Non-Antibiotic Approaches to the Management of Lyme Disease

172 Pages·2013·1.77 MB·English

by  Yvonne Lin

Non-Antibiotic Approaches
to the
Management of
Lyme Disease and Co-infections

Steven Harris, MD
Lyme
Affiliations:
Clinical Consultant, Igenex Inc.
CEO Pacific Frontier Medical Inc.
B31
“This is the most complex bacterial organism I know of.”

Casjens, personal correspondence 11/03

• Linear genomic chromosome with 910 kbp.

• 12 linear plasmids.

• 9 circular plasmids.

• 300% more plasmids than any other known bacteria.

• Tremendous amount of prophage DNA.

• There are 133 functional genes.

• Very few genes are metabolic.

• Does not require iron for metabolism.

• Casjens, S et al. A Genome in Flux: The twelve Linear and Nine Circular Extrachromosomal DNAs of an Infectious Isolate
oof the Lyme Disease Spirochete Borrelia Burgdorferei. Molec Microbiol. 35: 490-516
Bb FUNCTIONAL CHARACTERISTICS

Characteristic Clinical Significance
• Avoids antibody detection and
Often An Intracellular Organism
avoids lysis from most beta-lactam
(Dorward D, 9th International Conference
antibiotics which do not penetrate
on Lyme Borreliosis, 1998.)
cells. Bb is not present in high
numbers in the blood

Microaerophilic • Helical Bb will tend to move away
from oxygen-rich areas in vivo and
(Barbour AG, et al. “Borrelia’s Strategies
for Survival”, Science, 1987, No. 237, pp. reside in fascia, cartiledge,
403-411) epineureum and other oxygen poor
areas.
• Helical Bb may be inactivated and
Heat Sensitivity
destroyed upon exposure to
(Barbour AG, et al. Science, 1987)
temperature of 40 oC for 3 hours.
Bb FUNCTIONAL CHARACTERISTICS

Characteristic Clinical Significance
• Helical Bb thrives in slightly acidic
PH Sensitivity
environments (7.0 - 7.3). It forms
Donta ST, Tetracycline therapy for chronic
an acidic vacuole intracellularly for
Lyme disease. Clinical Infectious Dis
25:suppl 1(July 1997):352-356 protection

Epitope Switching • Bb alternates its outer surface
Seller KP, Weiss JJ. Immunity to Lyme proteins preventing sustained
disease: Protecdtion, pathology and immune recognition & attack.
persistence. Current opinion in Immunology

1996; 8(4): 503-9
• Jarisch-Herxheimer reactions can
Stress Mediated Toxin Release
complicate treatment, as well as
clinically guide physicians in
diagnosis and effectiveness of
treatment.
Bb FUNCTIONAL CHARACTERISTICS

Characteristic Clinical Significance
• In vitro generation time is 12-36
Slow Division Cycle
hours. In vivo, it is much longer,
(Burrascano J, 9th International
perhaps even 14 - 28 days. Length
Conference on Lyme Disease; 11/03;
MacDonald AB, et al. Clinical implications of of treatment must contain adequate
delayed growth of the Lyme disease division cycles, e.g., 10 day course
spirochete, Borrelia burgdorferi. Acta Trop of pcn for Group A beta-hemolytic
1990; 48(2):89-94)
streptococcus covers about 500

division cycles. A similar course for
Bb assuming 24 hour division cycle
would last 2 years.
Plasma Mediated Resistance
• Beta-lactam and tetracycline
resistance likely with sustained
treatment
Bb Surrounds Itself With Host’s
• Avoids detection from immune system.
Own Lymphocyte Cell Membrane
(Doward D, et al. Clinical Infect Dis, 1997)
Bb FUNCTIONAL CHARACTERISTICS

Characteristic Clinical Significance
• Destroys bodies defensive
Bb Actively Attacks
weapons
Lymphocytes, Macrophages,
Natural Killer Cells
(Doward D, et al. Clinical Infect Dis, 1997)

Bb Selectively Binds • In addition to direct destruction of
Oligodendria cells; These Cells myelin by bacterium, the host
antibodies may in effect attack
Are Responsible For Synthesis
myelin while targeting Borrelia to
and Maintenance Of Myelin.
which myelin is in close contact,
(Garcia Monco JC, et al. Adherence of the
thus simulating genuine MS.
Lyme Disease spirochete to glial cells and
cells of glial origin. J Infect Dis 1989; 160:
497-506)
Bb FUNCTIONAL CHARACTERISTICS
Characteristic Clinical Significance
Induction of Cytokine Releases • Inflammatory response causes
(TNF alpha, IL1, IL6) severe multisystem effects.
Part of effective immune
Prevention of other Cytokine
response is blunted.
Releases (IL2)

(Chiao Jw, Abstract 7th International
Conference on Lyme Borreliosis, 1994;
Defosse DL, et al. In vitro and in vivo
induction of tumor necrosis factor alpha by
Bb. Infect Immun 1992; 60: 1109-1113)
Bb FUNCTIONAL CHARACTERISTICS
Characteristic Clinical Significance
Bb Can Change Its Morphology To
Cell-Wall Deficient Cysts
1. Cysts Are Heat, Pressure and
Oxygen Resistant.
Cystic Forms Of Bb Are Probably A

Main Reason For Treatment
2. Cysts Are Resistant To All
Resistance And Relapse.
Antibiotics Except Tinidazole,
Metronidazole and
Hydroxychloroquinine.

3. In Vitro, Cystic Bb Can Readily
Revert Back To Helical Bb.

(Brorson O, Brorson SH, “Transformation of Cystic Forms of Bb To
Normal Mobil Spirochetes”, Infection, 1997, No. 25, pp. 240-246; Alban PS, Johnson PW, Nelson DR. Serum-starvation-induced
changes in protein synthesis and morphology of Borrelia burgdorferi. Microbiology 2000;146 (P1):119–27. Bruck DK, Talbot ML, Cluss RG,
Boothby JT. Ultrastructural characterization of the stages of spheroplast preparation of Borrelia burgdorferi. J Microbiol. Methods 1995; 23:219–
28; Preac-Mursic V, Wanner G, Reinhardt S, Wilske B, et al. Formation and cultivation of Borrelia burgdorferi spheroplast L-form variants.
Infection 1996; 24:218–26)