4 Viral Genetics VGV-L Candidate For Treating Chronic Lyme Disease

On Friday I posted about the use of Filgrastim and Ceftriaxone for treating persisting symptoms in a Lyme disease case study as well as the use of Rituximab for treating CFS/ME. I also touched upon Viral Genetics' VGV-L or targeted peptide therapy for treating chronic Lyme disease, and wanted to write an entry about this treatment on its own.

What I can tell you is to some degree limited by the fact that VGV-L's exact design and mechanism is proprietary in nature, so I can only report based on what the researchers and Viral Genetics choose to disclose. But hopefully, what I post here and future publications by Dr. Karen Newell Rogers will shed some light on the matter.

Dr. Karen Newell Rogers from Texas A & M is in the middle of contributing to the following three papers which seem to have a relationship between VGV-L and chronic Lyme disease:

• S. Harris, E. W. Newell, R. P. Tobin, C. P. Harvey, N. Kurzman, E. M. Hechinger, P. Cipriani, and M. K. Newell. 2010. Comparative Analysis of Peptide Binding, MHC alleles, and B cell activation in patients meeting CDC criterion for Chronic Lyme Disease. (manuscript in preparation).
• E. Connick, R. Schlichtemeier, J. Folkvord, R. Tobin, C. P. Harvey, and M. K. Newell. 2010. TLR activation of human peripheral blood B cells can be reversed by peptide treatment. 2010. Manuscript in preparation.
• Cabrera, J. and M. K. Newell. 2010. Polyclonal TLR-induced B cell activation is controlled by Peptide-dependent B cell death (manuscript in preparation). 

All three in preparation, but I think they are tightly related to the same research and stem from this previous publication:

 M. K. Newell, R. P. Tobin, J. H. Cabrera, M. B. Sorensen, A. Huckstep, E. M. VillalobosMenuey, M. Burnett, E. McCrea, C. P. Harvey, A. Buddiga, A. Bar-Or, M. S. Freedman, J. Nalbantoglu, N. Arbour, S. S. Zamvil, and J. P. Antel. 2010. TLR-Mediated B Cell Activation Results in Ectopic CLIP Expression that Promotes B Cell-Dependent Inflammation. Journal of Leukocyte Biology.
Online e-Pub. July 14, 2010.

 Link to free full text this publication: http://www.ncbi.nlm.nih.gov/pubmed/20631258

Originally, I found one patent for this technology online:

http://www.faqs.org/patents/app/20100166789

In this patent, the portion attributed to Lyme disease states:

 "[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."

However, I just found out that there are additional patents on this technology of which I was previously unaware. These patents contain a great deal of detail about what these targeted peptides can do and their effect on polyclonal B cells:

http://www.faqs.org/patents/app/20090258027
http://www.faqs.org/patents/app/20100034839
http://www.faqs.org/patents/app/20100166782
http://www.faqs.org/patents/app/20110118175

In addition to the above published paper on CLIP expression, Viral Genetics published the following excerpt in its research newsletter which explains what VGV-L does for HIV in easy-to-understand terms - substitute "Lyme disease" for "HIV" here:

"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

One thing which I have thought of (and heard a few patients mention in passing) is that this candidate drug is only for treating inflammation and would only address an autoimmune angle relating to chronic Lyme disease.

However, this is not the case:

If you read the full patents, VGV-L's technology works not only to reduce inflammation, it also works to rebalance the immune system so that it is focused on fighting infection in a targeted manner. And in terms of treatment with VGV-L, patients may not just receive VGV-L alone - but also receive a bacterial antigen and antibacterial (possibly also antiparasitic and/or antiviral)  therapy concurrently to treat their condition.

Refer to this patent: http://www.faqs.org/patents/app/20110118175.

Here is the excerpt from the patent concerning the treatment of infections using this technology - including Lyme disease:

[0169] Bacterial diseases that can be treated or prevented by the methods of the present invention are caused by bacteria including, but not limited to, mycobacteria, rickettsia, mycoplasma, neisseria, Borrelia and legionella.

[0170] Although Applicant is not bound by a specific mechanism of action it is believed that the CLIP inhibitors of the invention displace CLIP from MHC class I and cause down regulation of Treg activity and/or activation of effector T cells such as γδT cells. Downregulation of regulatory function of Treg activity prevents suppression of the immune response and enables the subject to mount an effective or enhanced immune response against the bacteria. At the same time the Treg cell may shift to an effector function, producing an antigen specific immune response. Thus, replacement of CLIP with a peptide of the invention results in the promotion of an antigen specific CD8+ response against the bacteria, particularly when the peptide is administered in conjunction with a tumor specific antigen. Activation of effector T cells also enhances the immune response against the bacteria, leading to a more effective treatment.

[0171] One component of the invention involves promoting an enhanced immune response against the bacteria by administering the compounds of the invention. The compounds may be administered in conjunction with an antigen to further promote a bacterial specific immune response. A "bacterial antigen" as used herein is a compound, such as a peptide or carbohydrate, associated with a bacteria surface and which is capable of provoking an immune response when expressed on the surface of an antigen presenting cell in the context of an MHC molecule. Preferably, the antigen is expressed at the cell surface of the bacteria.

[0172] The compounds of the invention may be used in combination with anti-bacterial agents. Examples of such agents to treat bacterial infections include, but are not limited to, folate antagonists (e.g., mafenide, silver sulfadiazine, succinylsulfathiazole, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfasalazine, sulfisoxazole, pyrimethoamine, trimethoprim, co-trimoxazole), inhibitors of cell wall synthesis (e.g., penicillins, cephalosporins, carbapenems, monobactams, vacomycin, bacitracin, clavulanic acid, sulbactam, tazobactam), protein synthesis inhibitors (e.g., tetracyclines, aminoglycosides, macrolides, chloramphenicol, clindamycin), fluoroquinolones (e.g., ciproloxacin, enoxacin, lomefloxacin, norfloxacin, ofloxacin), nalidixic acid, methenamine, nitrofurantoin, aminosalicylic acid, cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide, rifampin, clofazimine, and dapsone.

I don't know entirely what the researchers intend to use as a bacterial antigen... An Osp? They are suggesting a peptide or carbohydrate, though, and not a highly immunogenic lipoprotein from the cell's outer membrane - even though that's what I think they would have to use if they were to use an antigen. Reading ahead, though, there is the potential that any of a number of Borrelia burgdorferi antigenic products may be used.

Both items #0171 and #0172 have wording which implies that they are optional treatments, as they use the word, "may be administered"  or "may be used" rather than "will be administered" or "will be used", respectively. I would assume that whether or not these individual treatments are applied depends entirely on the individual patient and their needs and clinical diagnosis.

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 a more targeted immune response towards bacteria rather than the overload that polyclonally expanded B cells can be.

One of the more fascinating sections of the patent is towards the end. The researchers give a number of examples of how their technology was applied and what the results were. Example 13 of this patent appears relevant to demonstrating how Borrelia burgdorferi activators affect tissue and about eliminating excessive B cells which cause inflammation in tissues. They did an in vitro post-mortem study of these actions in mice:

Example 13 - TLR Activators Promote CLIP-MHC HLA Association and CLIP Inhibitor Peptides Reduce an TLR Activator Promoted CLIP-MHC HLA Association

[0480] Methods

[0481] Preparation of Cells: Mice were Sacrificed by Cervical Dislocation. Spleens and lymph nodes were removed; the tissues were minced through cell strainers to create single cell suspensions; red cells were lysed using buffered ammonium chloride followed by addition of phosphate buffered saline and centrifugation to wash out the ammonium chloride; and the cells were counted using trypan blue exclusion to determine live versus dead cell discrimination and to determine the number of cells per tissue.

[0482] Treatments: The spleen or lymph node cells were treated in vitro with various stimuli (TLR activators: CpG ODN (Alexis), LPS (Sigma), Polyl:C (BD Pharmagen), Pam3Cys (Genway); IL-4 (BD Pharmagen), anti-CD40 monoclonal antibody (BD Pharmagen), both IL-4 and anti-CD40 antibody and OspA and Osp C (Genway) and the cells were cultured for the indicated time periods. The cells were grown in RPMI 1640 medium supplemented with standard supplements, including 10% fetal calf serum, gentamycin, penicillin, streptomycin, sodium pyruvate, HEPES buffer, 1-glutamine, and 2-ME as well as (where indicated) the stimuli listed above. The cells were incubated at 37° C. in an atmosphere containing 5% CO2 and approximately 92% humidity. The cells were incubated for 3, 24, and 48 hours. At each time point, the cells from that experimental time were harvested and stained for flow cytometric analysis of cell surface expression of CLIP (MHC Class II invariant peptide/IAb, Santa Cruz) by using the commercially available anti-mouse CLIP/IAb peptide, anti-mouse B220, anti-mouse CD4, anti-mouse CD8, and anti-mouse FoxP3 (all commercially available from Becton Dickinson/Pharmingen). Harvested cells were stained using standard staining procedure that called for a 1:100 dilution of Fitc-anti-mouse CLIP/IAb or isotype control. Following staining on ice for 25 minutes, cells were washed with PBS/FCS and resuspended in 100 microliters and added to staining tubes containing 400 microliters of PBS. Samples were acquired and analyzed on a Coulter Excel Flow Cytometer. The data were analyzed using FloJo software.

[0483] Results

[0484] B cell death, including total B cell death and % CLIP positive B cell death in cells treated with a TLR activator (CpG ODN) alone or in combination with MKN3 in the presence or absence of CLIP was assessed. The results are shown in FIG. 12. FIG. 12 is a line graph having a double Y axis, on one side depicting % total B cell death (diamonds, representing CpG ODN alone and squares representing CpG ODN+MKN3) and on the other side depicting % CLIP+ B cell death (triangles, representing CpG ODN and CLIP alone and Xs representing CpG ODN+MKN3 and CLIP). The data reveal that CpG ODN cause an initial increase in B cell death which after 72 hours appears to level off. The CpG ODN+MKN3 data demonstrate that MKN3 is capable of preventing the increase in B cell death.

[0485] Changes in CLIP positive B cells in spleen versus lymph nodes were also assessed. FIG. 13 is a line graph having a double Y axis, on one side depicting % CLIP+ B cell numbers in spleen (light gray square with solid lines representing CpG ODN alone and dark gray square with solid lines representing CpG ODN+MKN3) and on the other side depicting % CLIP+ B cell numbers in lymph nodes (diamonds with dashed lines representing CpG ODN alone and light gray square with dashed lines representing CpG ODN+MKN3). In both spleen and lymph nodes the addition of the peptide to the cells with CpG ODN resulted in less CLIP positive B cells.

[0486] CLIP positive B6.129 cultured B cells (H-2b haplotype) and H2M-/- (from C3H HeJ mice) cultured B cells were also examined in the presence or absence of treatment with a number of different TLR activators. The data is shown in FIGS. 14A and 14B. As shown in the Figures, several TLR activators were able to induce levels of CLIP+ B cells.

Just so it's clear, this isn't the treatment a patient would receive - Dr. Newell Rogers and her colleagues won't be breaking your neck and removing your tissues if you sign up for a clinical trial, okay?

This is an example of an experiment they did to show that VGV-L technology is effective in reducing the number of ineffective B cells which cause inflammation. The end result measured this change, and also measured the end of the sordid relationship between TLR-promoted CLIP MHC-HLA association in the immune system.

[Edited Apr. 3, 2012: Removed mention of CLIP positive cells - these cells need to be removed not added. ]

Now time for a brief lesson in immunology, based on what normally happens in immune response:


Terminology:
MHC = major histocompatibility complex; key components of T cell immunity. Think of them as immune response genes.
HLA = human leukocyte antigen (think of earlier discussions on this blog about HLA-DR4 and HLA-DR11, and different alleles which respond to infection differently)

So the story goes, B cells express MHC class II. Once antigen has been bound on the antigen receptor on the B cell, the antigen and its receptor are sucked into an endosomal compartment inside the B cell. Then the endsomal compartment fuses with another compartment, the lysosome.

Antigens are broken down into smaller pieces inside the lysosome and then loaded onto the MHC class II component, then the MHC is transported to the B cell surface where the B cell displays the antigen to a CD4+ T cell. This T cell is also known as a helper cell, of which there are two types - Th1 and Th2.

Susceptibility or resistance to many diseases appears to be determined by the genes encoding Major Histocompatibilty Complex (MHC) molecules. Often referred to as immune response genes (or IR genes), these molecules are the key players in restricting T cell activation.

T cells, both CD8 and CD4 positive T cells, recognize antigens only when the antigen is presented to the T cell in association with MHC class I (expressed on all nucleated cells) or MHC class II molecules (expressed on cells that present antigens to CD4+ T cells), respectively.

To sum up:

1. B cells express MHC class II.
2. Different people produce different levels of allele variation in MHC locus.
3. Because of this genetic difference, some people are more or less vulnerable to certain diseases.
4. The B cell's expression of MHC class II  is noticed by CD4+ T cells.
5. These CD4+ T cells are known as helper cells - of which there are two types, Th1 and Th2.
6. CD4+ T cells are a major player in our immune systems for fighting infection.
7. These helper cells do not kill - they activate and direct other immune cells. They are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.

Look at these handy diagrams as an overview to what happens with B cells, MHC molecules, and T-cells...

Or, if your learning style is better geared towards watching videos, watch this one (warning: might be preceded by an ad, which you can mostly skip):

A simple overview of the immune system [Time: 5:56]
 

If you've gotten this far, right about now you might be asking yourself, "So what's the big deal? Why is it an issue that there are excess B cells, and how getting rid of them going to make a difference in fighting off Lyme disease if I have a chronic infection?"

Good questions. 


Obviously, you can see so far that one reason to not have certain B cells around is that they trigger autoimmune responses. No one wants that. But there are other reasons to avoid an overzealous non-specific B cell response.

Let me unwind the answer, step by step.

Google "polyclonally expanded B cells Borrelia" and tell me what you find. Or, read on and I'll tell you what I found:

Remember that study on Borrelia burgdoferi that Tunev and Barthold did, where it was noted that there was an outsized yet seemingly inadequate immune response to Borrelia burgdorferi found in lymph nodes? One with ill-formed B cells? This one: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002066 ?

Well, the phenomenon that's happening there is somewhat different from what is happening in polyclonal B cell activation in general. In polyclonal B cell activation, there can be lots of B cells which are produced which are non-specific. In this case, in Tunev and Barthold's research, a notable percentage of the B cells were Borrelia burgdorferi antigen specific - yet the cells were of low quality and inadequate to the task.

That's different than what is generally understood to be the typical polyclonal B cell activation, which is what I think is the hypothesis behind this treatment, VGV-L. In both cases, what one observes is an overwhelming number of B cells being produced.

[Edit Apr. 3. 2012: Updated correction to describe Tunev and Barthold difference in outcome of B cell activation.]

Polyclonal b cell activation has been thought to be a useful immune defense mechanism early in acute infection. What has not been investigated as much is how it might be a damaging process in chronic infection and immune dysregulation.

And there has been some argument in the microbiological world about whether polyclonally expanded B cell generation is essentially good or evil - the pros of cons of which are discussed in detail in this paper, "Polyclonal B cell activation in infections: infectious agents’ devilry or defense mechanism of the host?"

It's important to settle this argument because dysregulated and mis-targeted B cell antibody responses could result in autoimmunity, whereas impaired antibody responses during an actual infection could result in an immune deficiency.

Either way, over time it has become clearer that the production of these B cells relates to the appearance of an IgM response, and the relevance of the presence of an IgM response - particularly a prolonged IgM response - has also become a subject of heated discussion. See: "IgM in microbial infections: Taken for granted?"

But I digress...

This early paper from 1992 which is about Borrelia's relationship to polyclonal B cell activation, "Evidence for B-Lymphocyte Mitogen Activity in Borrelia burgdorferi-Infected Mice" (full text), has this to say in its abstract:

"We have used the murine model for Lyme disease described by Barthold et al. (S. W. Barthold, D. S. Beck, G. M. Hansen, G. A. Terwilliger, and K. D. Moody, J. Infect. Dis. 162:133-138, 1990) to determine whether the B. burgdorferi B-cell mitogen is expressed during active infection.

To correlate arthritic changes with immune events, we have studied two strains of mice injected with B. burgdorferi; one of them, C3H/HeJ, developed severe disease, and the other, BALB/c, developed only mild disease. C3H/HeJ mice displayed a persistent 10-fold increase in circulating immunoglobulin G (IgG) levels, a 2-fold increase in IgM levels, and a 15-fold increase in peripheral lymph node B-cell numbers, providing evidence of mitogenic activity. Infected BALB/c mice also had evidence for mitogen activity, since the IgG level in serum increased three- to fourfold. 

The bulk of the increase in circulating IgG levels was not directed against B. burgdorferi antigens, supporting the occurrence of polyclonal B-cell activation. Analysis of IgG isotpes pointed out a contrast between C3H/HeJ and BALB/c mice in that levels of all isotypes were elevated somewhat in both strains of infected mice but IgG2a levels were much more dramatically increased in the C3H/HeJ mice (28-fold) than in the BALB/c mice (4-fold). In this study, interleukin-6 levels were found to be persistently elevated in the serum of infected C3H/IHeJ mice. Interestingly, interieukin-6 levels in serum were much lower in the infected BALB/c mice. These findings indicate that the B. burgdorferi mitogen is active in infected animals and may contribute to the inflammatory and immune response to infection."

Right from the start, you get the idea that this paper is going to tell you that the presence of these polyclonally activated B cells have a relationship to IgM and IgG levels.

This is relevant, very relevant - because it can reflect how antibodies to Borrelia burgdorferi are present and how they are picked up in serological testing like ELISA and Western Blots.

Meaningful excerpts from this paper include:

"Immunological abnormalities, including hyperactive B cells, elevated IgM levels in serum, lymphadenopathy, impaired natural killer function, and delayed development of humoral immunity, have been documented in patients with Lyme disease (11, 16, 29, 30, 32). This has suggested a possible involvement of the specific or innate host responses in the pathogenesis associated with stage 2 and 3 disease(32)."

"Because of the persistent nature of infection and the ability of the organism to gain access to the joint and other tissues (5, 15, 29), a B-cell mitogen present during infection could play a role in the pathology of Lyme disease. To support this possibility, it was important to determine whether the mitogen functioned in vivo. This paper provides evidence that a B. burgdorferi mitogen is active in vivo in infected animals.

Three lines of evidence support the conclusion that B-cell activation in vivo is polyclonal or oligoclonal in addition to being antigen specific. 

First, the level of IgG in serum in infected mice was elevated about 10- to 15-fold, with the value ranging from 10 to 15 mg/ml (Fig. 1C). In comparison, the amount of IgG specific for B. burgdorferi antigens was approximated at 0.6 mg/ml (Fig. 2). 

Second, the number of B lymphocytes in peripheral lymph nodes of infected animals was increased 10- to 15-fold, with a 5-fold rise in the ratio of B to T cells (Fig. 4). The number of B cells also increased about twofold relative to the number of T cells in spleens from C3I/HeJinfected mice. 

Third, the IgG titer in the serum of infected animals to an unrelated antigen, ovalbumin, was increased 10- to 15-fold, which resembles the increase in the total IgG level (Fig. 3). 

These findings suggest that levels of autoreactive antibodies might be also expanded in infected animals, although anti-collagen antibodies were not identified. Because CD5+ B cells have been shown to produce autoreactive antibodies and are selectively increased in patients with rheumatoid arthritis (7), we determined whether they were expanded in B. burgdorferi-infected animals. No selective increase in the number of B cells of this lineage were found in C3H/HeJ animals at any stage of infection. Further studies are required to determine whether autoreactive antibodies are generated during infection."

So their initial experiment to see if there was an overwhelming B cell response provides us with evidence that yes, there is, and also - while there is a high IgG response, only a small percentage of IgG produced is B. burgdorferi specific. There was at the time no indication that autoreactive antibodies were involved.

(This process can be a precursor to autoimmunity developing - but that's later on.)

A later paper, from 1997, "Why is chronic Lyme Borreliosis chronic?"(full text), also brings up a host of issues related to TLRs, MHC class II, and the relationship between B and T cells in lymph nodes.

Doesn't it seem a little prescient?

"The question remains whether downregulation or even loss of MHC class II molecules on LCs might influence a patient's disease susceptibility. It is MHC class II molecules that bind antigenic peptide fragments, present them to CD4+ Th cells, and induce cytokine secretion and IgG secretion by B cells [55]. In vitro investingations have shown that MHC II class molecules are downregulated on antigen-presenting cells after coculture with Th cell clones in the presence of antigenic peptides of tetanus toxoid or staphylococcal superantigen, which elicit a strong HLA-DR-restricted T cell response.

Several hypotheses were suggested as the cause of this down-regulation. 

(1) Downregulation occurs when antigenic peptides catabolized in macrophages are recognized by CD+4 helper T cells, in order to control the size of a T cell clone and provide a homeostatic mechanism [55]. (2) Downregulation occurs for completion of T-B cell collaboration after antigen presentation, limiting excessive T cell help to the triggered B cells, or (3) it occurs for focusing the T cell repines to one or a few immunodominant peptides.

(4) LCs of patients with AIDS express decreased amounts of MHC class II molecules. Polyclonal B-cell activation, as seen in these patients and in patients with ACA, could cause the appearance of autoantibodies or immunocomplexes that interact with LCs and block their surface-staining characteristics [45]. (5) IL-10, originally identified as a product of Th2 cells, has a significant inhibitory influence on the antigen-presenting functions of macrophages and LCs by downregulation of MHC class II molecules. In fact, LCs pretreated with IL-10 were converted from specifically sensitizing to specifically tolerogenic antigen-presenting cells in vitro and in vivo [56]. In other studies treatment of LC cultures with IL-10 inhibited to upregulation of HLA-DR [57].

(6) Downregulation is initiated for establishment of self-tolerance. This downregulation can protect the antigen-presenting cell by inhibiting the presentation of self-antigens [58]. On the other hand, the downregulation of MHC class II antigens on LCs could result in inadequate presentation of antigens in lymph nodes, which in turn may reduce activation and proliferation of both B and T cells and the secretion of relevant cytokines. This may be what happens in CLB."

Dr. Karen Newell Rogers et al recent patent has this to say about TLRs (Toll Like Receptors) and B cells:

"Many bacteria and viruses produce substances, collectively called Toll ligands, that elicit an immediate response from an individual's immune system. These Toll ligands appear to promote inflammation by activating a wide variety of immune cells to bring them rapidly into battle against the invading pathogen. 

In most cases, these events correlate with a healthy and productive immune response to the pathogen. However, in some cases the Toll ligand binds to a Toll-like Receptor (TLR) on lymphocytes and non-specifically activates immune cells called B and T lymphocytes that would normally to respond to infectious pathogens with an exquisitely specific response. When Toll ligands activate B cells in a non-specific way, the non-specific activation is a pro-inflammatory event that may result in uncontrolled, or even auto-reactive, production of antibodies. When a B cell is activated non-specifically, we have discovered that the B cell expresses an important, small self-peptide called MHC class II invariant peptide, CLIP. In most individuals, a control cell, known as a T regulatory cell (Treg for short), has been shown, to kill the activated B cell.

During a viral or bacterial infection, non-antigen specific B cells in close proximity to an inflammatory or inciting lesion could manage to become activated in a bystander fashion. In those cases, CLIP would remain in the groove and get transported to the cell surface of the B cell. Its presence on the cell surface can be undesirable because if CLIP gets removed from the groove by a self antigen, the B cell would be in a position to present self antigens to self-reactive T cells, a process that could lead to autoreactivity and autoimmune disease. 

For some B cells this may result in death to the B cell by a nearby killer cell, perhaps a natural killer (NK) cell, unless the antigen receptor on the B cell has engaged antigen. Antigen recognition would thereby provide a survival signal for the B cell. However, if a killer cell doesn't remove the potentially autoreactive B cell and it encounters a CD4+ T cell that can recognize that antigen (most likely one that was not in the thymus) the B cell might receive additional help from a T cell specific for the antigen that now occupies the groove (antigen binding location in the MHC molecule). Alternatively, a nearby cell whose job it is to detect damaged self cells, may become activated by the self antigen-presenting B cell. Such a damage detecting cell is, for example, an effector T cell (Teff) such as a gamma delta T cell, also referred to as a γδT cell (γδ refers to the chains of its receptor). The γδT cell can then seek out other sites of inflammation (for example in the brain in MS, in the heart for autoimmune myocarditis, in the pancreas in the case of Type I Diabetes). Alternatively, the γδT cell might attempt to kill the CD4+ T cell that may respond to self antigens."

So based on all this, I think one has to consider that the complex interactions within the immune system related to B. burgdorferi infection have to be paid close attention to - and not just any persisting spirochetes themselves.

I am really interested in seeing what VGV-L - along with supportive and antibacterial treatment together - can do for chronic Lyme disease. It appears it not only prevents autoimmune responses to infection, but redirects the immune response so it can better target infection.

I do wonder, though,  how VGV-L would handle a situation where many B cells are being created and a good percentage of them are antigen specific but are of low quality - such as those mentioned in Tunev and Barthold's research.

* It may be that Lyme disease is more like HIV in that inflammation may allow or facilitate the spread of spirochetes as it encourages vlsE recombination. See: http://www.jimmunol.org/content/167/6/3383.long for one example.

Additional Resources:
Interview with Dr. Karen Newell Rogers: http://www.timeforlyme.org/TFL_newsletter_july_2011_q_a.htm
Marketwatch on VG Pre-IND submission to FDA: http://www.marketwatch.com/story/viral-genetics-submits-pre-ind-document-for-lyme-disease-drug-candidate-to-fda-2012-03-07

[Edit Record: This page was edited 2 times on April 3, 2012.]

If you've made it this far and still want to learn more about VGV-L, there are other posts on this subject on the site. Begin with this link: http://campother.blogspot.com/2012/04/notes-posted-on-vgv-l.html

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

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0 More On Lyme Disease In Australia On The Today Tonight Show

There's been increased interest from my readers in learning more about Lyme disease in Australia, so I decided I would offer an update on the situation for everyone including my northern hemisphere readers who are interested in new developments there.

Last week, the Australian television news show, Today Tonight, posted a segment on Lyme disease in Australia and how it has become a controversial issue as a number of Australians who have never left the country were bitten by ticks and developed symptoms very much like those of Lyme disease.

As far as it is known, the bacteria which causes Lyme disease has not been detected in ticks in Australia - unless the researchers mentioned in the previous episode of Today Tonight which was covered here have finally discovered it.  Without their official announcement, though, it has been the situation that cases of Lyme disease within the country which have been confirmed were attributed to infections acquired overseas. Any recent reports of Lyme disease contracted within Australia have become controversial.

This week, Today Tonight has posted another segment about a man, Robert Sotur, who became ill on the job after numerous tick bites and won a government workmans compensation case due to an infection with Lyme disease.

This is pretty notable because he received compensation for a disease that the Federal Government, the Australian Medical Association, and Australian State Governments all say doesn't exist in Australia.

View the video of the show and transcript here: http://au.news.yahoo.com/today-tonight/health/article/-/12972227/lyme-disease-compensation/

A lawyer, David Jones (yes, seriously, David Jones - wonder how much tiresome joking he gets about that name), who is working on behalf of over fifty patients who never left Australia yet have come down with Lyme disease-like symptoms in Australia made this statement to Today Tonight:

"There needs to be an acceptance that there are many people within our community that are having symptoms that are Lyme or Lyme-like, and Governments need to take these people seriously. They need to commission the research, and they need to determine whether or not this disease, or a disease like it, exists here in Australia.”

He's right. If one man has won a workmans compensation case within Australia for falling ill after tick bites, there will likely be others. More than fifty, judging from his caseload alone. But there will be far fewer cases if the research is done to find the causative agent of this disease and to treat people for it as soon as possible.

If it is a bacterial agent, then unlike Ross River Virus and other viral infections which are more well known throughout Australia - early treatment can prevent more serious symptoms and potential permanent damage, and in the worst case scenario - death, as in the case of Karl McManus.

Given the limited amount of recent surveillance and examination of ticks for an indigenous spirochete that could cause a condition similar to Lyme disease - if not the potential importation of Borrelia spirochetes from neighboring Asia - it is not clear what reality is. The last major study to discover if Australian ticks harbored a spirochete similar to one that causes Lyme disease was conducted over 15 years ago. The situation may be different now.

Australian support groups for patients with tickborne illnesses have not only reported being bitten by ticks and falling ill afterwards - some have also reported infestations of bird mites preceding the onset of their symptoms. If this is the case, there may be more than one pathogen and more than one vector responsible for an overlapping set of symptoms in patients. Careful and thorough research is needed to sort it out.

My advice to any Australians reading this is whether or not the controversy of the existence of Lyme disease in your country is resolved soon that you do what you can to protect yourself from tick bites. Learn how to properly remove a tick to minimize the risk of infection, find a place to send your ticks for analysis, and educate yourself about the spectrum of symptoms which are related to ALL tickborne diseases and not just Lyme disease.

Tularemia was discovered in Tasmania last year and there is evidence beyond a doubt of its presence. Lyme disease now appears to be a possibility. And then there are those mosquito-borne and tickborne conditions of which many Australians are already familiar with such as Ross River Virus, Barmah Forest Virus, Tick Typhus, and Tick Paralysis - none of which you want if you can avoid them.

See a doctor if you suspect you have contracted a tickborne infection - remember, it may or may not be Lyme disease and treatment will be different for coinfections. But do go as soon as possible in order to prevent serious and potentially long-lasting complications.

And last but not least:

Petition your government, CSIRO, and local universities to do more research on tickborne illnesses including Lyme disease. Make sure you have your own homegrown research teams that will investigate the possibility of Lyme-like illnesses from pathogens transmitted by both bird mites and ticks. Ask Australian scientists to pave their own path and to not feel obliged to model all their investigations and guidelines for treatment based on those found in the northern hemisphere until it is more certain what is happening. In the meantime, treatment will probably be empiric and based on history, symptoms, and test results.

Here is a helpful link with short videos on the prevention of tick bites and safe removal of ticks:

Rather than just "Slip, Slap, Slop", learn to "Cover, Check, Clasp"?: http://campother.blogspot.com/2011/06/video-tick-removal.html

Fine-nosed tweezers are your friends, and not flame throwers and lighters...

Links to Australian tick bite related posts on this site:

About the first Today Tonight show this year on Lyme disease:
http://campother.blogspot.com/2012/02/lyme-disease-in-australia-on-today.html

On the outbreak of Tularemia in Tasmania late last year:
http://campother.blogspot.com/2011/11/tickborne-disease-outbreak-hits.html

On the use of marsupial cathelicidin peptides to fight infection:
http://campother.blogspot.com/2011/11/two-notable-antibiotic-articles-long.html

On Australian research on the relationship between tick bites and red meat allergies:
http://campother.blogspot.com/2011/04/tick-bite-you-stick-to-eating-fish-and.html

On Google search trends, and how Australians rank in the search for information on Lyme disease using Google:
http://campother.blogspot.com/2011/07/google-trends-on-lyme-disease.html

Links to Australian resources on Lyme disease outside of this blog:

CSIRO Public Health Advice on Ticks:
http://www.publish.csiro.au/?act=view_file&file_id=NB04047.pdf

The Karl McManus Foundation:
http://karlmcmanus.org/

Lyme Disease Association of Australia:
http://www.lymedisease.org.au/

Lyme Green Australia blog:
http://lymegreenaustralia.blogspot.com/

This work by Camp Other is licensed under a Creative Commons
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0 US HR Bill 3699 Would Put Tax Payer Funded Science Behind Pay Walls

US HR Bill 3699: I have a stake in this one. Many people have a stake in this one. I think that tax payer funded scientific research should be open access and published online as it has been in PLoS ONE and PubMed.

I value high quality peer-reviewed research. It's important. And peer-reviewed journals with high standards and ethics are necessary.

Given the amount of work involved, I think it's okay for privately funded research to be behind a pay wall for certain period of time - publishers need to recoup their money for editing and publishing journals which include not only research papers but articles, letters, and reviews.

Once more knowledge milestones are met and that privately funded research becomes effectively dated then it would best be released into the wild where the general public and students at community colleges and high schools could access it for free.

But this bill? This bill would ensure charging access to tax payer funded research.

An excerpt from the Doing Good Science blog on Scientific American web site pretty much sums up my own thoughts about it:

"The public is all too willing already to see public money spent funding scientific research as money wasted. If members of the public have to pay again to access research their tax dollars already paid for, they are likely to be peeved. They would not be wrong to feel like the scientific community had weaseled out of fulfilling its obligation to share the knowledge it builds for the good of the public. (Neither would they be wrong to feel like their government had fallen down on an ethical obligation to the public here, but whose expectations of their government aren’t painfully low at the moment?) A rightfully angry public could mean less public funding for scientific research — which means that there are pragmatic, as well as ethical, reasons for scientists to oppose the Research Works Act."

Read more commentary about this at the Doing Good Science blog on the Scientific American web site:
http://blogs.scientificamerican.com/doing-good-science/2012/01/06/the-research-works-act-asking-the-public-to-pay-twice-for-scientific-knowledge/

The original text of US HR Bill 3699:
http://thomas.loc.gov/cgi-bin/query/z?c112:H.R.3699:

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10 Video: Tick Removal

I've been spending some time today looking for good videos on how to properly remove a tick and also what tools are best to have in your toolkit.

I've seen some really, really bad videos. Some American guy removing a tick from his leg when drunk (no, he did not do a good job) and some Australian guy removing a tick from his abdomen starting with spraying insect spray on the embedded tick.

As a reminder to those reading along: Do NOT spray or ignite ticks with insect spray and/or a flamethrower when removing them, especially while intoxicated on any substance.

Where was I? The videos. Right.

A lot were poorly lit and filmed so far from the bite area that it was out of focus - and others, while well-made with 3D animation of a tick in all of its glory - contained errors or missed important points.

I'm still looking for something better to post here. Until I get my own copy of Pixar studio software and can make my own tick removal animation, these will have to do - unless you're reading along and have found better examples.

Please feel free comment with links to the best tick removal videos you've found online and tell me why you think they are worthwhile. In the meantime, check out the two below, and pass them on to kids and adults alike.

This first one is an animated film from Canada.

It's simple and to the point, and aimed at children - but the advice and information given applies to adults, too.

Tick Talk - The Adventures of a Not-So-Super-Villian [Time: 3:30]



This second one is a short film from a woman in the UK who is close to someone with Lyme disease, and while the prices for items in her tick kit are in quid, her feedback about various tools is useful to hear.

Ticks - Human Survival Kit [Time: 2:23]



I went to many well-known informational Lyme disease web sites and have been surprised they did not have any video - animation or otherwise - showing the procedure for how to remove a tick, though they did provide pictures and instructional text.

As always, keep the following in mind when removing a tick:

• Do not burn or use any substance on tick
• Do not grasp, squeeze, or twist body of tick with tweezers (tick twister is an exception)
• Grasp tick close to the skin with tweezers
• Pull tick straight out
• Use antiseptic on skin
• Disinfect tweezers
• Wash hands thoroughly
• Always see a physician for possible diagnosis, testing, and treatment
• If desired, save tick to be tested at tick testing laboratory

In the United States, here are some well-known tick-testing labs:

IGeneX Labs, Palo Alto, CA: 800-832-3200
MDL, Mt. Laurel, NJ: 877-269-0090
NJ Labs, New Brunswick, NJ: 732-249-0148

If anyone would like to share their experience with getting their tick tested at any of the above labs or another lab, that would be appreciated.

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2 Wolfram Alpha On Lyme Disease Diagnosis

So, I'm not sure how familiar my readers are with Wolfram Alpha. If you've ever heard of the Mathematica software package, these are the guys that created it.

Wolfram Alpha is an online tool that uses computational algorithms and data modeling to output objective information on a variety of topics.

In other words: It takes statistics and facts from numerous sources and creates a database on given topics on the fly.

(To learn more about what Wolfram Alpha's online tool does, go here: http://www.wolframalpha.com/tour1.html)

You can go to their homepage and type any term into their search engine and it will build a page based on that term and nothing but that term. Instead of a list of different link results like you see on Google, you get one page with many different kinds of information on that term or topic.

So for fun, I typed "Lyme disease" into their homepage.

The link for that query is this: http://www.wolframalpha.com/input/?i=Lyme+disease

Now, as part of the output for that query, I received the following table of data:

This is one of those moments where my head is breaking, and I can see where they are drawing their data from in the notes below the table - so I need to follow up and see if I can look at the original source for this data.

But just based on what I'm looking at right now, the words "Oh my god, where are they getting these numbers?" escaped my lips.  

According to the footnote, the data is not CDC based, but is based on actual patient visits to US healthcare providers between 2006-2007. I have to wonder why Wolfram Alpha is mining data from this source and not more recent NAMCS/NHAMCS statistics or another source, but it is interesting to see something that is not CDC for a change.

The data in this table does and does not reflect what I've observed online in the Lyme disease patient community.

For one thing, the chart states far more men than women contract Lyme disease and are diagnosed for it than women.  Yet the number of women I see online who discuss Lyme disease outweighs the number of men a great deal.

After reading Polly Murray's book, The Widening Circle, why women are more active online participants and more activist in general has been made more clear to me: the children. If you are sick with Lyme disease, that's bad enough - but if your child is sick, that's worse, and mothers seem to be more likely than fathers to reach out for answers and support online to help not only themselves but their children. (Sorry dads, I don't like the dissing either, and I'm sure a lot of you are active in your child's health - but statistically speaking more women do end up dealing with their kids' health issues for whatever reason.)

This reaching out and forming support groups began with women way before the internet - the internet is just an extension of what happens in real life.

(By 1992 there were over 100 patient support groups for Lyme disease - which kinda chips away at this idea that Lyme disease is a disease spread by reading the internet. What was the internet in 1992? Usenet?*)

But in this table, it's saying far more men get Lyme disease, and I see fewer of them online.

Okay, so another thing about this table,  just so the reader is clear on what they're reading, it doesn't take 22 doctors for one woman to achieve a diagnosis for Lyme disease here, even though I've heard so many stories about this phenomenon - no, what the table means is that for every 22 office visits a doctor sees, one of them will be a woman that gets diagnosed with Lyme disease. 

That one in six visits for men seems really high to me - too high, if you ask me - but in reading the fine print these are estimates and estimates which are weighted for US demographics (how? in what manner?).

I think what's striking about this one year of data is the extrapolation of just how many patients were diagnosed with Lyme disease over the course of 131,748 doctor visits. 

86,700 people in one year... is that closer to reality than the CDC reported 40,000 or so?

I really don't know how much stock to put in this data at all. I feel like writing Wolfram and asking them what gives. How was the estimation made and weighed and why are they drawing their data from NAMCS/NHAMCS - and if so, can they get more recent data or is this it? 

I'm thinking it would be more accurate a head count to get diagnosis numbers from doctors rather than the CDC, because not all cases are reported - but I don't know how reliable these numbers are or how the estimation was computed.

Update:

Just to add to this, check out this other table generated from the same data set:

Interesting.

Now look at the ratio for the number of  men who are diagnosed with Lyme disease to the number of women.  And now look at the total number of estimated cases. 

The only factor changed for initial data output was from "primary diagnosis at visit" to "any diagnosis at visit". What exactly does this mean?

Update #2:

Well, isn't this interesting. I googled "NAMCS" and my first result was this:

http://www.cdc.gov/nchs/ahcd.htm

On this page, we learn:

"The National Ambulatory Medical Care Survey (NAMCS) is a national survey designed to meet the need for objective, reliable information about the provision and use of ambulatory medical care services in the United States. Findings are based on a sample of visits to non-federal employed office-based physicians who are primarily engaged in direct patient care. 

The National Hospital Ambulatory Medical Care Survey (NHAMCS) is designed to collect data on the utilization and provision of ambulatory care services in hospital emergency and outpatient departments. Findings are based on a national sample of visits to the emergency departments and outpatient departments of noninstitutional general and short-stay hospitals."

So wait. This IS data from a survey the CDC knows about?

What percentage of these diagnosed cases are included in the CDC Lyme disease reported cases?

Why aren't these diagnosed cases mentioned on the reporting page for Lyme disease as a separate category of cases -  even if doctors did not fill out an official report?

Or are they mentioned somewhere on the CDC Lyme disease pages and I've missed it? Anyone want to confirm this for me?

Update #3:

Pointed out by an anonymous commenter on the blog just now - from the same page above:

Wow,  let's give the women lots of Ativan and give the guys none?

After reading this, we're all going to need Ativan.

Where they hell are these numbers coming from, though? The footnote here is really not useful.

And I'm sorry, if I am feeling sick with Lyme disease, getting it up is the last thing that would be on my mind... that must refer to a preexisting drug regimen. Even then... ouch.

I really have to wonder about these numbers.

Update #4 (hopefully the last?):

Okay, so I think I've answered some of my own questions here:
http://www.cdc.gov/nchs/ahcd/ahcd_faq.htm

Q. How are the data used? 

A. NAMCS and NHAMCS data are used to statistically describe the patients that utilize physician services and hospital outpatient and emergency department services, the conditions most often treated, and the diagnostic and therapeutic services rendered, including medications prescribed. The data are used by public health policy makers, health services researchers, medical schools, physician associations, epidemiologists, and the print and broadcast media to describe and understand the changes that occur in medical care requirements and practices. The data are disseminated in the form of public health reports, journal articles, and microdata files. 

Q: Can the ambulatory medical care surveys be used to find out how many people have a certain diagnosis?

A: No. The ambulatory medical care surveys (NAMCS and NHAMCS) are not based on a sample of the population. They are based on a sample of visits rather than a sample of people. The data can be used to find out how many ambulatory care visits were made involving a certain diagnosis. To get an idea of utilization of ambulatory care in the population, the number of visits can be divided by the population of interest to get a rate of visits for a diagnosis of interest.

Okay, partially answered. I still have to wonder how public health policy makers, epidemiologists, etc. use this data, though... and how closely this sample of visits maps to reality.

I really don't think anyone has a true picture of how extensive Lyme disease is and how many people have persisting symptoms of Lyme disease pre- and post-antibiotic treatment, and it would be useful to know how many cases physicians actually diagnose and treat versus report to the CDC as those are different numbers.

Even then, these surveys are only representational of doctor caseloads over a one week period during a given year - they are not solid figures.

* This is not all there was, but there were only 26 web sites in the world at the end of 1992.

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4 Top 10 Tips For Doing Your Own Lyme Disease Research

Here are my top 10 tips to share for doing your own Lyme disease research. Pretty simple and straightforward - and if you have any to add, please share in comments below.

1) Use the scientific, Latin terms for everything. You can use common terms, too, but Latin will give you more results and more specific results.

Examples:

Instead of "Lyme disease" use "Borreliosis".
Instead of "Neuro Lyme" use "neuroborreliosis".
Instead of "Lyme bacteria" or "infection" use "Borrelia burgdorferi".

2) Find out which terms microbiologists and scientific researchers use in their own papers and classes and then apply them to your search.

Examples:

Instead of "coinfection" use "polymicrobialism" or "polymicrobial".
Instead of "can't think straight" use "cognitive symptoms".
Instead of "spinal tap" use "lumbar puncture".
Instead of "shooting and burning pains" use "paresthesia".
Etc. - you get the idea.

Look at online and offline medical dictionaries for words that describe your symptoms and plug those into a search engine.

3)  Move your search away from general Google search to Google Scholar. You can get specific results for only scientific papers and patents that way.


4) Whenever you don't understand a term, use Wikipedia for an explanation.

I add a note of caution here: Wikipedia is not always right, though it usually is correct on basic science definitions.

If you aren't sure, double-check by doing a more general search and rely on college and university web sites for definitions. You may want to restrict your domain search to .edu web sites.

5)  Read educational institution web sites in general.

You may be surprised to find out what research is being done now on Lyme disease and coinfections which hasn't been published yet. Bookmark these items and check PubMed for the university name and researcher(s) name(s) periodically, as a paper will eventually be published.

6) Passively collect research information on your own web site or inbox by using RSS feeds.

If you look at the right column of this page and scroll down, you will see a number of Lyme disease and other disease-related and alternative medicine articles that are directly getting posted to this site all the time.

You can do the same with your own web site - or if you don't have a web site - by using an RSS reader or by subscribing to an RSS feed that gets sent to your email address.

This way, research comes to you and you don't have to always go do a search for it.

7) Look at major professional organizations' web sites - even if you may not agree with everything said - at least you will know what's going on.

Read the IDSA's web site periodically and be aware of how they view the issues around Lyme disease and infectious diseases in general. See what the NIH, CDC, and organizations have to say, and even more, dig deeper and look at what people from those organizations say in their research on PubMed and other online publication hubs. Some of what you find may surprise you.

8) Look at major online science web sites geared towards  a more general audience  (not specifically written for professionals) periodically.

Science Daily is a good example of this, and if you look at the bottom of each article, you will often see a link to the original paper or source on which they based their article. Check out the original source for more information - often it leads to finding out about other research the same researchers did on Lyme disease and coinfections.

Also, use the search function in Science Daily to look up terms such as "Lyme disease", "Borrelia", "Babesia" and even "Malaria". You may find interesting articles and older research from their archives this way.

9) Buy microbiology, acarology, and entomology text books for cheap and used at college bookstores which are trying to get rid of all old textbooks, "fire sales",  Amazon.com, and independent used bookstores near you.

While these textbooks can be dated, you might find information in them that could be useful and give you ideas of where to search next. Note that a lot of the basic information on Lyme Borrelia hasn't changed - but there has been a more refined and detailed understanding of what Borrelia is about over time, though, and those details need to be picked up by reading more recently published papers and books. (I say this, stating that a lot of Lyme disease research I see being cited online for and by patients is a bit outdated - we need to update these sites to reflect the state of the science.)

(You can also see if any friends or relatives have some lying around they're willing to lend or give to you.)

10) Search various libraries online, and participate in your local interlibrary loan program.

Can't afford that $500. book on microbiology? See if you can borrow it through your library's interlibrary loan program.

You will usually have a shorter time limit on borrowing books that are in high demand - some books have to be returned in a week. So if you need more time to work on it, ask someone to copy select passages for you from it to make notes on them later after you return the book.

Also, in many areas you can sign up for a program that will allow others to pick up books for you at the library on your behalf if you are housebound and too ill to go out - see if your area has one and sign up if you need it. This is good program to use in general for any material you may want to borrow for your own personal use.

And a bonus, Number 11:

Have a family member, friend, or friend of a friend who is already studying clinical microbiology, molecular biology, and/or genetics (immunology is helpful, too) help you decipher what you don't understand - and to tell you whether or not they think the findings are significant and which questions are not answered by a particular study that would be useful to have answered.

This may be a tricker bit, because not everyone is going to either have the time to respond to your request for help on this or hold the belief that your research is not worth the effort because they may believe that Lyme disease cannot persist and you are wasting your time.

Unfortunately, this is the truth of it - but in the true spirit of scientific inquiry and basically being stubborn, some people may be willing to help you at least a little bit.

My advice here is the less well-known the person is to you, the better it is to keep personal details out of the query. Also, keep your email or discussion brief, polite, and to the point while avoiding discussing the controversy. This is not to invalidate or dismiss your experience - but being said out of practicality and diplomacy: Busy people are more likely to respond to something in an unbiased fashion if you keep it simple and short.

Happy researching!

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34 News: Institute of Medicine Releases Lyme Disease Workshop Summaries

Source link: http://www.iom.edu/Reports/2011/Critical-Needs-and-Gaps-in-Understanding-Prevention-Amelioration-and-Resolution-of-Lyme-and-Other-Tick-Borne-Diseases.aspx?utm_medium=etmail&utm_source=Institute+of+Medicine&utm_campaign=04.20.11+Report+-+Lyme+Disease+%26+Other+Tick-Borne+Diseases&utm_content=New+Reports&utm_term=Media

To read the Workshop Summaries, click on the link at the top and look in the righthand column - you'll see gray buttons that say "Download Report" or "Read Report Online For Free". If you want to download a pdf of the report, you'll need to supply your email address and other info. If you just want to view it online, click "Read Report Online For Free" and there will be no request for personal information.

Once you select "Read Report Online For Free", by the way, you have an opportunity to download a 21 page summary of the report (direct download) by clicking on a link for it on the lefthand column. Otherwise, the full report is 468 pages long.

[CO update: The 21 page summary gives the barest of outlines of what was discussed, along with a list of those who attended - you are much better off reading the 468 page report.]

One thing to note here is that this appears to be a report on what was discussed at the Institute of Medicine (IOM) workshop on tickborne diseases in October 2010 and not a final position piece stating the IOM's consensus on how Lyme disease and tickborne infections should be approached through research, prevention, or treatment.

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18 Tick bite you? Stick to eating fish and poultry; avoid red meat?

I say the above not just because there have been health benefits from cutting back on your consumption of red meat - but because in the past couple of years, a number of people who have been bitten by ticks have developed a delayed anaphylactic allergic reaction to red meat. Now there is further evidence that there is a connection between tick bites and this reaction.

Anaphylaxis is the most serious form of allergic reaction a person can get, and it can be fatal. Typical symptoms include swelling of the tongue and throat, itching, hives, trouble breathing, low blood pressure, and shortly thereafter - an inability to breathe at all.

People with severe allergic reactions to food - such as peanuts - are advised to carry a medical device called an epinephrine pen (commercial name, Epipen). The "pen" is a portable injection device with a small cartridge of epinephrine and a preservative in it which is injected into the side of a person's leg at a 90 degree angle and held there for 10 seconds before removal. This injection is not the end of treatment - it is only meant to help until EMTs or paramedics arrive; an ambulance must be called if someone has an anaphylactic reaction.

So, when I say this is serious - it is. People have died from anaphylactic reactions. Having Epipens on hand is critical if you know you have this condition. Your odds of survival are greatly improved if you have them and use them early in the onset of serious symptoms.

If I seem to be pretty concerned about this issue, I am - I know a number of people with serious allergies, including one with a peanut allergy - and they have to carry these pens and avoid certain restaurants all the time.

Weird thing about this anaphylactic response in people who have had tick bites is that everyone who had the reaction used to have no problem eating red meat prior to the bites - and also, the anaphylactic response doesn't turn up until 3 to 6 hours after consuming the red meat. Usually an anaphylactic response shows up 5 to 30 minutes after consuming the wrong food - and is a reaction to protein in the food. In this case - even though it's meat that is the trigger - a carbohydrate is the source of the reaction.


The research states it is mostly people who have been bitten by the Lone Star tick who develop this allergic reaction. But since you might not know which kind of tick bit you, you might want to avoid beef, lamb, and pork in your diet - and maybe even cow's milk - just to be on the safe side. Besides... Fish, turkey, and chicken are usually leaner sources of protein and have less saturated fat anyway - it's good for you.

Source publication:
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. The Journal of Allergy and Clinical Immunology. (In Press) Scott P. Commins, MD, PhD, Hayley R. James, BS, Libby A. Kelly, MD, Shawna L. Pochan, CNM, MPH, Lisa J. Workman, BA, Matthew S. Perzanowski, PhD, MPH, Katherine M. Kocan, PhD, John V. Fahy, MD, Lucy W. Nganga, MD, Eva Ronmark, PhD, Philip J. Cooper, MB BS, PhD, Thomas A.E. Platts-Mills, FRS.

Abstract source: http://www.jacionline.org/article/S0091-6749(11)00344-7/abstract

Newspaper article from 2010 on patients in southeast US: http://www.roanoke.com/news/roanoke/wb/253939

What's interesting is that Dr. Commins did research on IgE antibodies and anaphylaxis caused by carbohydrates present in red meat and thought there might be a relationship to tick bites when he did this earlier research.

To quote from this previous publication,

"Initial attempts to clarify the possible causes of development of IgE antibodies to α-gal included investigation of parasitic infections as an inciting event. Sera from patients with documented helminth infections, however, do not consistently contain IgE antibodies to α-gal (data not shown). Interestingly, more than 80% of the patients in the present cohort report being bitten by ticks before having symptoms; a similar scenario has been recently described in a group of Australian patients.³¹Therefore the implications of IgE antibodies to α-gal might extend well beyond the southeastern United States, and we are pursuing the possibility that bites from ticks or tick larvae of the genus Amblyomma are responsible for triggering the production of IgE antibodies to α-gal."

The interesting part for me, too, is that he mentions that a similar scenario has been described in a group of Australian patients.  When you think "Lyme disease", most people think the eastern coast of the United States. Most people don't think of people on the west coast - let alone Australia - getting ill from tickborne infections. But it happens, and I suspect it happens more frequently than most people are aware.

There has been a lot of controversy downunder as to whether or not one can get any sort of tickborne infection from ticks in Australia. The common belief held by many for a long time was that outside of tick paralysis, ticks in Australia don't carry diseases like ticks do in the northern hemisphere.

That's changing.

A lot of discussion about Lyme disease in Australia was spurred by the July 2010 death of Karl McManus, an actor on the set of the TV show, Home and Away. Karl was bitten by a tick in Australia in 2007 while filming outdoors on the set and went on to develop a flu-like illness followed by many symptoms of neuroborreliosis. More information on Lyme disease and other tickborne infections in Australia can be found at the Karl McManus Foundation web site.

Due to stories such as Karl's and of a number of Australians who state they have had symptoms of tickborne infections - even though they have not traveled outside Australia - it is clear more needs to be done to investigate the situation. More research is needed there to show how extensive tickborne infection is in Australia, and a greater awareness about the symptoms of tickborne infections outside of tick paralysis (fairly well known by Australians and supposedly completely reversible if the tick is removed right away) is needed by the Australian public and doctors.

There are five kinds of hard-bodied Ixodes ticks - as well as other ticks - that could spread infection in the country. Note that there are no Lone Star ticks in Australia - so what is causing the serious allergic reaction mentioned above? So far, I only found limited research available and accessible online referring to the citation source below [31] which is The Association between Ixodes Holocyclus Tick Bite Reactions and Red Meat Allergy by Sheryl van Nunen, Kate O’Connor, Suran Fernando, Lesley Clarke, and Richard X Boyle, which was published as part of a poster session at the Australasian Society of Clinical Immunology & Allergy's 18th Annual Scientific Meeting in 2007 in Western Australia.

If any of my readers from Australia know more about this session or anyone has more information about this, please let me know in comments.

Earlier research, in full text:
Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose. The Journal of Allergy and Clinical Immunology. Volume 123, Issue 2 , Pages 426-433.e2, February 2009. Scott P. Commins, MD, PhD, Shama M. Satinover, MS, Jacob Hosen, BS, Jonathan Mozena, MD, Larry Borish, MD, Barrett D. Lewis, MD, Judith A. Woodfolk, MBChB, PhD, Thomas A.E. Platts-Mills, MD, PhD

Read entire publication for free: http://www.jacionline.org/article/S0091-6749(08)01931-3/fulltext

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