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Lyme Disease

Updated: Mar 18

The most commonly reported vector-borne disease in the United States and one of the more commonly overlooked causes of ongoing symptoms which persist leaving clients both physically and mentally disabled. Disappointingly, most of conventional medicine believes this to be a very rare disease that is easily treated with just a single round of #antibiotics so when individuals experience symptoms beyond this, they are often dismissed.


Lyme is caused by the spirochete Borrelia burgdorferi, which is transmitted to humans and animals who have been bitten by infected deer ticks, also called black-legged ticks; however, #Lyme has also been reported on lone star ticks, American dog ticks, flies, mosquitos, and spiders. Borrelia has been cultured from semen and vaginal secretions in serologically positive patients and there are many similarities to syphilis, so Lyme has the potential to be a sexually transmitted disease.


Lyme ticks begin to appear when temperatures raise above forty-five degrees. I've heard it suggested to apply catnip oil to your legs and to sprinkle the herb, catnip, onto your socks, which is certainly safer than DEET. If you wear white socks, you'll better identify the little black bugs as well. Leave your clothing outside once you get home, to avoid bringing ticks inside.


Once an infected deer tick has bitten its human host, the transmission of bacterium can take anywhere from a few hours to more than a day. Deer #tick bites frequently go undetected in humans because of the deer tick's extremely small size. Larval and nymphal deer ticks are typically no larger than the head of a pin, and a bite may be evident only with careful examination. The concern is this bacterium traveling through the bloodstream and integrating itself into various areas of the body, causing a variety of mild to severe symptoms.


Lyme disease as first discovered in Old Lyme, Connecticut, in 1975, when a cluster of individuals presented with uncommon arthritic symptoms. In less than two years, 51 cases of "Lyme arthritis" had been described and I. scapularis was linked to transmission. It wasn't for another five years that B. burgdorferi was identified, and serologic testing was available in another two years. From that initial cluster of individuals in 1975, Lyme disease has risen to endemic proportions in the northeast and upper midwestern United States. Serology became available in 1984 and in 1987 it was a reportable disease, but it wasn't until the 1990's that the CDC began surveilling Lyme disease.


Black Legged Deer Tick

More than 30,000 cases of Lyme disease are reported each year in the United States from health departments in every state and the District of Columbia; however, it is suspected that up to ten times as many cases go unreported. Additional research estimates that 300K individuals to 400K individuals file medical claims based on a diagnosis of Lyme disease with a large one large U.S. insurance company each year. Interestingly, less than 4 percent of primary care providers admit to having diagnosed and treated Lyme disease.


At Eden Family Practice, LLC, nurse practitioner, Dr. Penny Lane, has both diagnosed Lyme disease and treated clients for years who suffer this challenging disease. We do take a functional and integrative approach, combining both traditional and progressive therapies to provide treatment that addresses the entire individual. We work to identify and restore the underlying cause of the medical conditioning, and a path towards lifelong vitality.


Unfortunately, tick-borne illness an be difficult to define, and symptoms may vary greatly between individuals. We use to believe this was hard to get and easy to treat, and that you would know if you've been bitten. Today we recognize that it is easier to get and can be hard to treat. For some, symptoms are sudden, acute, and characteristic of Lyme disease. For others though, symptoms present a little more gradually, or appear significantly after the initial bite. We also recognize today that the previous standard testing, the ELISA, isn't entirely reliable.


The Classic Bull's Eye Rash


The saliva from an infected tick of the I. scapularis genus transmits B. burgdorferi into the skin while feeding, which then allows it to enter the bloodstream, triggering the immune system, and then causing the bacterium to establish itself locally, spreading outward into the dermis. This creates the hallmark symptom, the bull's eye rash, which is the result of the immune system's inflammatory response to the invading organism.


Interestingly, the protein plasma of the spirochetes from the B. burgdorferi prevent the bacterium from being identified by the immune system, so typically where neutrophils would step in to eliminate the bacteria, they fail to do so allowing the spirochetes to proliferate and survive. The same protein plasma and the production of spirochetes reduce or alter the receptor sites of surface proteins that are normally targeted by antibodies, inactivating the complement system and allowing the bacteria to be deposited in the extracellular matrix. This makes it difficult for the immune system cells to reach the bacteria essentially persevering itself within the body for years without causing symptoms.


The bacteria has a special interest in collagen-rich tissues such as the brain, nervous system, joints, and muscles, including the heart, as their primary food source. Hence, many people will experience joint pain or other symptoms associated with these areas as a result. In short, Lyme disease is a multisystem disease that can have a range of effects on the overall health of its host.



Lyme disease is typically described in three clinical phases or stages categorized as Early Localized disease (stage one), Early Disseminated disease (stage two), and Late Chronic disease (stage three).


Early Signs & Symptoms of acute Lyme Disease


These are typically quite subtle and often overlooked. The diagnosis of Lyme disease is a combination of clinical symptoms, reports of known tick bite, and history of being in a tick-abundant area. Serologic testing can be helpful but not always conclusive. When the disease is well established, during the second or disseminated stage of Lyme disease, serologic tests are nearly always positive. There is a higher tendency for the testing to be falsely negative within the first thirty days but when a positive Lyme titer is noted, antibiotics are prescribed.


The initial symptom is typically the erythema migrans, or the bull's eye shown above, which usually migrates from the site of the tick bite and appears as a solid red expanding blotch or a central ringed spot. Eighty percent of those bitten will identify this rash which typically appears three to thirty days after transmission of the Lyme disease, and is an average of five to six inches in size. The rash usually persists for three to five weeks and may be warm to touch, but not usually painful or pruritic. Cellulitis, spider bite, ringworm, eczema, MRSA, dermatitis, and urticaria are commonly confused with the bull's eye rash of Lyme disease.


Not all those who acquire Lyme disease present with the bull's eye rash and if early localized disease is not treated, these individuals may develop multiple secondary circular rashes as spirochetes spread throughout the body. Associated symptoms are similar to a nonspecific viral illness or are flu-like such as pyrexia (fever), chills, cephalgia (headache), extreme fatigue, weakness, anxiety, irritability, depression, and multiple edematous lymph nodes. The GSQ-30 Global Symptom Questionnaire is a reliable instrument to assess symptom burden both during the acute and post-treatment of Lyme disease.


Following this initial stage, the bacteria spreads throughout the body via the lymph system or bloodstream. When untreated, the joints, nervous system, and cardiovascular system become involved. Individuals will present with extreme fatigue, migrating myalgia (muscle pain), and arthralgia (joint pain). These symptoms may occur as early as 7 to 14 days after exposure but may occur six months after infection and present as joint pain and swelling with synovial fluid findings suggesting an inflammatory process. How long the tick is attached and whether it was engorged are two of the most important factors to consider when assessing risk of transmission.


Treatment is crucial within the first one to two weeks (up to thirty days) when the individual still has rash and flu-like symptoms, or neurologic complications can occur in a secondary stage or early disseminated stage of Lyme disease. Paresthesia in the extremities (abnormal sensation of the skin), pain and weakness can occur, as well as Bell palsy (paralysis of the facial muscles), cranial neuropathies, and visual disturbances. A classic triad of #meningitis, cranial neuropathy, and radiculoneuropathy has been described, although these may not always occur simultaneously.


Other neurologic complications which may occur include meningitis-type symptoms such as fever (100 degrees to 102 degrees), stiff neck, and severe #headaches. Subtle cognitive difficulties can occur at this stage as well, such as becoming forgetful short-term memory loss, personality changes, #insomnia, altered mental states. Encephalitis, encephalomyelitis, and subtle encephalopathy may also occur.


Cardiac manifestations may occur, usually within a month or two of infection, including conduction abnormalities such as atrioventricular heart block. This is less common than systemic disease, occurring in approximately ten percent of those infected. In the disseminated stage of disease, individuals may experience chest pain, difficulty breathing, #fatigue, syncope, heart palpitations or dysrhythmia and develop #myocarditis or pericarditis. Other symptoms may include conjunctivitis, keratitis (inflammation of the cornea), or uveitis and mild hepatitis or splenomegaly may result.


Second or Disseminated Stage of Lyme


This is the point at which serologic testing is almost always positive. When treated early, with antibiotics, Lyme is almost always cured. Additional antibiotic treatment may be required for the small percentage of individuals with recurrence of symptoms. About 20 percent who are treated, still go on to have post-treatment Lyme disease, which may present as #fibromyalgia, chronic fatigue syndrome, or irritable bowel syndrome; however, most who do suffer these conditions post-Lyme were undiagnosed and subsequently untreated - and have no memory of a bull's eye rash.


Lyme disease can progress into this late stage months to years after the initial tick bite, which may result in substantial morbidity, especially from #arthritis. These symptoms are a bit distinct from what is typically named "post-Lyme disease syndrome," which refers more to the symptoms which are more nonspecific, such as fatigue.


Symptoms post-treatment supported by B. burgdorferi-positive cultures and polymerase chain reaction, which has a highly sensitivity for Borrelia bacteria, support the diagnosis of a persistent infection. Individuals without evidence of B. burgdorferi infection who present with a group of persistent symptoms are considered to have a chronic form of Lyme disease. The International Lyme and Associated Disease Society (ILADS) share that failure to fully eradicate the infection may result in the development of a chronic form of Lyme disease that may cause increased morbidity.


Those who do endure long-term Lyme are thought to be those with more resilient bacterium which either evade the immune system and or which morph into ways that allow the bacterium to be resistant to antibiotic treatment, requiring alternative treatments or dosing strategies.


Chronic Lyme Disease


Lyme disease can become chronic either because it wasn't fully eradicated initially, or because the immune system couldn't fully manage fighting the infection, which often leads to significant physical and mental impairment. Chronic Lyme disease is estimated to affect more than 1.5 million people in the United States.


Many of the acute Lyme disease symptoms are also present in chronic Lyme. Joint pain and severe fatigue are common. Depression, #anxiety, brain fog, mood swings, emotional lability, suicidal thoughts, and cognitive dysfunction are common neuropsychiatric problems. Issues with fetal brain development can occur when a pregnant woman has Lyme's disease. Sudden onset aggressiveness and violence has been observed in some individuals later realized to have Lyme or even Lyme coinfections, particularly Bartonella. Alzheimer's Disease, immune dysfunction, inflammation, neuropathy, and cardiovascular symptoms are other conditions consistent with chronic Lyme.


Lyme disease has been referred to as the "Great Imitator" because it resembles and mimics many other diseases, often leading to a misdiagnosis. For example, before Lyme disease was recognized, it was mistaken for juvenile #arthritis.


Diagnostic Testing


Without laboratory data, the bull's eye rash is the only clinical finding which can exclusively allow for a diagnosis. Direct and indirect approaches have been used when the bull's eye wasn't immediately identified. These include cultures and techniques that identify B. burgdorfer, as well as efforts to evaluate antibodies.


The culture is the diagnostic standard, but it isn't routinely available. The CDC and IDSA recommend serology as the initial diagnostic test. This is a two-step process, initially with an enzyme-linked immunosorbent assay (ELISA), followed by a Western blot to confirm the diagnosis. This identifies antibodies that the immune system makes in response to the bacteria, so in the majority of cases, antibody testing is the most reliable a few weeks after initial infection when the levels of antibodies are at their highest. However, since most people haven't any idea when they were bitten, this tool can prove unreliable. The Western blot omits significant bands as well, such as dKa31 and dKa34. The 83-93 specific or significant bands are 23-25 kDa, 31 KDa, 34 kDa, 39 kDa, and 83-93 kDa.


Further, IgG and IgM can persist for years so are not an indication of ineffective treatment or chronic infection; therefore, repeated serologic testing for documentation of treatment effectiveness or cure is not recommended. My experience is that many will have positive IgG and most will have positive IgM. In most infections though IgM peaks after exposure and then drops off about four months while IgG is just peeking at that time. Lyme's is more a modulation of both IgM and IgG with no real perfect timing for identifying either. A new IgG enzyme-linked immunosorbent assay called the C6 peptide assay has comparable sensitivity and specify to the standard two-tier protocol.


Molecular testing is a newer technique which amplifies trace amounts of DNA which can then be used to determine with a very high probability the identity and the source of the DNA, including several additional vector borne pathogens. Our practice can offer both of these options and discuss with you their role in your diagnosis. Deer ticks have been associated with Lyme, Babesia, Bartonella, Powassan virus, anaplasmosis, tularemia, and tick paralysis. The Lone Star tick has been associated with STARI, human monocytic ehrlichiosis, tularemia, tick paralysis, RMSF, and Alpha Gal Allergy and the American dog tick has been associated with human monocytic ehrlichiosis and RMSF. There is also the Western Black legged tick associated with Lyme, Babesia, anaplasmosis, and bartonella and the Wood tick, associated with RMSF, tularemia, tick paralysis, Q fever and the Colorado tick fever.


An adult female dog tick is on the paper clip but within it from left to right is the Adult male, adult female and two nymph deer ticks.
An adult female dog tick is on the paper clip but within it from left to right is the adult male, adult female and two nymph deer ticks. Photo Credit: James Occi MA, MS

Igenex offers testing, for which our practice has utilized. They can bill through Health Lab and they accept most commercial insurances, but not market place plans like Indiana Medicaid or IU Health. Medical Diagnostic Laboratories (MDL) also accepts most insurances. RED Lab tests for Borrelia species only. Vibrant Wellness can test for Lyme, as can Armin Lab and Infecto Lab.


Lyme's disease is a clinical diagnosis. An experienced clinician can diagnose Lyme in spite of negative two tier testing or even without it. However, it typically takes about two years for individuals to be diagnosed because there is delay in finding someone familiar with this presentation.


Treatment Considerations for Post-Treatment Lyme Disease


Prevention is key, certainly. Remove ticks within 24 hours of attachment as this is quite effective at preventing Lyme. If you see a tick on your body or a family member's, utilize a fine-tipped forcep, grasping the tick as close to the skin as possible without compressing the body. For engorged #ticks or ticks that have been presumed to be attached for 36-hours or longer, antimicrobial prophylaxis with a single 200-mg dose of doxycycline is recommended for adults if it can be given within 72 hours of tick removal and there is at least at 20 percent rate of tick infection with B.burgdorferi in the area. Children eight years or older also may be given a single dose of 4 mg per kg of doxycycline (maximum dose of 200mg) for prophylaxis. This would not be recommended however, for pregnant women or children younger than eight years.


Treatment is then a bit controversial though for a number of reasons. First, whether the focus should be towards the bacterium, B. burgdorferi, or towards other causes of continued disease manifestation can be a challenge, as continued symptoms may be evidence of previous treatment failure or its consequence. Either way, it is clinical symptoms which drive treatment.


Conventionally, early Lyme is treated with oral antibiotics most typically, specifically doxycycline 200 mg twice per day for adults and amoxicillin for children, and then more aggressive intravenous regimens are reserved for those with neurologic or cardiac symptoms, sometimes even refractory Lyme arthritis (Theophilus et al., 2015). When long-term Lyme is identified, months, even years of antibiotics may be prescribed, although certainly one might question if continued symptoms are an autoimmune response particularly in light of four randomized controlled trials demonstrating no benefit from prolonged antibiotic therapy. The American Academy of Pediatrics, American Academy of Neurology, American College of Rheumatology, and IDSA do not recommend prolonged antibiotic therapy.


Other approaches are Hydroxychloroquine 200 mg daily or twice daily (changes intracellular pH), Amoxicillin 1000 mg three times daily with Probenecid 500 mg three times a day, or Cefuroxime 500 mg twice daily. Herxheimer reaction is possible. Treatment is typically four-to-six weeks, then the diagnosis is reevaluated for any residual symptoms. Further treatment is provided until the client is asymptomatic. While the initial treatment may fail due to inadequate dosing or persistent infection from pleomorphic forms of Borrelia which may lead to chronic infections of spirochetal, L-form/spheroplast, or round body form. If the L-form/spheroplast, treatment must be intracellularly and bacteriostatic, which may be the Doxycycline, Azithromycin 250-500 mg daily or Clarithromycin 500 mg twice daily, or even Minocycline 100 mg twice daily. If the spirochetal infection, then we work on attacking the cell wall with Amoxicillin 1000 mg three times daily with probenecid 500 mg three times daily, or Amoxicillin/Clavulonic acid XR 2000mg twice daily, or even Bicillin LA 1.2 million units twice per week, Cefuroxime 500 mg twice daily, Cefdinir 300 mg twice daily or Ceftriaxone 2 gms twice daily intravenously. Finally, if round body form, Metronidazole 500 mg two or three times daily is typically offered, or Tinidazole 500 mg twice daily or Hydroxychloroquine 200 mg twice daily. Grapefruit seed extract has also been used successfully, at 500 mg three times daily.


Immune Health is Most Important


These approaches though puts the individual at significant risk for C. difficile, not to mention the plethora of additional risks associated with antibiotics, particularly long-term. From an integrative and functional wellness perspective, our goal is to support the entire body. We work to decrease inflammation, decrease immune dysregulation, and reduce autoimmune activation. Even if antibiotics are utilized, this approach is important, as this bacterium can elude the immune system, change its morphology, and adapt to antibiotic treatments.


When we can help eliminate immune system triggers, the body can better function and be more effective at eradicating the bacteria on its own, allowing for fewer or shorter treatment protocols and fewer side effects. Consider that more than 70 percent of the human immune system is located in the gut, so optimizing gut barrier integrity and immune function within the gastrointestinal tract is a key component of treatment. The intestinal tract needs to have tight junctions within the gut to prevent pathogens and toxins from passing through, and fight intruders like bacteria, viruses, mold, fungal infections, yeast infections, food allergies, stress, and everything else thrown at it.


Our goal is to find a diet most advantageous to you, through mediated end-cell testing and epigenetic review. This is a foundational approach to healing from Lyme. Various co-infections transmitted in a tick bite can disrupt the gut microbiota, which promotes gut dysfunction and systemic inflammation. This leaky gut result can put our bodies at risk even further, inviting a cascade of negative effects. Individuals may have some biofilm that needs treatment as well. Systemic enzymes that may prove helpful include Lumbrokinase, Nattokinase, Serrepeptase, or InterFase Plus. Stevia, Xylitol, Biocidin, Grapefruit Seed Extract, Lauricidin, and BFM-1 from Beyond Balance.


We then need to address the imbalance and abnormal immune response, and chronic up-regulated oxidative stress. Our IV Nutritional therapies are excellent options for this approach. We can offer antioxidants, minerals and vitamins which are better absorbed intravenously. Because Lyme can evade the immune system and because individuals with chronic Lyme have a suboptimal ability to detoxify, chelation may be appropriate so we can work to reduce the body's burden through aggressive detoxification. When Lyme is present, often so are toxic metals, mold toxins, persistent organic pollutants, and so much more.


Energy is key to recovery in any illness or disease and chronic Lyme is certainly no different. We can offer tools to assess your mitochondrial function (energy within each cell) and offer interventions for resuscitating your mitochondria, either through oral nutraceuticals or intravenous therapy.


Addressing Gut Health


Our hormones and neurotransmitters are by-products of our gut health, so when facing dis-ease, these often need evaluated and balanced as well. We can't ignore our nervous system health, the limbic system, known also as fight-or-flight, which can really enrage our immune system. Addressing the molecules of emotion alongside immune modulators or mast cell activation is necessary for many with chronic Lyme. We don't however, just offer hormones to correct the imbalance as this ignores all the underlying issues and will not help you long-term. We heal in our safe, relaxed place, not while our body is fighting the war.


Old school thinking believed that the nucleus was the brain of every cell, but today we understand the membrane to be the mecca-center. This is where the cell reacts to its environment, and this part of the cell is made of fats, so healthy fats make better fats. Phosphatidylcholine is a healthy fat found in abundance in our healthy membranes, so we will address this as well.


Dr. Lane has embraced both the science and art of healing, gaining training in both pharmaceutical and botanical antimicrobials for treatment. Herbs can suppress opportunistic pathogens and do so without destroying non-harmful flora, which provides a significant advantage over pharmaceutical antibiotics which target both pathogenic and beneficial bacteria. Other plant-based botanical supplements can be used to support the immune system and other physiological and biochemical systems to boost your body's innate ability to heal.


The whole leaf Stevia extracts have been found effective against the Lyme disease causing pathogen, B. burgdorferi, and all its known morphological forms. Studies have already identified Stevia as not having mutagenic, teratogenic, or carcinogenic effects, and it does appear to be safe at high dietary intake levels (Theophilus et al., 2015). Cat's claw, Japanese Knotweed, Sarsparilla, Guaiac resin, Stillingia root, Prickly ash bark, boneset herb, isatis root, lomatium root, Andrographis, Foundation Formula, Advanced Biotic, A-L Complex and a few others are additional botanical treatments. More recently I've heard the herbalist, Margi Flint, recommend teasel root. I've also had clients share they have used Allicin 600, which is an ingredient of garlic, and GSE liquid concentrate, which is an organic liquid grapefruit seed extract, about 5 to 10 drops at a time, in a little juice. Saunas. Hot tubs. Steam baths.


The reality is that while antibiotics can be a powerful tool in the fight against Lyme disease, it is also important to recognize that not every person will respond the same. Antibiotics can also be damaging to the gut. Even when effective, a plan for restoring the gut and limbic system is vital for ongoing health. Treatment may not be effective because other infections are also simultaneously complicating the individual, so these too need to be addressed.


Complementary Therapies for Treatment of Lyme


A combination of other modalities can also be part of the treatment plan for chronic infections for most individuals. Disulfuram (Tetraethylthiuram, aka Antabuse) is an approach with growing popularity as it's safety profile is better understood and it is showing great effectiveness. Dr. Buhner has several books on treating Lyme with botanical medicine which are well respected as well. Dr. Rawles is another.


Ozone therapy has been used to treat a wide range of conditions, and in the past few years has gained recognition for its success in treating Lyme disease. The multi-system illness in late stage Lyme really does demand a broader approach to treatment than simply addressing the infectious component. Immune dysregulation and mitochondrial dysfunction become an integral component of therapy. Ozone therapy provides an effective solution due to its antimicrobial activity and ability to improve immune and mitochondrial function.


Nutritional IV therapy can help build up nutrients and replenish your body to help you better tolerate treatment and heal. We can offer antimicrobials, anti-inflammatory agents, #antioxidants, chelaters, and oxygen therapy in our IV Lounge here at Eden Family Practice, LLC. We also have an exceedingly complex detoxification program that not only works through your #epigenetics, liver and kidney functions, but also #trauma and #somatic healing.


Far infrared saunas are yet another option. This approach helps to increase body temperature and can be beneficial in supporting detoxification, a key component to recovering from Lyme. Far infrared light is absorbed by the skin and can provide immune support throughout the healing process by increasing circulation, which allows other treatment modalities to reach all areas of the body in a more efficient manner. Infrared sauna can also provide pain relief by relaxing muscles and support whole body detoxification. Lyme disease can make it harder for the body to naturally release harmful chemicals and heavy metals in the body.


Low dose immunotherapy, craniobiotic technique (CBT), lymph drainage therapy (LDT), photobiotic light therapy, and peptide therapy are additional therapies, but addressing limbic or polyvagal impact is also imperative. We have a multitude of approaches we offer our clients in this regard, including yoga specific for healing the entire body - mind, body, and spirit. If you want further information on how we can help you, join one of our Meet the Doctor sessions by booking online. These are free and allow you to identify if we might be a good fit for your journey.


Co-Infections that May Challenge Treatment


Bartonella may undermine treatment for Lyme. Testing for this co-infection is poor, typically done through PCR and IgM and IgG. This often presents with painful soles, painful ribs, acute anxiety, severe neurologic manifestations, gastrointestinal symptoms, and stretch marks. Bartonella is treated with Doxycycline, Minocycline, Sulfamethoxazole DS, Rifampin/Rifabutin, Quinolones, and Methylene Blue. Herbal options are Cat's Claw, Houttuynia, Red Sage Root, BLt, MC Bar1/2 and Herbal Biotic.


Babesia is another co-infection that can challenge Lyme treatment. Testing is through IgM/IgG, FISH, and PCR. Weakness, chills, sweats even drenched at night, fever, and air hunger are potential symptoms with Babesia. Treatment is typically with Atovaquone/proguanil, Atovaquone with Zithromax or Coartem or Krintafel or even Disulfiram. Herbal treatments for Babesia are Cryptolpeis, Artemisia, Black Walnut, Crypto Plus, MC Bab-1/2/3, and A-Bab.


Ehrlichia and Anaplasma are tested through IgM/IgG and may also accompany #leukopenia, thrombocytopenia, and elevated liver function tests. Distinct symptoms include high fever, severe headaches, muscle pain, and fatigue. Treatment is with Doxycycline, Minocycline, or Rifampin/Rifabutin. Cat's Claw, Japanese Knotweed, Sarsparilla, Andrographis, Foundation Formula, Advanced Biotic, and Red Sage Root are botanical options.


References

Theophilus, P. A. S., Victoria, M. J., Socarras, M., Filush, K. R., Gupta, K., Luecke, D. F., & Sapi, E. (2015). Effectiveness of stevia rebaudiana whole leaf extract against the various morphological forms of borrelia burgdorferi in vitro. European Journal of Microbiology and Immunology, 5(4), 268-280.

Wright, W. F., Riedel, D. J., Talwani, R., & Gilliam, B. L. (2012). Diagnosis and management of Lyme disease. American Family Physicians, 85(11), 1086-1093.

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