Complexity and Controversy

Complexity and Controversy

• Complexity and Controversy

infectious illness affecting all organ systems

• infectious illness affecting all organ systems

• Ubiquity: reported in every state, and all northern continents

• Pattern recognition: inflammation

• Diagnosis! Not always straightforward

• Key to successful early treatment is timing

• Keys to long-term treatment for chronic case is fortitude, compassion, and flexibility

Avoid missing the early case~

• Avoid missing the early case~

• How chronic Lyme affects the patient:

• loss of physical functioning,

• loss of mental functioning

• loss of employment,

• loss of joy and emotional stability,

• loss of relationships,

• psychospiritual crisis

Lyme disease is caused by a tick-borne spirochete, Borrelia burgdorferi.

• 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

Borrelia burgdorferi

• Borrelia burgdorferi

• Borrelia andersonii

• Borrelia miyamotoi

• Borrelia bissettii (DN 127)

• Borrelia garinii

• Borrelia afzelii

• Borrelia japonica

Conventional thought: Ticks only

• Conventional thought: Ticks only

• Ixodes scapularis, pacificus, dentatus

• Amblyomma americanum, the Lone Star tick

• Ixodes ricinus: Scandinavia-Russia-N Africa

• Ixodes persulcatus, Haemaphysalis flava: Japan

• http://www.pasteur.fr/recherche/borrelia/Bb_strains_alphabetic.html

• Fleas? Ctenocephalides felis also harbors Bb

Mammals and birds

• Mammals and birds

• Migratory

• Climate change

Placental transmission

• Placental transmission

• Transfusion: current testing is for hep B and C, HIV, HTLV, syphilis, Chagas, West Nile Virus (see John Hopkins and American Red Cross). AABB says you shouldn’t donate if you’ve ever had babesiosis. CDC says you can donate if you’ve finished treatment.

• Sexual transmission

Erythema Migrans onset 7-14 days after bite

• 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

IdentifyUS LLC
320 Needham St., Suite 200
Newton, MA 02464
http://identify.us.com
[e-mail]$20 per specimen or image evaluation (species identification, stage of development & estimated feeding duration). Turn-around time is usually the same day the specimens are received. Digital images, if of sufficient quality, can be uploaded to the web site for even faster service. Imaging instructions are provided on the website.

• IdentifyUS LLC
320 Needham St., Suite 200
Newton, MA 02464
http://identify.us.com
[e-mail]$20 per specimen or image evaluation (species identification, stage of development & estimated feeding duration). Turn-around time is usually the same day the specimens are received. Digital images, if of sufficient quality, can be uploaded to the web site for even faster service. Imaging instructions are provided on the website.

Arthralgias,

• 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 (afzelii)

Occurs months to years after infection and often a period of latency

• 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

Nonsensical fatigue

• Nonsensical fatigue

• Headaches

• Any palsy, neuropathy or tremor

• Joint pain, especially knees, neck, upper back

• Muscle pain and/or fasciculations

• Rashes: especially EM, but any asymmetrical rash;recovered, persistent, or intermittent

• Cyclic symptoms, esp every month

• New palpitations

http://www.cdc.gov/lyme/healthcare/clinician

• http://www.cdc.gov/lyme/healthcare/clinician

• Enzyme Immunoassay (EIA)OR Immunofluorescence Assay: If negative consider alternative diagnosis

• If positive, and symptoms >30 days, do IgG WB

• If positive, and symptoms <30 days, do IgG and IgM WB

antibodies,

• antibodies,

• antigen,

• PCR,

• T-cell response,

• culture

PCR: low yield

• PCR: low yield

• Lyme antigen

• Coyle’s research

Initial lag time to seroconversion

• Initial lag time to seroconversion

• Conversion of IgM to IgG

• sensitivity of ELISA

• sensitivity of WB

• WB comparison: Igenex vs other

• C6LPE

• afzelii and garinii

• Coyle’s research

aka iSpot

• aka iSpot

fussy bug:

• fussy bug:

• long incubation, preferred media, preferred surfaces

low CD57, low WBC

• low CD57, low WBC

• possibly low IgG3 or slightly elevated ANA

• normal ESR, CRP

• first-degree heart block

Babesia, Bartonella, Ehrlichia, Anaplasmosis...

• Babesia, Bartonella, Ehrlichia, Anaplasmosis...

antibiotics,

• antibiotics,

• herbs,

• oxidative therapies,

• silver

Artemisinin

• Artemisinin

• Cat’s Claw/Samento/Banderol

• Stephen Buhner

Ozone

• Ozone

• Hydrogen Peroxide

• Doxycycline 200mg bid

• Amoxicillin 500mg tid

• Cefuroxime 500mg bid

• All the above are given for 14-21 days

Doxycycline 100mg qid or 200mg bid with food

• 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

Ceftriaxone 2gm qd for 10-28 days

• 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

Milder symptoms present for less than one year with multiple Erythems Migrans lesions, constitutional symptoms, and lymphadenopathy,

• 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. 

Doxycycline 100mg bid

• 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

This includes encephalopathy's and radiculopathies, Bannwarth syndrome

• 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”

Symptoms present greater than one year, more severely ill patients, and those with prior significant steroid therapy or any other cause of impaired immunity: 

• 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. 

Doxycycline 100mg bid

• 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

This includes encephalopathy's and radiculopathies, Bannwarth syndrome

• 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”

Onset of the following symptoms within 6 months of a documented case of Lyme that has been treated by IDSA guidelines

• 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

Keep trying until you find a regimen that works, and use it while the patient continues to improve on it.

• Keep trying until you find a regimen that works, and use it while the patient continues to improve on it.

• Listen to the patient.

• Don’t give up on the patient.

• What does the patient need besides direct treatment for Lyme?

three forms of lyme (spirochete, L-form, cyst)

• 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

Sci Transl Med. Jul 3, 2013; 5(192): 192ra85. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.Kalghatgi S1, Spina CS, Costello JC, Liesa M, Morones-Ramirez JR, Slomovic S, Molina A, Shirihai OS, Collins JJ.

• Sci Transl Med. Jul 3, 2013; 5(192): 192ra85. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.Kalghatgi S1, Spina CS, Costello JC, Liesa M, Morones-Ramirez JR, Slomovic S, Molina A, Shirihai OS, Collins JJ.

• Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics-quinolones, aminoglycosides, and β-lactams-cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic-induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.

Immune evasion

• Immune evasion

• Mutate surface proteins. Encysting. Biofilm.

• Using proteins that look like ours (ID badges), to avoid recognition and therefore destruction by complement pathway.

• Using proteins that look like ours (feeding misinformation), to activate the immune system non-productively.

Modulation of it’s surface antigens, OspA and OspC

• 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. Functional immune deficiency. New or worsening allergic reactivity.

• Delayed conversion of IgM to IgG

anti-inflammatory: diet, herbs, proteolytic enzymes

• anti-inflammatory: diet, herbs, proteolytic enzymes

• lymphatics: walking, skin brushing, massage

• gastro-intestinal: probiotics, regularity

• liver support: phase I and II

• brain/nerves: B12, good fats, omega-3s, neurotransmitters

• methylation, glutathione

• Immune support: medicinal mushrooms, IgG

Emotional/spiritual support

• Emotional/spiritual support

• Consider less aggressive or more aggressive treatment

• Consider complaint: system-based support

• Consider backdrop of patient’s biochemical individuality, such as methylation deficiency

• Consider backdrop of patient’s environment, such as mold in the house….

• Refer