first. One only needs to look at cases of psychiatric presentations of Lyme disease - however controversial they are - to at least ask if it isn't a possibility based on the patient's clinical history and limited response to common antidepressants.

Ask those chronic Lyme disease patients who have already taken antidepressants and have seen therapists just how well they have done. Ask. Quite a number of us have already tried exactly what some doctors suggested we do, when they thought we had depression and that is why we felt as crappy as we have. Either they're wrong, or partly wrong, or the drugs they prescribe us just aren't doing the trick.

Depression. Ha. If it is depression, well, then where are the clinical trials where antidepressants and long term antibiotics are used to treat chronic Lyme disease, so we can see the outcome? How about a third treatment arm with therapy alone? At least you'll give us patients a space of our own to swear at and curse modern medicine for not doing more for us.

There's more...

"As the CDC gently points out, mentioning other diagnoses that have been favorite catch-alls, “Your doctor may want to treat you in ways similar to patients who have fibromyalgia or chronic fatigue syndrome. This does not mean that your doctor is dismissing your pain or saying that you have these conditions. It simply means that the doctor is trying to help you cope with your symptoms using the best tools available."

And no one knows what exactly causes fibromyalgia or chronic fatigue syndrome. Obviously XMRV has been taken off the table as a cause for chronic fatigue syndrome - but some other virus or another agent may be the cause of this condition.

In any case, neither of these conditions have clear etiology, so you could be trading one mystery for another. None of which are well understood. And all of which are treated symptomatically, and all of which the drugs prescribed (with the exception drugs such as Lyrica, which is the first drug specifcally prescribed to treat fibromyalgia - which also has the unfortunate side effect of potentially causing suicidal behavior) are being offered based on an educated guess that they might work and, well, patient anecdote. They're prescribed off-label for these mysterious conditions of unknown etiology.

So how is treating chronic Lyme disease with antibiotics any different in this respect, until more research comes in on how to better treat it? Until we better understand the cause?

It may be that while long term antibiotic use for everyone with persisting symptoms may not hold up in small scale clinical trials that it may hold up in individual situations for particular patients with specific backgrounds - backgrounds which may not have been widely represented in the trials which have been held to date. Often it takes years for a wider population using a given drug or treatment regimen to expose its side effects and benefits - the outcomes are not always obvious at first.

And the last bit from the Slate:

"Disregarding my own advice about not taking an anecdote as data, I have my own story about chronic Lyme disease. A friend of one of my brothers had been suffering for years from headaches, fatigue, a sense of despair, a belief that she wasn’t worthy of her job or her boyfriend. She was diagnosed with chronic Lyme disease and was treated with antibiotics, which were ineffective. What she wasn’t treated for, and could have been, was severe depression. She killed herself."

I am very sorry for your loss, no matter what the cause. This is the tragic loss of one woman's life, and it may have been prevented.

I don't know, though, and I don't know the full story either way. I only have your anecdote.

She could have had undiagnosed Lyme disease. She could have had depression. She could have had something else entirely. She could have had more than one problem which included depression.

If depression is a concern, I recommend anyone with any illness see a therapist because in many cases therapy is equally as effective as antidepressants. And if that doesn't help, cautiously try out an antidepressant that is neuroprotective if no other biological or organic cause can be found for the depression. But certainly, if one continues to have the same symptoms while on antidepressants and begins an empiric course of antibiotics later and finds those symptoms begin to lift, well, then go with what works and maybe science does not immediately have all the answers. Sometimes symptoms which appear psychiatric in nature can have an infection as their cause.

So, anyway...

Whether or not persistent bacteria is the cause of all or some patients' symptoms, in my opinion, is still up for grabs. And at this point, many patients have either made the decision to ignore the results of the three small clinical trials which have been completed, or beg for more research on treatment to help us, or both.

I am a pro-science, pro-research person with a history of skepticism. I am skeptical about my own damn disease. And yet, no one has given me any particular advice in mainstream medicine or science as to what to do about it.

You might want to send your money directly to UC Davis or Tulane University for private research instead. But don't come kvetching to me that I'm running off to an LLMD because my primary care provider referred me to one.*

That's just more complaining - rather than addressing the root of the problem in the first place. Those of us in pain can only wait so long and do nothing for so long...

* True story.

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

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3 NOTES: House Subcommittee Hearing On Lyme Disease

Here are some very rough notes from today's hearing on Lyme disease in Washington, DC. Please be aware that notes on about 5 minutes of testimony are missing towards the end of the day's hearing. If the webcast is archived, viewers may wish to refer to it to make their own notes.

House Committee on Foreign Affairs, Subcommittee on Africa, Global Health, & Human Rights hearing

2PM EDT
Tuesday, July 17, 2012
2172 Rayburn HOB
Washington, DC, USA

"Global Challenges in Diagnosing and Managing Lyme Disease - Closing Knowledge Gaps"

OPENING REMARKS

CHRIS SMITH - CHAIR - NJ Rep

We have a missed decade on Lyme disease research
Chris mentions chronic Lyme disease controversy
Mentions bill to establish tickborne disease committee and take fresh look at all the scientific approaches to Lyme disease
Mentions some history about Lyme disease including Borreliosis in Europe and discovery in Lyme, CT
2010 - 20,000 cases reported, but actual number of maybe 300,000 cases in US in 2010
North America Borrelia burgdorferi s.s.
Different species = different manifestations of disease
Clinical manifestations come in three stages
Mentions two distinct views of Lyme and research conflicting
Hard to catch, easy to cure vs. easy to catch, hard to cure
IDSA states short course of abx ok - anything else is risky
ILADS says the science is unsettled
One or more cause of chronic Lyme disease symptoms is possible, including persistent infection
Persistent symptoms could be due to a combination of persistent infection and immune problems

Three areas we need to took at:
1) diagnostics
2) post treatment symptoms
3) available treatments in light of science

CDC: 2 tier serological testing, but should be used for surveillance not diagnosis -unfortunately it is used for diagnosis by some doctors instead of clinical diagnosis
Europe: 8 immunoblots were shown to have a wide range of sensitivity and specificity
Bolen/NIAID: Lyme multistage disease is difficult to diagnose at any stage
Dr. Eshoo: Has exciting info on new diagnostic tools

Persistence: IDSA says Lyme disease cannot be persistent
Chris Smith says there is plenty of evidence that it can persist past antibiotic treatment
Mentions Barthold's studies and persistence in animal model studies
Mentions possible mechanisms of persistence studies: morphological changes (cell wall deficient, biofilms, etc)

Counterargument by IDSA: there are no convincing arguments that post treatment persistent Lyme disease infection is possible.
Chronic Lyme disease is a misnomer according to IDSA.
IDSA treatment guidelines should be based on best science - Smith argues they don't take into consideration possibility of persistent infection and deny patients needed treatment.

Chris Smith reports that the IDSA, NIH, and CDC were invited to the hearing today. The IDSA representative had scheduling conflict, and they were requested to testify at a very near future date before the subcommittee.

MS. BASS

Mentions the serious concern of missing early diagnosis
States few cases of LD in CA - MS. Bass says she thinks Lyme disease is under reported in CA especially in Central Valley
"Deer ticks" aptly named, as deer can carry 1000 ticks on their back on average.
But white footed mice are now known to be major carriers of the disease.
Other animals are now suspected including birds.
Need new solutions and explorations.
Changes in temperature, weather, and precipitation and their role in spread of Lyme disease should be examined.
Improved detection of early disease is contributing to higher reported numbers to some degree.
Local health departments are increasing awareness in spring and summer.
How can we improve awareness with limited budgets and resources?
Work with WHO to prioritize the disease esp in emerging areas such as Asia.

Rep. GIBSON

This is constituent driven. Major issue in upstate NY. (After he retired from army, so many people are suffering from LD and are confused and medical community is divided over its treatment. A Lyme disease task force would resolve this. Need more awareness about disease and diagnosis. Need to make sure money goes to right place. Money has gone into similar place before and the results were the same.

Most encouraging is research to be published in next year about role of confections in persistent symptoms.

WITNESS TESTIMONY

DR. STEPHEN BARTHOLD, UC DAVIS

Borrelia persists normally in immune competent host
i.e. mice rats hamsters gerbils guinea pigs dogs nonhuman primates
antibiotics are likely to fail under some circumstances if not many circumstances
finds self in contentious field - is somewhat of a pariah
we know in pre-immune stage animals can be cured
in immune stage, animals are not easily cured by antibiotics
Only a few places are really studying post antibiotic treatment Lyme - my group, Finland, NY, Louisiana... [?]
Ceftriaxone, Tigecycline, Amoxicllin, Zithromax: spirochetes are shown to survive these antibiotics in animal models
clonal population of Lyme disease spirochetes -> given antibiotic treatment -> results in non cultivable but living spirochetes
Transcribing RNA = metabolically alive spirochetes
exoplant -> carries infection from Bb infected animal to naive animal

Completed study, hope to publish it soon: 12 month post treatment resurgence of spirochetes found in mice.
what is significance of these spirochetes?
viruses can re-ignite and cause disease - question is: can spirochetes?
The answer is not known yet; something unique is going on with Bb and needs further study

DR. RAPHAEL STRICKER
San Francisco, CA - LLMD

speciality in internal medicine, ILADS Vice President
has 2,000 LD patients
number of patients has grown exponentially in past 15 yrs
patients all over the world Canada Brunei Costa Rica UK even NJ
reflects an increasing rate of LD around the world
Lyme disease is the most common TBD

patients develop muscle, joint, neurological, and cardiac symptoms
despite common disease, doctors are ignorant of how to diagnose and treat:
a bulls eye rash may be absent (50% not seen)
patient may be unaware of tick bite (some bitten by poppy seed size tick)
patients have a wide range of symptoms - doctors are often unaware of this wide range

testing remains problematic (not standardized and insensitive)
treatment has evolved in haphazard fashion (IDSA guidelines only address acute infection; standard guidelines ignore more chronic and severe form)
LD has become international medical disaster
thousands of patients suffer from undiagnosed and untreated Lyme disease
and even though it is all over media
the IDSA sits by and does nothing

State of California is grateful to state health board for forming a state Lyme disease advisory board
for requiring mandatory laboratory reporting of Lyme disease to Department of Health just like system for reporting STIs
California has a physician protection law which allows doctors to treat Lyme disease patients as they deem appropriate
Stricker thinks a model for a Lyme disease national advisory board could stem from CA state model

We need CDC and NIH to abandon failed Lyme disease research programs
need them to have targeted research for better tests just as they did for AIDS
need to have more research on treatment of chronic Lyme disease
need to get them to look at evidence and discard dogma about what chronic Lyme disease is
we need for them to listen to patients and how they are affected

Almost 2 decades ago Dr. Joe Burrascano testified before the Senate. He said, "The very existence of 100s of LD support groups, etc underscores many problems which exist in real world of LD." Two decades later and it's the same story.

DR. MARK ESHOO
IBIS Biosciences, Abbott Labs

Need to develop better diagnostic tests
number cases steadily increasing
Lyme disease is severely under reported
Babesiosis is also important
Babesiosis can be mistaken for malaria (Babesia looks similar to malaria under the microscope, too)
Other TBDs are also present

Lyme spread by ticks to mice, and then ticks infect more mice
mice become chronically infected with Lyme disease
bacteria evolved to evade immune system, especially immune privileged sites (e.g. skin, joints)
humans can have long lasting or chronic infection
those infected develop neurological and joint problems
best time to treat is early in infection
most typical early symptoms are bulls eye rash, flu-like, fatigue, aches

CDC 2 tier test - involves indirect detection of antibodies; has 3 problems:
1) can take Lyme patient more than 3 wks for immune system to detect infection
2) interpretation of 2 tier tests can be subjective and change outcome
3) even after treatment, patient can remain positive… controversy over how long to treat patient (weeks? months? years?)

Abbott Labs is looking directly at presence of DNA of pathogens
Sensitive direct assay of organism is historically very difficult because spirochetes are present in small numbers
Abbott made an assay with 8 independent tests to detect the presence of bacteria in blood
they use large volume of blood
and find way to amplify the presence of small numbers of bacteria (bacterial DNA) in blood

Eshoo et al did a study which could find organism very early in infection in doctor's office (refer to abstract) in 62% of patients

Another area of research Eshoo is working on:
variations of strains may determine type and severity of disease
need to study 100 different strains of Bb and what makes them different in terms of impact of disease

We need more government research and funding
- sensitive test for direct detection early in infection before dissemination (monitor responses to treatment
- find out cause of PTLDS. A direct diagnostic tool would be useful
- need to increase research into diff Borrelia strains differences and their role in human infection

PAT SMITH, LDA USA

LD called yuppie or housewife disease
patients have been referred to by some doctors as being paranoid, hysterical, hypochondriac, etc. without any evidence and without looking that something else could be wrong
many advocacy organizations in the world have been victimized in peer reviewed publications
Many patients confide they'd rather have cancer than Lyme disease due to the misunderstanding and controversy over the disease
Patients want studies which solve their dilemmas (such as doctors don't believe they're sick, answer the question "Why isn't the government doing anything?")
The outcome of small clinical trials/studies put a coffin the nail for treatment of chronic Lyme disease and for a number of reasons, these studies were inadequate.
The conclusion was that no treatment is effective for long term Lyme.

Lyme in the south - there are many myths. Myths that:
No lyme disease can be found in south or west
No reservoir hosts in the south
Deer ticks on lizards prevent Lyme disease in ticks all throughout the south
Deer ticks in south do not bite people (?!)
These claims are not scientifically backed.

Patients are overburdened with medical problems.
There are cutbacks in public health depts. so number of cases are unknown.
Pharmacists who won't fill prescriptions for Lyme disease patients in some places.
Munchausens by proxy charges are made toward mom's who treat kids with Lyme disease with long term antibiotics.

Guidelines that are written by researchers and not clinicians are problematic
IDSA is against any sort of treatment for CLD - either antibiotics, alternative treatment, or the use of supplements
CDC surveillance criteria for Lyme disease has formed basis of IDSA guidelines and this is problematic
patients can die of Lyme disease: study of 114 patients who had Lyme disease who died. After they died, most terminal events for which LD was known as the underlying cause have listed on their death certificate a reported cause of death which researchers stated were thought to be unrelated to Lyme disease. Only one patient was said to have died of complications of Lyme disease directly. Question that.

Has seen recorded 22 point IQ drop in kids with Lyme disease due to infection affecting brain
kids have killed themselves due to Lyme disease - due to pain and due to disbelief by peers and others of their having the disease

Pat Smith has had 2 daughters affected by Lyme disease

CDC, NIH, IDSA were absent at hearing and she thinks they are avoiding responsibility when they were invited to be part of the process to help patients.

EVAN WHITE, NYC
Patient - Had Chronic Lyme Disease

(wife just had baby, he is on SKYPE  - his life is now normal being part of point of his testimony)

20 yr advocate borne out of very tragic case of his own Lyme disease due to being given limited antibiotic treatment
at end he is now well because of conscientious doctors
today is father and practicing attorney and employer.

he says his case is an illustration: if not for long term treatment, none of this would be possible

so many people do not have benefits he had
if they had access to treatment, they would be contributing members of society
his story has happy ending
he is fighting for fellow Lyme patients to have same access to treatment
he is advocating for change in limited guidelines

his case study is that short term treatment did not work
long term treatment helped him recovered
he was ill at 11 yrs old
missed school due to flu-like symptoms
doctor did diagnose Lyme disease and he was given 1-2 wks of antibiotics
after 2 weeks he did not get better
the response to not recovering after 2 wks was that PT and psych therapy was needed after those 2 weeks
daily his condition deteriorated
he was a 12 yr old who trusted his doctor
but 6 months later so bad could not do anything
could not go to school, had trouble getting out of bed
blood test showed Lyme disease and confections were very much present months later

here is devastating result of un (or under treated) Lyme disease
6 months of no treatment sent him into tailspin
he vastly deteriorated, went from active athletic child to one who couldn't care for himself
had muscle atrophy, neurological problems
60 lbs at age 13, called a vegetable, and doctors were confused by his state
doctors put him in children's rehabilitation care
did brain scan
it revealed Lyme disease's affect in its passing the BBB: hypoperfusion
he had trouble reading and talking
and was surrounded by doctors who had no idea why he was in condition he was in
2 yrs bounced from hospital to hospital
6 months in children's hospital

went home and parents arranged for appt with LLMD
the LLMD "got it" and had their own personal experience with the disease - not just treating other patients
he had long road ahead for recovery but this was his turning point
he was on long term antibiotics coupled with supplements
2 year crawl to get out of that place
even if it were 10 yr crawl that would have been ok with him
stopped using wheelchair
got out of bed
began to take care of self
began to read again
began to be able to communicate again
got him on trajectory to become person he is today and fully recovered

hoping through this testimony that patients who are affected can get treatment they need to recover from chronic Lyme disease
the net effect of current guidelines restricting treatment deprives so many if not all from having health care option to seek long care treatment that does work for many patients so that they can recover and live long healthy lives

Rep. SMITH

intro Stella in UK

STELLA HUYSHE-SHIRES
Lyme Disease Action (UK)

UK doctors not taking patients seriously
Department of Health accreditation of Lyme Disease Action, Lyme Disease Action is now considered an unbiased source of information on Lyme disease in the UK
papers say Lyme Disease is overdiagnosed
public say it is underdiagnosed
what is the evidence?
we don't know incidence of Lyme disease in the UK
One GP practice finds it 20x greater than numbers which are reported
1300 cases found in one year may mean there are really more like 26,000 cases in UK

survey:
23% patients found ot have Lyme disease but the rest with similar symptoms were diagnosed with CFS
there is concern CFS patients are misdiagnosed and have Lyme disease
on the flip side maybe
100 people year in clinics in UK may be misdiagnosed with Lyme disease
But in a CFS clinic - 40% patients were misdiagnosed with CFS

Why is LD difficult to diagnose and what can be done about it?
we need unequivocal tests and clear guidelines
none exist in UK
most doctors haven't seen Lyme enough and rely on blood tests for diagnosis in UK

unreliable info on internet, certain labs, etc only part of story even if there is an element of truth in it
European challenge of more than one strain of Bb adds to complexity of test issue
Scotland uses more bands in its lab than other locations - leading to different line drawn for positive test results and access to treatment

Most treatment recommendations based on opinion not evidence
need other stakeholders to investigate Lyme disease
Lyme Disease Action (UK) is working with James Lind Alliance to engage doctors in more awareness of LD in patients and in general

The biggest challenge globally is recognition of unknowns in Lyme Disease
All across Europe there is a polarization of opinions along IDSA/ILADS poles
and there may be reluctance to climb out of one's entrenched view of Lyme disease

In Northern Europe doctors rely heavy on test results - similar issues found there.
In Central Europe, doctors have more experience: Lyme is a big problem, doctors say the tests are not good enough; doctors say they don't know how to effectively treat all patients.

Politics are a problem.
Uncertainty of the science is a problem.
Politics prevents recognition of the uncertainties.

QUESTION AND ANSWER SESSION (Rep Smith/Rep Gibson ask questions)

HUYSHE-SHIRES

A: HPA guidelines come from IDSA
Worse thing when patients are told symptoms are in their head
IDSA only recognizes visible arthritis then patient may get further tx
HPA does follow IDSA guidelines
indiv doctors sometimes make indiv clinical decision
case studies London school of hygiene (4-5 yr period) - some patients did not recover after initial course of abx, then some not after second, then some had a third. Between each treatment, patients were believed and found rising antibody levels.
Doctors will say adequate tx occurred, but it's adequate in terms of meeting guidelines but not in terms of effectively treating patient

BARTHOLD

Q: Are proposals being rejected for research at NIH?

A: Peer review is an issue. Peers are divided just are anyone else in Ld community
have direct exp in prejudicial statements in grant application reviews - peer view of applications does not get over the barrier
NIH is struggling to fund investigators
young people are not entering science, old people are leaving
in that environment combination of things - anything controversial having difficulty being funded
made NIH call for application on research on persistence after antibiotic treatment
only suggestion is his
we scientists are always looking for money. Follow the money.
NIH invests in biodefense then people gravitate towards biodefense research.

STRICKER

Q: Rep.brings up conflicts of interest and suppression of data in IDSA guidelines review.

A: IDSA hearing was organized by IDSA and no treating physicians were on the committee
Even though guidelines were flawed they were ruled acceptable.
Stricker encouraged by Dr Eshoo's research and development of advanced early testing.

["To date no antibiotic treatment treats biofilms." - attribution?]

Q: Rep comments to Barthold: issue of "mopping up" after antibiotics
host immune system must mop up remaining spirochetes... Explain.

BARTHOLD

A: using biofilm analogy: there is a population of microorganisms, some of which are dormant
dormant non-dividing bacteria are universally tolerant of antibiotics and are not dividing or active metabolically
Borrelia: we know it is dividing and disseminating and susceptible to antibiotics early on but during the immune phase in animals there is a 10 fold reduction in population (not necessarily in biofilms) and what is found are non-dividing spirochetes; they are dormant and antibiotics are not touching them
What is unique is they grow out but they cannot be cultured - they may be attenuated.


STRICKER

A: Borrelia has molecular machinery to make biofilms according to Dr. Stricker.
Stricker states cell wall deficient form evades antibiotics and it needs to be researched more.

Q: Rep. Asks Dr. Eshoo: How close are you to coming up w new test and why is Big Pharma not getting further involved?

ESHOO

A: It's a small market according to BP and takes lots of money and time to invest.
Lot of people in medical community say current test is good enough.

Eshoo thinks sensitivity needs to be improved and tests need to be improved to end the controversy.

Who wants to be infected for 3 weeks or more untreated waiting for a positive blood test? Nobody.

Rep. Q to Stricker:

Are there people outside the IDSA guidelines panel who notice there's a problem [with testing]?
Does Dr. Francis Collins (NIH director) say "What is wrong here? Why is this a persistent bone of contention?"

STRICKER

A: Blumenthal investigation found there are 14 people in the IDSA who control guidelines, testing, and diagnostic guidelines of Lyme Disease. The rest of the IDSA (8,000 people) defer to this group.

PAT SMITH, Lyme Disease Association

LDA has Scientific and professional review board
It is voluntary board
If issues need to be addressed or LDA is considering funding research, the board is asked to comment on it using their expertise
CALDA, LRA, etc also rely on this board

STRICKER

Q: Rep. [?]: you have 2,000 patients. What is your takeaway from this huge patient number and how are they when they find you?

A: Number of patients exceeds CDC reporting. That's one thing it tells me. Number of those affected may be 10 fold higher.
Many come after yrs of misdiagnosis and no treatment.
70% of patients get better. He finds this gratifying and he turns a deaf ear to the controversy because of outcome.
Uses long term antibiotic treatment.
Published study last year on neurological patients needing 6-12 months of antibiotic treatment to improve.

[5-6 minutes of testimony notes missing]


COMMENTS NEAR END

8.75 million dollar research fund Chris Smith says has been put forward. Chronic Lyme is supposed to be included in this research. How should the wording for the law be improved and how can there be better oversight to get money to the right place?

Barthold said: Follow the money.
If you enlarge the pot and spend it on research that's already been done, we get nowhere.
If we and NIH recognize persistence after treatment as an issue, then new research would be done on this issue.
A more narrowly focused call for applications would help if NIH would agree with that - research on chronic symptoms and the biology/pathology of the organism.

Dr. Eshoo said the field needs support to get off the ground and that RFAs must be specifically targeted toward solving narrowly defined problems.

PAT Smith has concern research money goes to post Lyme disease syndrome and not chronic Lyme disease - which is a different condition.
Patient perspectives on issues of the disease is important and knowing how it's affecting them is important.
Advocates, treating physicians, and patients need to be involved in the process of determining what needs to be researched.

Q: Rep. Gibson: How do you expand Lyme literacy among old and new doctors?

STRICKER

A: ILADS has preceptorship program. Can learn about diagnosis and treatment of Lyme disease. Program is funded privately. Mentor doctors who want to get involved sign up.

Stricker has trouble finding physicians willing to get involved due to controversy. This has had a chilling effect on mentorship.


Q: Rep Gibson: is that because state med board may censor them?

A: Yes. Though state has protection law, the risk censoring by board and other doctors may still go on.

Has 27 studies in table in written testimony (table 2) showing persistence in humans after IDSA guidelines-based treatment.

BARTHOLD

We need to know what is happening in humans but animals allow us to extrapolate models. Many people are using animals but looking only at acute early phase of infection. Not many people are looking at chronic persistent infection in animals. Fewer than five labs worldwide are studying this but it is the most important aspect of the disease.

HUYSHE-SHIRES

Borrelia has been isolated in patients after initial treatment - there are some cases recorded in published papers.
Some people improve after longer treatment
We need more investigation to determine how to better diagnose and treat Lyme disease

IDSA guidelines are accepted in the UK
Summary of recommendations for treatment by European Federation of Neurology Specialists (organization name needs fact checking) - make the point that in neurological Lyme there are no good trials of more than 28 days antibiotic treatment for neuroborreliosis.
They base this on opinion because there is no trial in Europe for longer term treatment of neuroborreliosis.

There are some trials which show good recovery, but at most 60-70% patients experience a good response. A patient does not consider 7 of 10 people responding to treatment as being a rate that is excellent.

PAT SMITH

Children are most affected by Lyme. They have more complications and are greatly impacted by their peers and teachers and what they are saying about them.

It is appalling what comments are being made about students who are ill with Lyme who cannot make it to school because they are too sick. No one wants to stay at home with their mother from school for four years.

One problem is inadequate early antibiotic treatment may lead to a poor antibody response and negative tests, which then put child at further risk for being disbelieved for having Lyme disease.

Some family services will take kids away from parents if those parents treat one child with antibiotics for chronic Lyme disease. This is serious and kids are psychologically damaged by the disease as well as the response from society and their community towards their illness.

We have the knowledge and tools in this country to stop this.

HUYSHE-SHIRES

1-3 people in UK are believed to have expertise on Lyme in UK, and those 1-3 apply IDSA guidelines and support them
NHS did not make any needed changes to their guidelines even though they should be made to suit the UK patient population

ETHAN WHITE

If sick, seek out people who will lead you to knowledgeable doctors who will offer treatment for Lyme disease.

SOME CLOSING COMMENTS

Barthold thinks people on both sides are good people, and he thinks we need to move past contentiousness and work together to help those affected by Lyme disease.

We need to work to get out of entrenched positions and get to the bottom of what's happening using science.

It's time for people to get together and show their cards and be willing to act in the best interest of patients and work past this contentiousness.

---

Comments:

Will be adding links relevant to this testimony soon.

If anyone who gave testimony at the hearing reads these notes and sees a correction that needs to be made, please request correction in comments and I will revise this post.

UPDATE - July 17:

Original testimonies are now available for download including additional materials from each of the witnesses. Scroll down this page for pdf files: http://foreignaffairs.house.gov/hearings/view/?1455

UPDATE - July 19:

Ustream has two streaming video archives of the hearing available at the following links:

http://www.ustream.tv/recorded/24058724

http://www.ustream.tv/recorded/24060689

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2 Anonymous Comments On Chronic Lyme Disease

Last year someone who identified only as "anonx" wrote some interesting comments on last January's blog post on quorum sensing, "How bacteria "talk" and how to make them shut up". (There is a fascinating video there by researcher Bonnie Bassler. I highly recommend checking it out.)

To my knowledge, comments on Blogger do not get syndicated on post rss feeds - though one can request rss comments separately. I think that anonx's comments are worth taking another look, so I have decided to repost select excerpts of them here. (Refer back to the original comment thread for the CO side of the dialog, if needed.)

Anonymous January 21, 2011 5:06:00 PM HST
persister cells
quorum sensing
round bodies
blebs
biofilms made of borrelia
biofilms made of a mix of pathogens
symbiosis in all its forms and iterations
intracellularity
the cascade of genospecies and strains
quiescence and dormancy
transfections
borrelia stuck in B cells with CLIP attached
the role of toll-like receptors&inflammation
the growing list of possible co-infections
xmrv
new view of PANDAS that goes way beyond strep...
molecular mimicry

guess I'll stop here but I could go on --you just need a little proof: not just proof it is happening but proof that treating it will end the illness. that's the problem.

Anonymous January 21, 2011 11:03:00 PM HST

Don't you think that looking at persistence in isolation could be futile, given the large number of people treated for years without cure? Persistence could be the imperceptible spark that incites an immune tsunami. What if it is easier to treat the tsunami --by its nature outsized and blatant and in your face-- than the spark which, though present and incendiary, we cannot find? Is it possible that the yin and yang nature of the fight has prevented a view of the system overall? What if a tiny amount of infection has caused a huge inflammatory response? What if that infection is hiding in B cells because a glitch in the system has prevented T cells from recognizing the foreign invader, and thus, from finishing the job? What IF to get rid of the persistent infection, you must treat immune dysfunction first? So no ...I don't think it is as simple as you say, or that by conceiving the issue along the old paradigms of the fight, raging fruitlessly for 30 years, you will get what you want ... unless of course, it is really as simple as you suggest. I mean, what if you prove persistence, but it still won't bring a cure?

Anonymous January 22, 2011 11:57:00 AM HST

regarding the four trials cited, they do in fact show benefit to retreatment for fatigue and pain --and thus, in fact do not match with the wording of the conclusions rendered or (in the case of two of three authors) forced down those authors throats by the powers that be. There is actually ample evidence in these trials to suggest a benefit to retreatment and longer treatment --and in the case of the Klempner trial, serious issues with methodology. But as you say, the outcome of these trials must be detached from pathophysiology --what is the mechanism of the benefit? That question the trials do not address.

Still, to detach infection from immune response is just plain wrong-headed. We are 10% by weight bacteria, and most of those organisms are beneficial. The question is --which are the pathogens, and how do those pathogens do us in? In every case, inflammation and cellular immunity are going to play a role.

Anonymous January 22, 2011 11:15:00 PM HST

It is a very complicated problem, as you say.

It is TRUE that if you suppress inflammation infection would spiral out of control: The murine studies on borrelia and toll-like receptors show that to be right.

But here's the thing: Most researchers, even most of the IDSA researchers, don't actually deny that organisms can persist. They just deny that those quiescent remaining organisms are driving the continued symptoms --they say these persisting borrelia are too few, and too dormant. And they would cite the research on quorum sensing to support their case.

As I see it, it is not really persistence you need to prove, but rather, the mechanism by which persistence at the low level research suggests drives the disease. Inflammation is not the only immune mechanism --cellular immunity or dysfunction thereof can play havoc, too, and persistent infection could drive it in an endless loop.

Also: Treatment studies without knowing more about pathophysiology can work against you, because --hell-- they are just empiricism on top of empiricism, more wandering in the dark.

I contend you need more basic biology to target such studies, strategically. If you were to move forward without that, you would need an elaborate methodology with many variables and large enough numbers of patients to test for many possibilities and separate the data from the noise. And with Lyme patients still so ill-defined, with no test extant for active infection ...

Makes my head spin. A hundred million dollars would help.

Anonymous January 23, 2011 1:34:00 PM HST

Other,

My comments refer specifically to the Barthold work, with which I am extremely familiar. Barthold's findings of small numbers of dormant, quiescent spirochetes within collagen across the range of mammalian species following treatment have been well-known inside the mainstream (though published only recently) for decades. There is no great rush to debunk Barthold, whose research really is beyond dispute --Barthold himself being an especially meticulous and careful scientist. What his critics say, however, is that these spirochetes are not active enough and not numerous enough to cause disease. (to wit: issue of quorum sensing.) Barthold theorizes otherwise, contending that the small numbers of chetes may provoke an outsized --but heretofore undetected-- cytokine cascade that causes the disease. Barthold would classify this cascade under the heading of INFLAMMATORY response. This is his theory --and a powerful one that should be explored.

You may have noticed that NIH has begun to test the Barthold work with a study of xenodiagnosis, but patients are protesting that study for fear that the ticks used might not be as naive as claimed: And really, given the confusion over pathogens involved, who knows?

Other theories of persistence to pursue include the impact of round bodies AND the work of Newell, who finds Borrelia stuck inside B cells because of a dysfunction in MHC.

In the case of Newell, especially, the notion is that persistent infection can never be cured without correcting the recognition dysfunction of MHC. In other words, even though the disease is driven by persistence, Newell says you have to correct the immune problem first.

And by the way, both she and Barthold insist you can never entirely clear borrelia infection with antibiotics alone --you need the immune system to do the final kill, and so you must have an immune correct FIRST, even if the driver is persistence.

Or it could be the round bodies... but whatever it is, it is complicated --and simply fueling the fight of persistence versus immunity isn't helpful.

There is a difference between what patients use to get well right now --the ax in the form of huge quantities of endless suppressive antibiotics-- and what they should want for the future --the chisel, which could well be an immune correction that allows infection finally to be resolved. There should be a divide between the effort to protect a Lyme doc in the here and now and the direction of research for the future --but it is hard for a lot of people to understand this.

I agree with you that if we knew the mechanism we would have a target --and that is why I am so equivocal if not outright squeamish about the continued treatment trials some patients are calling for.

What are they treating? --and if they don't really know, there is a big risk that study could bury them deeper and darker than ever before.

anonx

Anonymous  January 23, 2011 7:27:00 PM HST

Given current state of knowledge immune treatments could backfire, big time --as the literature shows. If you look at the work on toll-like receptors you find a genetic curve for inflammatory response to borrelia ranging from almost nothing to off-the-charts and everything in between. That is just one immune parameter, and there are many others. These parameters could vary for every infection or strain and every person. Therefore it is possible with current state of knowledge that suppressive abx are really the best we have... there needs to be a crunching of data to understand what we are looking at --otherwise, it is just stumbling in the dark. The amazing thing is that the IDSA crew has gotten away with such a grotesquely oversimplified story of this disease for so long --and that to explain it, they perpetuate the explanation that it is a psychosis instead of a complex spectrum of infection and immune response. But by giving an oversimplified rejoinder, patients have hurt their cause, too.

In a gross way one could do a study treating infection, treating immune issues or treating both: but this would be very crude without more data up front.

anonx


Comments:

So I do have a few comments on this, now that it's nearly a year and half since these comments were posted. My thoughts on the matter have shifted over time, and after exposure to more research.

• I'd like to see evidence that Borrelia burgdorferi is hiding in B cells in vivo. That would be informative. There has been some mention of Bb being intracellular in a few in vitro studies and one in  vivo study; we need more.
  
• This anonymous author may be on to something, and it may be that the host immune response may need to be addressed in order to manage the remaining infection if it is still present. Not enough is known, but when I read about filgrastim and rixtuximab and how they have some positive effect on a patients with persisting symptoms of Lyme disease or CFS/ME,  I think that adjusting the host immune response is an avenue worth exploring. It should have been explored more years ago.
• I still think the trials must be detached from pathophysiology. My position on this has not changed. Treatment trials have done nothing to provide evidence of persistence of Borrelia burgdorferi one way or the other.

• I strongly agree we need more basic biology research. The anonymous author's comments on the role the immune system plays in infection are noteworthy. But we also need to know what is going on if the infection does persist in some form. Is there a persister phenotype? Ongoing research into persister phenotypes should not be neglected. But I wouldn't leave all research at that, because there are other hypotheses to consider.

• One thing I wonder about is the issue of quorum sensing and efficiency sensing, and if blebs or vesicles play any role in the dissemination and pathogenesis of Borrelia burgdorferi. Blebs as a form of communication are observed in other bacterial species, and perhaps Bb uses blebs and vesicles in a different manner and they are not part of cells undergoing apoptosis. Plasmid DNA and outer surface lipoproteins have been found within blebs; there is some suggestion of blebs containing adhesins... I think there's more to blebs than meets the eye.

• Anonymous said, "There is a difference between what patients use to get well right now --the ax in the form of huge quantities of endless suppressive antibiotics-- and what they should want for the future --the chisel, which could well be an immune correction that allows infection finally to be resolved. There should be a divide between the effort to protect a Lyme doc in the here and now and the direction of research for the future --but it is hard for a lot of people to understand this." I keep reflecting on what they wrote, and its implications. Is there a more targeted approach which could be designed to help treat patients?" I think they are right - there is no reason why patients cannot ask for protection for the treatment they are receiving now while promoting research on new and different treatments. I think VGV-L is one effort in this direction, but I am not sure it will work. There is a lot of complexity involved.

• Last but not least, my anonymous commenter said this: "The amazing thing is that the IDSA crew has gotten away with such a grotesquely oversimplified story of this disease for so long --and that to explain it, they perpetuate the explanation that it is a psychosis instead of a complex spectrum of infection and immune response. But by giving an oversimplified rejoinder, patients have hurt their cause, too." 

I think there's a lot of truth in that last statement. Now, what does one do about it?

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