Tuesday, August 30, 2011

8 Round Two: Lyme Disease Research Scavenger Hunt

So I  began a little online scavenger hunt game here at Camp Other, and we completed round one about two weeks ago.

So far, since only one entry has been submitted by Rita - Rita, you are the winner of round one by default. I say even without competition for that round, take a bow for the work you put into researching your answer for round one.

Now I'll present those who wish to play along with our basic game instructions and round two of the scavenger hunt:

This is an online scavenger hunt to determine which Lyme disease research being conducted in which universities and colleges involves or has involved members of the 2006 Lyme disease guidelines group.

I'm going to list Lyme disease related research either completed or currently being done in Column A, and in Column B, list the educational institution where the research was (or is) being conducted.

How to play:

Match the research in Column A with the correct educational institution in Column B.
Determine if members of the department involved are A) currently doing research with a member of the 2006 Lyme disease guideline authors or B) have worked on any research in a past with said guideline author(s).

Write your matches and mentions of any guideline authors in a comment and submit your comment for posting.

You can use google, Wikipedia, and any on and offline tools for your answers.

Roughly one week (perhaps we should make this two?) after I post a round, I'll post the correct answers as well as post the next round of the game. I intend to run the game for several weeks - end date to be announced later.

If anyone wins all rounds, after that win is confirmed, the next post I write will be based on the winner's selected topic of choice and include hand-drawn illustrations by me.


Research Description
Educational Institution
1)
  • Established the rhesus monkey model of Lyme disease.
  • Discovered an immune evasion mechanism that Borrelia burgdorferi, the spirochete that causes the disease, may use to cause persistent infections.
  • Discovered that B cells produce the regulatory cytokine IFN-gamma in animals infected with B. burdoferi.
  • Discovered that spirochetes elicit not only inflammatory but also anti-inflammatory cytokines from monocytes, thus contributing a method to control the inflammation they themselves cause.
A) Medical College of Wisconsin
2) B. burgdorferi binds to members of a family of receptors on the surface of human cells termed "integrins", which are important in many cellular processes, including inflammation and blood vessel growth.  Using a phage display library of B. burgdorferi genomic DNA, we identified a B. burgdorferi protein that mediates bacterial binding to β3-chain integrins, and have defined portions of this protein that participate in integrin recognition. Our current work focuses on determining the role of Borrelia-integrin recognition in the course of infection and the development of Lyme disease in the mouse model.  We have also studied the mammalian cell response to B. burgdorferi strains that do or do not express the β3-chain integrin ligand, and by microarray analyses, have identified several signaling/regulatory pathways that show integrin-ligand specific changes in expression. Some of these may be important to the ability of this organism to disseminate from the site of the tick bite to other tissues. We also discovered that another B. burgdorferi protein, BBB07, signals through integrin α3β1 to promote a proinflammatory response in human chondrocytes, which may contribute to the pathogenesis of Lyme arthritis.  Our phage display library was also used in vivo to identify B. burgdorferi proteins that bind to vessel walls in specific tissues such as the joint and heart, and further characterization of these proteins is underway. B) Tulane University
3) Critical to this work has been our development of green fluorescent protein (GFP) reporters that enable us to track live spirochetes in ticks and mice. Our live-imaging studies have fundamentally changed our understanding of the transmission process. In order to reach the mouse, spirochetes disseminate through the midgut into the salivary glands in order to access the salivary stream which they “ride” into the vertebrate host. We have found that dissemination of spirochetes in ticks is actually biphasic. In the first phase, which we have termed “adherence-mediated migration, spirochetes replicate in close association with differentiating midgut epithelial cells, “working” their way as aggregates or networks to the base of the epithelium. In the second phase, they transition into typically motile spirochetes, complete the penetration through the midgut, and then move on to the salivary glands en route to the mouse. Most recently, we have found that spirochetes lacking RpoS are deficient in this process and we are developing various strategies to identify the RpoS-dependent genes involved. C) University of Connecticut

There is much to learn from playing this game in and of itself that you gain something whether you win or lose. (I also have a point to make in playing it, and I'll reveal it at the end of the series... It might not be the point you suspect I'm going to make.)


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Monday, August 29, 2011

3 Antiscience letter and conflicts of interest

Since I finally had the opportunity to read the full text of the antiscience and Lyme disease advocacy letter in the Lancet, someone asked me if the letter had any stated conflicts of interest attached to its full text version.

Yes, it does - and here is the stated conflicts of interest portion:

Conflicts of interest
PGA has served as a consultant for Oxford Diagnostics and has participated in expert testimony in two medicolegal suits about possible Lyme disease. He has equity interest in Johnson & Johnson, no products of which are referred to in this article. RJD is part owner of and has stock in Biopeptides Corporation, no product of which is referred to in this article, has received payment for providing expert testimony in malpractice cases and holds patents on vaccine and diagnostic technology with SUNY at Stony Brook Biopeptides. JSD has received support for travel to meetings from DiaSorin and has licence of US patent 5,955,359 to Focus Diagnostics; none of these declarations are directly related to the contents of this article. JJH has served as an expert witness in several medicolegal cases concerning Lyme disease and has equity in Abbott, Bristol-Myers Squibb, Johnson & Johnson, and Merck; no products from these companies are referred to in this article. EMcS was a former programme officer for Lyme disease at the US NIH. RBN has served as an expert witness in malpractice litigation involving Lyme disease. EDS is a board member of the American Lyme Disease Foundation, for which no compensation is received. He has reviewed medical records for the Metropolitan Life Insurance Company and has provided medicolegal testimony. GPW is a board member of the American Lyme Disease Foundation for which no compensation is received, has served as an expert witness in malpractice cases involving Lyme disease, has research grants from the NIH/Immunetics, BioRad, DiaSorin, and BioMerieux to study diagnostic tests for Lyme disease, none of which is mentioned in the manuscript, and has equity in Abbott, a company not known to have any approved product for Lyme disease. JSB, RJD, JSD, JJH, RBN, EDS, ACS, and GPW have served on the panel for the 2006 IDSA Lyme disease guidelines. JSB, SO'C, SKS, ACS, and AW declare that they have no conflicts of interest.


Related to this, here are your questions of the day:

Does having these conflicts of interest affect how the authors of the letter act in the treatment of Lyme disease, if the authors engage in determining the outcome of insurance cases for Lyme disease treatment, develop vaccines and diagnostic tests, and write up guidelines for the treatment of Lyme disease? At what point does one say that one has a conflict of interest versus because one is considered an expert they are called upon to make these decisions by others? How does one separate the two?

In the Lyme disease controversy, Lyme disease patient advocates have pointed out IDSA Lyme disease guideline panelists' conflicts of interest in the past, and in the full text of this letter, the authors pointed out conflicts of interest being held by ILADS members. Is pointing out these conflicts of interest being done in the interest of fairness or in order to engage in a negative campaign against the other party?

Is there anyone out there who is free of conflicts of interest who is involved in the Lyme disease controversy? How do you know they are free of conflicts of interest?

Now that this letter has created a stir in the Lyme disease patient community, what's next? For anyone who has read the full text of the original letter, what is the best next step for resolution of this controversy? Brainstorming is welcome.

Addendum: Regarding Abbott, see this link on their research assays and ask why there isn't a better diagnostic test available for patients.

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Sunday, August 28, 2011

2 Admin: Writer's Scatter, Rather Than Writer's Block

A more personal note here from CO:

I think I have the opposite of writer's block at the moment, and I'm calling it writer's scatter. While Lyme disease has left me with shoddy memory at times (Did I leave the water running? Did I leave something in the toaster?) in terms of concentration I am all over the map. I can be intensely focused on something for hours and the rest of the world disappears, or I can be so mentally scattered my mind will not rest on one idea at a time for more than a minute or two.

This is where I am at the moment, and it looks to all the rest of the world like ADHD. Except... for the most part, people don't see me as being hyperactive when my butt is firmly planted to the sofa all the time. But if they could see inside my mind, then what they'd witness is a very different phenomenon. It's one that is making it very hard to write about any one thing now.

I'll give you a peek into my stream of consciousness at the moment, so you can see just how many branches are splitting off the old mental tree:

I'm thinking of the letter that was recently published to the Lancet which I've ranted about, and the reception to that rant. A lot of people visited this site in the past couple days to read that rant, but only few people commented on it here. Why is that?

I'm thinking about how being a doctor is different from being a researcher and what that means when someone is discussing treatment versus discussing evidence-based medicine. Are these two things always the same things? Are they different things? When is and isn't that okay?

I'm thinking about the use of ketamine in mice to sedate them during experiments and wondering how that might influence the outcome of testing the effect of Borrelia burgdorferi on the immune system. I even wrote a post about it months ago but have never posted it, thinking few people would want to read about it.

I'm thinking about this stack of paperwork I have to sort through and find irritating to do so. I have to make some phone calls in the morning. I need to sign and put some forms in the mail. I am bound to not do half of what I need to do even if I write it down.

I'm thinking about my posts from months ago where at the bottom of each, I've written "to be continued in part 2" or "more in a future post on this topic", and part 2 hasn't been written nor has a future post addressed that topic. Where do I begin, when so many other topics and news have grabbed my attention and inspired me to write - and these old threads which have been postponed have not?

I'm thinking about how readers have suggested topics for me to write on and I haven't gotten to those, either.

I'm thinking about how it is that on some Lyme disease support groups - if you don't share the same opinion as the majority does and your difference of opinion makes others bristle rather than ask questions out of curiosity - how difficult that is for you to find support when you are already marginalized by illness.

I'm thinking about how the hell the kitchen is going to get clean given the state it's currently in. It looks like someone put a detonator in the crockpot and it went off. Five alarm chili just might mean anyone who looks in that kitchen is going to be alarmed... It is going to take a long time for me to do anything about it and I can only chip away at it for a few minutes at a time before my arms get too worn out.

I'm thinking about coming up with my own lazy bachelor with a chronic illness cookbook. It must include mixed drinks and easy snacks. Some of the recipes need to burn the roof of your mouth and clean out the sinuses, too. I don't want these recipes to be bland by any stretch of the imagination.

I'm thinking about all my friends who were in the path of the hurricane and lost their power. (Mine is fine, thankfully.) I've heard from most of them - their basements are soggy but they are alive and mostly well.

I'm thinking about how a year ago I told someone I don't want to be defined by this disease and I want my life back. And here I am, writing this damned blog. How did that happen? I swore I would get better and never do something like this. Yet here I am.

My ears are ringing. I need more sleep. So I'll end things here for the night.

Besides, I will just continue to have more random thoughts racing through my head like this until I pass out.

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0 News: In Wisconsin, Illnesses spread by ticks on rise

The Wisconsin Rapids Tribune has this article on tap today:

Illnesses spread by ticks on rise

Excerpts:
Consistent testing and an increase in deer ticks are driving up the number of tick-borne illnesses reported annually in Wisconsin, health officials said.

Statewide, cases of the bacteria infections anaplasmosis and ehrlichiosis -- both spread by deer ticks -- increased 70 percent from 2009 to 2010, when 546 cases were reported, according to state data.

"It's nice to be able to pick (anaplasmosis and ehrlichiosis) up, so a patient can be properly treated," said Diep Hoang Johnson, an epidemiologist for Wisconsin's Division of Public Health. "If lyme disease (tests) come back negative, they may not get treated and they may have one of these diseases."
and
"Marx said the increase in tick diseases other than lyme likely is because of more efficient testing and health care providers' improved efforts to report the illnesses."

Comments:

It's important to keep in mind that not every tick bite leads to a case of Lyme disease, and a negative Lyme disease test result does not necessarily mean the patient does not have Lyme disease (antibodies may not have been present at the time the test was taken) - nor does it indicate what other tickborne infections a person may have such as Ehrlichiosis or Babesiosis (as well as a few viruses which are spread by tick bites).

It's important for doctors and patients to familiarize themselves with the range of tickborne infections which are out there and be aware of the symptom spectrum for all them, as well as for doctors to take a detailed history from patients to see where they have traveled and resided to determine which tickborne diseases they are at greater risk of contracting. This provides a starting point for which coinfections to test for - but is by no means definitive as these diseases spread and even change in geographic location and density.

Read more of this news article at: http://www.wisconsinrapidstribune.com/article/20110828/CWS0101/108280518/Illnesses-spread-by-ticks-rise

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Tuesday, August 23, 2011

21 Letter: Antiscience and ethical concerns associated with advocacy of Lyme disease

Well, it's time for a little commentary on a recent publication which has been making the rounds in the Lyme disease patient community - this time on a letter which has been published to the Lancet recently. The letter is basically about those who believe Lyme disease can be a chronic, difficult to diagnose disease are part of an antiscience movement, and how the media, politics, and advocacy groups have supported unorthodox views concerning Lyme disease and other tickborne infections.

I'll post the excerpts in full first, and then a second time with my commentary interspersed.



Excerpts from: Antiscience and ethical concerns associated with advocacy of Lyme disease.

Auwaerter PG, et al. Lancet Inf. Dis. Aug 22 2011.

Aspects of Lyme disease advocacy are an important example of this antiscience movement. For the purposes of this Personal View, we will define this antiscience outlook to also include the promotion of pseudoscience and science that has weak credibility or validity because of fundamental flaws in its design or poor reproducibility.

For two decades, many Lyme disease activists have portrayed Lyme disease, a tick-borne infection, as an insidious, ubiquitous, difficult to diagnose, and often incurable disease, which causes mainly non-specific symptoms such as chronic fatigue, musculoskeletal pain, and neurocognitive dysfunction that can be treated only through the use of antibiotics for months or years.

As with other antiscience groups, some Lyme disease activists have created a parallel universe of pseudoscientific practitioners, research, publications, and meetings, arranged public protests and made accusations of corruption and conspiracy, used harassment and occasional death threats, and advocated legislative efforts to subvert evidence-based medicine and peer-reviewed science.
Politicians, the media, and the public have been left trying to discern the scientific facts from the pseudoscientific ones, with many regarding both as equally valid as they try to be fair and balanced.

When such inappropriate and uncritical weighting occurs, public and government officials unknowingly come to accept or even endorse highly unconventional and sometimes dangerous theories and therapies.

Many individuals who represent themselves as Lyme disease activists and LLMDs hold and promote views of a tick-borne infectious disease that is inconsistent with credible scientific evidence. Although relatively small in number, their effect should not be underestimated.

Their unorthodox perspectives and resulting practices have contributed to injury and even deaths of patients. Millions of dollars have been spent refuting their claims, and thousands of hours have been spent responding to false allegations, legal threats, congressional queries, and other harassments.

At a time when unnecessary healthcare expenditures are being scrutinised and widespread bacterial resistance has been linked to overuse of antibiotics, it is particularly important that unsubstantiated treatments be avoided.

This situation is not likely to end anytime soon. As with other antiscience groups, many Lyme disease activists are well funded and often connected to influential political and media sources.

Treatment of Lyme disease with long-term antibiotics is profitable for LLMDs and can be falsely reassuring to patients, who believe that they have a debilitating chronic infection and thus do not seek diagnosis and treatment for other disorders.

There is no deficiency of either new patients or activists. The medical anthropologist Sharon Kaufman wrote that “Information technology has transformed the way trust and knowledge are produced”. Most people now find medical information on the internet, and the websites of LLMDs and activists are often viewed as legitimate and reliable sources of information, which they may not be.

Such misplaced trust has also contributed to a similar situation in Europe, with increasing pressure being brought on authorities there to sanction the use of prolonged antibiotic treatment for patients without credible evidence of Lyme disease by groups such as the German Borreliosis Society and Dutch Lyme Association. This ill-founded advocacy is being extended to other, less common, tick-borne infections (and to non-Ixodes tick-transmitted pathogens such as Bartonella).

In conclusion, activists, through public appeal and political lobbying, have managed to divert attention away from existing evidence-based medicine in their quest to redefine Lyme disease. There is a serious concern that they will further endanger the public’s health unless responsible physicians, scientists, government leaders, and the media firmly stand up for an evidence-based approach to this infection that is based on high-quality scientific studies.

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Sunday, August 21, 2011

1 Immune + Infection = HLA-DR alleles determine responsiveness to Borrelia burgdoferi

Recently I've been reviewing the relationship between specific genetic haplotypes and alleles and the development of chronic Lyme arthritis. One speculation that I had made early on was that I suspected chronic and persisting symptoms were the result of both immune dysregulation and persisting infection - and here is one paper which points out this may be the case...

HLA-DR alleles determine responsiveness to Borrelia burgdoferi antigens
Bettina Panagiota Iliopoulou, Mireia Guerau-de-Arellano, and Brigitte T. Huber. Arthritis Rheum. 2009 December; 60(12): 3831–3840.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828865

The authors of this particular paper wrote up their own informative article, Sometimes It's All In Your Genes with descriptions of their project for the layperson. I highly recommend reading it, as it is an educational and easily readable description of their research in greater detail from the perspective of the researchers themselves.

In the above study, researchers experimented with mice who have the genetic profiles of HLA-DR4 (which is related to developing arthritis) and HLA-DR11 (which is predicted to clear spirochetes quickly).They infected both groups of mice with Borrelia burgdorferi and monitored their ability to clear spirochetes and develop signs of arthritis.

According to the researchers, mice with HLA-DR4 alleles produced lots of interferon gamma and very few antibodies to the spirochete - whereas those with HLA-DR11 alleles produced lots of antibodies but no interferon gamma.

To translate:

Interferon gamma = Produces LOTS of inflammation, which hurts and sucks.
Very few antibodies = Nothing much to fight off the infection.
Lots of antibodies + No Interferon gamma = Fight off infection while having little or no inflammation.

When you look at the paper itself, this is of particular note:
"We found that DR11 tg mice mount a vigorous Ab response, but are defective in IFN-γ production. In addition, Bb-infected DR11 tg mice had decreased spirochete burden compared to DR4 tg mice, measured by qPCR of Bb DNA. This is in contrast to DR4 tg mice, which produce an inflammatory response characterized by high level of IFN-γ production, in accordance with our published results (10). Furthermore, the Ab response to Bb-antigens was significantly lower than that of DR11 tg mice, which is consistent with the higher spirochete burden observed in DR4 tg mice after Bb-infection. Thus, our data provide a possible explanation for the differential regulation of the immune response in DR4+ and DR11+ patients upon Bb-infection; namely, HLA-DR4 would predispose individuals to chronic Lyme arthritis by generating an inflammatory milieu to Bb-infection, while HLA-DR11 would exert a protective role through the production of anti-spirochetal Abs."
So, to review, in this study:

HLA-DR4 mice have a significantly lower antibody response to Bb antigens compared to HLA-DR11 mice.

HLA-DR4 mice have a significantly higher inflammatory response (measured as Interferon gamma or IFN-γ ). (It sounds as if HLA-DR11 has no real inflammatory response.)

HLA-DR4 mice have a significantly higher spirochetal load compared to HLA-DR11 mice.

If you look at figure 5b & c (if I'm to read the caption properly based on the full text) the amount  of spirochetal DNA present in an ear punch sample was twice as high in the HLA-DR4 mice compared to the HLA-DR11 mice, and the amount of spirochetal DNA present in the joints appears to be about 6 times higher in HLA-DR4 mice compared to the HLA-DR11 mice.

That's a huge difference.

To add to this, the study also immunized two groups of mice with these alleles with rOspA and found out that:

HLA-DR4 mice mount a poor response to rOspA.

HLA-DR11 mice mount a strong antibody response to rOspA. They have a good humoral response.



So upon learning this, of course there are more questions:

  1. How does this study apply to humans with Lyme arthritis?
  2. How does this study apply to humans with post-treatment chronic Lyme disease?
  3. How does this data relate to findings in the recent Alaedini paper about those with post-treatment chronic Lyme disease having had infections for a long time (and Alaedini's speculations about different antibody responses and a possible need for more aggressive treatment)?
  4. How does this data relate to Steere's study suggesting an additional month of antibiotic treatment is needed for some patients with Lyme arthritis?

    (Re:"Patients with Lyme arthritis were treated with oral antibiotics for one or two months, and in those for whom the arthritis did not resolve, IV antibiotics were administered for an additional month. If they had persistent arthritis despite three months of antibiotics, patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs).")
  5. How does the existence of more virulent and quickly disseminating RST of Bb affect hosts which are HLA-DR4 versus HLA-DR11?
  6. What kind of mice were studied in this recent study by Barthold et al?
  7. Is there a reason found here as to why some people experience relief with longer courses of antibiotics? Is it because they just don't have an immune response needed to clear the infection but antibiotics both help keep infection under control plus act as an anti-inflammatory in the presence of interferon gamma?

So much to think about here, tying these studies together.

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0 Video: Baloney Detection Kit

I found this video narrated by Michael Shermer, a skeptic, which discusses a 10 question baloney detection kit which is similar in nature to Carl Sagan's Baloney Detection Kit.

I recommend it for its straight-forward approach and good questions to ask - and though it is made by the Dawkins foundation, its focus is not about religion but on questioning evidence.

Check it out...

[Video time: 14:40]




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Friday, August 19, 2011

13 More on Genetic Haplotypes and Lyme Arthritis

So, the more I read, the more unanswered questions there are. Staying on top of all the latest research becomes a job in itself.

Earlier this week, I posted a variety of papers which showed a potential (according to the authors, statistically significant) relationship between haplotype and the development of chronic Lyme arthritis.

Then my attention was drawn to this 2008 paper, and I realized I shouldn't have stopped at papers in 2007 before writing my post about genetic haplotypes...

Human Homologues of a Borrelia T cell Epitope Associated with Antibiotic-Refractory Lyme Arthritis

Source:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075570

Abstract

Antibiotic-refractory Lyme arthritis, which may result from infection-induced autoimmunity, is associated with HLA-DR molecules that bind an epitope of Borrelia burgdorferi (Bb) outer-surface protein A (OspA165−173) and with T cell reactivity with this epitope. One potential mechanism to explain these associations is molecular mimicry between OspA165−173 and a self-peptide.

Here, we searched the published human genome for peptides with sequence homology with OspA165−173. The two peptides identified with the greatest sequence homology with the OspA epitope were MAWD-BP276−288, which had identity at eight of the nine core amino acid residues, and T-span758−70, which had identity at six residues. MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not. However, neither peptide bound all of the HLA-DR molecules associated with antibiotic-refractory Lyme arthritis. Among 11 patients, nine had T cell reactivity with OspA161−170, six had responses to MAWD-BP276−288, and three had reactivity with T-span758−70, but reactivity with the self-peptides was lower than that induced by the spirochetal epitope.

Thus, there remains an association between OspA165−173 and antibiotic-refractory Lyme arthritis, and infection-induced autoimmunity is an attractive hypothesis to explain this outcome. However, molecular mimicry due to sequence homology between OspA165−173 and a human peptide seems unlikely to be the critical mechanism.



I suppose I have to keep reading more research?

What's the present model for the cause of chronic Lyme arthritis these researchers are supporting again?

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Thursday, August 18, 2011

5 Abstract: A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade

A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent. Schuijt TJ, Coumou J, Narasimhan S, Dai J, Deponte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Van't Veer C, Hovius JW, Fikrig E. Cell Host Microbe. 2011 Aug 18;10(2):136-46.

Source: http://www.ncbi.nlm.nih.gov/pubmed/21843870?dopt=Abstract

Comments:

It occurs to me that a lot of the concern from the Lyme patient community over the use of vaccines could be eliminated if R & D shied away from human vaccine development.

Mice and other animals in the woods could ingest oral vaccines which could prevent the transmission of Borrelia burgdorferi to reservoir hosts on which ticks feed. Not only that, but this could have an extended effect of helping pets, too.

I think creating oral vaccines to block transmission of Bb to animals and pets is a good idea.

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Tuesday, August 16, 2011

24 Do Different Genetic Haplotypes Matter?

It seems people are still holding on to the HLA-DR2 and HLA-DR4 concept of subgroup autoimmunity (subgroups of Lyme disease patients who do not respond to additional antibiotic treatment) in the Lyme disease community.

I get the impression that hypothesis has been dropped by a number of researchers in favor of a new one - except in the case of patients with Lyme arthritis. (I don't think HLA-DR2 is associated with Lyme disease, either, and HLA-DR4 is associated with Lyme arthritis.)

I came across this recently:

National Institute of Allergy and Infectious Diseases, NIH: Impact on Global Health (2009) by Vassil St. Georgiev, PhD

Chapter 22.1 Lyme Disease (Lyme Borreliosis, Lyme Arthritis)
Section 22.1.5.4 The Role of Autoimmune Reactivity in Lyme Disease

"In NIAID-supported clinical studies, case subject patients with PTCLD* were compared with control subjects without such symptoms for the presence of several human leukocyte antigen (HLA) class II (DRB1 and DQB1) genetic markers, some of which are known to be associated with the expression of autoimmune reactivity. The results obtained did not support the involvement of an autoimmune mechanism in PTCLD (24). However, because not all autoimmune diseases are associated with specific HLA haplotypes, these findings do not necessarily exclude that possibility. Definitive proof would clearly involve demonstrating the presence of significant levels of relevant autoimmune antibodies and/or autoreactive T cells in patients with PTCLD but not in treated control subjects without such symptoms. A greater frequency of DRB1*0401, which has been reported to be associated with antibiotic-treatment-resistant arthritis, was noted in the case subject patients; although this finding appeared to be nominally significant (p < 0.05), its biological significance is ambiguous because none of the case subjects considered had symptoms of inflammatory arthritis. (http://www3.niaid.nih.gov/research/topics/lyme/research/autoimmune/)"
* In this NIAID-NIH document, PTCLD stands for Post Treatment Chronic Lyme Disease.

24) Klempner MS, Wormser GH, Wade K, Trevino RP, Tang K, Kaslow R, and Schmid C. (2005) A case-control study to examine HLA haplotype associations in patients with posttreatment chronic Lyme disease. J. Jinfect. Dis. 192(6), 1010-1013.

Now this is an interesting piece of information.

This book from the NIAID-NIH is stating following about patients with PTCLD in NIAID-supported studies:

1) Patients with chronic Lyme disease were compared against control subjects with the same genetic markers and the results did not support an autoimmune mechanism for chronic Lyme disease.

2) Not all autoimmune diseases are associated with specific haplotypes.

3) Those patients with chronic Lyme arthritis have had their condition strongly associated with DRB1*0401.

4) None of the case subjects in trials had inflammatory arthritis. None.

I find this particularly interesting since the one statement many patients have made is that some researchers have pegged chronic Lyme disease patients as having an autoimmune disorder, when the research in this regard is fuzzy. What indicates to some researchers today that post-treatment chronic Lyme disease is an autoimmune disorder, if it isn't specific haplotypes which are at risk of developing persisting symptoms?  A different molecular mimicry model than that which leads to Lyme arthritis? A different model of persisting symptoms entirely?

I also find it interesting that none of the case subjects had inflammatory arthritis. I don't know how clinicians defined the criteria for inflammatory arthritis and if they did any serology for inflammation, but I can say that I have had joint swelling, muscle pain, and shooting nerve pain during the course of my illness. That none of the case subjects in trials had inflammatory arthritis comes as a surprise to me.

According to research there is a relationship between a specific haplotype and Lyme arthritis. This is just one such example:

From Persistent arthritis in Borrelia burgdorferi-infected HLA-DR4-positive CD28-negative mice post-antibiotic treatment. Iliopoulou BP, Alroy J, Huber BT. Arthritis Rheum. 2008 Dec; 58(12):3892-901.:
"METHODS:We have previously shown that CD28(-/-) mice develop intermittent monarticular Lyme arthritis that is responsive to antibiotics. Since there seems to be a link in humans between persistent arthritic manifestations post-antibiotic treatment and the HLA-DR4 allele, we generated DR4+/+CD28(-/-)MHCII(-/-) mice, infected them with Borrelia burgdorferi, and subsequently treated them with antibiotics.

RESULTS: Thirty-eight percent of the B burgdorferi-infected DR4+/+CD28(-/-)MHCII(-/-) mice, but none of the B burgdorferi-infected CD28(-/-)MHCII(-/-) mice, remained arthritic post-antibiotic treatment. A significant fraction (36%) of these mice, but none of the mice in which arthritis resolved, had serum antibodies to outer surface protein A of B burgdorferi. After abrogation of active B burgdorferi infection, the inflammatory reaction in mice with persistent joint inflammation was restricted to the joints, since their draining lymph nodes were no longer enlarged. Increased CD20 and interferon-gamma messenger RNA expression in the inflamed joints of these mice suggested a possible role of B cells and inflammatory cytokines in the pathogenesis of persistent arthritis post-antibiotic treatment.

Conclusion: The establishment of this murine model allows, for the first time, the elucidation of the immunologic events that lead to persistent Lyme arthritis post-antibiotic therapy in genetically susceptible individuals."
So according to this, little over a third of the mice with a specific allele remained arthritic after antibiotic treatment, and of this third, about a third of them developed antibodies to OspA.

My questions are: How is it that the remaining roughly two thirds of the mice did not remain arthritic? How is it that two thirds of them did not develop antibodies to OspA?

There are many papers written about the association between specific alleles and development of chronic Lyme arthritis:

1993 - Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi.

2001 - Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis. (This is where molecular mimicry as a cause of Lyme arthritis is mentioned.The abstract states: "...only one human protein was identified, lymphocyte function associated antigen-1 (hLFA-1), that had sequence homology with OspA (165-173) and predicted binding in the DRB1*0401 molecule.")

2004 - Molecular characterization of the OspA(161-175) T cell epitope associated with treatment-resistant Lyme arthritis: differences among the three pathogenic species of Borrelia burgdorferi sensu lato. (Borrelia that causes Lyme disease in Europe does not usually lead to chronic Lyme arthritis.)

2006 - Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide (Concluded that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic-refractory Lyme arthritis and might play a role in the pathogenesis of the disease.)

2007 - Clonal Diversification in OspA-specific Antibodies from Peripheral Circulation of a Chronic Lyme Arthritis Patient

A number of these are Steere's papers - not surprising since he has written so much about the rheumatological aspect of Lyme disease. And some of it is not his research, and I could find a few more by others.

I'm looking for more research on chronic Lyme disease's connection to haplotypes and alleles outside of the Lyme arthritis model. The NIAID-NIH book, written in 2009, states there is no connection.

So to sum up:

1) Particular alleles or haplotypes are not associated with chronic Lyme disease as a whole.

2) Particular alleles or haplotypes are associated strongly with chronic Lyme arthritis.

Hm.

Glossary

allele: is one of two or more forms of a gene.Sometimes, different alleles can result in different traits, such as color. Other times, different alleles will have the same result in the expression of a gene. See more info. at: http://en.wikipedia.org/wiki/Allele

haplotype: a combination of alleles (DNA sequences) at different places (loci) on the chromosome that are transmitted together. A haplotype may be one locus, several loci, or an entire chromosome depending on the number of recombination events that have occurred between a given set of loci.See more info. at: http://en.wikipedia.org/wiki/Haplotype

Additional information: http://en.wikipedia.org/wiki/Category:HLA-DR_haplotypes

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Monday, August 15, 2011

3 Round One: Lyme Disease Guidelines Research Scavenger Hunt

So, I've decided to start a little game here on Camp Other blog. It is an online scavenger hunt to determine which Lyme disease research being conducted in which universities and colleges involves or has involved members of the 2006 Lyme disease guidelines group.

I'm going to list Lyme disease related research either completed or currently being done in Column A, and in Column B, list the educational institution where the research was (or is) being conducted.

How to play:

  1. Match the research in Column A with the correct educational institution in Column B.
  2. Determine if members of the department involved are A) currently doing research with a member of the 2006 Lyme disease guideline authors or B) have worked on any research in a past with said guideline author(s).
  3. Write your matches and mentions of any guideline authors in a comment and submit your comment for posting.

You can use google, Wikipedia, and any on and offline tools for your answers.

Roughly one week after I post a round, I'll post the correct answers as well as post the next round of the game. I intend to run the game for several weeks - end date to be announced later.

If anyone wins all rounds, after that win is confirmed, the next post I write will be based on the winner's selected topic of choice and include hand-drawn illustrations by me.


Round One: Lyme Disease Scavenger Hunt
Research Description Educational Institution
1) We ask the question what genes in the B. burgdorferi genome are responsible for the pathogenesis and long-term survival, and how can these genes be identified? Our strategy is to analyze the B. burgdorferi virulence determinants by Signature-Tagged Mutagenesis in combination with Luminex®-based high-throughput screening procedures, and infectivity studies to identify genes and gene products required for infectivity in a mouse model. We are also exploring the etiology of an emerging tick-borne disease, Southern Tick-Associated Rash Illness.

A) Michigan State University
2) Our laboratory studies Borrelia spirochetes and the diseases they cause, Lyme disease and relapsing fever. After transmission of Borrelia through bites of certain tick species, both Lyme disease and relapsing fever are characterized by the spread of bacteria via the bloodstream, which may lead to the infection of multiple organs such as the skin, heart, joints, and brain. While these pathogenic processes are not yet well understood on the molecular level, the involved virulence factors identified so far have been surface lipoproteins.

A first project identifies lipoprotein sequence determinants, membrane protein complexes and chaperones involved in spirochete lipoprotein export.We are currently using fluorescent proteins as markers for protein localization in live Borrelia cells to determine the sorting signals for surface and subsurface lipoproteins. Using biochemical and novel genetic approaches, we are also in the process of characterizing the lipoprotein export machinery in Borrelia burgdorferi, the Lyme disease spirochete. These studies will ultimately help in the design of novel intervention strategies for spirochetal infections.
B) The University of Texas
3) My career goal is to help reduce the burden of human, wild animal, and domestic animal disease through improved understanding of disease systems. I approach this goal by conducting novel research to elucidate the ecology of maintenance and transmission of zoonotic pathogens, so as to identify key targets within disease cycles for interventions that will reduce disease risk.My dual training in wildlife disease ecology and veterinary medicine allows me to combine ecological and epidemiological principles, field techniques, molecular analytical tools, and medicine to address important problems in ecosystem health at the population level.Thus far, I have studied the ecology of two vector-borne disease systems in North America - West Nile virus and Lyme disease.
C) University of Kansas

There is much to learn from playing this game in and of itself that you gain something whether you win or lose. (I also have a point to make in playing it, and I'll reveal it at the end of the series.)

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Saturday, August 13, 2011

1 Paper: Evaluating Research Quality

This is a brilliant, well-written publication, Evaluating Research Quality, on how to assess the quality of research you are reading - written by Todd Litman at the Victoria Transport Policy Institute - which is "an independent research organization dedicated to developing innovative and practical solutions to transportation problems".

Read Evaluating Research Quality Here: http://www.vtpi.org/resqual.pdf

Todd provides a number of examples of what makes good, well-informed research and what is biased, ill-informed research, drawing from examples in the transit sector but also general examples such as the source of statements such as "Eskimos (Inuit) have 23 words they use to describe snow" and ideas such as "AIDs doesn't kill people, antiviral medication kills people".

The entire document is well worth a look from start to finish, and the "Sixty Four Methodological Potholes" table is an interesting and extensive read. It's more detailed than Carl Sagan's Baloney Detection Kit and highlights some of the same illogical fallacies and bias some have presented in their publications and arguments.

This specific portion could be applied (and I should probably more stringently apply these pointers to papers reviewed here) to Lyme disease research and all research in general, so I want to share it. Credit goes to Todd Litman and the Victoria Transport Policy Institute, who allow republication with credit. (Thanks, guys.)

Research Document Evaluation Guidelines

The guidelines below are intended to help evaluate the quality of research reports and articles.

Desirable Practices
  1. Attempts to fairly present all perspectives.
  2. Provides context information suitable for the intended audience. This can be done with a
    literature review that summarizes current knowledge, or by referencing relevant
    documents or websites that offer a comprehensive and balanced overview.
  3. Carefully defines research questions and their links to broader issues.
  4. Provides data and analysis in a format that can be accessed and replicated by others.
    Quantitative data should be presented in tables and graphs, and available in database or
    spreadsheet form on request.
  5. Discusses critical assumptions made in the analysis, such as why a particular data set or
    analysis method is used or rejected. Indicates how results change with different data and
    analysis.Identifies contrary findings.
  6. Presents results in ways that highlight critical findings. Graphs and examples are
    particularly helpful for this.
  7. Discusses the logical links between research results, conclusions and implications.
    Discusses alternative interpretations, including those with which the researcher disagrees.
  8. Describes analysis limitations and cautions. Does not exaggerate implications.
  9. Is respectful to people with other perspectives.
  10. Provides adequate references.
  11. Indicates funding sources, particularly any that may benefit from research results.

Undesirable Practices
  1. Issues are defined in ideological terms. “Straw men” reflecting exaggerated or extreme perspectives are use to characterize a debate.
  2. Research questions are designed to reach a particular conclusion.
  3. Alternative perspectives or contrary findings are ignored or suppressed.
  4. Data and analysis methods are biased.
  5. Conclusions are based on faulty logic.
  6. Limitations of analysis are ignored and the implications of results are exaggerated.
  7. Key data and analysis details are unavailable for review by others.
  8. Researchers are unqualified and unfamiliar with specialized issues.
  9. People with differing perspectives are insulted and ridiculed
  10. Citations are primarily from special interest groups or or popular media, rather than from peer reviewed professional and academic organizations.

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Friday, August 12, 2011

7 Tracking Lyme Disease in Dogs May Help Protect Humans: MedlinePlus

For the study,  a team led by Dr. Paul Mead, a CDC medical epidemiologist, used data from 46 states on human and canine Lyme disease prevalence.

Comparing the data, Mead's team found that when 1 percent or less of the dogs tested positive for Lyme disease, the risk of people becoming infected was low. However, when more than 5 percent of the dogs were infected, the risk to people was high.


Read More Here: Tracking Lyme Disease in Dogs May Help Protect Humans: MedlinePlus


Comment:

This is the kind of low cost surveillance data I think should have been collected all along - and let the vets do the data collection and reporting. I think it makes sense to use dogs to determine potential risk to humans because dogs roam around more and get in the tall grass - they go where the ticks are whereas people try to stay away from them. I consider a dog another potential piece of dragging white flannel flag.

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Wednesday, August 10, 2011

4 News: Abbott Introduces New Vector-Borne Pathogen Test

Excerpt:
Abbott's Ibis Biosciences today introduced a new molecular assay to detect a wide variety of vector-borne microorganisms, including those known to cause Lyme Disease, Rocky Mountain Spotted Fever, Babesiosis, Ehrlichiosis and Anaplasmosis.

The PLEX-ID™ Vector-borne test, which is intended for non-diagnostic use, has been designed to support bioresearch, environmental surveillance, and other activities central to the detection and identification of vector-borne pathogens.

Dr. Eshoo led a study in which vector-borne disease surveillance researchers in New York and Connecticut collected 299 blacklegged ticks. The ticks were analyzed using the Ibis technology for a wide range of vector-borne microorganisms. Results showed that two-thirds of the ticks were infected with B. burgdorferi, the agent of Lyme disease, and a third of these positive ticks contained other tick-borne co-infections such as Babesia microti or Anaplasma phagocytophilum. The research demonstrated that the Ibis technology can detect and identify B. burgdorferi as well as co-infection in ticks with other vector-borne pathogens quicker than traditional lab methods.

READ MORE >>>


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Tuesday, August 9, 2011

12 Paper: Alzheimer's disease - a neurospirochetosis.

Miklossy has recently published a work on a probable causal relationship with infection with spirochetes in the brain and Alzheimer's disease which has many people talking. Here's the abstract:

Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
Judith Miklossy
Journal of Neuroinflammation 2011, 8:90 doi:10.1186/1742-2094-8-90
Published: 4 August 2011

Abstract (provisional)

It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill.

The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls.

Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD.

The pathological and biological hallmarks of AD were reproduced in vitro. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD.

Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity.

As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.


Comments:

These are my preliminary comments, I may come back at some point to revise them.

This paper is one in a long line of research by Dr. Miklossy on the relationship between infection and Alzheimer's disease, with a much earlier similar work being "Alzheimer's disease - a spirochetosis?"

Those of you who were interested in reading the paper on which this abstract was based may also find the following full text of interest:

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide
Stephanie J. Soscia, James E. Kirby, Kevin J. Washicosky, Stephanie M. Tucker, Martin Ingelsson, Bradley Hyman, Mark A. Burton, Lee E. Goldstein, Scott Duong, Rudolph E. Tanzi, Robert D. Moir.
Source link: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009505

And there are examples of other papers not by Dr. Miklossy in a similar vein which may be of interest:
http://www.ncbi.nlm.nih.gov/pubmed/19560105
http://www.ncbi.nlm.nih.gov/pubmed/19958038

I realize that a number of Lyme disease patients - especially those with persisting neurological symptoms - are probably reading the abstract and feeling somewhat nervous about their future potential for developing Alzheimer's disease. However, I want to point out a few pieces of information from the paper itself which highlight two important items:

1) That we don't know exactly what causes Alzheimer's disease yet and

2) That in the samples studied, the majority of Alzheimer patients' brains of those sampled which were infected did not contain Borrelia burgdorferi spirochetes.

Before everyone reading along rests easy, though, you might want to take note that the analysis states that in those samples studied, there is a strong statistical correlation with the presence of other spirochetal bacteria in the brains of patients with Alzheimer's disease.

Graph showing that Alzheimer disease patient
samples contained more oral spirochetes and B.
burgdorferi compared to control groups.
Miklossy's meta-analysis points out that the majority of those brains sampled and studied show evidence of infection, mostly by non-syphilitic Treponema. Other studies point out that C. pneumoniae and Herpes Simplex Virus Type 1 (HSV-1, oral herpes - cold sores - which many people get) are also associated with Alzheimer's disease.

Yet while many are infected with such virus, most people do not go on to develop Alzheimer's disease. Why is that? Is one specific kind of pathogen the precursor that leads to beta amyloid plaques?

This said, spirochetes - especially periodontal ones, but also Borrelia burgdorferi - may play a role in the development of Alzheimer's disease.

Miklossy states in her paper:
"When considering all studies (Table 1, Fig. 1) detecting all types of spirochetes and their specific species, their frequency was 8 times higher in the brain in AD (90/131= 68.7%) compared to controls (6/71 = 8.45 %).The difference is statistically significant (P = 1.7 x 10-17; OR = 23; 95% CI = 9-71, N = 202). The association remains strongly significant when the 12 cases with mild AD-type changes (P = 1.5 x 10-19, OR = 26, 95% CI = 10-80, N = 214) or those cases where spirochetes were analyzed in the blood were also included (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247)."

Those are some crazy P values.

I am still looking at those studies which are referred to in Table 1, Figure 1 of Miklossy's recent paper: of the Bb studies, 3 are small scale studies by MacDonald, some by Miklossy, and then a few by others. I think more sample studies would be good... I also want to read up on their methods more.

It should be noted that 8 out of 10 of the spirochetal studies in the top half of the table are by Miklossy, and only 2 by McLaughlin. And there is only one specific periodontal spirochetal study mentioned by Riviere et al, 2002... Is anyone else doing research in this area?

But I digress...

Once Miklossy outlined the statistical analysis of the studies and the correlation between the presence of pathogens in the brain and Alzheimer's disease, she continued with an outline of how the pathogenesis of spirochetal infection leads to the development of specific immunological responses and reactions within the brain. This part is the most difficult to summarize, but the intention is to show how similar the unfolding pathogenesis of spirochetal brain infections is to the development of Alzheimer's disease.

Later on, Miklossy shows how to apply Koch's Postulates and Hill's Postulates to the studies conducted, though there isn't a full cycle of re-infection or true xenodiagnosis done from the samples extracted. This is something I would like to see in a new study.

The notable part of the conclusion, for me, is this part:
"Spirochetes are able to escape destruction by the host immune reactions and establish chronic infection and sustained inflammation. In vivo studies with long exposure times will be necessary to efficiently study the sequence of events and the cellular mechanisms involved in spirochete induced AD-type host reactions and Aβ-plaque, “tangle” and “granulovacuolar” formation. The characterization of all types of spirochetes and co-infecting bacteria and viruses is needed, in order to develop serological tests for the early detection of infection. The pathological process is thought to begin long before the diagnosis of dementia is made therefore, an appropriate targeted treatment should start early in order to prevent dementia."
The basic message to take from this paper if you are a Lyme disease patient is that last sentence there:

"The pathological process is thought to begin long before the diagnosis of dementia is made. Therefore, an appropriate targeted treatment should start early in order to prevent dementia."

Regardless of the significance of the findings, early diagnosis and treatment of tickborne infections is paramount to reduce the risk of future problems. Something we all already knew.

My general thought about this meta-analysis is that more studies are needed and a larger collection of samples taken from Alzheimer disease patients need to be analyzed using similar means and methods. I think there is more that needs to be known about the relationship between any pathogenic invasion and the development of Alzheimer's disease.

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Monday, August 8, 2011

0 Blog Log: Lyme Jello

Someone sent word of this blog to me in email, and I hopped over there and took a look at it and agreed it was a good read so far.

Not only that, but this art is fantastic. It describes in one image the dilemma all of us face with being placed under our collective diagnostic labels - whatever they are:

"Let's Not Make A Deal" - Artwork from julieridl.wordpress.com Creative Commons License

Awesome.

Hats off to you, Julie - you're a great artist and you capture the experience of being a Lyme disease patient with persisting symptoms so well.

See more of Julie's work and writings at: http://www.lymejello.com/
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4 Comments on Comments On Yet Another Lyme Disease Article

So here we go again, another article on chronic Lyme disease - this time one which is more about the patients' experiences, and a little about the controversy on extended treatment.

Between May and September, the newspapers are full of individual patient stories about their experiences with Lyme disease. So many so, that on any given week if I google "news" and "lyme disease" and select the past week for articles, I'm bound to see several from across the continental United States.

There are so many individual stories at this point that I could make a blog out of them in and of themselves. I don't, though, because there are just too many of them, and I would have less time to write about other  Lyme disease and tickborne infection topical posts.

And after a while, the sad truth is that so many of these stories begin to sound very much like the first one I read. It's overwhelming. It's sad. I can't write about everyone's sad stories every day, though they do need to be heard.

Mainly, what I want to do is point out some comments or specific kinds of comments on this article - and provide both general commentary and a little constructive feedback on why they are not helpful in gaining support for more people to take this condition seriously - let alone gaining support for more research into chronic Lyme disease.

But even then, I am eventually going to tire of this because the comments begin to look the same the more one reads these kinds of news articles. The authors' names will change, their professions will change, and there will be pro-this and anti-that, and still... same content in the comments.

We need change.

This is getting has gotten old.

I'm weary.

Comments and questions on paraphrased random comments:

"If you researched this illness and talked to patients who were intelligent healthy people with no history of hypochondria before a CL diagnosis you would maybe reconsider your stance."

I agree this is a good point to make. Thank you, whoever you are.

"Chronic lyme has been proved already,"

If it has, then why is there still a controversy?

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Friday, August 5, 2011

12 Antibodies linked to long-term Lyme symptoms

Nature has just published an article today on research which shows a relationship between post-Lyme disease syndrome and persistent infection.

Armin Alaedini at Weill Cornell Medical College in New York and his colleagues have found that patients diagnosed with post-Lyme disease syndrome have antibodies that suggest they carried the infection for an unusually long time. The finding, published in Clinical Immunology, might help the syndrome to be better understood, diagnosed and treated.

Bockenstedt is quoted in the article, saying, "This is the first study I've seen that shows some immunologic difference between someone who resolves their Lyme and someone who develops post-Lyme disease syndrome."

I highly recommend everyone checks it out, supporters and naysayers alike: The finding suggests that patients with chronic symptoms have experienced a prolonged infection.

Original Research:
Epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in post-Lyme disease syndrome. Abhishek Chandra, Norman Latov, Gary P. Wormser, Adriana R. Marques, and Armin Alaedini. Clin. Immunol. http://dx.doi.org/10.1016/j.clim.2011.06.005 (2011)

Comments:

I'm withholding any further comments on the content of the paper until I read the full text, but am open to discussing the contents and context of the article from Nature in comments.

READ MORE: http://www.nature.com/news/2011/110805/full/news.2011.463.html

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Thursday, August 4, 2011

0 News: New bacterium found causing tick-borne illness ehrlichiosis in Wisconsin and Minnesota

 ScienceDaily (2011-08-03) -- A new tick-borne bacterium infecting humans with ehrlichiosis has been discovered in Wisconsin and Minnesota.

Experts say the new species from the Ehrlichia genus can cause a feverish illness in humans.

The new bacterium, not yet named, has been identified in more than 25 people and found in black-legged ticks, also known as deer ticks (Ixodes scapularis), in Minnesota and Wisconsin. Researchers used culture and genetic analyses.

Citing from the article, this is important to know:

"Doctors need to know to test for ehrlichiosis in the two states so the diagnosis is not missed. However, traditional blood antibody tests may offer misleading results and fail to accurately identify the new species. A specific antibody test for the new bacterium has been developed by the CDC but isn't widely available. Instead, a molecular blood test that detects DNA from the new Ehrlichia species is the preferred method for detecting this disease in symptomatic patients."

READ MORE: http://www.sciencedaily.com/releases/2011/08/110803174745.htm#

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Wednesday, August 3, 2011

17 Abstract: Invasion of eukaryotic cells by Borrelia burgdorferi requires β(1) integrins and Src kinase activity

Due to ASM's copyright terms on this journal, it's my understanding that I can't post the entire abstract for this publication here - even though abstracts are pretty much something I have long considered open source and commonly shared. Most scientists do - so to find out that some publishing companies and journals don't even want people to repost abstracts seems... well... strange to me.

How else does one promote their work to other people? I'd consider it free promotion for the full publication!

However, I wanted to share it with you however I could, because I think it's of value:

Invasion of eukaryotic cells by Borrelia burgdorferi requires β(1) integrins and Src kinase activity. Wu J, Weening EH, Faske JB, Höök M, Skare JT. Infect Immun. 2011 Mar;79(3):1338-48. Epub 2010 Dec 20.

Read The Abstract Here: http://www.ncbi.nlm.nih.gov/pubmed/21173306

This abstract relates directly to this post I made recently:
http://campother.blogspot.com/2011/07/fibroblasts-and-lyme-disease-sample.html

It's about how Lyme disease spirochetes may be able to hide from the immune system inside other cells, especially fibroblasts. The above study is more research related to this topic, so I recommend reading my recent post for background then looking at the above abstract on PubMed.

Read More

Monday, August 1, 2011

16 Abstract: Chronic Tick Associated Poly-organic Syndrome

Diagnosis and treatment challenges in patients with chronic Tick Associated Poly-organic
Syndrome (TAPOS) - Case series
A. Radulescu, M. Flonta, D. Tatulescu
University of Medicine and Pharmacy, Cluj, Romania,
The Teaching Hospital of Infectious Diseases, Cluj, Romania
Int J Infect Dis 2010;14

Background: Chronic Lyme disease is often considered in case of long lasting miscellaneous symptoms after tick bites. Despite new codified diagnosis algorithm and treatment persistent signs and symptoms frequently occur. The aim of the study was to assess the diagnosis of Tick Associated Poly-organic Syndrome (TAPOS) and to evaluate the treatment’s efficacy.

Methods: A consecutive case series of patients referred to the Cluj-Napoca Teaching Hospital of Infectious Diseases (January 2006 -October 2009) revealed 52 patients with TAPOS. Inclusion criteria were: more than 18 years of age, chronic symptomatology, positive Borrelia burgdorferi serology and/or tick-bite. Data was collected through chart review and medical observation. We used two clinical scores classifying the diagnosis of TAPOS. All patients were seropositive for IgM and/or IgG antibodies to Borrelia burgdorferi (EIA and western blotting). Treatment regimen was established according to the literature data. They received intravenous ceftriaxone, 2 g daily for 21-28 days and doxycyline 200 mg daily for 21 days. Patients with persistent symptoms were retreated with the same regimen.

Results: The baseline assessment documented that the most frequently reported symptoms were neuropsychological (90%), systemic (98%) and articular (23%). The sex ratio was 0.26 (41 women, 11 men), the average age was 43.2 ±12.6 years. Only 7 patients experienced erythema migrans, 57% had tick exposures and Borrelia burgdorferi serology was 92% positive [44 (84%) IgM positive, 19 (36%) IgM and IgG positive]. According to both clinical scores all patients were classified as “very probable” or “probable”. All patients were evaluated at 3 months showing a decrease in the number and intensity of signs and symptoms and the same serologic pattern. Ten patients were 2-3 times retreated due to persistent clinical picture, all presenting mood disorders or depression. No case of clinical aggravation or serious adverse events was reported and Jarish-Herxheimer syndrome was observed just in two cases. Most of the patients remained with at least one neuropsychological complaint.

Conclusion: Diagnosis of miscellaneous Borrelia burgdorferi chronic infection is challenging but should be always considered if prolonged symptomatology or tick related. Treatment regimens are not standardized, we appreciate as reasonable shorter 6 week regimens.



Comments: 

First of all, "Tick Associated Poly-organic Syndrome" or TAPOS - is this a new name Romanian doctors have come up with for what Dr. Benjamin Luft was referring to as a "Lyme Borrelia Complex" at the IOM workshop in October 2010 - or instead of Chronic Lyme disease? It's an interesting name, and I'm wondering where the "Poly-organic" part comes in.

The statements "Ten patients were 2-3 times retreated due to persistent clinical picture" and "All patients were evaluated at 3 months showing a decrease in the number and intensity of signs and symptoms and the same serologic pattern", caught my eye. Presumably, those ten patients also experienced a decrease in the number and intensity of symptoms as well as in their serologic pattern - so retreatment was a benefit for them.

So, let's look at the treatment: "They received intravenous ceftriaxone, 2 g daily for 21-28 days and doxycycline 200 mg daily for 21 days." Should one assume based on their report that those ten patients were treated with up to 4 months of  IV ceftriaxone plus 84 days of doxycycline - or is that off? Two to three times the baseline treatment seems to put the upper range in that ballpark.

"No case of clinical aggravation or serious adverse events was reported and Jarish-Herxheimer syndrome was observed just in two cases."

Boy, does that sound very different from the other reports from the American clinical trials on extended antibiotic treatment for chronic Lyme disease. One of the reasons extended treatment with IV antibiotics was recommended against was because of serious adverse events such as line infections. On a large scale, how often do line infections occur in thousands of patients worldwide? It's a risk, but is it that difficult to prevent with proper care?

I find it interesting that these case studies were shown at a poster session at the 14th ICID. An international professional infectious disease conference - pretty much showing a conclusion where chronic infection treatment is mentioned as not being standardized and setting 6 week regimens as being reasonable.

Wait a minute... doesn't this case series treatment study sound very similar to one of the American clinical trials on extended antibiotic treatment for chronic Lyme disease?

[Camp Other goes to new window, googles...]

I guess it is somewhat similar to the 2001 Klempner trials, but the fact that multiple retreatments were permitted under the case studies are a noted difference among other differences. I think for me, I'm wondering what the full text stated, and not just the abstract - in order to see the authors' line of reasoning on the dosage and regimen - but also wondering why there was only a three month followup on patients after treatment? Where are these post-treatment Romanians today, and how are they doing?

I have more questions...

Patients had the following serology at the start of their studies: [44 (84%) IgM positive, 19 (36%) IgM and IgG positive. How was it IgM positive-only patients were included in the study, when other researchers have stated that a sustained IgM response to Bb with no IgG response means the test was a false positive? (I'm not pushing this idea, as I am still working on the whole "how are new and newly intense IgM bands significant" issue - just putting it out there for the overview.)

"All patients were evaluated at 3 months showing a decrease in the number and intensity of signs and symptoms and the same serologic pattern."

Two questions here: What symptoms and signs did they have to begin with, and what changed, objectively and subjectively?

What does it mean to state in the above sentence, "the same serologic patterns"? Did all patients serological results remain the same across the board despite treatment?

"Most of the patients remained with at least one neuropsychological complaint."

What is the cause or what are the causes of the neuropsychological complaints?

Also, even if the authors reported a decrease in the number of signs and symptoms of infection three months post-treatment, how close were patients to their pre-infective state of health? This is always the question for which I want an answer - especially after reading through the results of treatment trials mentioned in the IDSA 2006 Lyme disease treatment guidelines - results which did not always post a clear outcome of cure.

There are a lot of unanswered questions on this abstract - hopefully getting the full text some time will help in answering them.

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Lyme Disease

Borrelia

Bacteria

Microbiology