0 Placeholder: ILADS 2012 Conference Remarks

Coming soon... ILADS 2012 Conference Remarks - watch this space.

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0 Late November Newsletter From Camp Other

There are a few announcements I'd like to make today...

For those of you who are here for the first time, via Twitter: Welcome to Camp Other blog. I'm glad to see you here, and I look forward to having interesting discussions with you both here and on Twitter.

Whether you are new to this blog or a returning visitor, the following announcements may help you make sense of what's been happening here at Camp Other blog:

An Effort to Change Writing Style and Reporting

Joining Twitter is a recent move I made in the past couple of weeks in order to pick up more great writing on science and links to posts from science bloggers.

In some ways, this is great because I'm learning more, and I recommend following those I follow because there are a lot of interesting articles out there. But in other ways, this is a humbling experience because there are so many good writers out there - and once I've read them, I can't help but notice there is room for improvement here.

I'm not a professional blogger and do what I do for my own education and share it with others. I never attempted to make this blog a profitable enterprise because I felt that the information was something everyone should have and I wanted to remain neutral by not being funded by anyone who could be perceived as having editorial influence over my posts. This is how it has been - and this is how I want this site to continue - even if someday I manage to become a professional writer in the future.

Open source or not, after reading more science blogs and articles, I can only see that learning from those already in the trenches longer than I have been will teach me how to be a better blogger for everyone.

One thing I am already noticing, unfortunately, is that blogs which are more accessible than mine in some way - those which reach a wider audience, or those which are high volume and have short,  focused posts - are blogs which are going to be difficult for me to emulate.

Reason being: I am suffering from a medical condition which affects my cognitive abilities and energy. My ability to either stay focused on one topic or publish a brief post is challenged due to having chronic fatigue and trouble focusing.

Ironically, having more fatigue doesn't translate into shorter posts - it comes coupled with altered executive function in my brain - so I can ramble on and write a long post yet have trouble getting to the point.

I'd like to make an effort to change this, but where to begin? I could use some advice as to how to overcome these stumbling blocks and make my blog not only more easily readable for a wider audience but also optimize and work with the cognitive abilities I do have.

REMOVED: The Poll On What Causes Persisting Symptoms of Lyme Disease

For almost a year, a blogspot poll widget was on the upper lefthand corner of this blog. It asked readers to select among a number of choices as to the cause for persisting symptoms in patients after initial treatment of Lyme disease.

In recent weeks I have been monitoring the output of this widget and decided in all fairness it needed to be removed because votes were not being recorded and displayed accurately: One week I would see a score of over 110 votes, and the following week it would dip down to 93 - only to waver between 97 and 92 in the following weeks.

Any poll should be gaining and not losing the total number of votes. So it got voted off the Camp Other island, and I won't be using that widget again. Other online sources reported similar issues with this widget as well, and had I known in advance it was a problem, I would have used a different poll widget.

Despite this setback, know that each choice and the most recent results will be discussed in a future post.

A sneak preview: A little over 90% of readers who responded to the poll thought that Lyme disease can be a chronic and persisting infection after initial treatment - while a little over 30% thought persisting symptoms that occur after initial treatment are caused by an autoimmune condition.

The Challenge Of Being Both A Patient And Researcher: Bias

I placed a request on Twitter earlier today asking followers for any information on scientists who study the disease they themselves have - and in particular, blog about it.

I'm hoping to ask them a few questions about how they handle the issue of bias, and how they sort out other research they read about their own condition in order to know which leads to follow, which leads are cold, and which leads are questionable.

One of the walls I find myself banging against as I continue to write this blog is my concern over the issue of bias: Can a patient research their own disease and its causes and treatment without bias, or is there always going to be a certain amount of bias in what one reads and writes about because one is a patient?

Not sure I can sort out all the issues around this, but I wanted to bring up the question because I think it is an important one. I'd like to explore this more.

Sick, Symptomatic, And Struggling

I mention it only in passing because I am still not posting as frequently as I hoped:

I'm not doing so well lately. I suspect the symptoms I'm having are due to a new condition and I am in the middle of getting referrals to specialists to help sort it all out. In the meantime, hopefully I can find a way to continue to do research and blog more regularly.

And there is a certain level of frustration I'm experiencing here which is difficult to put into words, but it basically boils down to, "I'm sick and tired of being sick and tired, and sick of being poked, prodded, biopsied, scanned, bled, x-rayed, ultra-sounded, and analyzed in general."

I am not a number... but I have felt like one. (I'd rather say, "I am not a number, I'm a free man" - but I'm not sure how many of you reading along would catch that ref.)

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2 A Pocket Review of Dr. Steere's NEJM Reinfection Editorial

I finally had the opportunity to sit down and read Dr. Steere's editorial which accompanied Nadelman et al's study, "Differentiation of Reinfection from Relapse in Recurrent Lyme Disease".

Before I comment on the editorial, I want to acknowledge the research which was accomplished in the study as it deserves more attention.

I think it was an interesting study on two counts:

One, it showed that in a group of 17 patients, it was highly unlikely that a patient would get reinfected with the same genotype of Borrelia burgdorferi compared to one with which they'd previously been infected. Does this suggest that patients have some form of immunity to specific genotypes - or is this a reflection of random chance of infection with specific genotypes?

Two, it provided evidence in two patients that a person can be infected with one genotype of Borrelia burgdorferi in skin - while an entirely different genotype can be found in the blood. The significance of this has yet to be determined, but it does raise some interesting questions about the nature of Borrelia burgdorferi infection. How often are patients coinfected with different types of Borrelia burgdorferi? Are these genotypes competitive in any way? Can one genotype affect a patient more profoundly than the other? If there is a delay in treatment, can one genotype be more effectively treated than another?

The findings from this study inspire curiosity and more questions about the nature of Lyme disease.

Thoughts on the editorial, "Reinfection versus Relaspe in Lyme Disease"

Now that I have acknowledged two interesting findings from the Nadelman reinfection study, I have to say that unlike the connections made by Dr. Steere, I do not see the relationship between data presented in this study and patients who have been infected with Lyme disease and continue to have persisting symptoms after initial treatment.

Any good study and its findings stand on their own and an editorial on them by the authors themselves is usually unnecessary. The work should speak for itself, and I think this study does well to demonstrate a relationship between the presence of new genotypes and reinfection in a small group of patients who were bitten by ticks in the same geographic location.

If there is an editorial accompanying research, it should in some way enhance or broaden our understanding and appreciation of the findings - and by extension, lead our curiosity to new horizons.

Unfortunately, Dr. Steere's editorial is not additive in nature. It does not add nuance to or a greater appreciation of the reinfection study - nor does it address the kind of questions raised above which directly apply to his study. Instead, his editorial seems to stretch the findings' significance in order to provoke discussion on chronic Lyme disease based on claims that a small percentage of patients' erythema migrans rashes have been thought to indicate a relapsing infection.

References
Robert B. Nadelman, M.D., Klára Hanincová, Ph.D., Priyanka Mukherjee, B.S., Dionysios Liveris, Ph.D., John Nowakowski, M.D., Donna McKenna, A.N.P., Dustin Brisson, Ph.D., Denise Cooper, B.S., Susan Bittker, M.S., Gul Madison, M.D., Diane Holmgren, R.N., Ira Schwartz, Ph.D., and Gary P. Wormser, M.D. Differentiation of Reinfection from Relapse in Recurrent Lyme Disease. N Engl J Med 2012; 367:1883-1890November 15, 2012DOI: 10.1056/NEJMoa1114362
Allen C. Steere, M.D. Reinfection versus Relapse in Lyme Disease. N Engl J Med 2012; 367:1950-1951November 15, 2012DOI: 10.1056/NEJMe1211361

ALSO, to read my detailed report on the Nadelman reinfection study, see:
http://campother.blogspot.com/2012/11/what-does-reinfection-study-have-to-do.html

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0 Lyme Research Alliance Response To Reporting On Reinfection Study

The executive director of the Lyme Research Alliance responded to the New York Times' article, “New Infection, Not Relapse, Brings Back Lyme Symptoms, Study Says” which refers to the Lyme disease reinfection study recently published in the NEJM:

http://www.nytimes.com/2012/11/23/opinion/lyme-disease-study.html

(original text removed in observance of NYT copyright policy.)

Current Active Research Projects which are listed on LRA's site:
http://www.lymeresearchalliance.org/research_projects.html

---

For the most part, I agree with Mr. Wild's statement. I only have some questions about this sentence: "This limited study supports the theory that Lyme is effectively treated by one short course of antibiotics, yet numerous scientists vehemently disagree."

I would have phrased it differently and stated it as "This limited study supports the theory that Lyme disease is always effectively treated by one short course of antibiotics, yet numerous scientists vehemently disagree."

There is a body of research which provides evidence that Lyme disease is not always effectively treated with one short course of antibiotics - even the IDSA's 2006 Guidelines state up to 10% of early acute cases of Lyme disease result in treatment failures. Those same guidelines cite studies on late stage Lyme disease cases which are treated according to the guidelines, yet patients are recorded as having relapses and not returning to their former health pre-infection.

In addition to the guidelines, there are case studies, research studies, and individual patient reports of relapsing symptoms after initial treatment.

At the same time, not everyone who contracts Lyme disease goes on to have persisting symptoms after initial treatment. The reason why some patients develop chronic Lyme disease and some do not is not clear. A delay in receiving initial antibiotic treatment appears to play a role - and the genotype of bacteria infecting a given patient and the patient's immune profile may also play a role in development of persisting symptoms. More research is required to understand the cause of chronic Lyme disease.

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1 What Does The Reinfection Study Have To Do With Chronic Lyme or Post Lyme Disease?

Last week, a number of media outlets wrote articles referring to a study published in the New England Journal of Medicine (NEJM), "Differentiation of Reinfection from Relapse in Recurrent Lyme Disease".

Since I wanted to see what was actually stated in the study, I acquired a copy of the full text of this publication to see for myself why the authors might have given some journalists the impression that chronic Lyme disease - or even post Lyme disease syndrome - does not exist.

Side note: One important thing to know is that at the time I wrote this entry, I had not read the accompanying editorial by Dr. Steere which was published in NEJM. Given that the current entry was written based only on the study itself and has gotten quite lengthy, I will be writing separately about the editorial in the future.

Summing it up

After reading through the paper, if I had to give a one sentence summary of what this study accomplished, this sentence at the end of it summed it up fairly well:

"These data, in conjunction with available clinical and epidemiologic evidence, show that repeat episodes of erythema migrans in appropriately treated patients were reinfections and not relapses."

If I'm to take it at face value, what this study does is provide evidence that when patients were properly treated early for previous erythema migrans (EM) rashes in the past and they presented with new EM rashes with obvious tick bites - they almost always contained a different kind of Lyme disease than one with which the patients had previously been infected. And with early treatment of patients found with new EM, most of those patients will go on to be fine until they are reinfected again.

Seems to make sense to me.

This is what the study appears to have discovered, so at first glance I had yet to see what the findings in this paper have to do with evidence that chronic Lyme disease does not exist. Nor did I see where this study provides evidence that post Lyme disease syndrome does not exist, either.

However, after digging a little deeper, I found one statement which suggested that data found in this study implied that chronic Lyme disease does not occur:

"[...] some persons have attributed recurrent episodes of erythema migrans to relapses in patients treated with recommended courses of antibiotic therapy; they cited experiments in animals that showed persistence of B. burgdorferi despite antibiotic treatment."

This was about as close as I could get to finding a statement in the study that chronic Lyme disease does not occur, as the majority of the content of the paper focuses on the fact that new erythema migrans are associated with new infections.

But one thing which I have stated before was that when it comes to Lyme disease, the rash is not the disease. The rash is a symptom of early infection. Untreated, it will eventually disappear. It may never recur during the same episode of infection. And in the meantime, depending on the strain one has, host factors, and without proper treatment, the infection will disseminate and spread to areas of the body far removed from where the rash first appeared.

Because the patients in this study were treated either during the first sign of cutaneous infection or very early disseminated infection, they were far more likely to have been successfully treated than patients for which there was a delay in treatment or patients who were improperly treated (say with a shorter duration, or possibly a less effective or an incorrect antibiotic) earlier.

Anyway, I have a few remarks on the paper:

On the significance of EM rashes under other conditions

One of the concerns I mentioned elsewhere after reading online article after article was that journalists had not mentioned how EM rashes were relevant not only as a symptom of early infection but at other points.

To some degree - and to my satisfaction - one paragraph of the study covered other reasons EM rashes would appear outside of the first sign of infection, and mentioned that an EM rash can show up and disappear only to reappear in untreated patients and also inappropriately treated patients.

This is important to note, and I would hope that family and urgent care doctors can use the presence and timing of an EM rash relative to other symptoms to determine when more treatment is required. Dr. Jorge Benach has stated that satellite EM rashes which erupt within weeks to months after the initial EM are a sign of disseminated infection.[1] Dr. Brian Fallon of the Columbia University Lyme and Tickborne Disease Research Center has also made the same observation.[2] Combined with other clinical evidence and symptom presentation, patients with these rashes may require additional oral or intravenous antibiotic treatment.

Patients with new EM rashes have been reinfected.

In addition to the summary statment cited earlier, one should take note of this particular passage in the study:

"Patients were treated with standard courses of antibiotics at each episode of erythema migrans, with subsequent resolution of the skin lesion or lesions."

The key words to keep in mind here are: "erythema migrans" and "appropriately treated patients".

This study is about early acute Lyme disease including early disseminated infection. The patients who were followed during the course of the study were all treated for signs of early acute Lyme disease - not late stage, persisting disease.

Based on this, I suspect the authors want readers to take away from their study is that these 17 patients who have an EM rash and are treated early in their infection have successful resolution of their Lyme disease - and any new EM rashes they have are a sign of a new infection which requires more antibiotics.

In other words: Early treatment is the key to greater success in treating Lyme disease effectively.

The value of finding different OspC RST types in different EMs.

The keystone of the study is the evidence that different OspC RST types are found in each episode of EM when patients are followed over time.

What does OspC RST strain mean? Citing a definition from an earlier paper:

"Two genetically linked typing systems, one based on sequence variation of outer surface protein C (OspC) and the other on ribosomal RNA intergenic spacer type (RST), have been used to classify US B. burgdorferi strains.

OspC typing divides B. burgdorferi strains into 21 genetically distinct types, 16 of which have been identified in the northeastern United States and RST divides B. burgdorferi into three groups.

RST1 corresponds to OspC genotypes A and B; RST2 corresponds to OspC types F, H, K, and N; and RST3 corresponds to the remaining 10 OspC types, including D, E, G, and I.

In the northeastern United States, infection with OspC type A (the most common RST1 strain) or OspC type K (the most common RST2 strain) accounts for approximately 60% of Lyme disease cases; and all of the OspC types within the RST1 and RST2 groups account for approximately 80% of cases. RST3, the least common type, is the most diverse, although infection with OspC type I accounts for approximately half of the RST3 cases.

Because RST typing of isolates may miss differences within groups and because OspC typing may lead to small groups, more information for clinical correlations can be obtained from the use of both typing systems."[3]

The above description of how OspC RST typing is taken from the paper, "Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease".

What is known not only from this paper but from many other papers is that different genotypes of Borrelia burgdorferi exist and may affect the clinical presentation of Lyme disease over time.[4-11]

And as time goes on, new genotypes are also found to spread hematogenously. However, it is important to keep in mind that just because a genotype can disseminate easily does not mean it is going to cause as much inflammation or have a particular tissue tropism.

For example:

"[...] However, when mice were infected by tick bite, as in the natural infection, RST 1 isolates displayed higher densities in blood, but the number of spirochetes in the heart or bladder was similar with either RST 1 or RST 3 strains (14). This suggests that in the natural infection, smaller numbers of RST 3 organisms, which may not be detectable in blood, are still able to spread to the joints and cause infection there. Consistent with this observation, the frequencies of B. burgdorferi genotypes in human patients in the current study were similar in EM skin lesions and in joints. Thus, it seems that all 3 RSTs have a similar predilection for dissemination, but larger numbers of RST 1 organisms are more often detectable in blood."[12 ]

According to research to date, the B. burgdorferi RST1 (OspC type A) genotype - followed by the RST3 (OspC type I) genotype - cause greater inflammation and more severe disease than other genotypes, establishing a link between spirochetal virulence and host inflammation.[ 3]

It gets more complicated from here. Researchers are still learning how these different genotypes and subtypes interact with their hosts and host immunity.

According to research (as is stated above) OspC type A RST1 and OspC type K RST2 account for approximately 60% of Lyme disease cases in the northeastern United States.

Judging from other publications, northeastern US OspC genotypes more or less break down into this list:

- Osp type K RST2 accounts for about 40% of that 60%.
- OspC type A RST1 accounts for 20% of that 60%.
- 20% of northeastern United States genotypes are mostly other RST1 and RST2 types.
- The remaining 20% are a mix of RST3 which is dominated by OspC I RST3.

That these different genotypes exist and have different pathogenicity is a fairly recent discovery and it is only just beginning to be understood.

More is understood about more common OspC types than less common RST3 strains which are highly variable and found less frequently in animal and human hosts. Additional research on these genotypes is needed.

So what kind of OspC RST types did patients have in this study on reinfection? It's a good question to ask, because if patients have genotypes of Borrelia burgdorferi which are more likely to lead to dissemination, then they (potentially) have a greater chance of invading more immune-privileged spots, such as joints, tissues, organs, and the central nervous system.

Based on a review of the overall breakdown of different OspC RST types in this study, they did align somewhat with previous research on northeastern United States genotypes.

OspC K RST2 was the dominant genotype found in skin, followed by a mix of OspC RST3 types then OspC RST1. That OspC RST3 types were more common than OspC RST1 differed from earlier research. Blood samples were somewhat different than those found in skin, with a combination of RST1 and RST3 types collectively outnumbering OspC RST2.

There are some data sets which were not collected during this study which I would have wanted to see. For one thing, Borrelia burgdorferi samples were not taken from synovial fluid or cerebrospinal fluid (CSF) for OspC RST typing. We would also be missing any data from tissue biopsies as these are not routinely done, and are rather invasive for the patient. On the immunological side, the genetic backgrounds of patients with specific HLA-DRs were not revealed.

How this study does (or doesn't) relate to Chronic Lyme disease or post Lyme disease syndrome

Patients with early disseminated infection were said to have had fever, arthralgias, headache, or fatigue which were present during the first episode of EM. The authors expanded on this point over time, demonstrating that in these 17 patients, early disseminated infection and more invasive genotypes (such as ospC A RST1 or ospC I RST3) were handily cured with a prompt course of antibiotics and that any future symptoms would be related to a new infection and not a relapse.

Based on the OspC type data, the only way I can see that this study might be trying to disprove the existence of chronic Lyme disease is the authors' position that the evidence demonstrates that the same virulent strains found during the first episode EM rash that were treated were not present during the second episode in any patient. Therefore, by their deduction, the Borrelia bacteria did not persist in the time between EM rash episodes.

In their opinion, evidence of a relapse would have been shown if the patient's samples demonstrated that the same Borrelia burgdorferi genotype would be present during both episodes of EM.

However, is this the only conclusion one can draw from such a study? I have unanswered questions about it.

Can the genetic background and varying immune system responses affect the course of Lyme disease in host mammals? (I already know the answer is yes here, but what I know is mostly about animal models. Is enough known about this as it relates to people?)

How likely it is that an existing genotype of Borrelia burgdorferi found in tissues and CNS will migrate to the blood and EM rashes during ticks feeding on humans?

In the study, given that in two patients the genotype of Borrelia burgdorferi from one skin sample did not match the genotype of that found in blood during the same episode, is there a possibility that in a handful of cases, antibiotics could successfully treat the EM rash produced by one genotype while not successfully treating a more virulent and invasive genotype if the infection had advanced for some time without treatment - say to more remote tissues such as organs or the CNS?

Could a previous infection with a Borrelia burgdorferi genotype with specific tissue tropism coexist with the onset of an EM rash containing a new genotype?

What happens if a patient has previous infection in which no EM rash was present or seen and it goes untreated - then that patient acquires a new infection with an EM rash on top of the first infection?

I don't know the answer to these questions or how likely these scenarios are, but I suspect the last one I mention above is not entirely uncommon.

Either way, based on the patient background which is supplied in this study we cannot know because patients are reported as being treated successfully during the early stages of infection.

I also don't know how often it occurs that a patient has persisting symptoms after initial treatment for Lyme disease and a new erthyema migrans is never seen during the course of their persisting symptoms.

Given my experience as a patient, I can only make the observation that other patients in my situation seldom report seeing new rashes during the course of their condition. I think researchers should take a close look at the subset of those patients who are most severely ill and are housebound - they are an important subgroup to study because their odds of reinfection are very low.

Related to this, there is one immediate key difference I also see between the patient group studied and chronic Lyme disease patients:

The patient population in this group received a course of antibiotics each time an EM rash presented itself. Because they were treated early, presumably they had a good chance at recovering completely from their infection.

Chronic Lyme disease patients and their doctors alike report that many chronic Lyme disease patients' conditions are discovered late, and symptoms and serology often reflect those of late stage Lyme disease patients - not early acute or early disseminated patients.

It is this difference which makes me wonder about the applicability of such a study to a condition such as chronic Lyme disease or post Lyme disease syndrome.

Patients with late stage Lyme disease are less effectively treated with antibiotics and can be refractory to treatment; studies cited in the 2006 IDSA Lyme disease treatment guidelines indicate that a fair percentage of late stage Lyme disease patients do not fully recover after antibiotic treatment - though the reason why is not entirely clear.[13]

Development of an autoimmune-like condition has been hypothesized by the IDSA and various researchers as being the cause for persisting symptoms after initial infection, while other researchers suspect persisting infection might occur in some patients.

In the end...

The study provides evidence that in 17 patients who are properly treated with antibiotics shortly after EM rashes appear, their infections resolve and they get new infections.

If one supports a model of chronic Lyme disease and thinks that Borrelia burgdorferi can persist in the human host past initial treatment, then this study won't provide evidence either way as to whether or not this is the case:

Part of the definition of chronic Lyme disease hinges on patients having been treated late in infection and/or treated improperly early in infection only to go on to develop later stage Lyme disease in the future.

If one applies this definition, it is important to note that none of the patients in this study had a delay in treatment and proceeded to late stage symptoms before receiving antibiotic treatment. None of the patients were reported as showing signs or symptoms of Lyme disease between episodes of EM rashes; patients experienced only acute Lyme disease which was promptly treated. None of the patients were remarked as being part of the 10% of patients with acute Lyme disease who experience early antibiotic failure, either.[13]

The study participants fit the characterization of the majority of Lyme disease patients who successfully recover from Lyme disease with early treatment - but it does not characterize those patients who do not.

Conversely, if one supports a model of post Lyme disease syndrome, this study won't provide evidence either way as to whether or not this is the case:

None of the patients in this study were reported on followup after a six month interval after any EM rash and subsequent treatment as having developed symptoms indicative of post Lyme disease syndrome. None of the patients were remarked upon as having any particular HLA-DR associated with the development of antibiotic refractory Lyme arthritis - or any potential marker for post Lyme disease syndrome.

If patients have been symptom-free between episodes, this suggests that early treatment aborted the possibility of more serious infection, that patients had a genetic background which made it less likely they would develop antibiotic refractory Lyme arthritis, and/or perhaps early treatment in this small group led to avoidance of post Lyme disease syndrome as well.

Things I Ponder:

• The good news: If the results of this study can be extrapolated to a larger patient base, early treatment of Lyme disease as soon as one sees a new EM rash is more likely to lead to a positive outcome for the patient.
• The bad news: This study says nothing about patients who either neither see a tick bite nor get a rash yet begin show other clinical signs of Lyme disease. Doctors have no easy way of diagnosing these patients and current IDSA guidelines do not cover management of such patients.
• Patients were treated during early to early disseminated infection, when they were most likely to have a positive outcome from antibiotic treatment regardless of the genotype found in their samples.
• There is no information provided about the health and quality of life of enrolled patients. Do they have any preexisting conditions? Have they ever been diagnosed with any condition with symptoms which overlap with those of Lyme disease? How does one make the distinction between these conditions and any symptoms associated with any stage of Lyme disease outside of an EM rash?
• The timing, method, and duration of antibiotic treatment for each patient for each episode was not disclosed. Did all patients receive a course of oral doxycycline, or did some with more disseminated infections receive IV Ceftriaxone? This could have an impact on having a positive post-treatment outcome.
• Regardless of which treatment patients received, how can family and urgent care doctors apply the data from this study to their practice? Hopefully they will see an EM rash and treat patients immediately, but unfortunately this does not always happen in clinical practice as not all EM rashes are properly diagnosed. (e.g. ringworm, eczema, etc.)
• If infections had advanced past the early stage, I wonder which genotypes would have been found in other sample types had they been taken (synovial, CSF, other tissues). Would they have matched earlier research in previous papers or would they have been different?
• Over time, is there a change in the kind of genotypes which infect human hosts? Do these genotypes have a "competitive" nature? How much lateral gene transfer occurs?
• This study applies to the northeastern United States and to infections from Ixodes scapularis ticks. It does not apply to tick bites from Lone Star ticks, which are beginning to outnumber Ixodes scapularis ticks in some areas of the northeast and may carry different infections.
• The public needs to be reminded that different ticks can carry different infections and look for other symptoms of those which may not be EM rashes.
• Babesiosis and Rocky Mountain Spotted Fever are two other infection which come to mind where prompt treatment is necessary.

Well, this is what came to mind after reading this study.

Any questions? Comments?

Next up: Reviewing Dr. Steere's accompanying editorial...

Citations:
1) Dr. Jorge Benach. Presenting at SB Southampton Dean's Lecture Series. Video posted Apr. 20, 2010. http://www.youtube.com/watch?v=TR-aY_S8q2E Approximate Timestamp: 40:20. "Multiple EM rash is sign of disseminated Lyme disease and requires IV or parenteral antibiotics."
2) Columbia University Lyme and Tick-borne Diseases Research Center, http://columbia-lyme.org/patients/ld_lyme_symptoms.html Downloaded November 21, 2012.
3) Strle K, Jones KL, Drouin EE, Li X, Steere AC. Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease. Am J Pathol. 2011 Jun;178(6):2726-39.
4)Wormser GP, Brisson D, Liveris D, et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis 2008;198:1358-1364
5) Wormser GP, Liveris D, Nowakowski J, et al. Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease. J Infect Dis 1999;180:720-725
6) Seinost G, Golde WT, Berger BW, et al. Infection with multiple strains of Borrelia burgdorferi sensu stricto in patients with Lyme disease. Arch Dermatol 1999;135:1329-1333
7) Liveris D, Varde S, Iyer R, et al. Genetic diversity of Borrelia burgdorferi in Lyme disease patients as determined by culture versus direct PCR with clinical specimens. J Clin Microbiol 1999;37:565-569
8) Jones KL, Glickstein LJ, Damle N, Sikand VK, McHugh G, Steere AC. Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease. J Clin Microbiol 2006;44:4407-4413
9) Wang IN, Dykhuizen DE, Qiu W, Dunn JJ, Bosler EM, Luft BJ. Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto. Genetics 1999;151:15-30
10) Dykhuizen DE, Brisson D, Sandigursky S, et al. The propensity of different Borrelia burgdorferi sensu stricto genotypes to cause disseminated infections in humans. Am J Trop Med Hyg 2008;78:806-810
11) Wei-Gang Qiu, John F. Bruno, William D. McCaig, Yun Xu, Ian Livey, Martin E. Schriefer, and Benjamin J. Luft. Wide Distribution of a High-Virulence Borrelia burgdorferi Clone in Europe and North America. Emerg Infect Dis. 2008 July; 14(7): 1097–1104.
12) Strle K, Jones KL, Drouin EE, Li X, Steere AC. Analysis of Borrelia burgdorferi Genotypes in Patients with Lyme Arthritis: High Frequency of RST 1 Strains in Antibiotic-Refractory Arthritis. Am J Pathol. 2011 Jun;178(6):2726-39.
13) Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006;43:1089-1134

Additional Resources:

• An update on the diagnosis and treatment of early Lyme disease: "focusing on the bull's eye, you may miss the mark".
• Detection of established virulence genes and plasmids to differentiate Borrelia burgdorferi strains. http://iai.asm.org/content/early/2012/01/23/IAI.06326-11.short
• Crowder CD, Matthews HE, Schutzer S, et al. Genotypic variation and mixtures of Lyme Borrelia in Ixodes ticks from North America and Europe. PLoS One 2010;5:e10650-e10650. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010650
• Whole-genome sequences of thirteen isolates of Borrelia burgdorferi. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028687/
• Blog entry: Let's Not Be Rash About Erythema Migrans
  
  
  
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0 CO Comments on "The Pseudoscience of Chronic Lyme"

During the weekend, Ed Yong, who writes for Discover magazine's Not Exactly Rocket Science blog, of alerted me on Twitter to Cassandra Willyard's blog post on The Last Word on Nothing blog - "The Pseudoscience of Chronic Lyme". Not wanting to pass up the opportunity to comment on some journalists' bungling of how to interpret the significance of the New England Journal of Medicine (NEJM) published study, Differentiation of Reinfection from Relapse in Recurrent Lyme Disease, I decided to stop by and read what Cassandra and others had to say and leave a few comments.

So far, commenters are asking good questions and pointing out some logical oversights in what we have read, which is constructive.

I don't know that I recommend it for casual reading for a number of chronic Lyme disease patients, though - particularly if you are in a headspace where you are currently very angry about your condition being treated dismissively and can't hold up to reading anything which is skeptical about the existence of chronic Lyme disease. But I will say that if you can handle it, it might be worth it to stop by and periodically read the comments.

So far, I've left two comments on Cassandra's blog in response to her original post and another commenter:

"I’ve been following the issue of chronic Lyme disease closely for a number of reasons, and anecdote aside, think that the situation surrounding the diagnosis and treatment of Lyme disease and other tickborne diseases is more complex than most of the media has led the public to believe.

I hear that Lantos – like Dr. Lawrence Zemel of the Infectious Disease Society of America – has more or less stated that half of those patients who claim they have chronic Lyme disease have no evidence of having prior or active Lyme disease. Lantos stated, “Only 7–31% had active Lyme disease and 5–20% had previous Lyme disease,” he writes. “Among the remainder, 50–88% had no evidence of ever having had Lyme disease. Most of these patients had either an alternative medical diagnosis or a functional somatic syndrome such as chronic fatigue syndrome or fibromyalgia.”

If this is in fact the case, then we are still looking at up to 51% of the patient population in this group as either having had Lyme disease or currently having it – meaning that up to little more than half of patients’ persisting symptoms do correlate with evidence of having Lyme disease.

It is this population of which I am a part of, having had a textbook case of Lyme disease – known tickbite in endemic area, an EM rash, flu-like illness, severe joint pain and swollen lymph nodes – the whole nine yards – only to be followed by years of ongoing symptoms I did not have pre-infection.

So, when someone brings up the pseudoscience of “chronic Lyme disease”, understand that I might get a little testy because it seems almost inevitably, the cases which are highlighted in skeptical discussions are those Lantos states do not have evidence of Lyme disease. Whether that is accurate or not, what about the rest of us? (Side note: chronic fatigue syndrome and fibromyalgia are problematic diagnoses in their own way, too, as they are of unknown etiology.)

I want to know as much as the next person exactly what has led to persisting symptoms. After doing the research on my condition to the extent I have, I’m coming to the conclusion that more research is necessary. I am skeptical about their being “sides” to this debate in the first place and also think science has not come to a full understanding about the process behind why we have persisting symptoms.

Embers et al’s recent study on persistence of Borrelia burgdorferi after antibiotic treatment in Rhesus macaques brings up the question of persistent infection after antibiotic treatment. More research is required on this, and persistence studies such as an NIH-NIAID xenodiagnosis study where patients with chronic Lyme disease are bitten by lab-raised ticks in order to see if they pick up the infection are underway. On the autoimmune angle for finding cause, Bockenstedt recently published a paper showing gfp concentration of Borrelial antigens in tendon* tissue in mice, and the hypothesis is spirochetal antigens cause persisting symptoms long term. See this Research Blogging blog post for more info: http://spirochetesunwound.blogspot.com/2012/11/inflammatory-spirochete-debris-left.html

So one cannot avoid that persisting symptoms after initial infection and treatment or delayed treatment is an issue; the research is there and being conducted on it.

But in the meantime, people are suffering, and voting with their feet: The vast majority of patients in my situation think there is something to the persisting infection hypothesis, and treat with long term antibiotics. A number of them recover and report improvement in symptoms while on treatment.

Yes, it is anecdotal – true. And it doesn’t support the outcomes of some of those small clinical trials which were conducted. But perhaps instead of dismissing them, someone could step in and collect the data on these patients (with their consent, of course) based on how they are currently being treated, what the patient base is and common factors of different subpopulations, and so on – and see if any commonalities float to the top? This could be informative, to study patients who have made the decision to accept this treatment and see how they fare."

And the second comment:

While I have not read the full text of the study yet, I agree that your logic path is one I traveled as well. An EM or “bull’s eye” rash is a key part of the case definition for acute Lyme disease – however, it’s not always present with infection, nor do all EM rashes signal the presence of infection.

Much of the media’s write-up on this study has conflated the existence of reinfection with the nonexistence of a chronic condition connected with Lyme disease – but it has also left out a huge chunk of the story about the significance of EM rashes in Lyme disease infection.

Dr. Jorge Benach of Stonybrook University has stated that if multiple “satellite” rashes show up weeks to months after initial infection, that the bacteria has disseminated. This may mean the patient needs a different course of treatment at this stage, so new rashes in this situation are important to separate from new EMs from a new infection.

Dr. Benjamin Luft has been doing extensive mapping of the genetics of different strains of Borrelia burgdorferi and has discovered some strains create a rash but no infection, some create a rash and infection, and some create no rash and infection. These strains can have varying targets within the body; varying levels of virulence.

And not long ago, Horizon Press published a book, “Borrelia: Molecular Biology, Host Infection, and Pathogenesis”, and it mentions big gaps in patient management around EM rashes: Some people who were screened to be subjects in studies were seropositive for Lyme but have never had ANY symptoms – whereas others went on to develop a case of late stage Lyme disease. (See pp. 501-502)

This is problematic for patients and doctors alike, who may have difficulty diagnosing the cause for the patients’ symptoms with no prior history/evidence of Lyme disease.
(Serology might help – but you have to suspect Lyme disease first.)

(As an aside, you might want to check out this discussion on Lymenet Europe: http://www.lymeneteurope.org/forum/viewtopic.php?f=6&t=3856 – if only because of the references offered.)

So, I am concerned about the emphasis on rashes and think either one has to suspect Lyme disease based on other symptoms and potential exposure to ticks – or we need better testing… Solid direct detection tests would be great, but we don’t have one yet. I’m waiting to see what GMU does with its nanotrapping test development… It’s antigen based; hopefully superior to existing serological tests. But again: First one must suspect Lyme, and if there is no EM rash present, where do you begin?

* That should have been "joint" tissue, not "tendon".

When I wrote these comments for their intended audience, my goal was to focus on what by their standards would currently count as evidence they relied on in order to focus on the relevance of erythema rashes in infection. I avoided discussion of other issues I could have gotten into - such as the accuracy of early serological testing and differences in antibody response during infection - because my focused comment was already long and thought these topics were not as closely related.

One thing that has changed between the time I posted these comments and now: I now have a copy of the full text of the NEJM reinfection paper. So I am in the process of reading it, examining the data, and seeing how the authors correlate their findings with chronic Lyme disease. More later...

Edited to Add: When I talk about being skeptical about there being "sides" to the debate, what I am really meaning to say is that while two sides have developed over time, the only side that really matters is the truth.

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