Overview of Lyme Disease (LD)
Lyme disease is the most frequently reported multisystem vector-borne illness in the U.S. caused by the spirochete Borrelia burgdorfi (Kugeler, Farley, Forrester, & Mead, 2015). It is transmitted to humans through the bites of blacklegged ticks; I. scapularis, endemic to areas in the northeast, mid-Atlantic, and north-central U.S, and I. pacificus on the Pacific coast (Barbour & Fish, 1993). It is worth noting that Lyme disease – albeit it has yet to be classified as such – is pandemic (Cameron, 2016). Counties in northeastern states have the highest incidence of Lyme disease, demonstrating an increase of >320% between 1993-2012; the patient resides in Northern Virginia and lives on a golf course backed by a nature reserve, and is an avid hiker in dense woods. She also has a family history of dermatologic and rheumatologic symptoms, often indicative of an inflammatory response such as a tick bite. Environmental, ecological, and social factors that influence the incidence of Lyme disease include human behaviors, such as hiking in dense woods or through wildlife reserves, living amongst nature, building new communities in areas that were once favorable to deer, and new growth in open fields that have since emerged new forests and thus, new populations of deer (Barbour & Fish, 1993; Kugeler, Farley, Forrester, & Mead, 2015). Genetic factors influence Lyme disease, specifically Borrelia burgdorfi-induced cytokine production and responses. Cytokines play an integral role in keeping the immune system functioning optimally by defending against pathogens, as well as in the pathophysiology of immune-mediated diseases (Oosting, et al., 2016). In their study, Oosting, et al. (2016) demonstrated a strong correlation between age and its influence on Borrelia-induced IL-22, in addition to other genomic factors contributing to this response such as decreases IFN-γ. They also reported the importance of HIF-1α regulation of glucose metabolism because of its connection with Borrelia-induced cytokine production. Other genetic factors influencing the development of Lyme disease include age, gender, and BMI via circulating mediators; seasonality also play a role in lieu of its major impact on inflammation and cytokine responses (ter Horst, et al., 2016). Lyme disease is transmitted from a mother to the fetus (Walsh, Mayer & Baxi, 2006).
Effectiveness of Conventional Therapy
According to the CDC (2015), the appropriate and historical process for testing and detecting antibodies to Borrelia burgdorferi (B. burgdorferi) in patients suspected of having Lyme disease (LD) consists of a two-tiered approach that includes enzyme-linked immunosorbent assays (ELISAs) based on sensitive enzyme immunoassay (EIA) or immunofluorescent assay (IFA) using whole-cell sonicate (WCS) as a first-tier test, followed by supplemental separate IgM and IgG immunoblots, or Western Blot (WB), for confirmation. However, this two-tiered approach and standard of practice since 1995 lacks specificity, with false positive rates of 30% despite medical centers achieving specificity as high as 95%; this has not been replicated in clinical practice (Jin, Roen, Lehmann, & Kellermann, 2013; Wormser, et al., 2013). The major drawback of this standard of practice regards the inter- and intra-laboratory variation, causing false-positive results through over-interpretation of IgM blots (Branda, Linskey, Kim, Steere, & Ferraro, 2011). In fact, only 10%-50% of patients will present detectable antibody responses in culture-confirmed early stage LD (Theel, 2016). In addition to these inaccuracies, the use of WB is timely and costly. Thus, this standard antibody testing for Lyme disease does not rule out Lyme disease. The historical standard of practice for detecting LD is failing, with failed diagnoses contributing to ever increasing incidence rates.
According to the CDC (2016), the treatment of antibiotics early in the stages of Lyme disease (LD) is enough to help individuals recover quickly and wholly. Doxycycline, amoxicillin, or cefurozime axetil are the common antibiotics utilized, with intravenous treatment of ceftriaxone or penicillin used for patients with cardiac illnesses and/or neurological dysfunction. The CDC (2016) also cites symptoms can last beyond 6 months, termed post-treatment Lyme disease syndrome (PTLDS), without adequately addressing resolution beyond stating that funding by the National Institutes of Health (NIH) demonstrates often patients will recover after weeks of treatment with oral antibiotics. However, antibiotic treatment is garnered with arguments for and against its use, how long it should be administered, and whether or not tick-borne illnesses and co-infections exist.
• Bloodwork: C3a, C4a, TGF-beta-1, MMP9, CRP, MSH, VIP, HLA DR, AGA IgA/IgG, ACTH/Cortisol, VEGF, ACLA IgA/IgG/IgM, ADH/Osmality, Leptin
• Lyme disease test (Immunetics/2-tiered approach, or NanoTrap)
• VCS vision test ($15; https://www.survivingmold.com/store1/online-screening-test/purchase-vcs)
• ERMI/HERTSMI test ($290, ERMI / $155, HERSTMI www.mycometrics.com)
• Dr. Shoemaker Protocol for CIRS/Lyme Disease
Most of the blood work is covered by insurance with only a small portion out of pocket, (depending on the plan). The NeuroQuant is typically around $100, not covered by insurance. The ERMI or HERTSMI tests cost $155-295 depending on which test is utilized, neither are covered by insurance. The cholestyramine, a binding agent, is often covered in part by insurance with just standard co-pay but this does vary between insurance programs. Supplements are all out of pocket, and range in price. The most costly of the supplements is the phosphotidylcholine, which averages $200/bottle.
Effectiveness of Complementary Therapy
A systemic review and meta-analysis conducted by Waddell, et al. (2016) summarizes evidence on the accuracy of diagnostic testing, as well as testing regimes, in North America at different stages of Lyme disease. Of note, the two tests that provided superior sensitivity and specificity were the Immunetics® C6 B. burgdorferi ELISA™ and two-tiered approach using C6 antibody and a whole cell sonicate (WCS) screening test facilitated by Branda, et al. (2011). They conducted their study in three stages (where stages 1 and 2 were considered early infection and stage 3 was late disease) and compared 3 test strategies for sensitivity; 2-EIA algorithm, C6 EIA alone, and the standard 2-tiered algorithm recommended by the CDC. The C6 testing alone, along with with 2-EIA algorithm, in early disease had similar sensitivity and both were greater than that of the standard 2-tiered test (61% and 64%, respectively, vs 48%; P=0.03 and P=0.008). For late disease, they obtained 100% sensitivity with all 3 strategies. The specificity of the 2-EIA algorithm equaled that of the standard 2-tiered test, yet both had greater specificity than C6 testing alone (for both, 99.5% vs. 98.4%; P=0.01). The positive predictive value (PPV) for the 2-EIA algorithm was 70%, in comparison to 66% for the standard 2-tiered testing and 43% for C6 alone. While sensitivity is comparable, the authors argue the new 2-EIA-algorithm approach is worthwhile in lieu of added labor and cost because of the strength behind the specificity.
Another up and coming test for Lyme disease is the urine Nanotrap, which measures for the presence of Outer surface protein A (OspA) proteins sensitive for picking up Lyme. The Nanotrap Lyme Antigen (LA) test is highly sensitive and specific for the detection of B. burgdorferi within a patient’s urine sample, detecting with confidence during the earliest stages of infection (Ceres Nanosciences, Inc. , 2017). Using a hydrogel biomarker with amine containing dyes to capture microparticles has resulted in close to 100% capture and extraction yield of the target antigen, with a 100 fold increase in sequestering and concentrated LD antigens (Douglas, et al., 2011). Magni et al. (2015) conducted a study where they utilized Nanotrap particles to concentrate urinary OspA with highly specific anti-OspA momo-clonal antibody (mAb) detection of C-terminus peptides, which is conserved across infections of Borrelia species but is homologous to sequencing in humans. The sensitivity was 1.7 pg/ml (lowest limit of detection), and pretreatment of 24/24 newly diagnosed patients with an EM rash who were positive for urinary OspA resulted in no false positives. The specificity of the urinary OspA test for clinical symptoms was 40/40, and the specificity of the OspA antigen test for later serology was 87.5% (21 urinary OspA positive/24 serology positive, Chi squared P=4.072e-15).
Dr. Shoemaker’s Lyme disease and CIRS Protocol
Dr. Shoemaker believes the assessment of underlying biomarkers and inflammatory data, as well as the use of NeuroQuant testing, which provides insight to neurological injury in addition to establishing endpoints for targeted central nervous system therapies, establishes the foundation for treatment. 95% of patients with symptoms that continue beyond antibiotics, who were confirmed for LD, have a genetic basis for their illness – HLA DR by PCR (Shoemaker, 2014). Thus, innate immune inflammatory responses realized in Lyme disease that failed to improve with antibiotic treatment highlighted a new path, one that included paying attention to C4a, TGF-beta-1, and T-regulatory cell abnormalities that resolved once the toxin aspect was addressed, leaving patients to rebuild their lives.
The protocol recommended by Dr. Shoemaker is a successful anti-inflammatory therapy aimed at fixing T-reg cells because, in his words, if you do not the patient will not get better. After antibiotic treatment, the steps of the protocol (Vosloo; n.d.), which also govern the treatment for CIRS – a biotoxin illness itself, are:
Step 1: Remove from source of inflammagen exposures. Perform an Environmental Realtive Mold Index (ERMI) test through http://mycometrics.com, which will indicate mold exposures that will need remediation in order for the home to be safe, by using a cloth provided by Mycometrics to collet dust relevant in causing CIRS (inflammatory responses). Levels of C4a should be tested and used as a parameter for treatment; typically in Lyme disease patients, C4a ranges between 6,000 and 8,000.
Step 2: Reduce circulating biotoxin burden. Using cholestyramine, a binding agent for lowering cholesterol, helps sequester and remove inflammagens that are typically reabsorbed and recirculated in bile causing sustained inflammatory illness. In LD patients with elevated MMP9, symptoms may be exacerbated, which can be attenuated with a low-amylose food diet and high dose of fish oil (2.4g EPA:1.8 DHA) with meals. If fish oil is not enough Actos, which is more effective, can be used but it does carry a bladder cancer black box warning; however, those with leptin <7 should stick with fish oil as Actos has a leptin lowering effect.
Step 3: Remove biofilm dwelling resistant staphylococci that keep MSH low. Eradicating MARCoNS (if any) with BEG nasal spray when low MSH, as MARCoNS secrete exotoxins A and B from biofilm communities which shelters microbes against body defenses and antibiotics. Typically this step occurs a month after step 2, and ranges from a 4-week treatment onward, depending on retesting results. If after 4-weeks MARCoNS are still present, the BEG nasal spray is continued another 4-weeks and follows in such intervals until they are eradicated. Typical BEG spray consists of Bactroban (Mupirocin) 0.2%, Edetate Disodium (EDTA) 1%, Gentamicin 0.5%, 2 sprays in each nostril 3 times per day. In resistant cases, Rifampin 300mg twice a day for one month may be used; however, this has higher incidence of side effects and should be used with caution.
Step 4: Eliminate further inflammation in an already upregulated immune system by avoiding gluten. In this step, the correction of elevated serum anti-gliadin antibodies through the avoidance of gluten takes place. Serum IgA and IgG anti-gliadin antibodies should be monitored, and if positive, there is immune loss of tolerance with resultant inflammatory dysfunction due to exposure of gluten. Thus, a gluten-free diet should be followed for treatment over the course of 3 months, or longer, with retesting to confirm antibodies are negative.
Step 5: Correct androgen levels, provide endocrine support — especially adrenal and gonadal. Increased cytokines and leptin levels result in HPA dysfunction, impacting neuro-endocrine dysfunction. Test pregnenolone, estrogens, androstenedione, DHEA, testosterone, and estradiol. Repeat testing every 4-8 weeks intervals until serum levels are within normal range. Refrain from administering exogenous testosterone if possible. VIP nasal spray corrects for aromatase overactivity.
Step 6: Correct blood ADH/osmality. Neurotoxicity in CIRS and LD illnesses results in low and below detection levels of AVP/ADH and increased serum osmality (too concentrated and thick). Thus, symptoms of dry mouth, thirst, urination frequency, increased sweating, static electricity/shocks are often seem in these patients. Desmopressin may be used with caution, 0.2mg every other night for 10 days, then retest.
Step 7: Correct MMP9 (Matrix Metalloproteinase 9), enzymes associated with inflammation. A low amylose diet in conjunction with high dose fish oil (2.4g EPA:1.8g DHA) will help decrease inflammation, pain, and dysfunction. Inflammation attacks the joints, brain, nerves, muscles, and lungs.
Step 8: Correct low VEGF (Vascular Endothelial Growth Factor) to improve oxygen delivery to cells. Low VEGF contributes to oxygen deprivation at the core of CIRS, and VEGF improves capillary blood flow supporting new blood vessel growth. When compromised, so is aerobic energy production. Again, low amylose diet in conjunction with high dose fish oil (2.4g EPA:1.8g DHA) is the treatment.
Step 9: Correct elevated C3a levels to improve oxygen delivery to cells and decrease inflammation. C3a promotes pathological inflammation, and there is substantial overlap symptomatically between Lyme-complex illness and CIRS inflammation. Ubiquinone, or CoQ10, 150 mg or more per day for at least 10 days is the treatment for elevated C3a, along with reducing and/or eliminating statin use as it depletes T-cell activation, macrophage activation, and leads to vascular wall inflammation.
Step 10: Correct elevated C4a levels to improve oxygen delivery to cells and decrease inflammation. C4a indicates the degree of inflammation as well as the treatment response. If it is high, it causes a myriad of problems including cognitive decline, increased smooth muscle contraction, vascular permeability, release of chemotactic factors followed by capillary hypofusion and low tissue oxygen. Further, energy production is impeded causing a decrease in ATP yield from 38 ATP down to 2 ATP per glucose molecule. Treatment for C4a includes VIP nasal spray.
Step 11: Correct elevated TGF-Beta-1 (Transformation Growth Factor Beta 1) to restore immune regulation and balance. TGF-Beta-1 is an important biomarker of biotoxin illness with regulatory functions in multiple tissues and pathways, including repairing normal T-regulatory cell function preventing autoimmunity, affecting DNA replication, and stimulating production of type I and II collagen and fibronectin. It also has a dose-dependent response with levels of MMP-9; as levels of TGF-Beta-1 increase so does MMP-9, increasing brain permeability. Treatment includes two options: oral losartan starting at 12.5mg per day, increasing to 25mg twice daily if tolerated well, or the use of VIP nasal spray.
Step 12: Correct low VIP (Vasoactive Intestinal Polypeptide) to restore neuro-regulation to re-establish normal systems function. VIP restores immune regulation, and this is the final step in the 12-step protocol. In order to begin VIP treatment, the patient must pass the VCS (visual contrast sensitivity) APTitude test, which measures neurological function. The test, found at survivingmold.com costs $15 for one test, though one can purchase multiple tests if future testing will be required. Additionally, the patient must not be exposed to an ERMI <2 (or HERTSMI 2 <10), all MARCoNS must be negative on the API Staph nasal culture, and they must have normal serum lipase levels.
The first dose of VIP should be in office with 15-minute pre- and post- administration blood testing to ensure safety and measure the magnitude of response. Pre-VIP labs include VIP, MSH, C4a, TGF-Beta-1, MMP-9, VEGF, and Lipase. 15-minute post-VIP 50mcg intranasal administration labs include TGF-Beta-1 and Lipase. 30-days post-VIP commencement labs include stress echo for PASP, Lipase, C4a, TGF-Beta-1, VCS, changes in symptoms, hydration, and blood pressure. When symptoms improve, and TGF-Beta-1 levels, VCS, and Lipase levels are normal, reduce VIP to 50mcg twice per day for 30 days. Reduce again to only 50mcg one daily for an additional 30 days, and then discontinue. Complete a re-evaluation in 6 months.
If you, or someone you know, are suffering from Lyme Disease and its associated risks, visit https://www.survivingmold.com/shoemaker-protocol/find-a-physician-in-my-area to locate a certified practitioner in your area.
Knowledge is key; be an advocate of your own health! The more you know, the more you grow…in optimal health!
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