Friday, March 30, 2012

7 Did Isabel Diterich Have The Cure For Chronic Lyme Disease?

One researcher whose papers I've been reading recently is Isabel Diterich's. Several years ago she published two papers on Lyme disease which grabbed my attention because they not only revealed a hypothesis of immunosuppression caused by Borrelia burgdorferi spirochetes - but they also revealed a potential cure for chronic Lyme disease.

I say "potential" here with this caveat:

While the treatment did appear turn a man who was disabled into what sounds like the picture of health for at least eight years, he had to take filgrastim for almost two weeks. And filgrastim is an immune modulating drug which can have serious side effects in some people - there have even been a few fatalities.

However, most of the people who have suffered serious side effects from filgrastim were cancer and leukemia patients who already had serious health problems and were at greater risk for being affected by the drug. And most patients - including cancer patients - experience less dramatic effects of fatigue and joint pain from the use of filgrastim - something Lyme disease patients suffer with anyway.

Scary sounding as it is to take a drug which has the risk of serious or even fatal side effects, one has to consider that if better and safer immune modulating drugs could be developed - along with antibiotics - together they might be the cure for chronic Lyme disease.

To quote from Isabel Ditrech's 2003 thesis, "Immunomodulation and new therapeutic strategies in Lyme borreliosis":
"5.3.1 Case report

A 51 year old patient with a history of frequent exposures to tick bites presented with polyarthritis in the fingers and feet. Arthritic destruction of synovial clefts mainly in the metacarpophalangial and in the proximal interphalangial joints of fingers and feet could be demonstrated by X-ray. Low, but clearly positive, serum titers of Borrelia IgG by ELISA and immunoblot (p100 +++) and a negative IgM-ELISA (both MaxPettenkofer-Institute, Munich, Germany) corroborated diagnosis of late stage Borrelia infection.  
A standard two week i.v. treatment with 2 g/day Ceftriaxone (Rocephin,Hoffmann LaRoche, Grenzach-Whylen, Germany) led to transient improvement of symptoms, i.e. subjective decline of arthritis, that lasted for eight weeks. Then, the inflammatory symptoms returned and became progressively worse, indicating that the treatment had probably failed.  
We hypothesized that persistence of Borrelia might be due to a disabled immunocompetence of the patient. Therefore, we tested whether a complete eradication of the pathogen could be achieved by combining immunosupportive treatment with antibiosis. The experimental treatment regimen, applied with the informed consent of the patient, was as follows: First week 2 g Ceftriaxone (Rocephin ) i.v. daily, second week 480 µg s.c. Filgrastim (Neupogen, Amgen, Thousand Oaks, USA) every second day, and third week 2 g Ceftriaxone daily plus 300 µg Filgrastim every second day (Figure 5.1). Neutrophil counts were determined by a Coulter STKS counter (Coulter, Krefeld, Germany)"
So this lays out the background of this individual case report on one patient. What were the results? More quoted from the above thesis:
"5.4.1 Patient case report

The combination therapy of Ceftriaxone plus Filgrastim was well tolerated. Only after the first injection of Filgrastim the patient reported acute but moderate pain in the previously affected joints i.e. the shoulder, fingers and knees. 
Circulating neutrophil counts increased from 1400 to 17000 cells/µl within 24 h after the first Filgrastim injection. Monocyte numbers increased about two-fold, while there was little effect on lymphocytes (Figure 5.2a). The plateau of neutrophil counts at about 17000 cells/µl blood was maintained until one day after the end of treatment.  
The subjective symptoms disappeared during the following six weeks after the treatment. The patient reported that he was able to resume previously abandoned sporting activities including mountain climbing and downhill skiing. Moreover, fine mechanical skills needed for piano playing were restored. 
After three months, the Borrelia IgG titer was negative. The intensity of the immunoblot at this time point was significantly reduced (from +++ to +) and two years later it was negative. Eight years after treatment the patient is still free of arthritic symptoms."
Source:
http://kops.ub.uni-konstanz.de/bitstream/handle/urn:nbn:de:bsz:352-opus-9814/Diss_formated_ENDVERSION.pdf

So it seems like at least for this patient, this method of treatment changed their life so that they could return to all the things they used to do that they loved. I would have liked to know more about this patient and how he is doing today, given it has been years since this study was completed.

And I'd like to know if a similar treatment plan would work for me and everyone else suffering with chronic Lyme disease. To take ceftriaxone and filgrastim for a couple weeks - or something similar, but with fewer side effects - only to be done with this nightmare and get on with my life would be fantastic.

It would mean no more attempts at long term antibiotic treatment and experimentation with alternative medicine. I would just get treatment for three weeks and be done with it... Sounds like a plan to me.

Reflecting on this, over the years there have been anecdotes - stories I've heard passed around Lyme disease support groups - about the occasional chronic Lyme disease patient who went on to discover they had cancer, went through chemotherapy and other supportive treatment for their cancer - only end treatment not only going into remission from cancer  - but saying that they think their chronic Lyme disease is cured, too.

These stories have been around for a while, but I've never personally known anyone who went through this process. It would be great to get a confirmation from their doctors and families that after chemotherapy and supportive treatments, they had a notable and lasting improvement and feel like their old selves again. What if a drug like filgrastim played a role in their recovery?

This isn't the only example of a chronic condition where the cause has been unknown and the symptoms can be debilitating and lead to years of loss of productivity and physical pain... let's consider chronic fatigue syndrome, also known as CFS/ME or CFSIDS.

A study completed last year in Norway showed that rituximab had a profoundly positive effect on people with CFS/ME. In this study, a few people seemed to go into complete remission from their CFS and returned to work and led normal lives. It didn't work for everyone - 40% of study participants did not experience improvement from the drug. It's unknown why. But that it worked so well for the rest of treated patients deserves a closer look because it begins to reveal the mechanisms behind what causes CFS/ME.

While there has been speculation that chronic fatigue syndrome and chronic Lyme disease (CLD) are the same condition, a recent study on the different proteins found in the cerebrospinal fluid (CSF) of both CFS and CLD patients has challenged this notion. At least in terms of objective evidence, the proteins in the CSF of both groups are different. However, what if part of the underlying process behind what causes these conditions is the same?

Quoting the above well-written article from the Phoenix Rising ME web site, let's look at the mechanism behind rituximab and what it does in people with CFS/ME:
"Rituximab is believed to deplete B-cells in two ways; by recruiting other members of the immune system to attack them and by locking on a receptor on the B-cell that tells the cell to kill itself. B-cells are an integral part of the immune response. Until they are activated, B-cells quietly troll the blood, collecting and digesting molecules called antigens that appear to be suspicious. Once they are digested they place bits of them on MHC molecules for T-cells to inspect. If the T-cells decide those molecules came from a pathogen, they turn around and turn the B-cells on – transforming them into antibody producing machines (‘plasma cells’) that can generate from 100s to thousands of antibodies per second.

These antibodies or immunoglobulins are specifically manufactured to attach to a pathogen and physically stop it from locking onto our cells. The antibodies also alert macrophages to come gobble up the pathogen and they turn on other parts of the immune system. B-cells are key players in the immune response but if they go too far; if they get too zealous, they can mistakenly attack our own cells and overactive B-cell activity has been implicated in many auto-immune disorders."
If this sounds familiar to you, then you might have been reading about Viral Genetics' targeted peptide therapy, VGV-L, for treating chronic Lyme disease.

Viral Genetics' patent states the following about treating chronic Lyme disease:
"[0116] It is believed according to the invention that Borrelia burgdorferi also produces a Toll ligand for TLR2. Replacement of the CLIP on the surface of the B cell by treatment with a thymus derived peptide with high affinity for the MHC fingerprint of a particular individual, would result in activation of the important Tregs that can in turn cause reduction in antigen-non-specific B cells. Thus treatment with thymus derived peptides could reactivate specific Tregs and dampen the pathological inflammation that is required for the chronic inflammatory condition characteristic of Lyme Disease. With the appropriate MHC analysis of the subject, a specific thymus derived peptide can be synthesized to treat that subject. Thus individuals with all different types of MHC fingerprints could effectively be treated for Lyme disease."
An easier-to-understand explanation can be found elsewhere - this research report revealed how VGV-L is used to treat HIV. In this instance, just substitute "chronic Lyme Disease" for "HIV" and you can get a picture of what VGV-L does:
"The conventional approach to HIV vaccines, for example, is to develop therapeutic vaccines to stimulate immune system response. The problem with the conventional approach is that the infected cells are camouflaged and not visible to the body’s immune system. The body’s powerful T-cells are unable to seek out and destroy the infected camouflaged cells because they cannot recognize that the cell is infected.

To understand the issue, think of the Klingon space ship on Star Trek that has its cloaking device activated. The U.S.S. Enterprise has no way of knowing where the enemy is in space. The only hope it has in winning the battle is for the Klingon vessel to be de-cloaked and, once revealed, use their ammunition to destroy it. What’s worse in the case of HIV is that while the infected cell is cloaked, it is also effectively setting off an alarm that triggers the immune system to create inflammation. Why is this important? It turns out that this inflammation is critical for allowing the HIV virus to spread to even more cells.

Many other viruses and bacteria also trigger inflammation but, unlike HIV, the inflammation does not necessarily allow or facilitate the spread of the virus or bacteria itself. However, in these cases, the inflammation itself is harmful because it creates a hostile and inflamed environment that provides the necessary components for a potential autoimmune reaction that can cause the immune system to attack and damage one’s own body. Viral believes that diseases such as Lyme Disease, Multiple Sclerosis and others involve this inflammatory mechanism.

To use the Star Trek metaphor, what Dr. Newell Rogers has developed with TPT is a de-cloaking device for the body’s immune system to use in its pursuit of invaders. Through the development and use of computational biology programs and databases, Dr. Newell Rogers and her team have created a way to remove the camouflage that is cloaking the infected cells, flagging them with custom peptides that allow the body’s immune system to seek out and destroy them.

The key discovery of the TPT platform is that a self-peptide (in other words, one that is naturally produced and a healthy part of one’s normally functioning immune system) called ―CLIP2 that was until now thought only to exist primarily inside certain immune system cells, is sometimes displayed on the outside of cells, thus leading to harmful inflammation. Dr. Newell Rogers discovered that the products of some pathogen invaders such as viruses and bacteria, when picked up on the surface of certain immune system cells, sometimes incorrectly cause those cells to display CLIP externally (i.e. ―ectopically).

Normally, when an invader strikes, this process may promote needed inflammation early in infection, but it is quickly controlled when a more specific, immune response takes over, allowing a highly-targeted immune response to be marshaled against the pathogen. However, when CLIP is improperly displayed, displayed for too long or displayed chronically, the immune system is marshaled to promote a broad and unspecified inflammation without the specific targeting, leaving open the possibility that this inflammation actually turns against one’s own cells. Replacing CLIP is the focus of Viral’s Targeted Peptides because it turns off the harmful alarm."
Read more from the source - including about individual MHC genetic profiles here: http://www.viralgenetics.com/investors/press-releases/Research_2.0_Report_Feb1_2011.pdf

They're using Star Trek metaphors to describe this... I think that's pretty geeky. Awesome.

So, it seems that whether there is current infection or not, VGV-L may be one way to effectively treat chronic Lyme disease and lower inflammation due to runaway immune dysregulation. And if infection is currently present, then it looks like VGV-L will trigger T cells that recognize the infection and summon functional B-cells to fight it.

Now, getting back to Isabel... Remember Isabel, the researcher who used filgrastim and ceftriaxone to treat a patient with chronic Lyme disease about a decade ago? Yes, that Isabel.

Well, she wrote another paper, along with Rauter, Kirshning, and Hartung: "Borrelia burgdorferi-Induced Tolerance as a Model of Persistence via Immunosuppression"

The abstract states:
"If left untreated, infection with Borrelia burgdorferi sensu lato may lead to chronic Lyme borreliosis. It is still unknown how this pathogen manages to persist in the host in the presence of competent immune cells. It was recently reported that Borrelia suppresses the host's immune response, thus perhaps preventing the elimination of the pathogen (I. Diterich, L. Härter, D. Hassler, A. Wendel, and T. Hartung, Infect. Immun. 69:687-694, 2001). Here, we further characterize Borrelia-induced immunomodulation in order to develop a model of this anergy. 
We observed that the different Borrelia preparations that we tested, i.e., live, heat-inactivated, and sonicated Borrelia, could desensitize human blood monocytes, as shown by attenuated cytokine release upon restimulation with any of the different preparations. Next, we investigated whether these Borrelia-specific stimuli render monocytes tolerant, i.e. hyporesponsive, towards another Toll-like receptor 2 (TLR2) agonist, such as lipoteichoic acid from gram-positive bacteria, or towards the TLR4 agonist lipopolysaccharide. Cross-tolerance towards all tested stimuli was induced. Furthermore, using primary bone marrow cells from TLR2-deficient mice and from mice with a nonfunctional TLR4 (strain C3H/HeJ), we demonstrated that the TLR2 was required for tolerance induction by Borrelia, and using neutralizing antibodies, we identified interleukin-10 as the key mediator involved."
Source: http://iai.asm.org/content/71/7/3979.full

Where have I heard something like this before? Oh, Dr. Karen Newell Rogers - that's right - she discussed this at a recent Lyme disease research conference:

"[...]Some researchers would argue that chronic inflammation requires the continuous presence of bacteria, whereas others would suggest that continuous presence of bacteria does not always result in inflammation and that exacerbations of chronic symptoms could result from infection with a different organism--or that chronic symptoms could re-cur from unrelated pro-inflammatory events. Potentially reconciling these seemingly conflicting perspectives on the mechanism of Lyme disease may be the effect of Borrelia burgdoreri’s bacterial by-products on Toll Like Receptors, (TLR)-mediated immune activation. 

TLR appear to be the “gate-keepers” of an inflammatory response. Bacteria, including Borrelia, produce products that, by binding to TLRs on the cell surface, promote leukocyte activation, cytokine production, and acute inflammation. In some genetic backgrounds of mice, acute inflammation is sufficient to fight off infection and resolve disease. In other mouse strains, the pathogens, or in this case the bacteria, get past TLR-induced inflammation and remain symptomatically undetectable in cells and tissues (Barthold, etc); Barthold et al. have found that no matter how severe or mild the disease in any of the genetically inbred strains of mice, there was no more inflammatory disease when the bacteria were eliminated."
And where else have I heard about IL-10 production before? Oh, right - Rituximab, and research on gender differences in antibody response to Borrelia burgdorferi...

From the previously mentioned Phoenix Rising ME article:
"While Rituximab is busy destroying B-cells there is also evidence that it may actually be turning on NK cells – which, of course, habitually underperform in CFS. Rituximab also appears to increase production of IL-10 – a key anti-inflammatory cytokine that may be a protective agent in ME/CFS – and reduces levels of the powerful pro-inflammatory cytokine tumor necrosis factor. A review article suggested that Rituximab was able restore Th1/Th2 balance in the immune system. These results suggest Rituximab could be working as an immunodulator helping to re-balance the immune response by turning down the over-activated parts of it and bumping up the under-active ones."
All this ties together quite nicely, it seems, with other research I have listed here - forming a master hypothesis with different pieces. Does it hold up to scrutiny? Tell me - I'd love to hear your ideas.

But here is the master hypothesis, in its infancy:

1) Host genetics play a role in the ability of mice (and possibly people!) in clearing Borrelia burgdorferi infections. See:

http://campother.blogspot.com/2011/08/immune-infection-hla-dr-alleles.html

The host's genetic background in developing chronic infection is, however, open to debate - and may not play as big a role in disease as Borrelia burgdorferi s.l.'s genetic diversity/VlsE recombination on different plasmids:

http://campother.blogspot.com/2011/08/do-different-genetic-haplotypes-matter.html
http://campother.blogspot.com/2011/08/more-on-genetic-haplotypes-and-lyme.html

2) The genetics of Borrelia burgdorferi strains play a role in how quickly they disseminate into host tissues and also how well they can generate inflammation - which leads to overstimulation of the immune system in production of poor quality plasma b-cells, but also, ironically, immune suppression because of the mechanisms Isabel Diterich and Karen Newell Rogers describe. Refer, also, to Tunev and Barthold et al's research, "Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation":

http://campother.blogspot.com/2011/06/paper-borrelia-burgdorferi-rst1-ospc.html
http://spirochetesunwound.blogspot.com/2011/07/does-borrelia-burgdorferi-cause.html
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002066
http://spirochetesunwound.blogspot.com/2010/07/antigen-presentation-in-bloodstream-how.html (refer to other research on relationship between b-cells/plasma cells and T cells)

It could also be that not having enough iNKT cells is an issue:
http://www.pnas.org/content/105/50/19863.full.pdf

2a) The changing pattern of antigenic variation during this time may also be why patients produce an undulating immune response in measured antibodies which echo a more drawn-out response similar to relapsing fever:

http://campother.blogspot.com/2012/02/paper-course-of-antibody-response-in.html
http://campother.blogspot.com/2011/08/antibodies-linked-to-long-term-lyme.html (read comments, too)
http://www.ncbi.nlm.nih.gov/pubmed/9108482
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772371/
http://www.ncbi.nlm.nih.gov/pubmed/11544329
http://campother.blogspot.com/2011/07/lyme-disease-western-blots-and-antigen.html

It may not be that the tests are lousy for measuring antibodies which are present to Borrelia burgdorferi. It may be that the antibodies are not present because they are tied up in immune complexes.

2b) There is also the possibility that Borrelia burgdorferi is occasionally intracellular in nature, though there is not enough in vivo evidence to support this. If so, it would also explain why an undulatory immune response might be present:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067508/?tool=pubmed
http://campother.blogspot.com/2011/07/fibroblasts-and-lyme-disease-sample.html

Whether or not items #2a and #2b are relevant here remains to be seen - the main point is that Borrelia burgdorferi can lead to both overstimulation of the immune system as well as immune suppression.

Based on this, I surmise that may not be that blood tests are so lousy at detecting antibodies produced by the presence Borrelia burgdorferi. It may be that there is no reliable way to detect the presence of infection by correlating them with the presence of antibody responses (seronegative Lyme disease).

3) What gender you are and your hormone levels and metabolism may play a role in persisting symptoms and prolonged infection as well, so there is ALSO a metabolic cause behind chronic Lyme disease. How well the immune system can respond to initial infection to begin with seems to play a role in developing chronic Lyme disease, as even 10% of acute cases of Lyme disease result in treatment failure.

http://campother.blogspot.com/2012/03/lyme-disease-presents-differently-in.html
http://campother.blogspot.com/2012/01/two-new-hypotheses-for-chronic-lyme.html (read comments, too)
http://www.ncbi.nlm.nih.gov/pubmed/17438273 (this may provide the scientific link for the anecdotes that people who develop chronic Lyme disease generally were under more stress when they contracted the disease)

4) If there are persister cells, this is an additional consideration - throwing more antibiotics at a pathogen which is antibiotic tolerant when it is a persister cell will, at most, keep the infection from getting worse but it won't eliminate it.

http://campother.blogspot.com/2012/01/paper-persistence-of-borrelia.html
http://campother.blogspot.com/2012/02/blog-log-spirochetes-unwound-on.html

See also:
The research of Kim Lewis on persister cells: www.bu.edu/abl/files/killing_persisters.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145328/

And it may be that persister cells are more likely to be on the scene earlier, depending on how appropriate a given antibiotic is for treating specific genospecies - refer to item #2 above, but also:

http://campother.blogspot.com/2011/05/abstract-evaluation-of-in-vitro.html

5) Because the host has a sub-optimal immune system, even with long term antibiotics, a subset of the population will have trouble clearing the remaining spirochetes after antibiotics are stopped. Additional antibiotics plus a treatment which eliminates low quality plasma b-cells and promotes the activity of Treg cells which recognize current infection could overturn the dysregulated immune system.

What does this boil down to?

Easy: The argument of "is it a chronic infection or is it an immune disorder, possibly autoimmune" is a false dichotomy and too simplistic.

The circumstances which give rise to chronic Lyme disease are more complex than that, and if people want to solve the chronic Lyme problem, they have to roll up their sleeves and look at more puzzle pieces and how they fit together.

Image credit: 
Original image by Muns on Wikimedia Commons; derived image above by Schlurcher.


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Tuesday, March 27, 2012

0 The Wall Street Journal On The Increase Of Tickborne Diseases

Today, Laura Landro of the Wall Street Journal published an article in its Life & Culture section on "This Season's Ticking Time Bomb: Warm Weather Means Ticks Will Be Out Early; A 'Horrific' Season for Lyme and Other Diseases."

It sounds like a sensationalized piece from the title at first - but it's not. It's straightforward reporting on how this year the number of tickborne diseases will be on the rise due to earlier warm temperatures and how to protect your yourself and your family through interactive advice.

Laura's article outlines the typical topics around Lyme disease: symptoms, the difficulty of early diagnosis and treatment, the rising number of cases reported to the CDC over the past decade, and the steps one can take to prevent contracting Lyme disease.

There is also mention of a CDC study on the use of sprays to limit tick population and how a Connecticut scientist sets Japanese barberry on fire to remove it as a source of ticks' sheltering habitat.

For more information, check out Laura's article on the WSJ here:

http://online.wsj.com/article/SB10001424052702303404704577305630267988716.html?mod=WSJ_LifeStyle_Lifestyle_6

In addition to this article, Laura Landro also wrote a blog entry in the Health section, "Doctors Clash Over Best Treatments for Lyme Disease", which discusses the IDSA's treatment guidelines approach (short, and possibly not sweet) and ILADS treatment approach (in for the long haul) for patients with persisting symptoms.

In the blog, Paul Mead of the CDC, Leo J. Shea III of ILADS, and Kristin Schofield, founder of a central New York chapter of the Empire State Lyme Disease Association, are all interviewed.

Read and comment on her blog entry here, as I did:

http://blogs.wsj.com/health/2012/03/27/doctors-clash-over-best-treatments-for-lyme-disease/tab/comments/#comment-1553317


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Sunday, March 25, 2012

0 Lyme Disease Presents Differently In Women Compared To Men

Recently, Lauren A. Crowder, M.P.H. reported observations on some differences between women and men in response to Lyme disease in a poster at the International Conference on Emerging Infectious Diseases.

The short story: Women with Lyme disease display more clinical symptoms than do men with the disease and also are less likely to seroconvert following treatment, according to findings from a prospective cohort study involving 77 patients.


The study revealed the following observations:

  • Significantly more women than men reported joint pain, muscle pain, headache, back pain, heart palpitations, nausea, vomiting, anxiety, numbness and tingling, and changes in vision during at least one of six preplanned study visits with a physician.
  • At the initial study visit, a similar proportion of men and women (about 60% of each) tested negative for Lyme disease using the Centers for Disease Control and Prevention’s recommended two-tier testing criteria for serodiagnosis. At the first post-treatment interview, 70% of women who tested negative at the first pre-treatment visit remained negative, compared with only 35% of the men who initially tested negative.
Read more about this Lyme Disease Foundation funded study here:
http://www.internalmedicinenews.com/news/infectious-diseases/single-article/lyme-disease-presents-differently-in-men-and-women/1bf48578d5.html

And see the original source with study here:

SEE page 151 of ICEID 2012 Abstracts
March 11-14, 2012 | Hyatt Regency Atlanta | Atlanta, Georgia
(PDF) http://www.iceid.org/images/iceid_2012_finalprogram_final.pdf

Board 264. Another Difference between Boys and Girls: Sex-Based Differences in Lyme Disease.
L.A. Crowder, A. Rebman, V. Yedlin, M. Soloski, J.N. Aucott; Lyme Disease Research Foundation of Maryland, Lutherville, MD, USA, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.

This isn't the first time, however, that someone observed a difference between men and women's immune responses in relation to Borrelia burgdorferi.

Let's take the time machine back to Sweden, in 2004...

Lyme borreliosis reinfection: might it be explained by a gender difference in immune response?
Sara Jarefors, Louise Bennet, Elin You, Pia Forsberg, Christina Ekerfelt, Johan Berglund, and Jan Ernerudh
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782288/

This study had a different goal than Ms. Crowder's in that it was intended to measure the difference in immunological response between people of both genders who had only been infected once and those who had been reinfected with Lyme disease within a five year period.

The findings relevant to women in this case:
"...for the immunological response there were major differences between men and women. The women displayed higher spontaneous secretion of all cytokines measured, i.e. IL-4, IL-6, IL-10, IFN-γ and TNF-α. Spontaneous secretion, at an infection-free time-point, reflects the habitual immune status and may suggest what type of immunological defence an individual generally displays. For instance, allergy has been considered a Th2-type related condition and, accordingly, atopic individuals have higher spontaneous IL-4 expression than non-atopic controls.

Women of reproductive age are believed to handle infections better than men, having a stronger tendency to show Th1-type responses and expression of higher levels of pro-inflammatory cytokines, and they also develop higher antibody titres than men when vaccinated. However, the female immune response fluctuates with the menstrual cycle. In general, oestrogen has a stimulatory effect on the immune system whereas testosterone acts as a suppressor. When women enter the menopause their levels of oestrogen decrease and thereby the stimulatory effect diminishes, leading to an altered immune status. All except one of the women in our study were postmenopausal, and this could be a factor explaining why more women than men became reinfected with B. burgdorferi."
And...
"Serology was not performed on the individuals in this study because, at the time of EM diagnosis, only 30–40% of patients displayed antibodies to Borrelia. Studies following patients with culture-confirmed EM have shown that, although antibodies can be detected 10–20 years after initial infection, titres decline gradually during the first year."
A paper which cited the previous one discusses the functions of IL-10 in relationship to Borrelia burgdorferi:

Interleukin-10 alters effector functions of multiple genes induced by Borrelia burgdorferi in macrophages to regulate Lyme disease inflammation.
Gautam A, Dixit S, Philipp MT, Singh SR, Morici LA, Kaushal D, Dennis VA.

Source: http://www.ncbi.nlm.nih.gov/pubmed/21947773

To sum it up: IL-10 (an interleukin) which is produced in higher amounts in women than it is in men, is responsible for inhibiting the actions of some genes in Borrelia burgdorferi - but it is also responsible for empowering the actions of some genes, too.

What implication this has on infection in different genders remains to be seen and requires more study.

But what is already known about the role of inflammation in the presence of Borrelia burgdorferi is important to take note of here: Inflammation facilitates Borrelia burgdorferi's adaptation to its host; it stimulates antigenic variation and it leads to increased spirochetal burden in mice. So if this applies to humans: All that pain, swelling, and inflammation patients feel? It is good for the spirochetes, and it is bad for you.


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Friday, March 23, 2012

0 Babesiosis Fatality In Australia

Earlier this week, the Australian television show Today Tonight aired a story about a 56 year old man from New South Wales who died from Babesiosis. There is some concern by others that the man contracted the infection within Australia and not overseas, though more evidence is needed this is the case.

Babesiosis is a tickborne illness caused by a protozoan parasite, Babesia, which infects red blood cells and produces symptoms which are similar to those found in malaria. It can be subclinical and cause no to mild symptoms - but it can also lead to moderate and severe symptoms. And sadly, as we've seen - even kill people.

People who are most likely to have severe symptoms are the elderly, those with compromised immune systems, and those who do not have a spleen.

I know firsthand what Babesiosis is like because several months after I was bitten by a tick, new symptoms showed up in me which were indicative of an infection with Babesia. I also was fortunate to get a positive blood smear - not something which is easily accomplished in the lab.

The most obvious symptoms I experienced were an ongoing shortness of breath with the sensation of a vice-like grip around my ribs, breaking out into sweats at night, "flash" fevers, and anemia. There were other less known symptoms as well, but these are among the most common. Fortunately, I think (I hope) I have beat this coinfection, and it has not beat me.

As it stands, the United States has seen a number of its own deaths due to Babesia, and according to an article in the New York Times, in coastal Rhode Island, the number of cases of Babesia are around 25% less than those of Lyme disease - in an area which is highly endemic for Lyme disease. And not only is Babesia becoming quite common in northeastern states - it's spreading to the northern midwest as well and was already found on the west coast.

One important thing to be aware of is not only can Babesia be transmitted by ticks - it can be spread through the blood supply via donations and transfusions. Thus far, there are twelve people who have died from Babesia spread through blood transfusions in the US. It is unknown, though, how many people may have been infected with Babesia through the blood supply and currently carry a more subclinical infection that may become more evident later.

There is currently no blood screening test available for donations and transfusions, and research is underway to develop such a test to avoid spreading more Babesia through the blood supply. So I highly recommend that if you have to get surgery and know this in advance, that you blood bank your own blood in preparation in case you need a transfusion.

You can view the dramatic video of the Today Tonight story here [4:46 minutes, plus short ad]:




Read this link for a full transcript of the show:

http://au.news.yahoo.com/today-tonight/latest/article/-/13207421/tick-timebomb/

For more information about Babesia and Babesiosis, check out these links:

Specific to Australia: http://lymedisease.org.au/about-lyme-disease/babesiosis/

About the Lifecycle: http://www.stanford.edu/group/parasites/ParaSites2006/Babesiosis/lifecycle.html

About Treatment: http://emedicine.medscape.com/article/780914-treatment



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Wednesday, March 21, 2012

12 One Pill Of Doxycycline Is Not Enough To Prevent Early Lyme Disease


This paper is being passed around the Lyme disease patient community that has everyone's attention. It's about the most effective timing and the use of one 200 mg capsule of doxycycline as prophylaxis to prevent Lyme disease after a tick bite.

The bottom line from the authors of the study: One 200 mg capsule of doxycycline is totally ineffective in preventing Lyme disease if it is administered 48 hours after a tick bite.

And even if administered in less than 48 hours, it is no guarantee of successfully preventing infection.

The following commentary comes from Dr. Elizabeth Maloney:

Since 2001 the IDSA has been recommending preventive treatment of a single dose of doxycyline for tickbites under certain narrow conditions.  Piesman et al. have just published a new article concluding that if the treatment is given as little as 24 hours after the bite, only 47% of the mice were cured. Piesman also concludes that "Prophylactic treatment was totally ineffective when delivered ≥2days (48hrs) after tick removal." The IDSA recommends treating if:

  • Tick is estimated to have been attached for ≥36 hours (based upon how engorged the tick appears or the amount of time since outdoor exposure)
  • Antibiotic treatment can begin within 72 hours of tick removal 
"If the person meets ALL of the above criteria, the recommended dose of doxycycline is a single dose of 200 mg for adults and 4 mg/kg, up to a maximum dose of 200 mg, in children ≥ 8 years"

In 2004 Zeidner et al. noted that the "sustained release" doxy was curative, but regular doxy only 43% effective. [ Antimicrob Agents Chemother. 2004 Jul;48(7):2697-9. Sustained-release formulation of doxycycline hyclate for prophylaxis of tick bite infection in a murine model of Lyme borreliosis.]

In 2008 Dolan et al. reported on the success of 14 days of exposure to antibiotic bait formulations..

Am J Trop Med Hyg. 2008 May; 78(5):803-5.
A doxycycline hyclate rodent bait formulation for prophylaxis and treatment of tick-transmitted Borrelia burgdorferi.Dolan MC, Zeidner NS, Gabitzsch E, Dietrich G, Borchert JN, Poché RM, Piesman J.

Abstract

The prophylactic and curative potential of doxycycline hyclate formulated in a rodent bait at concentrations of 250 and 500 mg/Kg was evaluated in a murine model of Lyme borreliosis. 
Both bait formulations prevented tick-transmitted Borrelia burgdorferi infection in 100% of C3H/HeJ mice (N = 16), as well as cured acute, established infection in mice (N = 8) exposed to bait for 14 days
Spirochete infection was cleared in 88.9% to 100% of infected nymphs feeding on mice fed 250 and 500 mg/Kg antibiotic bait formulations, respectively. These data provide evidence for exploring alternative techniques to prevent transmission of Lyme disease spirochetes.

In 2011 Wisconsin Journal of Medicine published a review detailing the failure of one-dose doxycycline prophylaxis and proposing an alternative, more effective treatment option. (Maloney, B. The management of Ixodes scapularis bites in the upper Midwest. WMJ. 2011 Apr;110(2):78-81; quiz 85.) 
The full text article is available at: http://www.wisconsinmedicalsociety.org/_WMS/publications/wmj/pdf/110/2/78.pdf

This month Peisman and Hoigaard note that "prophylactic treatment was totally ineffective when delivered ≥2days after tick removal." [2 days = 48 hrs]

Ticks Tick Borne Dis. 2012 Mar 13. [Epub ahead of print] Protective value of prophylactic antibiotic treatment of tick bite for Lyme disease prevention: An animal model. Piesman J, Hojgaard A.

Abstract

Clinical studies have demonstrated that prophylactic antibiotic treatment of tick bites by Ixodes scapularis in Lyme disease hyperendemic regions in the northeastern United States can be effective in preventing infection with Borrelia burgdorferi sensu stricto, the Lyme disease spirochete. 
A large clinical trial in Westchester County, NY (USA), demonstrated that treatment of tick bite with 200mg of oral doxycycline was 87% effective in preventing Lyme disease in tick-bite victims (Nadelman, R.B., Nowakowski, J., Fish, D., Falco, R.C., Freeman, K., McKenna, D., Welch, P., Marcus, R., Agúero-Rosenfeld, M.E., Dennis, D.T., Wormser, G.P., 2001. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N. Engl. J. Med. 345, 79-84.). 
Although this excellent clinical trial provided much needed information, the authors enrolled subjects if the tick bite occurred within 3days of their clinical visit, but did not analyze the data based on the exact time between tick removal and delivery of prophylaxis. An animal model allows for controlled experiments designed to determine the point in time after tick bite when delivery of oral antibiotics would be too late to prevent infection with B. burgdorferi
Accordingly, we developed a tick-bite prophylaxis model in mice that gave a level of prophylactic protection similar to what had been observed in clinical trials and then varied the time post tick bite of antibiotic delivery. We found that two treatments of doxycycline delivered by oral gavage to mice on the day of removal of a single potentially infectious nymphal I. scapularis protected 74% of test mice compared to controls. When treatment was delayed until 24h after tick removal, only 47% of mice were protected; prophylactic treatment was totally ineffective when delivered ≥2days after tick removal. 
Although the dynamics of antibiotic treatment in mice may differ from humans, and translation of animal studies to patient management must be approached with caution, we believe our results emphasize the point that antibiotic prophylactic treatment of tick bite to prevent Lyme disease is more likely to be efficacious if delivered promptly after potentially infectious ticks are removed from patients.


There is only a very narrow window for prophylactic treatment to be effective post tick removal.

In my opinion, a study like this one should have been done long ago. How many studies were used to make the original determination that one 200 mg capsule of doxycycline would be an appropriate method of prophylaxis against Lyme disease? 

 And the obnoxious thing is, I was given this treatment! I had a tick bite, I had an EM rash, I was concerned about Lyme disease - and the first doctor I saw said there was no Lyme disease in the area in which I had been bitten, but I was given the one pill of doxycycline as some sort of consolation prize... The implication from the doctor being that the bite was most likely nothing to worry about and the pill being given to me to placate me.

Well, this prophylaxis apparently was not very prophylactic, now, was it?

I am pretty sure I saw the doctor 3-4 days after the tick bite, when I was given the prescription paper to fill it for one capsule of doxycycline.

This prophylactic approach never made sense to me from the day I first learned about the one pill preventative.

Since my failed experience of preventing Lyme disease, I've learned that different strains/subspecies of Borrelia burgdorferi disseminate at different rates, with different bacterial loads from different bites. If infection is present - one pill is hardly going to stop it. And if a coinfection is present, it may have an impact on the immune system which is hard to predict and may alter how effective an antibiotic is on the big picture.

One of the things I've learned in the past couple of weeks of doing research on Russian web sites about how patients are affected by Lyme disease and what treatments are given to patients there is that there is more of a sense of urgency of treating Lyme disease early and also aggressively. This is not to say that the Russian approach of managing Lyme disease is the best overall - they too have a problem with chronic Lyme disease - and so far as I can see, have not found the perfect treatment for it.

But if what I read so far is to be taken into account, then their approach has been to treat Lyme disease as early as possible and have doctors remove ticks as soon as one has a tick bite because research has shown the earlier a tick is removed properly, the greater the risk is reduced in transmitting infection.

In addition to encouraging immediate professional tick removal and early treatment during the acute stage, a number of medical clinics and web sites recommend a few days of prophylactic doxycycline - rather than one pill.

I am still looking for Russian research papers which support this approach - so perhaps take this information with some caution. But here are two sites which mention this approach which would appear to be legitimate resources:

First site, the equivalent of city council pages for  Lipetsk:

From an order marked:

ORDER KM Lipetsk region from 09.09.2004 N 523, SEC in the Lipetsk region dated 04.08.2004 N 78-ns, "ESTABLISHMENT OF Surveillance of Ixodes tick-borne borreliosis in the region" (with "GUIDELINES", "PLAN OF SCIENTIFIC AND PRACTICAL WORK on the prevalence of Ixodes tick-borne borreliosis in Lipetsk region for 2004 - 2005 HS. ")

Administration of Lipetsk Region

DEPARTMENT OF HEALTH
on September 9, 2004 N 523

SEC in the Lipetsk Region
on August 4, 2004 N 78-ns

ORDER ON Surveillance FOR Ixodes tick-borne borreliosis -- Excerpt:
"Carry an emergency antibiotic prophylaxis should be based only on display in the pathogen attached ticks. In the case of the pathogen in the vector and not later than 3 days. of tick suction in patients prescribed a course of doxycycline at 0.1 x 1 time per day for 5 days (children under 8 years of this antibiotic is not indicated).

Later on the third day from the time course of doxycycline tick suction extended to 10 days. Other antibiotics, which can be used for preventive treatment, drugs are prolonged penicillin: bicillin 3 or retapen (ekstentsillin) at a dose of 2.4 million units. intramuscularly once after a skin test on the individual tolerance of antibiotic.

Has a high efficiency combination drug amoxicillin with clavulanic acid (amoxiclav) to 0.375 g, 3 times a day, 5 days.
When carrying out emergency prophylaxis following should be considered (Appendix 9):
- Epidemiological history - a fact suction to the skin of ticks;
- Results of microbiological studies, parazitologo - detection of Borrelia in the attached ticks by dark-field microscopy or PCR;
- Start of antibiotic timing - as soon as possible after the suction (after the 5th day of tick suction inappropriate use of approved schemes), early prevention of borreliosis - a day after the suction of an infected tick Borrelia - can be recommended only when a negative result of the study attached ticks in the ELISA CEA antigen;
- A good individual tolerability of recommended antibiotics;
- Carrying antibiotics under medical supervision;
- Follow-up visit within 1 - 3 months after the course of antibiotic prophylaxis in SDS"

In Russian:

ПРИКАЗ УЗ Липецкой области от 09.09.2004 N 523, ЦГСЭН В Липецкой области от 04.08.2004 N 78-пв "ОБ ОРГАНИЗАЦИИ ЭПИДЕМИОЛОГИЧЕСКОГО НАДЗОРА ЗА ИКСОДОВЫМ КЛЕЩЕВЫМ БОРРЕЛИОЗОМ В ОБЛАСТИ" (вместе с "МЕТОДИЧЕСКИМИ РЕКОМЕНДАЦИЯМИ", "ПЛАНОМ ПРОВЕДЕНИЯ НАУЧНО-ПРАКТИЧЕСКОЙ РАБОТЫ ПО ИЗУЧЕНИЮ РАСПРОСТРАНЕНИЯ ИКСОДОВОГО КЛЕЩЕВОГО БОРРЕЛИОЗА НА ТЕРРИТОРИИ ЛИПЕЦКОЙ ОБЛАСТИ НА 2004 - 2005 ГГ.")

2.8. Экстренная антибиотикопрофилактика ИКБ

Проводить экстренную антибиотикопрофилактику следует только на основании индикации возбудителя в присосавшемся клеще.

В случае обнаружения возбудителя в переносчике и не позднее 3 сут. после присасывания клеща пациентам назначают курс доксициклина по 0,1 х 1 раз в сутки в течение 5 дней (детям до 8 лет данный антибиотик не назначают).

Позже третьего дня от момента присасывания клеща курс доксициклина продлевается до 10 дней. Другими антибиотиками, которые могут быть использованы для превентивного лечения, являются препараты пролонгированного пенициллина: бициллин-3 или ретапен (экстенциллин) в дозе 2,4 млн. ед. внутримышечно однократно после проведения внутрикожной пробы на индивидуальную переносимость антибиотика.

Высокой эффективностью обладает комбинированный препарат амоксициллина с клавулановой кислотой (амоксиклав) по 0,375 г 3 раза в сутки 5 дней.

При проведении экстренной антибиотикопрофилактики необходимо учитывать следующее (приложение 9):
- данные эпидемиологического анамнеза - факт присасывания к кожным покровам иксодовых клещей;
- результаты паразитолого-микробиологических исследований - выявление боррелий в присосавшихся клещах методом темнопольной микроскопии или ПЦР;
- сроки начала антибиотикопрофилактики - как можно раньше после присасывания (позже 5-го дня после присасывания клеща использование рекомендованных схем нецелесообразно), ранняя профилактика боррелиоза - через сутки после присасывания зараженного боррелиями клеща - может быть рекомендована только при отрицательном результате исследования присосавшегося клеща в ИФА на антиген КЭ;
- хорошая индивидуальная переносимость рекомендуемых антибиотиков;
- проведение антибиотикопрофилактики под контролем врача;
- контрольное обследование через 1 - 3 месяца после проведенного курса антибиотикопрофилактики на ИКБ.

Source: Network of Lipetsk Region http://lipetsk.news-city.info/docs/sistemsv/dok_oegvgi/index.htm

And then here's another, for Nizhny Novgorod State Medical University, which has been around since 1920:
"At the present time in Nizhny Novgorod and the region is high infection of ticks with borreliae, there are also ticks infected with tick-borne encephalitis. You must know the pattern of action in the case of tick suction.

First, you must remove the tick, while maintaining its viability. You can do it yourself or by contacting the trauma center in your area.

Remote mite be sent to study in Nizhny Novgorod Research Institute of Epidemiology and Microbiology. Academician I. Blokhina (St. Georgia 44, 433-76-55, 434-17-71, www.micro.nnov.ru). Within a day you will get the result of the study.

If the tick was infected with Borrelia, to conduct preventive 10-day course of doxycycline (T. Doxiciclini 0,1 to 1 m, 2 times a day).

If the tick was infected with tick-borne encephalitis, showed immunoglobulin, but the free drug can qualify only if after the bite was not more than 4 days."
The above, in Russian:

"В настоящее время на территории Нижнего Новгорода и Нижегородской области высока инфицированность клещей боррелиями, встречаются также клещи, инфицированные вирусом клещевого энцефалита. Необходимо знать схему действий в случае присасывания клеща.

Во-первых, клеща необходимо удалить, сохранив его жизнеспособность. Сделать это можно самостоятельно либо обратившись в травмпункт Вашего района.

Удаленного клеща необходимо отправить на исследование в Нижегородский НИИ эпидемиологии и микробиологии им. академика И.Н. Блохиной (Ул. Грузинская 44, 433-76-55, 434-17-71, www.micro.nnov.ru). В течение 1 суток Вам предоставят результат исследования.

В случае, если клещ был инфицирован боррелиями, необходимо проведение профилактического 10-дневного курса доксициклина (T. Doxiciclini 0,1 по 1 т. 2 раза в день).

Если клещ был инфицирован вирусом клещевого энцефалита, показано введение иммуноглобулина, но на бесплатный препарат можно претендовать лишь в том случае, если с момента укуса прошло не более 4 дней."
Source: http://www.nizhgma.ru/studentu/kafedry/infekc/uchmat/klesh/


So far as I can see, the use of a longer period of prophylactic treatment is advised - but the public health department also makes an effort to test the tick you have had on you for the presence of bacteria and viruses. The turn around time is less than 24 hours for results.

The only problem with this approach is that if you get a tick bite which is not obvious and it is not found right away, the odds of getting Lyme disease and/or Tick-borne encephalitis (TBE) are greater. Treatment may come too late to help a patient - particularly in the case of  TBE, where immunoglobulin for TBE and antiviral medication will only help if administered in under 72-96 hours after the tick bite.

There are three reasons I suspect Russia is more aggressive in its approach:

1) While the odds of getting TBE are lower than the odds of getting Lyme Borreliosis, TBE has a much higher risk of leading to acute severe illness and death. The older one is when they are infected with TBE, the higher the odds are of serious complications and fatality.

2) The most common strain of Borrelia people are infected with in Tomsk - a highly endemic area of Russia - is B. garinii, and a specific type of B. garinii quickly disseminates to the CNS more quickly than other strains. To prevent neuroborreliosis and widespread dissemination to other organs, a longer prophylactic course is needed as soon as possible.

3) Polymicrobial or coinfection is not uncommon. It is possible to be infected with both Lyme Borrelia and TBE, or more than one strain of Borrelia burgdorferi, and perhaps throw in Anaplasmosis in there as well. One has to be very careful of how to treat such cases - if TBE is present, it must be treated first since it moves fast, is more dangerous, and early antibiotic use is contraindicated in its presence.

All this said, I do wonder how it was determined that prophylaxis should be 5-10 days, based on circumstances surrounding the bite. This is a much longer course than the IDSA has suggested.

And frankly, this sort of treatment is what I wish I had if it would have prevented the situation in which I now find myself.

If you found this post interesting and informative, you may want to read this one as well:
http://campother.blogspot.com/2010/12/dr-david-volkmans-letter-to-idsa-lyme.html

Addendum [April 29, 2012]: I wanted to add the following passage from a paper from The Canadian Entomologist:
"Studies of the transmission dynamics of B. burgdorferi in I. scapularis indicate that the risk of transmission of strain B31 by a single bite from an infected tick is about 2% and that the risk increases with the length of time that the tick is attached (Hojgaard et al. 2008). 
When a tick first attaches, spirochetes are still found in the midgut and are producing outer-surface protein A (OspA), which helps spirochetes adhere to a midgut protein, TROPSA. When feeding begins, the spirochetes are exposed to warm mammalian blood and lowered pH, and OspA is downregulated while OspC is upregulated. Spirochetes then migrate from the midgut to the salivary gland and transmission to the vertebrate host can be achieved (e.g., Hojgaard et al. 2008). This delay in transmission explains why transmission is reduced when ticks are removed within 24 h of attachment (Hojgaard et al. 2008). 
In Europe, transmission of B. burgdorferi s.s. and B. afzelii by I. ricinus occurs in less than 24 h, but the risk of transmission still increases over time (Kahl et al. 1998; Crippa et al. 2002). In a further complication of the host—tick—pathogen interaction, B. burgdorferi s.l. is able to increase expression of an Ixodes salivary protein, Salp 15, to protect against complement-mediated killing of Borrelia by the host's innate immune system (Ramamoorthi et al. 2005). This protective effect was greater when the vector was I. ricinus rather than I. scapularis (Schuijt et al. 2008). The early expression of ospC appears to be essential for B. burgdorferi to escape innate immunity and disseminate in the host (Gilbert et al. 2007), and yet persistent infection of the host is only possible when ospC is downregulated after infection because acquired antibodies to OspC allow the spirochetes to be cleared (Tilly et al. 2007). Current understanding of the interactions of tick saliva and B. burgdorferi is discussed in Anderson and Valenzuela (2007)."
Source: http://www.bioone.org/doi/full/10.4039/n08-CPA04

Janet L.H. Sperling, Felix A.H. Sperling. Lyme Borreliosis in Canada: Biological Diversity and Diagnostic Complexity from an Entomological Perspective. The Canadian Entomologist 141(6):521-549. 2009 doi: http://dx.doi.org/10.4039/n08-CPA04

The above passage is important to note because it outlines the fact that the rate of transmission of spirochetes from the tick to its host varies based on a number of factors including Borrelia strain, the type of tick involved, Salp15 production levels, expression of ospC, and length of time the tick has been attached.

Based on this research, it is clear additional research is needed to determine if strains of Borrelia burgdorferi other than B31 in Ixodes scapularis and Ixodes pacificus would have differing transmission times tested under the factors mentioned. The same sort of studies would be beneficial for Europeans on Ixodes ricinus and other European Ixodes ticks.

[Edited March 22, 2012 - First paragraph said "100 mg capsule of doxycycline", was changed to "200 mg capsule of doxycycline".]


Image credit: Doxycycline 100 mg capsules. By Shorelander, Wikimedia Commons.


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Monday, March 19, 2012

2 Обзор Для русских читателей Лайм боррелиоза

Given what I learned about Russian treatment guidelines for Lyme disease - as well as a particular treatment plan from Serbia - I have decided to offer Russian Lyme disease patients (former and current) a survey.  I plan to give a similar survey to readers from other countries after this one...

Дорогие русские читатели этого блога,Благодарим Вас за посещение и чтение других блогов лагерь.Недавно я узнал от читателя, который лечился боррелиоз Лайма в Сербии, что оба вида антибиотиков выбрали и продолжительность лечения была отличной от той, которую мы обычно получают в Соединенных Штатах.

В результате, мне было интересно, о том, что различные руководящие принципы для лечения боррелиоза Лайма в разных странах. Я посмотрел на принципы Сербии лечения, но не могли найти их в Интернете. Потом я посмотрел на принципы лечения России по боррелиозом Лайма, и я нашел их, и разделяет их.


В поисках русских руководящие принципы для лечения боррелиоза Лайма, я узнал немного о том, как Лайм боррелиоза рассматривается врачей и медицинских вузов России. Я знаю, что мое понимание пациентов ограничен, однако.


Поэтому я хотел бы спросить вас, если вы могли бы пожалуйста, ответьте на несколько вопросов для меня о боррелиозом Лайма. Вы можете ответить с именем пользователя блоггер или быть анонимными - либо все в порядке.


Единственным требованием является то, что вы ни были Лайм боррелиоза в прошлом, или у вас есть боррелиоз Лайма сейчас.


Пожалуйста, ответьте на вопросы ниже, используя следующие инструкции:



1) ответы на русском языке первый, так что поисковые системы будут забрать свой комментарий и больше россиян будут видеть и поощрять участие.


2) Далее ваш ответ России, пожалуйста, напишите английский копию ответа так английских читателей, здесь можно понять ваш ответ.(Используйте translate.google.com или иной русско-английский перевод программы вы считаете хорошим, чтобы перевести ваш ответ.)


3) Имейте в виду, что существует предел в 4000 символов для каждого ответа. Если у вас есть длинный ответ, вы можете сделать комментарий.


Пожалуйста, обратите внимание: Все комментарии модерируются, то есть я рассматриваю их, прежде чем отправлять их в Интернете. Там может бытьзадержка между временем, когда вы входите в комментарий, и он показывает на странице. Я делаю это, чтобы избежать случайного спама и маркетинговыхсообщений.



Ну, вот ваши вопросы:


1) Есть ли у вас Лайм боррелиоза в прошлом?


2) Есть ли у вас боррелиоз Лайма сейчас?


3) Какие этапы или шаги Лайм боррелиоза у вас было в прошлом?Сейчас?


4) Было ли у вас укуса клеща и "быки глаз" сыпь?


5) Как долго времени между укусом клеща и лечение антибиотиками?


6) Какие у вас были симптомы?


7) Как долго вы были или вы больны?


8) Какое лечение вы получили для боррелиоза Лайма?


9) Как долго вы используете антибиотики?


10) Какие еще лекарства и методы лечения вы получите за Лайм боррелиоза (не антибиотики)?


11) После лечения, как здорово ты? Есть ли у вас остальные симптомы?Если да, то каковы ваши оставшиеся симптомы?


12) Как вы думаете, боррелиоз Лайма может быть хронической инфекции - даже после лечения антибиотиками? Считаете ли вы, никаких симптомов после лечения антибиотиками, свидетельствуют о аутоиммунное заболевание?


Спасибо за ваши ответы.Я понимаю, это очень много вопросов, но важно знать, какие проблемы у пациентов с Лайм-боррелиозом лица по всему миру. После Лайм боррелиоза является хроническим, то становится труднее лечить, и зная, как другие люди справляются с этой болезнью может быть полезным.


PS: Если вы знаете другие русские, которые пострадали с боррелиозом Лайма, пожалуйста, присылайте их сюда и попросить их ответить на эти вопросы тоже.


PPS: Я прошу прощения за использование Google Translate - это лучшее, что я мог сделать.

Dear Russian readers of this blog,

Thank you for visiting and reading Camp Other blog.

Recently, I learned from a reader who was treated for Lyme Borreliosis in Serbia that both the kind of antibiotics chosen and length of treatment was different from that which we usually receive in the United States.

As a result, I was curious about what different guidelines are for the treatment of Lyme Borreliosis in different countries. I looked for Serbia's treatment guidelines, but could not find them on the internet. Then I looked for Russia's treatment guidelines for Lyme Borreliosis, and I did find them, and shared them.

While searching for the Russian treatment guidelines for Lyme Borreliosis, I learned a little about how Lyme Borreliosis is viewed by doctors and medical universities in Russia. I know that my understanding about patients is limited, though.

So I would like to ask you if you could please answer a few questions for me about Lyme Borreliosis. You may answer with a blogger user name or be anonymous - either is okay.

The only requirement is that you have either had Lyme Borreliosis in the past or you have Lyme Borreliosis now.

Please answer the questions below using these instructions:

1) Respond in Russian first, so that search engines will pick up your comment and more Russians will see it and be encouraged participate.

2) Below your Russian response, please post an English copy of your response so the English readers here can understand your response. (Use translate.google.com or another Russian-English translation program you think is a good one to translate your response.)

3)  Be aware that there is a 4,000 character limit for each response. If you have a long response, you may want to make a new comment.

Okay, here are your questions:

1) Have you had Lyme Borreliosis in the past?

2) Do you have Lyme Borreliosis now?

3) What stages or steps of Lyme Borreliosis did you have in the past? Now?

4) Did you have a tick bite and a "bulls eye" rash?

5) How long was the time between the tick bite and antibiotic treatment?

6) What were your symptoms?

7) How long were you or are you sick?

8) What treatment did you receive for Lyme Borreliosis?

9) How long did you use antibiotics?

10) What other medicines and treatments did you receive for Lyme Borreliosis (not antibiotics)?

11) After treatment, how healthy are you? Do you have any remaining symptoms? If so, what are your remaining symptoms?

12) Do you think Lyme Borreliosis can be a persistent infection - even after antibiotic treatment?  Do you think any symptoms after antibiotic treatment are evidence of an autoimmune disorder?

Thank you for your answers.

I realize these are a lot of questions, but it's important to know what problems patients with Lyme Borreliosis face around the world. Once Lyme Borreliosis is chronic, it becomes harder to treat and knowing how other people are managing this disease could be helpful.

PS: If you know of any other Russians who have suffered with Lyme Borreliosis, please send them here and ask them to respond to these questions, too.

PPS: I apologize for using google translate - it's the best I could do.


Image credit:
English: Tomsk I railway station, Russia
Русский: Вокзал станции Томск I, Россия
by Alexander V. Solomin from Wikimedia Commons
This file is licensed under the Creative Commons Attribution 3.0 Unported license.



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

Recently, the results of an observational study on chronic Lyme disease in Norway were published in the European Journal of Neurology. (The full text of the study is behind a pay wall on Wiley - but otherwise you can read the abstract online.) According to the National Institute of Health (NIH) clinical trials database, the purpose of the study was:
"... to chart clinical and laboratory findings in Norwegian patients with symptoms attributed by themselves or their doctor to ongoing chronic Bb infection. Objectives are to assess laboratory findings in relation to established diagnostic criteria and to form a picture of the burden of symptoms and illness perception in this group of patients. The study is essentially exploratory, and is supposed to raise rather than to test hypotheses."
Based on this, it sounds like the authors' original expectations for this study were that the researchers would find out in a given population that among those who either suspect they have chronic Lyme disease and have it - and those who suspect they have chronic Lyme disease and don't have it - that it would be discovered what clinical differences and diagnostic markers would set them apart.

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

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

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

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

It would have been more productive for patients had the researchers taken additional steps to determine what exactly the cause of these symptoms were. But the study was not designed to take those additional steps and just left us with these basic data points:
  • Twenty patients (72%) had symptoms of an unknown cause; of them six met the criteria for Post Lyme disease syndrome (PLDS).
  • Fourteen patients (48%) had the presence of anti-Borrelia burgdorferi antibodies.
  • Eight patients (28%) had other well-defined illnesses.
The researchers stated, "None had evidences of persistent Bb infection, but whether current diagnostic criteria are functional in patients with longstanding complaints is controversial."

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

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

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

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

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

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

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

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

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

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

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

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

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



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