Complexity and Controversy The Lyme Enigma Complexity and Controversy

Lyme Life Cycle Lyme disease is caused by a tick-borne spirochete, Borrelia burgdorferi. Humans are an incidental host The lifecycle of the spirochete is predominantly between mice, deer and the deer tick. In CA ixodes pacificus is the vector and in the east coast it is ixodes scapularis The nymph deer tick is the most likely to transmit Lyme, and they are generally feeding in the spring and summer, adults feed in the fall

A closer look Borrelia burgdorferi is found in NA. But also B miyamotoi Borrelia garinii and afzelii are found in Europe. Or American patients returned from Europe. Ticks are not the only way to get Lyme: sexual and placental transmission

Early signs and symptoms of Lyme Erythema Migrans onset 7-14 days after bite Sore throat, myalgias, arthralgias, fever, chills, and headache within days to 2 weeks after infection If symptoms are severe and high fever is present consider co-infection with human granulocytic anaplasmosis(HGA) and Babesia. Babesia microti/duncani in the East and babesia duncani in CA

Early disseminated Lyme Arthralgias, Neurologic symptoms, headaches, cranial neuropathy, diffuse or focal mononeuropathy multiplex, lymphocytic meningitis, plexopathy, Radiculoneuropathy (Bannwarth syndrome) Cardiac symptoms syncope, dyspnea, chest pain, palpitations, A-V block Skin involvement-secondary erythema migrans, acrodermatitis chronicum atrophicans

Late Lyme disease Occurs months to years after infection and often a period of latency Joint and neurologic symptoms most common Sub acute encephalopathies, axonal neuropathies and peripheral neuropathy Bannwarth syndrome Neuropsychiatric symptoms

Diagnosis antibodies, antigen, PCR, T-cell response, culture

Direct testing PCR Lyme antigen Coyle’s research

Antibodies Initial lag time to seroconversion Conversion of IgM to IgG sensitivity of ELISA sensitivity of WB WB comparison C6LPE afzelii and garinii Coyle’s research

T-cell response aka iSpot

long incubation, preferred media, preferred surfaces Lyme culture fussy bug: long incubation, preferred media, preferred surfaces

Associated Lab Findings low CD57, low WBC possibly low IgG3 or slightly elevated ANA normal ESR, CRP first-degree heart block

Babesia, Bartonella, Ehrlichia, Anaplasmosis... Co-infections Babesia, Bartonella, Ehrlichia, Anaplasmosis...

Treatments antibiotics, herbs, oxidative therapies, silver

IDSA Treatment of early Lyme disease without significant neurological or cardiac symptoms Doxycycline 200mg bid Amoxicillin 500mg tid Cefuroxime 500mg bid All the above are given for 14-21 days

ILADS treatment of Erythema Migrans without other symptoms Doxycycline 100mg qid or 200mg bid with food Cefuroxime 1g bid Amoxicillin 1g tid with probenicid 500mg tid if pregnant dose Amoxicillin q6h Treat for 21 days If pregnant treat for 6 weeks and test for Babesia, HGA, and Bartonella

IDSA treatment of Lyme carditis Ceftriaxone 2gm qd for 10-28 days Doxycycline 100-200mg po bid for 10-28 days For AV block or myopericarditis use either of above regimes with appropriate inpatient monitoring. With resolution of heart block patient may be discharged home on po meds

ILADS Early disseminated Lyme Milder symptoms present for less than one year with multiple Erythems Migrans lesions, constitutional symptoms, and lymphadenopathy, Treat with oral therapy until no active disease for 4 weeks (4–6 months typical) using same antibiotic doses as outlined for Erythema Migrans  Pregnancy: As in Erythema Migrans, but duration as above. Treat throughout pregnancy, and do not breast feed. 

IDSA treatment of late Lyme disease arthritis Doxycycline 100mg bid Amoxicillin 500mg tid Cefuroxime 500mg bid Treat for 28 days If persistent or recurrent joint swelling retreat with another 28 days of above antibiotics or 2-4 weeks of IV ceftriaxone Then supportive therapy B-3

IDSA late neurologic Lyme disease This includes encephalopathy's and radiculopathies, Bannwarth syndrome Treat with ceftriaxone 2 gm qd for 2-4 weeks “Response to treatment is usually slow and may be incomplete” “Re-treatment is not recommended unless relapse is shown by reliable objective measures”

ILADS Late Disseminated/ Chronic Lyme Symptoms present greater than one year, more severely ill patients, and those with prior significant steroid therapy or any other cause of impaired immunity:  Treat adults and pregnant woman with 10 or more weeks of IV therapy , then oral or IM till asymptomatic for 6-8 weeks Children: IV therapy for 6 or more weeks, then oral or IM follow up as above.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours.  Ceftriaxone Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five or less days in a row per week).  Adults and pregnancy: 2g q12h, four days in a row each week.  Children: 75 mg/kg/day up to 2g/day  Cefotaxime Comparable efficacy to ceftriaxone; no biliary complications.  Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion.  Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.  *Doxycycline Requires central line as is caustic. Surprisingly effective, probably because higher overall, and spiked blood levels when given parenterally.  Always measure blood levels.  Adults: 400 mg q24h and adjust based on levels.  Cannot be used in pregnancy or in younger children.  Azithromycin Requires central line as is caustic.  Dose: 500 to 1000 mg daily in adolescents and adults.  Penicillin G IV penicillin G is minimally effective and not recommended.  Benzathine penicillin Surprisingly effective IM alternative to oral therapy.  May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed.  Adults: 1.2 million U three times per week (higher doses with large body habitus)  Adolescents: 300,000 to 2.4 million U weekly.  May be used in pregnancy.  Poorly studied but anecdotally effective  Vancomycin Observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns.  Use standard doses and confirm levels.  Imipenim and Unisyn Similar in efficacy to cefotaxime, but often works when cephalosporins have failed.  Must be given q6 to q8 hours.  Cefuroxime Useful but not demonstrably better than ceftriaxone or cefotaxime.  Ampicillin IV More effective than penicillin G. Must be given q6 hours. 

IDSA treatment of late Lyme disease arthritis Doxycycline 100mg bid Amoxicillin 500mg tid Cefuroxime 500mg bid Treat for 28 days If persistent or recurrent joint swelling retreat with another 28 days of above antibiotics or 2-4 weeks of IV ceftriaxone Then supportive therapy B-3

IDSA late neurologic Lyme disease This includes encephalopathy's and radiculopathies, Bannwarth syndrome Treat with ceftriaxone 2 gm qd for 2-4 weeks “Response to treatment is usually slow and may be incomplete” “Re-treatment is not recommended unless relapse is shown by reliable objective measures”

IDSA Post Lyme disease syndrome proposed definition Onset of the following symptoms within 6 months of a documented case of Lyme that has been treated by IDSA guidelines Fatigue Widespread musculoskeletal pain Complaints of cognitive difficulties Exclusion of any diagnosable disease

Why antibiotic treatments don’t work three forms of lyme (spirochete, L-form, cyst) biofilm tissue sequestration patient’s intolerance to treatment: toxicity, gastritis, mycosis, mitochondrial fatigue co-infections evolution of bacteria, i.e. resistance targeted vs comprehensive treatment strategy 25

Why treatments don’t work Immune evasion Using proteins that look like ours (ID badges), avoid recognition and therefore destruction by complement pathway. Mutate surface proteins. Encysting. Using proteins that look like ours (feeding misinformation), activate the immune system non-productively

Immune Evasion Modulation of it’s surface antigens, OspA and OspC Evades complement pathway: OspC, CD59-like complement inhibiting protein OspA potent neutrophil stimulator and inducer of IL-1b, TNF-a, and IL-6 Induces IL-10 initially to downregulate immune response Delayed conversion of IgM to IgG

Comprehensive Support anti-inflammatory: diet, herbs, proteolytic enzymes lymphatics: walking, skin brushing, massage gastro-intestinal: probiotics, regularity liver support: phase I and II brain/nerves: B12, herbals methylation, glutathione emotional/spiritual