Wednesday, September 28, 2011

0 Blog Log: Spirochetes Unwound on Flawed Study of Topical Antibiotics

Remember that article on topical azithromycin I posted earlier this month?

Our favorite spirochete blogger has some criticism about the research on which it was based here:

A flawed study claiming prevention of Lyme spirochete infection with topical antibiotics

Two recent papers tested the effectiveness of topical antibiotics in preventing Borrelia burgdorferi infection in mice following a tick bite. Infection by the Lyme disease spirochete was successfully halted in the Knauer et al. study from Germany1 but not in the Wormser et al. study conducted in New York.2 However a flaw in the Knauer study may have unfairly tipped the outcome in the antbiotic's favor. (I'll save the Wormser study for another post.)


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Tuesday, September 27, 2011

1 LDA-Columbia Lyme 2011 Conference Line-up

On October 1 and 2, there will be a combined LDA/Columbia-Lyme Conference held in Philadelphia, Pennsylvania.

Below is an outline of the conference speakers and topics...

Keynote Speaker: J. William Costerton, PhD
The Role of Biofilms in Chronic Bacterial Infections

Eva Sapi, PhD
Killing Borrelia: An impossible job?

Jason A. Carlyon, PhD
Interior Decorating: Anaplasma phagocytophilum Remodels Its Host Cell-Derived Vacuole into A Protective Niche

Richard Marconi, PhD, Co-Course Director
c-di-GMP Regulates Key Steps in the Enzootic Cycle of Tick-Borne Spirochetes

Chris Earnhart, PhD
Lyme disease vaccine: an update on recent progress

Dr. Ed Masters Memorial Lecture: Robert S. Lane, PhD
Diversity of Borrelia burgdorferi s.l. genospecies and genotypes in California, and Implications for human infection.

M. Karen Newell Rogers, PhD
A New Model of Intervention for Lyme Disease by Targeting Chronic Inflammation and Selective Aspects of Immune Activation

Robert Yolken, MD
Infections and Human Neuropsychiatric Diseases

Josep Dalmau, MD, PhD
Clinical spectrum and cellular mechanisms of autoimmunity to NMDA and other synaptic receptors

Dr. John Drulle Memorial Lecture: John Aucott, MD
Early microbiologic and immunologic events in Lyme disease

Reinhard K. Straubinger, PhD
Canine and equine Lyme borreliosis – The animals’ perspective of the disease.

Benjamin J. Luft, MD
Diagnostics: update on protein arrays and new Lyme assays

Brian Fallon, MD, Co-Course Director
What is Chronic Lyme Disease? Models and evidence

Andrew W. Walter, MD
Update on Ehrlichiosis and Hemophagocytic Lymphohistiocytosis in Children

Andrea Gaito, MD
Clinical Evaluation and treatment of Lyme Arthritis; An autoimmune perspective

Ingeborg Dziedzic, MD
What everyone should know about Eyes & Lyme Disease

Vijay Thadani, MD
Epilepsy update: Distinguishing Epileptic from Non-epileptic seizures

Steve Bock, MD
Complementary and Integrative Medical approaches to Chronic Tick-borne Disease

Elizabeth Maloney, MD
The treatment of Lyme disease - a critical review of the literature – lessons, gaps, and future research needs

I think this conference holds more scientific weight to it than other Lyme disease-related conferences I've seen, so if anyone is going to be in Philly and attends, please take notes to share with us all.

(I won't be able to attend as I have a previous commitment scheduled before I knew this conference was going to be held at this time in October.)

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Monday, September 26, 2011

0 Round Three: Lyme Disease Research Scavenger Hunt

I gave readers an extension until midnight of Friday the 23rd for participating on Round Two of the Lyme Disease Research Scavenger Hunt, and so far, no one has completed both Part A and Part B of Round Two.

Because of this, no one qualifies for Round Two and that round is forfeit. Readers playing along at home will have to compete in the remaining rounds and complete both Part A and Part B. So far, we have one winner of Round One, Rita.

(The answers to Round Two will be posted in a separate upcoming entry.)

Now I'll present those who wish to play along with our basic game instructions and round three 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.

How to play:

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.

Match the research in Column A with the correct educational institution in Column B.

THEN 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 two weeks 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 Three: Lyme Disease Scavenger Hunt
Research DescriptionEducational Institution
1) Lyme arthritis is an inflammatory disease with periods of inflammation and resolution. Eicosanoids are powerful lipid mediators of inflammatory responses which may be involved in disease processes. Cyclooxygenase-2 (COX-2) is upregulated during injury or infection and catalyzes the production of prostaglandins from arachidonic acid. Several commercially available drugs block this response (celebrex, vioxx) and act to suppress the symptoms of chronic inflammation (pain and swelling), but their effect on underlying disease processes is currently unknown. Treatment of mice infected with B. burgdorferi with these compounds does not inhibit their ability to develop Lyme arthritis, but it does prevent its natural resolution. Current experiments are exploring the mechanism for this examining: altered prostaglandin production; increased leukotriene production; and decreased lipoxin production.
A) University of Tennessee
2) iNKT cells play an important immunoregulatory role within the immune system. This function is regulated by endogenous and exogenous glycolipid antigen presentation by CD1d molecules. Thus, by using Borellia burgdorferi, the agent of Lyme disease, as the model system, we are working to elucidate the molecules involved with and the mechanism(s) of CD1d-antigen assembly. Additionally, by understanding how antigens load onto CD1d we can determine the molecular and structural features of the iNKT cell receptor-antigen interface. Elucidating glycolipid antigen processing and presentation and its recognition by iNKT cells will allow insights into how different responses are induced and how these immunoregulatory T lymphocytes function. This insight will advance our understanding of the physiological role of the CD1d antigen presentation system and iNKT cells within the context of the immune system.
B) University of Missouri
3) One major project is the development of a Reservoir Target Vaccine for the Control of Lyme Borreliosis. Borrelia burgdorferi causes Lyme disease (LD) and is the most common vector borne infectious disease in the United States. This spirochete is maintained in endemic areas of LD by cycling between wildlife reservoirs (i. e. white-footed mice, shrews, etc) and the Ixodes scapularis tick vector. Human disseminated infection can cause permanent damage to the nervous and musculoskeletal systems and currently, there is no vaccine approved for prevention of this disease. A promising method to reduce human LD incidence is to break the mouse-tick transmission cycle by eliminating the spirochete from the reservoir and from the ticks that feed on them. To accomplish this we have developed a wildlife oral bait vaccine based in OspA and are currently testing its efficacy in a field trial.
C) Vanderbilt University

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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1 The Curious Case Of Cholesterol

This article got passed on to me:

Scientists Disarm AIDS Virus’ Attack on Immune System

And you might be looking at that title, wondering what HIV has to do with Lyme disease.

Well, I'm wondering if there is any relationship...


"Scientists say they have found a way to disarm the AIDS virus in research that could lead to a vaccine. Researchers have discovered that if they eliminate a cholesterol membrane surrounding the virus, HIV cannot disrupt communication among disease-fighting cells and the immune system returns to normal.

Scientists have discovered that HIV needs cholesterol, which it picks up from the first immune cells it infects, to keep the virus' outer membrane fluid. That allows it to communicate with - and disrupt - the body's immune system."

Chlamydia apparently has a membrane with cholesterol in it, as does Borrelia burgdorferi (review this entry posted on Friday). I wonder if Borrelia burgdorferi can do the same thing to the immune system that HIV does? Does it disrupt communication among disease-fighting cells, too? It certainly does evade the immune system even though the immune system gives it a huge response when present.

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Friday, September 23, 2011

2 Speculation About Borrelial Blebs And Camouflage

I've read one abstract and one blog entry that are making me wonder about Borrelia burgdorferi's survival mechanisms - in particular blebbing and camouflage.

In this article on the MicrobiologyBytes blog, the author discusses how certain bacteria use sphingomyelins from their hosts in order to create their own lipids:

"Fifteen years ago, in a series of elegant studies, Hackstadt and colleagues showed that the obligate intracellular bacteria Chlamydia trachomatis save on their lipid needs by incorporating sphingomyelins (SMs) made by their host. Shortly after, Hatch and McClarty’s teams reported that several eukaryotic glycerophospholipids are also trafficked from the host to the bacteria, which replace host-synthesized straight-chain fatty acids by their own branched-chain fatty acids. Even cholesterol, a lipid rarely found in bacteria, was shown to accumulate in Chlamydia. As a result of this intense exploitation of host lipids, the composition of the bacterial membrane is closer to that of a eukaryotic cell than to that of a prokaryote.

Throughout their developmental cycle, chlamydiae reside within a membrane-bounded compartment, the inclusion. How they acquire host lipids remains an open question. Possible mechanisms studied so far involve vesicular trafficking from host compartments, including vesicular traffic out of the Golgi apparatus, fusion with multivesicular body–derived vesicles, and engulfment of lipid droplets."

Rerouting of Host Lipids by Bacteria: Are You CERTain You Need a Vesicle? (2011) PLoS Pathog 7(9): e1002208. doi:10.1371/journal.ppat.1002208
So this got me thinking about Borrelia, too, as Borrelia burgdorferi contains free cholesterol and cholesterol glycolipids. Cholesterol 6-O-acyl-β-D-galactopyranoside and its non-acylated form are significant components of membranes of the spirochete Borrelia burgdorferi.

Then there is this research which was brought to my attention:

Macrophages infected with Mycobacterium tuberculosis (M.tb) are known to be refractory to IFN-a stimulation. Previous studies have shown that M.tb express components such as the 19-kDa lipoprotein and peptidoglycan that can bind to macrophage receptors including the Toll-like receptor 2 resulting in the loss in IFN-a responsiveness. However, it is unclear whether this effect is limited to infected macrophages. We have previously shown that M.tb-infected macrophages release exosomes which are 30-100 nm membrane bound vesicles of endosomal origin that function in intercellular communication. These exosomes contain mycobacterial components including the 19-kDa lipoprotein and therefore we hypothesized that macrophages exposed to exosomes may show limited response to IFN-a stimulation.
Similar to what happens with Mycobacterium tuberculosis, Borrelia burgdorferi engages in blebbing, where vesicles form on the surface of the bacteria and are released. Each vesicle or "bleb" has been shown to contain lipoproteins, and some research has indicated these vesicles are not just an artifact or sign of cellular injury.

Gram-negative bacteria vesicles can contain various virulence factors such as toxins, proteases, adhesins, and lipopolysaccharide, which are utilized to establish a colonization niche, modulate host defense and response, and impair host cell function.

Some bacteria may selectively create vesicles with specific lipoproteins, such as Porphyromonas gingivalis - but in this bacteria, lipopolysaccarides (LPS) are thought to do the sorting. But Borrelia burgdorferi does not have LPS, so some other mechanism determines which lipoproteins are contained in vesicles.

In earlier research it was shown that not only do Borrelia burgdorferi create vesicles which contain outer membrane proteins and lipids - but they also have been shown to contain DNase I-resistant plasmid DNa - suggesting they were at least partially derived from the inner membrane.

So, now that I've pointed out these things, what am I wondering?

I'm wondering:

If like Chlamydia trachomatis, Borrelia burgdorferi also has a membrane that is more like a eukaryotic membrane? If so, can this contribute to its stealthy nature?

How much Borrelia burgdorferi really relies on its host for its own needs? Compared to other bacteria, Bb has a relatively small genome and is an obligate mostly-extracellular parasite, which means it needs to take what it needs from its host in order to survive. How does it build these lipid rafts and attach to endothelial cells?

If Borrelia burgdorferi creates vesicles or these blebs which contain a mix of outer surface lipids and proteins as well as some inner membrane components, is it possible that it leaves a trail of antigenic material behind it and moves into new areas undetected because its membrane does not produce the same immunological response that blebs or vesicles do?

Somewhat Related TriviaChikungunya virus can hide from the immune system inside apoptotic blebs. You think something is now innocuous and on its way out? Think again - these blebs carry the virus through the blood stream to other cells. This virus also manages to replicate inside macrophages while not causing any inflammatory effect. This is a reminder that Borrelia burgdorferi is not the only pathogen that does interesting and stealthy things!

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Thursday, September 22, 2011

0 Failure of Topical Antibiotics to Prevent Disseminated Borrelia burgdorferi Infection

Last week, I posted an article on how topical azithromycin could help prevent Lyme disease infection. And now, this new abstract has turned up on PubMed...

Failure of Topical Antibiotics to Prevent Disseminated Borrelia burgdorferi Infection Following a Tick Bite in C3H/HeJ Mice. Wormser GP, Daniels TJ, Bittker S, Cooper D, Wang G, Pavia CS. J Infect Dis. 2011 Sep 19. [Epub ahead of print]


A prior study in mice has shown that the timely application of topical antibiotics to the skin at the tick bite site could eradicate Borrelia burgdorferi infection. That study, however, did not evaluate antibiotic preparations that are considered suitable for use in humans. In this murine study, topical application of 2% erythromycin and 3% tetracycline preparations that are acceptable for use in humans was found to be ineffective in eliminating B. burgdorferi from the tick bite site or in preventing dissemination to other tissues. Reasons for the discrepant findings are discussed.

I find it very odd that they would choose erythromycin as a topical antibiotic for Borrelia burgdorferi - there is research that shows that Borrelia burgdorferi is resistant to erythromycin. I would have never thought to make that a choice for treatment. Tetracycline makes more sense.

How many previous studies of topical antibiotics for treating early Lyme disease have there been, and what have the outcomes been? How many have been done using suitable human antibiotic preparations versus ones only effective in animal subjects?

It seems to me that the researchers who filed this patent might already have a good idea of what might work - is this the same formulation that was used in the study I posted last week?

Composition C
Composition [mg]
Component per unit [1 g]
Azithromycin 150
Dermacryl 79 50
Klucel MF 25
Miglyol 812 50
Ethanol 94% (w/w) ad 1 g

Or is it different?

Results: There is no infection of Lyme disease detectable when composition C is applied to the area where the ticks were allowed to feed. The topical application of Formulation C results in antibody titers, which are not different from naïve mice (KELA values between 10 and 40), whereas the infected mice show KELA values of 160 to 400.

Especially, the tissue and serum samples taken from different parts of the mice 56 days after the tick bite show no Borrelia burgdorferi organisms when cultivated and no specific antigenes are detectable. Tissue probes are taken from heart tissue, bladder, joint and ear. The group of mice topically treated with Formulation C show complete absence of B. burgdorferi , whereas B. burgdorferi is detected in untreated mice, which are exposed to tick-feed.

The recultivation conditions of B. burgdorferi are suitable to detect B. burgdorferi in any morphological form known to date. Surprisingly, Formulation C was able to eradicate B. burgdorferi in a way, that no infectious agents of B. burgdorferi are detected in the target tissues of B. burgdorferi.

How were these tissue probes completed and could they have missed any bacteria? What about the parenchyma of the brain, since this is low passage N40 they're talking about? (Problematic in rodent studies - should be studied in other animals.) I wonder about the methodology...

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Wednesday, September 21, 2011

0 An accident leads Yale scientists to tick-borne disease in Russia

The Connecticut Mirror has an article on the backstory behind discovering that Borrelia miyamotoi leads to infection in people:

An accident leads Yale scientists to tick-borne disease in Russia

You've got to love this excerpt:
Fish's lab was studying Lyme disease transmission using ticks and mice, exposing ticks to mice that had been infected, and to others that had not. But the ticks exposed to uninfected mice appeared to be infected.

"I gave everybody in the lab hell for wasting a lot of time and resources and stuff, because they screwed up the experiment," said Fish, a professor of epidemiology at the Yale School of Public Health. "And they felt really bad and they couldn't understand how that happened."

In fact, the ticks had a different bacterial organism, not the one that causes Lyme, but a distant relation called Borrelia miyamotoi. It had been identified six years earlier in Japan, but no one knew if it caused illness in humans. Fish spent the better part of a decade trying to get funding to study it, with little success.

I guess I have these questions about this:

1) Has anything similar happened before in other experiments and we don't even know about it - this situation of having uninfected mice be infected by a different organism that is disease-causing?

2) Why wasn't there enough funding to study this? Who decides which projects get funded?

3) I noticed that Borrelia research at the NIH got a lot more funding in the past two years... What were the goals of the bulk of those projects?

I can probably find out the answer to #3 with some digging. The first two questions? Not as easy to answer.

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Tuesday, September 20, 2011

0 How To Avoid Sample Contamination

A quick and dirty primer for those who want to ensure that their samples do not get cross-contaminated with DNA from other bacteria, viruses, etc.:
  1. Use aerosol barrier pipette tips.
  2. UV-irradiate all workstations used for the setup of master mix preps and PCRs.
  3. Treat all surfaces and tube racks with a 10% bleach solution.
  4. Use frequent and careful glove changes.
  5. Perform DNA extraction, PCR setup, and PCR product analysis in different rooms.
  6. Use clean systems.
  7. Use a negative control such as UV-treated, deionized water.
  8. Do not do bacterial work, etc. during any human DNA extraction.
Follow these simple tips, and then when others look at your research and claim that Borrelia burgdorferi could only be found where it was due to  sample contamination, point out that a number of steps were taken to prevent it.

At what point when an experiment is repeatedly reproducible does one stop saying the end result was due to sample contamination and begin saying the end result was genuine?

What other steps can you take to prevent and eliminate sample contamination?

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Monday, September 19, 2011

0 Remember Borrelia miyamotoi?

There's an article in The New York Times today about a new tickborne disease caused by Borrelia miyamotoi:

While they're reporting this as a new illness, this strain of Borrelia was found in the United States in 2001, and at the time, it wasn't known for certain whether or not it caused disease in human hosts.

Now, Russians have evidence of human infection, and it is suspected a small percentage of people in the United States are infected with Borrelia miyamotoi. A Borrelia miyamotoi infection differs from a Borrelia burgdorferi one in that there is no bulls-eye rash and there are fevers that come and go (relapsing). Patients are also negative on standard Lyme disease tests.

Here's a link to the new paper from Russian researchers:

Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA, Toporkova MG, Maleev VV, et al. Humans infected with relapsing fever spirochete Borrelia miyamotoi, Russia. Emerg Infect Dis. 2011 Oct; [Epub ahead of print]


Borrelia miyamotoi is distantly related to B. burgdorferi and transmitted by the same hard-body tick species. We report 46 cases of B. miyamotoi infection in humans and compare the frequency and clinical manifestations of this infection with those caused by B. garinii and B. burgdorferi infection. All 46 patients lived in Russia and had influenza-like illness with fever as high as 39.5°C; relapsing febrile illness occurred in 5 (11%) and erythema migrans in 4 (9%). In Russia, the rate of B. miyamotoi infection in Ixodes persulcatus ticks was 1%–16%, similar to rates in I. ricinus ticks in western Europe and I. scapularis ticks in the United States. B. miyamotoi infection may cause relapsing fever and Lyme disease–like symptoms throughout the Holarctic region of the world because of the widespread prevalence of this pathogen in its ixodid tick vectors.

Someone will have to design a blood test that will include Borrelia miyamotoi infections. And for doctors who have been relying on a bulls-eye rash for a diagnosis of Borreliosis, it's way past time to look at the bigger picture.

Edit January 23, 2013:

To read more about Borrelia miyamotoi, relapsing fever spirochete, and how an infection with it can present differently from many cases of Lyme disease, check out:
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Thursday, September 15, 2011

2 Tom Grier Speaks On Coast To Coast

Tom Grier spoke on the AM radio show, Coast to Coast, early this morning. Tom Grier has worked in the pharmaceutical industry and has a BS in Chemistry and Biology and an MS in Medical Microbiology (Immunology) from the University of Minnesota.

Tom says:
"The main point is that Lyme gets into the brain, we can't test for it, and all the brain studies are done by physicians on their own nickel. We can get millions from the CDC and NIH for deer and tick studies but nothing for studies that prove the experts wrong and the patients are disabled by this disease."

Here is part one of that interview [No video; audio only.]:

The remainder of these videos (Part 3 and Part 4) can be found on Youtube.

Many additional (older) articles written by Tom Grier are available here:

Tom Grier has been working on a Lyme disease documentary for the past year and a half... I'm hoping to hear more about this.
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0 News: Topical Antibiotic Used For Early Lyme Disease Treatment

It may be that using a topical gel after a tick bite may be all that is needed to treat Lyme disease in the future.

Maybe... But I see a problem in this automatically because it doesn't address the presence of other tickborne infections...

Researchers Say Local Antibiotic Therapy Stops Lyme Disease

Reinhard Straubinger at Ludwig-Maximilians Universität (LMU) München has now shown, in an animal model, that application of a gel containing the antibiotic azithromycin to the site of the bite rapidly terminates the infection. The efficacy of this local antibiotic therapy for the treatment of borreliosis in humans is now being tested in a Phase III clinical trial.

Knauer J, et al. Evaluation of the preventive capacities of a topically applied azithromycin formulation against Lyme borreliosis in a murine model. Journal of Antimicrobial Chemotherapy online, Sept. 15, 2011.

Read More At The Link:
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Tuesday, September 13, 2011

0 New Lyme Disease Detection Tests

The latest buzz in the Lyme disease patient community is over Advanced Laboratory Services' new culture test for Borrelia burgdorferi.

The new test uses histology and growth characteristics in conjunction with fluorescent immunostaining to detect Borrelia burgdorferi. Positive results can be further confirmed using standard molecular biology methods (PCR) based on DNA sequencing.

The test is now available for use in all states except California, New York, and Florida, which require a higher level of lab certification for testing. Physicians can obtain lab test kits from ALSI in Pennsylvania.

(I'm still looking for more information on the design and development of this test. While it's been mentioned in numerous sources that it is based on Dr. Eva Sapi's research, I have only seen a citation for her work on morphological changes in Borrelia burgdorferi when exposed to different antibiotics in vitro where the new culture method is mentioned there only in passing.)

I'm keeping an eye on this test and look forward to hearing more about it. But I'm also very interested in hearing more about a new test to detect Lyme disease which was developed by this intelligent young woman, Temple Douglas.

Temple won the 2010 Intel Science Talent Search award for her project, Application of Hydrogel Nanoparticles for Early Lyme Disease Diagnosis. Here's an interview with her:

Temple, at age 18, conducted research on the application of hydrogel nanoparticles for early Lyme disease diagnosis. Her research provides a means to reduce the number of chronic cases of Lyme disease, thus saving many people from the associated complications. A clinical trial is being planned.

Not only was she an Intel Science Talent Search finalist, but she has a patent on this test,too:


I am looking forward to hearing about these clinical trials.

Which test is going to be the most sensitive and accurate?

Additional links:
Official Press Release For Advanced Laboratory Services [PDF file]:

Student's research paper on Lyme disease ranks nationally

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Monday, September 12, 2011

0 Science Articles Of Interest: C. difficile, Alzheimer's, and tinnitus

Since I haven't been doing a regular Friday Four column in some time, I haven't been posting about interesting articles as much lately. I wanted to take the time to point out a few which readers might take an interest in on combatting C. difficile, using antidepressants to fight Alzheimer's disease, and methods of stopping tinnitus in its tracks.

New way to treat common hospital-acquired infection: Novel approach may offer treatment for other bacterial diseases

 ScienceDaily (2011-08-22) -- Researchers have discovered a molecular process by which the body can defend against the effects of Clostridium difficile, an intestinal disease that impacts several million in the U.S. each year. A commonly acquired hospital infection, the disease has become more common, more severe and harder to cure mainly due to the emergence of a new, highly virulent strain of the bacteria that causes it.

Read More At This Link:

References: Host S-nitrosylation inhibits clostridial small molecule–activated glucosylating toxins. Tor C Savidge, Petri Urvil, Numan Oezguen, Kausar Ali, Aproteem Choudhury, Vinay Acharya, Irina Pinchuk, Alfredo G Torres, Robert D English, John E Wiktorowicz, Michael Loeffelholz, Raj Kumar, Lianfa Shi, Weijia Nie, Werner Braun, Bo Herman, Alfred Hausladen, Hanping Feng, Jonathan S Stamler & Charalabos Pothoulakis. Nature Medicine 17, 1136–1141 (2011)

Comment: The good news about this research is that a drug known as protein s-nitrosylation inhibited Clostridium difficile toxins from destroying intestinal cells, and upcoming clinical trials on human subjects will test this drug treatment.

Antidepressants show signs of countering Alzheimer’s

Widely used antidepressants may reduce the ominous brain plaques associated with Alzheimer’s disease, a new study in mice and humans finds.

Brain scans of people who have taken antidepressants reveal fewer clumps of the protein amyloid-beta, a target of Alzheimer’s prevention strategies, when compared with people who have not taken the drugs.

Many in the field voiced caution about the results. But if borne out by further study, the findings may point to a new, relatively safe way to treat and prevent Alzheimer’s disease...

Read More At The Link:

Comment: This makes me wonder how many different drugs we have in use for other purposes may be used to prevent Alzheimer's disease. If Alzheimer's disease is triggered by infection, would antibiotics plus antidepressants be a sensible treatment plan?

Tinnitus discovery could lead to new ways to stop the ringing

Neuroscientists at the University of California, Berkeley, are offering hope to the 10 percent of the population who suffer from tinnitus – a constant, often high-pitched ringing or buzzing in the ears that can be annoying and even maddening, and has no cure.

Their new findings, published online last week in the journal Proceedings of the National Academy of Sciences, suggest several new approaches to treatment, including retraining the brain, and new avenues for developing drugs to suppress the ringing.

"This work is the most clearheaded documentation to this point of what's actually happening in the brain's cortex in ways that account for the ongoing genesis of sound," said Michael Merzenich, professor emeritus of otolaryngology at UC San Francisco and inventor of the cochlear implant, who was not involved with the research. "As soon as I read the paper, I said, 'Of course!' It was immediately obvious that this is almost certainly the true way to think about it."

Read More At The Link:
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Thursday, September 8, 2011

0 Identification of membrane associated drug targets in Borrelia burgdorferi ZS7- subtractive genomics approach.

Identification of membrane associated drug targets in Borrelia burgdorferi ZS7- subtractive genomics approach. Shivkumar Madagi,Vijayakumari Mali Patil, Saremy Sadegh,Abhishek Kumar Singh, Bhavana Garwal, Atreyi Banerjee, Usha Talambedu,and Biplab Bhattacharjee. Bioinformation. 2011; 6(9): 356–359.


Lyme disease is an infectious disease caused by a spirochete Borrelia burgdorferi ZS7. This spirochete is most often spread by ticks. Single antibiotic therapy is sufficient for containment of the early stage progression of the disease but combinational therapy is more preferred in later stages. Research is in progress for the development of drugs against the pathogen, but till date no vaccines have been developed to effect the late stage infections.

There is a rapid rise in the cases of antibiotic-resistant population which is more than 10% of the total infected individuals. In such condition vaccine becomes the sole alternative for prevention. Therefore effective treatment includes antibiotic combination and combination of antigenic surfaces (for vaccine preparation). Thus, a comprehensive list of drug targets unique to the microorganisms is often necessary.

Availability of Borrelia burgdorferi ZS7 proteome has enabled insilico analysis of protein sequences for the identification of drug targets and vaccine targets. In this study, 272 essential proteins were identified out of which 42 proteins were unique to the microorganism.

The study identified 15 membrane localized drug targets. Amongst these 15, molecular modeling and structure validation of the five membrane localized drug target proteins could only be achieved because of the low sequence identity of the remaining proteins with RCSB structures. These 3D structures can be further characterized by invitro and invivo studies for the development of novel vaccine epitopes and novel antibiotic therapy against Borrelia burgdorferi.

Free Full Text Here:


I noticed that the authors stated that combination antibiotic treatment is more effective in late stage Lyme disease. What research have they read, what experience do they have which indicates this, and which combination of antibiotics works?

"There is a rapid rise in the cases of antibiotic-resistant population which is more than 10% of the total infected individuals." Does this mean that antibiotics do not work in these patients, and the infection remains - or does it mean something else, in terms of the authors' view? It's not clear to me what they think of this population.

"till date no vaccines have been developed to effect the late stage infections." - I'm wondering if something got lost in translation, because this phrase doesn't make sense. I'm guessing it means vaccines are thought to prevent infection and by extension, late stage infection? I can't see how a vaccine can affect late stage infection.

I welcome the development of new drugs for treating Lyme disease which are disease-specific and non-toxic, and hopefully come with fewer side effects than the choices available now. What will these antibiotics and/or drugs of the future look like? How will they work? How will patients feel when they take them?

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5 News: Border hopping ends for Canadian Lyme disease patients

Came across this article recently, Border-hopping ends for Lyme disease sufferers.


"Instead of draining their savings to seek controversial lyme-disease treatment in the United States, suffering British Columbians can now find a similar treatment close to home, at the offices of select naturopathic physicians.

The new option is due to a one-year-old regulation change in the province that allows naturopaths to prescribe drugs, once they pass a test."

MORE at the link:

So, apparently one can get extended oral antibiotic treatment for Lyme disease, but not as extensive as patients in the US have received under some LLMDs.

I wonder how much this is going to change how Lyme disease is treated in Canada? I can only hope that more cases are being diagnosed and treated early.

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Wednesday, September 7, 2011

5 Doctors Who Decide Long Term Antibiotic Treatment May Be Warranted

This article by a doctor, Eating Crow With Lyme, has been making the rounds on several Lyme disease support lists and sites.

A lot of patients are feeling vindicated that longer term treatment with antibiotics is gaining more support when they see a doctor who used to hew tightly to the IDSA Lyme disease treatment guidelines has changed his mind.

What made the difference for the doctor in this article? To quote from the source:

"What changed my mind? Personal experience. A family member began to suffer a wide variety of strange symptoms 12 years ago, including facial numbness, slurred speech, problems with balance, abdominal pain, and headache. After a few baseline studies, her physician informed her that she was depressed and offered antidepressants. She told the physician she had read about Lyme disease and requested testing. He refused, stating (as I had to several of my patients) that her lack of history of tick bite and the classic rash disqualified her from any consideration of Lyme disease. But she worked and lived on a farm, had pets in the house, cut her own firewood, and spent much of her day outdoors. Deer (carriers of the primary Lyme disease vector, the blacklegged deer tick) were as plentiful as cows on the farm. The ingredients were all there...

She changed doctors and her new physician agreed to order an ELISA antibody screening study for Lyme disease. It was negative, she was reassured, and further workup was deferred. But the symptoms persisted, gradually worsening with time. She developed heart rhythm disturbances, migratory joint and muscle aches, and increasing weakness. The Lyme studies were repeated, this time including the Lyme Western Blot. Again, she failed to meet Centers for Disease Control criteria for Lyme disease. Multiple specialists, including neurologists, rheumatologists, and cardiologists, saw her; no one could figure out what was wrong. I kept thinking, “This seems to fit Lyme disease, but the tests are negative ... Hey, what do I know, these guys are specialists; I’d best keep my mouth shut.” Finally she was seen by a Lyme specialist. He initiated aggressive therapy for what he recognized clinically, and what was shown on repeat testing, to be a raging untreated case of Lyme disease. After years of misery and tens of thousands of dollars in medical costs, she is gradually getting better."

This is one doctor's story about one patient, but there are many similar stories that have been told online by other patients.

Based on this, one doctor changed his position on what Lyme disease was about, and now sounds supportive of longer term treatment - at least for someone with this specific background and case.

This is only one short article. I wonder how many other patients this doctor has seen and has wondered if they, too, have been struggling with Lyme disease.

I can't say that long-term antibiotic treatment is the right treatment for all patients in every situation; clearly some people can't tolerate them and their long-term effect on people is not entirely known. They are not risk-free, and they do not work equally well for everyone. At the same time, for patients in which they do work and it helps them get their life back, I have to wonder why there isn't more research being conducted on those who have already improved and reclaimed their former lives - and to compare them in some objectively measurable way against those patients who are acutely infected or have been suffering with long-term symptoms.

I keep thinking back on my own doctors who treated me for multiple ear and sinus infections with multiple courses of antibiotics, and how there was no external scrutiny from their peers or the insurance companies over whether or not my doctors could switch my antibiotics or give me more antibiotics in order to rid myself of such infections... There was no required blood test that I had to take in order to receive more and/or different antibiotic treatment. Objective evidence of infection wasn't necessary; I returned to the doctor and told them I still felt lousy, described my symptoms, and he or she gave me a new prescription.

Lyme disease is treated differently from a sinus infection. Differently from an ear infection. Differently from a urinary tract infection. Different from skin wound infections. All because for some reason, the idea is that Lyme disease has been properly treated after 2-3 weeks of the same antibiotic. In every case. For every person.

But is that correct? The word "guidelines" is supposed to mean precisely that. If an individual doctor determines a patient needs more treatment, then to provide more is at the doctor's discretion, based on an examination and the patient's response to treatment.

How does one support more treatment in one instance without providing any objective evidence, and deny it in another instance, while requiring objective evidence?

Is the goal for a physician to improve the quality of life for a patient, maintain their quality of life to prevent it from getting worse, or to cure a patient?

Is the goal of a physician - and the role of a physician - at odds with the goal of a clinical researcher and their own role?

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Friday, September 2, 2011

0 On Explaining One's Position

I recently received a comment on a post in the past from someone who has identified as a skeptic, condemning this blog for offering any support for chronic Lyme disease as a concept. I'm not specifically linking to it now, but mention it on general principle because I think it reflects a misunderstanding on what I'm trying to do and my position in the controversy.

I mention in numerous places throughout this blog that I have a skeptical nature, and I have also had persisting symptoms since I contracted Lyme disease. I've stated that I think chronic Lyme disease could happen under specific circumstances, and I do not know how common that is nor is it clear to me what all such circumstances are. I've also stated that I'm not sure chronic infection is always the cause of persisting symptoms. I simply don't know.

Because of my background and who I have been, I have found it difficult to stand in the middle of the Lyme disease controversy and ask the basic question of, "What is this all about, anyway?". But that is the question I am asking, and while I have a lot of readers who are supporters - because I haven't firmly fallen into one camp, I have detractors, too.

On one hand, I can potentially be viewed suspiciously by some Lyme disease patients because I do write about autoimmunity and Lyme arthritis, and I do wonder if the disease itself leads to changes in the immune system which lead to chronic symptoms. The latest research on B cells in lymph nodes certainly align with my musings about this... On the other hand, I can potentially be viewed suspiciously by those who align with the IDSA because I think Lyme disease may be able to persist as an infection... Barthold's research on surviving spirochetes after antibiotic treatment in a mouse model can point to the possibility of persisting infection.

In a way, I really can't win. Someone is going to take issue with something I write regardless of what it is. And that's fine - I give them a venue to express their opinion even though I may disagree. Or perhaps I don't even have an opinion on a particular topic yet, and whatever information they are sharing isn't something I was aware of before they mentioned it.

My goal here isn't to always find consensus - though I appreciate and welcome it when it is found; agreeing on some ideas can be a form of progress provided the evidence is sound. My goal here is to learn about facets of this disease and tickborne illnesses in general, and how they impact society, individuals, and research, and what is the relationship between each of those aspects.

I actually wish more skeptics would drop by for a visit, have some scotch or a coffee, and just share what research they have under their belt which supports their view and knowledge which reflects their understanding of it. It is easy to say, "You're making a mistake in supporting the chronic Lyme disease model". Criticism is easy to come by, and attaching that criticism to the letter which was posted to the Lancet recently in no way supports the science underlying your position.

If you don't support the concept of chronic Lyme disease as possible, okay, but at least explain why you individually do not and give reasons about it from a biological, microbiological, and molecular biological point of view. That would be educational for everyone reading along.

That gets the focus back on the reason for controversy to begin with: A dispute over what is happening in patients with persisting symptoms.

We may actually agree on a number of points, even if I don't agree with you on all of them. But whether we agree or not, discussing conflicts of interest from either the ILADS camp or IDSA camp sidesteps the issue of what the research out there reflects about what is known and unknown about Borrelia. Where does the definitive knowledge about Borrelia end and where does the speculation begin? What is inconclusive? What requires more research at this point in time?

I am looking for common ground at times because I am tired of the controversy. And I am also looking for any tie breakers: Is evidence in category A stronger in this instance than it is in category B? What is the weight of the evidence? What if there isn't a preponderance of evidence yet?

So, this is the basis on which I want to engage in discussion with people on this blog. I can talk about the social aspects of it on a social post, and the political aspects of it on a political post - but mostly, I'd like to steer things back to what the data reflects and what results are. (And also what isn't reflected in the data and results but has yet to be known.)

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The Camp Other Song Of The Month

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