ABSTRACTS OF PUBLISHED RESEARCH
1. Oksi, J., et al., 1999, Borrelia burgdorferi detected by culture and PCR in
clinical relapse of disseminated Lyme Borreliosis. Annals of Medicine, 1999,
31(3):225-32. Of 165 patients treated for disseminated Lyme borreliosis with
three months or more of antibiotics (including a minimum of two weeks of
ceftriaxone), 32 had treatment failure. At follow-up, 13 patients with clinical
relapse were PCR or culture positive (10 PCR positive, 1 culture positive, 2 PCR
and culture positive). “In this study, culture or PCR-based evidence for the
presence of live spirochetes was obtained in more than 40% of the patients with
relapsed disease.” “The treatment caused only temporary relief in the symptoms
of the patients.” “We conclude that the treatment of Lyme borreliosis with
appropriate antibiotics for even more than 3 months may not always eradicate the
spirochete.”
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2. Climperman J., et al., 1999, Lyme meningitis: a one-year follow up controlled
study. Wien Klin Wochenschr, 1999, 111(22-23):961-3.
[Abstract:] “The results of our study revealed that Lyme meningitis frequently
occurs without meningeal signs and is often accompanied by additional
borreliosis persisted or occurred for the first time in several patients. They
were not infrequent even at the examination performed one year after therapy.”
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3. Petrovic, M., et al., 1998, Lyme borreliosis – A review of the late stages
and
treatment of four cases. Acta Cinica Belgica, 1998, 53(3):178-83.
A five-week treatment with doxycycline at a dose of 200 mg daily was prescribed.
Fatigue, arthralgia en myalgia seemed to respond positively to the initiated
therapy. However, they reappeared two weeks after cessation of doxycycline. …it
was decided to treat with ceftriaxone IM 2 g daily for three weeks. This
resulted in a complete resolution of the general symptoms. However, three weeks
later arthralgia of the knees and myalgia in both legs recurred. …Symptoms and
signs may improve only temporarily shortly after treatment, but re-emerge within
weeks or months.
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4. Weber, K., 1996, Treatment failure in erythema migrans: a review. Infection,
1996, 24:73-5.
[From the abstract:] “Patients with erythema migrans can fail to respond to
antibiotic therapy. Persistent or recurrent erythema migrans, major sequelae
such as meningitis and arthritis, survival of borrelia burgdorferi and
significant and persistent increase of antibody titres against B. burgdorferi
after antibiotic therapy are strong indications of a treatment failure. Most, if
not all, antibiotics used so far have been associated with a treatment failure
in patients with erythema migrans.”
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5. Mursic, VP., et al., 1996, Formation and cultivation of borrelia burgdorferi
spheroplast L-form variants. Infection, 1996, 24(3):218-26
[Persistence:] “…clinical persistence of borrelia burgdorferi in patients with
active Lyme borreliosis occurs despite obviously adequate antibiotic therapy…”
“The persistence of Bb even after therapy with antibiotics has been demonstrated
in cerebrospinal fluid (CSF), in skin, iris, heart and joint biopsies.” [Cysts:]
In vitro investigation of morphological variants of B. burgdorferi, in an effort
to explain the clinical persistence of active Lyme borreliosis despite
antibiotic therapy. The authors suggest that these atypical forms may allow
Borrelia to survive antibiotic treatment.
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6. Bayer, ME., et al., 1996, Borrelia burgdorferi DNA in the urine of treated
patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Infection,
1996, 24 No. 5.
The urine of 74.2% of patients previously treated with antibiotics for Lyme
disease was found to be positive for B.burgdorferi DNA using PCR testing. All
patients (n=97) had prior documented EM rash and had received a minimum of 3
weeks to 2 months oral or intravenous antibiotics. In 4 patients, PCR results
were temporarily negative after treatment, but became positive again 4-6 weeks
later. All patients suffered “continuing, often gradually worsening Lyme
disease-like symptoms. …it seems to be characteristic for most of the patients
in our study that, after antibiotic-free periods of a few months, they had again
become increasingly ill with neurological and arthritic symptoms, so that
treatment had been resumed.”
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7. Oksi, J., et al., 1996, Inflammatory brain changes in Lyme borreliosis. A
report on three patients and review of literature. Brain, 1996, Dec;119(Pt
6):2143-54.
“In one of the six analyzed brain tissue specimens [from a patient who had
received more than six months of antibiotic treatment prior to death, including
two 3-week courses of IV ceftriaxone], B. burgdorferi DNA was detected by PCR.”
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8. Mursic, VP., et al., 1996, Kill kinetics of Borrelia burgdorferi and
bacterial findings in relation to the treatment of Lyme borreliosis. Infection,
1996, 24(1):9-16
[Persistence:] “…the persistence of B. burgdorferi s.l. and clinical recurrences
in patients despite seemingly adequate antibiotic treatment is described.”
[Diagnosis:] “The patients had clinical disease with or without diagnostic
antibody titers to B. burgdorferi.”
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9. Waniak, C., et al., 1995 Rapidly progressive frontal-type dementia associated
with Lyme disease. Journal of Neuropsychiatry Clin Neurosci, 1995, 7(3):345-7.
[From the abstract:] “The authors report a case of fatal neuropsychiatric Lyme
disease (LD) that was expressed clinically by progressive frontal lobe dementia
and pathologically by severe subcortical degeneration. Antibiotic treatment
resulted in transient improvement, but the patient relapsed after the
antibiotics were discontinued. LD [Lyme disease] must be considered even in
cases with purely psychiatric presentation and prolonged antibiotic therapy may
be necessary.”
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10. Steere, AC., 1995, Musculoskeletal manifestations of Lyme disease. American
Journal of Medicine, 1995, 88:4A-44S-51S.
“…a 1-month course of oral antibiotics may not always eradicate viable
spirochetes.”
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11. Steere, AC., et al., 1994, The long-term clinical outcomes of lyme disease.
A
population-based retrospective cohort study. Annals of Internal medicine,
121(8):
560-7.
“Ten of the 38 patients with Lyme disease reported relapses within 1 year of
treatment…and had had repeated antibiotic treatment (5 patients with intravenous
ceftriaxone). …Patient 4, in addition, had had second degree atrioventricular
block with acute Lyme disease that resolved with penicillin treatment. Her
irregular rhythm recurred 2 years later, resolved temporarily with ceftriaxone
treatment, but progressed to complete heart block requiring a pacemaker.
…Patient 12…was treated with 2 weeks of parenteral penicillin. She later
developed a progressive speech disorder, bradykinesia, and abnormal ocular motor
function. Magnetic resonance imaging of the brain showed scattered white matter
lesions in the hemispheres and pons…she was re-treated with 2 weeks of
parenteral ceftriaxone in 1989 that had no effect on her neurologic symptoms.
During the time of observation, this patient died. At autopsy…[using] Dieterle
silver stain, a spirochete was present in the cortex and another was exterior to
a leptomeningeal vessel.”
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12. Lopez-Andreu, JA., et al., 1994, Treatment of late Lyme disease: a challenge
to accept. Journal of Clinical Microbiology, 1994, 32:1415-16.
“[The patient] received 2 g of ceftriaxone daily for 4 weeks. Marked early
clinical improvement was observed and continued for 3 weeks after therapy was
discontinued. He received 6 additional courses of intravenous antibiotics for 3
to 5 weeks’ duration (penicillin, doxycycline [two courses], and ceftriaxone
[three courses], and 1 oral antibiotic (azithromycin). His general condition
improved, but each antibiotic course was followed by a relapse.”
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13. Klempner, MS., et al., 1993, Invasion of human skin fibroblasts by the Lyme
disease spirochetes, borrelia burgdorferi. Journal of Infectious diseases, 1993,
167:1074-1081.
This study found that B. burgdorferi spirochetes can survive antibiotic
treatment through intracellular sequestion within firbroblasts. “In these
experiments, we demonstrated that fibroblasts and keratinocytes were able to
protect B. burgdorferi from the action of this B-lactam antibiotic [ceftriaxone]
even at antibiotic concentrations > or = 10 times the MBC of the antibiotic. The
protective effect was sustained for , or = 14 days and required viable
fibroblast monolayers…We have demonstrated the presence of intracellular B.
burgdorferi within HF [human fibroblasts] using laser scanning confocal
microscopy…The observation of viable spirochetes within fibroblasts coupled to
protection of B. burgdorferi from extracellular microbicidal antibiotics by
fibroblasts [19] suggests that B. burgdorferi may be among the small number of
bacteria that can cause chronic infection by localizing within host cells where
they remain sequestered from some antimicrobial agents and the host humoral
immune response.”
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14. Georgilis, K., et al., 1992, Fibroblasts protect the Lyme disease
spirochete,
Borrelia burgdorferi, from ceftriaxone in vitro. Journal of Infectious Diseases,
1992, 166(2):440-4.
[From the abstract:] “The Lyme disease spirochete, Borrelia burgdorferi, can be
recovered long after initial infection, even from antibiotic-treated patients,
indicating that it resists eradication by host defense mechanisms and
antibiotics. …Human foreskin fibroblasts protected B. burgdorferi from the
lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC.
In the absence of fibroblasts, the organisms did not survive…Fibroblasts
protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse
keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same
protective effect. Thus, several eukaryotic cell types provide the Lyme disease
spirochete with a protective environment contributing to its long-term
survival.” [From the article:] “An intracellular site of survival would provide
protection, since many of the antibiotics are much less concentrated in the
cells than in extracellular spaces…Possibly fibroblasts and keratinocytes are
the initial sites of this intracellular survival. This is especially relevant in
that the first contact between the spirochete and the host in Lyme disease
occurs in the skin.” (p.443)
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15. Feder, HM., Jr., et al., 1992, Persistence of serum antibodies to Borrelia
burgdorferi in patients treated for Lyme disease. Clinical Infectious Diseases,
1992, Nov;15(5):788-93.
[From the abstract:] “…we recalled 32 patients with Lyme disease from a primary
care practice a mean of 16 months after treatment…Nine of the 32 patients had
persistent or recurrent symptoms, and ELISA and immunoblot were not helpful for
identifying these nine patients.”
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16. Dattwyler, RJ., et al., 1988, Seronegative Lyme disease. Dissociation of
specific T-and B-lymphocyte responses to Borrelia burgdorferi. New England
Journal of Medicine, 1988, 319(22):1441-6.
[From the abstract:] “We studied 17 patients who had presented with acute Lyme
disease and received prompt treatment with oral antibiotics, but in whom chronic
Lyme disease subsequently developed.”
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17. Ann NY Acad Sci, 1988:468-70. Concurrent neocortical borrelisois and
Alzheimer’s disease.
“Spirochetes were visualized in imprint prepareations of freshly thawed frontal
lobe cortex with monoclonal antibody H5332, which specifically binds to the
outer surface membrane of Borrelia burgdorfer. Borrelia spirochetes were
recovered from cultures of freshly thawed cerebral cortex and hippocampus in
Barbour-Stoenner-Kelly medium. An unexpected observation was the identification
of cystic forms of the Borrelia spirochete in dark-field preparations of
cultured hippocampus and in imprints of hippocampus using the monoclonal
antibody H9724, which binds to class-specific axial filament proteins of
borrelia spirochetes.”
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18. Gruntar, et al., 2001, Conversion of Borrelia garinii cysticforms to motile
spirochetes in vivo. APMIS, 2001, May;109(5):383-8.
“Cystic forms (also called spheroplasts or starvation forms) and their ability
to reconvert into normal motile spirochetes have already been demonstrated in
the Borrelia burgdorferi sensu lato complex. The aim of this study was to
determine whether motile B. garinii could develop from cystic forms, not only in
vitro but also in vivo, in cyst-inoculated mice. The cysts prepared in distilled
water were able to reconvert into normal motile spirochetes at any time during
in vitro experiments, lasting one month, even after freeze-thawing of the cysts.
Motile spirochetes were successfully isolated from 2 out of 15 mice inoculated
intraperitoneally with cystic forms, showing the infectivity of the cysts. The
demonstrated capacity of the cysts to reconvert into motile spirochetes in vivo
and their surprising resistance to adverse environmental conditions should lead
to further studies on the role and function of these forms in Lyme disease.”